BCIS R&D Group Literature Review

September 2022

Prepared by Michael Mahmoudi, Paul Morris and Natalia Briceno
Edited by Michael Mahmoudi

Coronary Artery Disease

No need for routine non-invasive stress testing post-PCI

Routine functional testing or standard care in high-risk patients after PCI. NEJM 2022; 387:905-915

The optimal follow-up strategy for patients undergoing coronary revascularization who have high-risk characteristics is variable. Some studies have shown that functional testing is widely used in clinical practice with more than half of all such patients having had functional testing within 2 years of revascularization. The POST-PCI investigators conducted a randomized superiority trial to compare an active follow-up strategy of routine functional testing (nuclear stress testing, stress echocardiography, Exercise electrocardiography) examined whether a follow-up strategy that includes functional testing improved clinical outcomes. Patients (n=1706) who had undergone successful PCI with DES, bioresorbable scaffolds, or drug-coated balloon (for ISR) who had at least one high-risk anatomical feature (left main disease, bifurcation disease, ostial disease, CTO, multivessel disease warranting PCI of at least two vessels, a restenotic lesion, lesion length > 30mm or a lesion warranting a stent length of > 32mm, and bypass graft disease) or clinical characteristics (diabetes mellitus, chronic renal disease defined as serum creatinine ≥ 177 mmol/l or long-term haemodialysis, and enzyme positive ACS) were enrolled to a strategy of routine functional testing (n=849) at 1 year post PCI or standard care alone (n=857). Patients underwent routine follow-up at 6, 12, 18, and 24 months. The primary endpoint was a composite of MACE defined as death from any cause, MI, or hospitalization for unstable angina at 2 years. The mean age was 64.7±10.3, 79.5% were men, 21% had left main disease, 43.5% had bifurcation disease, 69.8% had multivessel disease, 70.1% had a diffuse long lesion, 38.7% had diabetes, 19.4% had an ACS, 96.4% were treated with DES, the mean number of stents per patient was 2.0, the mean stent length was 57mm, FFR was measured in 35.7% of the patients, and intravascular imaging was used in 74.4%. At 2 years, the primary endpoint was similar in the functional testing and standard care groups (5.5% vs. 6.0%; HR: 0.9; 95% CI: 0.61-1.35; p=0.62). There were no between-group differences with respect to the components of the primary outcome. At 2 years, invasive angiography had been undertaken in 12.3% of the functional testing group and 9.3% of the standard care group (p=0.62) had undergone invasive angiography. The rates of revascularization were also similar in the two groups (8.1% vs. 5.8%; p>0.05).

Reviving a failing heart with PCI

Percutaneous revascularization for ischemic ventricular dysfunction.

NEJM 2022 Online

The benefits of coronary revascularization in patients with significant left ventricular systolic dysfunction remains uncertain. A survival benefit in patients undergoing CABG in this population became apparent only after 10 years in the STICH trial. The REVIVED investigators examined whether coronary revascularization with PCI in addition to guideline directed optimal medical therapy (OMT) (n=347) as compared to OMT alone (n=353) improved event-free survival in patients with left ventricular ejection fraction (LVEF) ≤ 35%, extensive coronary artery disease (BCIS jeopardy score ≥ 6) and myocardial viability in at least four dysfunctional segments amenable to revascularization with PCI. The primary composite outcome was death from any cause or hospitalization for heart failure over a minimum follow-up period of 24 months. The major secondary outcomes were LVEF at 6 and 12 months, KCCQ overall summary score, the score on the EQ-5D-5L score, and NYHA functional class. The two groups were well matched for baseline characteristics. Median age was 70 years, 88% were men, 77% had NYHA class I/II, and 67% had no angina. The primary outcome occurred in 37.2% of the PCI plus OMT group and 38% of the OMT group (HR, 0.99; 95% CI: 0.78-1.27; p=0.96). The rates of death (31.7% vs. 32.6%; HR, 0.98; 95% CI: 0.75-1.27) and hospitalization for heart failure (14.7% vs. 15.3%; HR, 0.97; 95% CI: 0.66-1.43) were similar in the PCI plus OMT and OMT groups. The LVEF was similar in the two groups at 6 months (mean difference, -1.6 percentage points; 95% CI: -3.7-0.5) and at 12 months (mean difference; 0.9 percentage points; 95% CI: -1.7-3.4). Quality of life scores at 6 and 12 months favoured the PCI group but this difference diminished at 24 months. Of note, approximately 50% of the patients had 2V CAD and a median of two lesions and vessels were treated per patient which may be out of proportion to the extent of LV dysfunction. Other salient features include lack of description of the severity of stenoses, physiological assessment of the lesion, and lack of correlation of stenosis with previous ischemic/viability testing.

Secure compliance with the polypill

Polypill strategy in secondary cardiovascular prevention.

NEJM 2022; 387:967-977

Noncompliance with guideline directed optimal medical therapy is a frequently observed challenge faced by patients and healthcare providers. This is often associated with adverse clinical outcomes particularly in patients at the highest risk of adverse clinical events. A polypill strategy has been shown to improve compliance and lower cardiovascular event rates in trials of primary prevention.  The SECURE trial was a randomized phase 3 trial designed to assess the efficacy of a polypill strategy, as compared with standard care, with respect to major cardiovascular outcomes (defined as CV death, nonfatal type 1 MI, nonfatal ischemic stroke, or urgent revascularization) in patients older than 75 years of age or at least 65 years of age with at least one of the following risk factors: diabetes mellitus, mild or moderate renal disease defined as creatinine clearance 30-60 ml/min/1.73m² of body surface area, previous MI, previous coronary revascularization (PCI or CABG), or previous stroke. All patients had to have had a history of type 1 MI within the previous 6 months. The polypill contained any of three formulations Polypill AAR40-a single pill containing aspirin 100mg, ramipril 2.5, 5, or 10mg, and atorvastatin 40mg. The dose of the atorvastatin could be reduced to 20mg on clinical grounds in which case the Polypill AAR20 was used (same as AAR40 but reduced dose of atorvastatin at 20mg). In patients who were not on ramipril at baseline, treatment was commenced at 2.5mg; in those who were already on an ACE inhibitor, treatment was commenced at the equivalent dose of ramipril with the aim of reaching 10mg. Follow-up was undertaken at 6, 12, 18, 24, 36, and 48 months. At 6 and 24 months, adherence was checked using the eight-item Morisky Medication Adherence Scale. A total of 2499 patients were randomized (polypill=1258, standard care=1241). The median time between the index MI and randomization was 8 days. The mean age was 76±6.6 years, 31% were female, 77.9% had hypertension, 57.4% had diabetes, 51.3% had a history of smoking, mean systolic blood pressure was 129.1±17.7, and mean LDL was 89.2±37.2. Most patients in the polypill group (91.7%) received the 40mg formulation of atorvastatin as compared to 40.4% in the standard care group. 98.7% of patients in the standard care group received aspirin and 95.1% received an additional antiplatelet agent as compared to 94% in the polypill group. The primary endpoint was lower in the polypill group (9.5% vs. 12.7%; HR: 0.76; 95% CI; 0.60-0.96; p=0.02). All components of the composite outcome except for urgent revascularization were reduced in a consistent manner. The secondary outcome of CV death, MI, or stroke was also lower in the polypill group (8.2% vs. 11.7%; HR: 0.70; 95% CI: 0.54-0.90); p=0.005). All-cause mortality was similar in both groups (9.3% vs. 9.5%; p=0.79). Adherence was higher in the polypill group both at 6 months (70.6% vs. 62.7%; RR: 1.13; 95% CI: 1.06-1.20) and 24 months (74.1% vs. 63.2%; RR: 1.17; 95% CI: 1.10-1.25).

Routine pressure wire assessment not supported by RIPCORD-2

Routine pressure wire assessment versus conventional angiography in the management of patients with coronary artery disease: The RIPCORD 2 trial.

Circ 2022 Online

FFR-guided PCI has been shown to be associated lower resource utilization and improved clinical outcomes compared with angiography guidance alone. The value of FFR of all major coronary vessels at the time diagnostic angiography has not been established. The RIPCORD 2 trial was an 1100 patient prospective, multicentre, randomized trial that compared a strategy of coronary angiography alone versus coronary angiography + routine FFR assessment of all epicardial vessels of sufficient size amenable to revascularization to determine whether the latter strategy was associated with more effective resource utilization, improved quality of life, and better clinical outcome. In the angiography + FFR group, the median number of vessels examined was 4. There were no differences in the median hospital costs between the two groups (£4136 for angiography vs. £4510 for angiography + FFR; p=0.137) nor the median quality of life using the visual analog scale of the EuroQol EQ-5D-5L (75 vs. 75; p=0.88). The number of clinical events were death (5 vs. 8), stroke (3 vs. 4), MI (23 vs. 22), and unplanned revascularization (26 vs. 33) with a composite hierarchical event rate of 8.7% for angiography versus 9.5% for angiography + FFR (p=0.64). The study thus concluded that routine FFR at the stage of diagnostic angiography is not associated with reduction in cost or improvement in quality of life.

Alirocumab has favourable effects on plaque composition

Effect of alirocumab added to high-intensity statin therapy on coronary atherosclerosis in patients with acute myocardial infraction. The PACMAN-AMI randomized clinical trial.

JAMA 2022; 327:1771-81

PCSK inhibitors have been shown to result in significant reductions in LDL-C and improve clinical outcomes in patients with recent ACS. The PACMAN-AMI trial examined whether the addition of alirocumab to high-intensity statin therapy affected coronary atherosclerotic plaques in the non-infracted related arteries. Following PCU of the culprit lesion in the infarct related artery (IRA), eligible patients underwent intracoronary imaging of the non-IRA with OCT, IVUS and NIRS, and then randomized in a 1:1 fashion to receive either 150mg alirocumab (n=148) or placebo (n=152) biweekly via subcutaneous injection for 52 weeks.  Both groups also received rosuvastatin 20mg daily. Main inclusion criteria were age ≥ 18 years, successful PCI of the culprit vessel (STEMI=53%, NSTEMI=47%), suitability for intracoronary imaging with angiographic stenosis between 20-50% in the proximal segments of two non-IRAs, and LDL-C at baseline ≥ 125 mg/dl if not on a statin for 4 weeks prior to presentation or ≥ 70mg/dl if on a stable dose of a statin. Key exclusion criteria were left main or three vessel disease, history of CABG, severe chronic kidney or liver disease, and known statin intolerance. The mean age was 58 years, 18% were female, 10% were diabetic, and mean LDL-C was 152.4 mg/dl. At 12 months, the primary endpoint of change in mean percent atheroma volume from baseline for alirocumab was greater than placebo -2.13% vs. -0.92% (p<0.001). Mean change in maximum lipid core burden index within 4 mm was −79.42 with alirocumab vs. −37.60 with placebo (difference, −41.24; 95% CI: −70.71 to −11.77; p= 0.006). Mean change in minimal fibrous cap thickness was 62.67μm with alirocumab vs. 33.19μm with placebo (difference, 29.65μm; 95% CI: 11.75-47.55; p=0.001). Adverse events occurred in 70.7% of patients treated with alirocumab vs. 72.8% of patients receiving placebo. The change in LDL-C from baseline was -131.2 mg/dl in the alirocumab group vs. -76.5 mg/dl in the placebo group (p<0.001).

Valvular Heart Disease

Embolic protection remains a challenge

Cerebral embolic protection during transcatheter aortic valve replacement. NEJM 2022 Online

Embolization of biological material from either the aortic valve and/or the aorta may cause a periprocedural stroke in 2-2.5% of patients undergoing TAVI. The Sentinel cerebral embolic protection device (CEP) has been shown to be safe and effective in capturing debris in 99% of patients but the reduction in new cerebral lesion volume was not significant. The PROTECTED TAVR trial was a prospective, postmarket, multicentre, randomized, controlled trial designed to evaluate the efficacy of the Sentinal CEP in reducing stroke within 72 hours of transfemoral TAVI or before discharge. Stroke was defined as an acute episode of a focal or global neurologic dysfunction caused by vascular injury to the brain, spinal cord, or retina leading to haemorrhage or infarction. Disabling stroke, death, transient ischemic attack, delirium, major or minor vascular complications at the CEP access site, and acute kidney injury were also assessed.  Patients (n=3000) were eligible if they had AS and were scheduled to undergo transfemoral TAVI using a commercially available device. Patients were excluded if they had left common carotid or brachiocephalic artery stenosis >70% or the anatomical structure was unfavourable for placement of the CEP device. The mean age was 78.9±7.8 years, mean STS score 3.4±2.7, 40% were female, history of CVA/TIA was present in 8%, 8% had bicuspid AS, 3% had valve-in-valve procedure, a balloon expandable device was used in 64%, and duration of follow-up was 72 hours. The primary outcome was similar in the CEP and control groups (2.3% vs. 2.9%; difference -0.6 percentage points; 95% CI: -1.7 to 0.5; p=0.30). The rates of secondary outcomes for CEP and control groups were disabling stoke (0.5% vs. 1.3%; p<0.05), all-cause mortality (0.5% vs. 0.3%), stroke/TIA/delirium (3.1% vs. 3.7%), and acute kidney injury (0.5% vs. 0.5%).

Potential additional mechanism for stroke in TAVI patients

Cerebral microbleeds during transcatheter aortic valve replacement: a prospective magnetic resonance imaging cohort.

Circ 2022; 146:383-397

Cerebral microbleeds (CMBs) are frequently observed in elderly people and yet their clinical significance remains uncertain. The incidence of new CMBs and factors contributing to their formation in patients undergoing TAVI has not been previously examined. The current study prospectively examined a cohort of 84 patients with severe aortic stenosis that were referred for TAVI. Mean age was 80.9±5.7 years and 53% were female. On preprocedural MRI, 26% of the patients had at least 1 CMBs whilst following TAVI, new CMBs was observed in 23% of patients. In univariate analysis, a previous history of bleeding (p=0.01), higher total dose of heparin (p=0.02), a prolonged procedure (p=0.03), no protamine reversal (p=0.04), higher final ACT (p=0.05), lower final von Willebrand factor high molecular weight: multimer ratio (p=0.007) and lower final closure time with ADP (p=0.02) were associated with the occurrence of new postprocedural CMBs. In multivariate analysis, a prolonged procedure for every 5 minutes of fluoroscopy time (p=0.02) and postprocedural acquired von Willebrand factor defect for every lower 0.1 unit of high molecular weight: ratio (p=0.004) were independently associated with the occurrence of new postprocedural CMBs. Of note, new CMBs were not associated with changes in neurological outcome or quality of life at 6 months follow-up.

UK TAVI provides additional support for TAVI in the lower risk surgical patients

Effect of transcatheter aortic valve implantation vs surgical aortic valve replacement on all-cause mortality in patients with aortic stenosis. A randomized clinical trial.

JAMA 2022; 327:1875-1887

TAVI in intermediate and low-risk patients is being increasingly supported by data from randomized clinical trials. The UK TAVI trial examined whether TAVI was noninferior to SAVR in 913 patients (TAVI=458, SAVR=458) aged 70 years or older with severe symptomatic AS and moderately increased operative risk due to age or comorbidity. Key exclusion criteria were life expectancy < 1-year, previous AVR or TAVI, technically unsuitable for TAVI or SAVR, CAD for which surgical revascularization was required, primary aortic regurgitation, and severe mitral regurgitation. Other salient features included mean LV ejection fraction=5.7%, transfemoral access=92%, conscious sedation during TAVI=70%, 45% received the Sapien 3 valve, 14% Evolut/Evolut R, and 10% Lotus. The primary outcome was all-cause mortality at 1 year. There were 36 secondary outcomes including duration of hospital stay, major bleeding, vascular complications, requirement for a pacemaker, and aortic regurgitation. The median age was 81 years, 46% were female, median STS score was 2.6%, and 99.9% completed follow-up. At 1-year, mortality was 4.6% in the TAVI group and 6.6% in the surgical group (adjusted absolute risk difference of -2.0%; 1-sided 97.5% CI: −∞ to 1.2%; p < .001 for noninferiority). Of the 30 prespecified secondary outcomes, 24 showed no significant difference at 1 year. TAVI was associated with shorter hospital stay (median of 3 days vs. 8 days). TAVI was also associated with significantly lower bleeding complications (7.2% vs. 20.2%; HR: 0.33; 95% CI: 0.24-0.45) but significantly more vascular complications (10.3% vs. 2.4%; HR: 4.42; 95% CI: 2.54-7.71), pacemaker implantation (14.2% vs. 7.3%; HR: 2.05; 95% CI: 1.43-2.94), and mild (38.3% vs. 11.7%) or moderate (2.3% vs. 0.6%) aortic regurgitation. The rates of stroke were similar in the TAVI and SAVR groups (2.3% vs. 0.6%).

Expanding techniques for treating severe TR

6-Month outcomes of the TricValve sytem in patients with tricuspid regurgitation: the TRICUS EURO study.

JACC Cardiol Interv 2022; 15:1366-77

Bicaval valve implantation (CAVI) has emerged as a novel transcatheter strategy for indirectly treating the systemic manifestation of severe tricuspid regurgitation (TR) in patients ineligible for cardiac surgery or edge-to-edge repair. The Tricvalve system consists of 2 self-expanding valves designed for the SVC and IVC premounted in a 27.5-F delivery system. Caval anchoring is based on stent design, radial force, and the degree of oversizing. The TRICUS EURO study was a nonblind, nonrandomized, single arm, multicenter, prospective trial of 35 patients with symptomatic severe TR (grade ≥3 in a 5-grade classification) despite optimal medical therapy and NYHA functional class III or IV. The main exclusion criteria included severe right ventricular dysfunction, severe pulmonary hypertension (PAP≥65mmHg) and/or significant renal dysfunction (defined as serum creatinine >3mg/dl). The primary endpoint was quality of life (QoL) improvement measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) and NYHA functional class improvement at 6-month follow-up. The mean age was 76 ± 6.8 years, 83% were female, 20% were diabetic, and the overall EuroSCORE II was 5.8 ± 4.2. At 30 days, procedural success was 94%, with no procedural death or conversion to surgery. At 6 months, patients had a significant improvement in QoL from 42.01 ± 22.3 to 59.7 ± 23.6 (p=0.004) correlating with a significant improvement in NYHA class with 79.4% of patients noted to be in class I or II (p=0.0006). The rates of 6-month all-cause mortality and heart failure hospitalization were 8.5% and 20% respectively. There were 6 cases of major bleeding and 2 were access site related. The study represents the first comprehensive short-term analysis of a dedicated CAVI system and longer-term data are required to assess clinical benefits and haemodynamic effects upon the pulmonary and right heart status.

Miscellaneous

Hydration remains key for renal protection

Study evaluating the use of RenalGuard to protect patients at high risk of AKI. JACC 2022; 15:1639-48

Contrast-induced nephropathy (CIN) may occur in 2-7% of patients undergoing angiographic procedures. A variety of measures including hydration with sodium bicarbonate, N-acetylcysteine, and hemofiltration have been examined in randomized trials but no measure except adequate intravenous (IV) hydration and minimal contrast use have been shown to be effective strategies. The RenalGuard system (RG) is a device that delivers real-time isotonic IV hydration matched with frusemide-induced diuresis allowing hydration and contrast clearance thus preventing fluid overload and volume depletion. The STRENGTH study examined the superiority of RG over standard practice (considering the ESC guidelines including IV and oral hydration, the dose of contrast medium and staged procedure if necessary) in 259 patients with moderate to severe chronic kidney disease (estimated GFR 15-40 ml/min/m²) requiring complex coronary, structural, or peripheral procedures with an expected contrast injection of at least 3x the estimated GFR. The primary endpoint was the occurrence of CIN, defined as an increase in serum creatinine ≥ 0.3mg/dl and/or an increase of 25% of basal value at around day 3 or the requirement for dialysis within 5 days after the procedure. Secondary endpoints included a change in serum creatinine value and GFR at 12 months, % of patients on temporary or chronic haemodialysis at 12 months, and MACCEs. In the whole population, the mean age was 79 years, 50% were male, baseline GFR was 32ml/min/1.73m², 48% underwent PCI, 34% structural intervention (TAVI and LAA closure), and 18% peripheral intervention. The mean amount of contrast use was similar in both groups (116ml in the RG group vs. 104ml in the control group; p=0.26). The total fluid intake was higher in the RG group (6196ml vs. 1407ml; p<0.0001). The primary endpoint was similar in the RG and control groups (15.9% vs. 13.9%; difference=2.4; 95% CI:-7.1-12; p=0.62). At 12 months, there were no significant differences between the two groups. The rate of MACCEs were also similar at a median of 342 days (20.5% in RG group vs. 22.2% in the control group).

BCIS R&D Group Literature Review

September 2022

Prepared by Michael Mahmoudi, Paul Morris and Natalia Briceno
Edited by Michael Mahmoudi

Coronary Artery Disease

No need for routine non-invasive stress testing post-PCI

Routine functional testing or standard care in high-risk patients after PCI. NEJM 2022; 387:905-915

The optimal follow-up strategy for patients undergoing coronary revascularization who have high-risk characteristics is variable. Some studies have shown that functional testing is widely used in clinical practice with more than half of all such patients having had functional testing within 2 years of revascularization. The POST-PCI investigators conducted a randomized superiority trial to compare an active follow-up strategy of routine functional testing (nuclear stress testing, stress echocardiography, Exercise electrocardiography) examined whether a follow-up strategy that includes functional testing improved clinical outcomes. Patients (n=1706) who had undergone successful PCI with DES, bioresorbable scaffolds, or drug-coated balloon (for ISR) who had at least one high-risk anatomical feature (left main disease, bifurcation disease, ostial disease, CTO, multivessel disease warranting PCI of at least two vessels, a restenotic lesion, lesion length > 30mm or a lesion warranting a stent length of > 32mm, and bypass graft disease) or clinical characteristics (diabetes mellitus, chronic renal disease defined as serum creatinine ≥ 177 mmol/l or long-term haemodialysis, and enzyme positive ACS) were enrolled to a strategy of routine functional testing (n=849) at 1 year post PCI or standard care alone (n=857). Patients underwent routine follow-up at 6, 12, 18, and 24 months. The primary endpoint was a composite of MACE defined as death from any cause, MI, or hospitalization for unstable angina at 2 years. The mean age was 64.7±10.3, 79.5% were men, 21% had left main disease, 43.5% had bifurcation disease, 69.8% had multivessel disease, 70.1% had a diffuse long lesion, 38.7% had diabetes, 19.4% had an ACS, 96.4% were treated with DES, the mean number of stents per patient was 2.0, the mean stent length was 57mm, FFR was measured in 35.7% of the patients, and intravascular imaging was used in 74.4%. At 2 years, the primary endpoint was similar in the functional testing and standard care groups (5.5% vs. 6.0%; HR: 0.9; 95% CI: 0.61-1.35; p=0.62). There were no between-group differences with respect to the components of the primary outcome. At 2 years, invasive angiography had been undertaken in 12.3% of the functional testing group and 9.3% of the standard care group (p=0.62) had undergone invasive angiography. The rates of revascularization were also similar in the two groups (8.1% vs. 5.8%; p>0.05).

Reviving a failing heart with PCI

Percutaneous revascularization for ischemic ventricular dysfunction.

NEJM 2022 Online

The benefits of coronary revascularization in patients with significant left ventricular systolic dysfunction remains uncertain. A survival benefit in patients undergoing CABG in this population became apparent only after 10 years in the STICH trial. The REVIVED investigators examined whether coronary revascularization with PCI in addition to guideline directed optimal medical therapy (OMT) (n=347) as compared to OMT alone (n=353) improved event-free survival in patients with left ventricular ejection fraction (LVEF) ≤ 35%, extensive coronary artery disease (BCIS jeopardy score ≥ 6) and myocardial viability in at least four dysfunctional segments amenable to revascularization with PCI. The primary composite outcome was death from any cause or hospitalization for heart failure over a minimum follow-up period of 24 months. The major secondary outcomes were LVEF at 6 and 12 months, KCCQ overall summary score, the score on the EQ-5D-5L score, and NYHA functional class. The two groups were well matched for baseline characteristics. Median age was 70 years, 88% were men, 77% had NYHA class I/II, and 67% had no angina. The primary outcome occurred in 37.2% of the PCI plus OMT group and 38% of the OMT group (HR, 0.99; 95% CI: 0.78-1.27; p=0.96). The rates of death (31.7% vs. 32.6%; HR, 0.98; 95% CI: 0.75-1.27) and hospitalization for heart failure (14.7% vs. 15.3%; HR, 0.97; 95% CI: 0.66-1.43) were similar in the PCI plus OMT and OMT groups. The LVEF was similar in the two groups at 6 months (mean difference, -1.6 percentage points; 95% CI: -3.7-0.5) and at 12 months (mean difference; 0.9 percentage points; 95% CI: -1.7-3.4). Quality of life scores at 6 and 12 months favoured the PCI group but this difference diminished at 24 months. Of note, approximately 50% of the patients had 2V CAD and a median of two lesions and vessels were treated per patient which may be out of proportion to the extent of LV dysfunction. Other salient features include lack of description of the severity of stenoses, physiological assessment of the lesion, and lack of correlation of stenosis with previous ischemic/viability testing.

Secure compliance with the polypill

Polypill strategy in secondary cardiovascular prevention.

NEJM 2022; 387:967-977

Noncompliance with guideline directed optimal medical therapy is a frequently observed challenge faced by patients and healthcare providers. This is often associated with adverse clinical outcomes particularly in patients at the highest risk of adverse clinical events. A polypill strategy has been shown to improve compliance and lower cardiovascular event rates in trials of primary prevention.  The SECURE trial was a randomized phase 3 trial designed to assess the efficacy of a polypill strategy, as compared with standard care, with respect to major cardiovascular outcomes (defined as CV death, nonfatal type 1 MI, nonfatal ischemic stroke, or urgent revascularization) in patients older than 75 years of age or at least 65 years of age with at least one of the following risk factors: diabetes mellitus, mild or moderate renal disease defined as creatinine clearance 30-60 ml/min/1.73m² of body surface area, previous MI, previous coronary revascularization (PCI or CABG), or previous stroke. All patients had to have had a history of type 1 MI within the previous 6 months. The polypill contained any of three formulations Polypill AAR40-a single pill containing aspirin 100mg, ramipril 2.5, 5, or 10mg, and atorvastatin 40mg. The dose of the atorvastatin could be reduced to 20mg on clinical grounds in which case the Polypill AAR20 was used (same as AAR40 but reduced dose of atorvastatin at 20mg). In patients who were not on ramipril at baseline, treatment was commenced at 2.5mg; in those who were already on an ACE inhibitor, treatment was commenced at the equivalent dose of ramipril with the aim of reaching 10mg. Follow-up was undertaken at 6, 12, 18, 24, 36, and 48 months. At 6 and 24 months, adherence was checked using the eight-item Morisky Medication Adherence Scale. A total of 2499 patients were randomized (polypill=1258, standard care=1241). The median time between the index MI and randomization was 8 days. The mean age was 76±6.6 years, 31% were female, 77.9% had hypertension, 57.4% had diabetes, 51.3% had a history of smoking, mean systolic blood pressure was 129.1±17.7, and mean LDL was 89.2±37.2. Most patients in the polypill group (91.7%) received the 40mg formulation of atorvastatin as compared to 40.4% in the standard care group. 98.7% of patients in the standard care group received aspirin and 95.1% received an additional antiplatelet agent as compared to 94% in the polypill group. The primary endpoint was lower in the polypill group (9.5% vs. 12.7%; HR: 0.76; 95% CI; 0.60-0.96; p=0.02). All components of the composite outcome except for urgent revascularization were reduced in a consistent manner. The secondary outcome of CV death, MI, or stroke was also lower in the polypill group (8.2% vs. 11.7%; HR: 0.70; 95% CI: 0.54-0.90); p=0.005). All-cause mortality was similar in both groups (9.3% vs. 9.5%; p=0.79). Adherence was higher in the polypill group both at 6 months (70.6% vs. 62.7%; RR: 1.13; 95% CI: 1.06-1.20) and 24 months (74.1% vs. 63.2%; RR: 1.17; 95% CI: 1.10-1.25).

Routine pressure wire assessment not supported by RIPCORD-2

Routine pressure wire assessment versus conventional angiography in the management of patients with coronary artery disease: The RIPCORD 2 trial.

Circ 2022 Online

FFR-guided PCI has been shown to be associated lower resource utilization and improved clinical outcomes compared with angiography guidance alone. The value of FFR of all major coronary vessels at the time diagnostic angiography has not been established. The RIPCORD 2 trial was an 1100 patient prospective, multicentre, randomized trial that compared a strategy of coronary angiography alone versus coronary angiography + routine FFR assessment of all epicardial vessels of sufficient size amenable to revascularization to determine whether the latter strategy was associated with more effective resource utilization, improved quality of life, and better clinical outcome. In the angiography + FFR group, the median number of vessels examined was 4. There were no differences in the median hospital costs between the two groups (£4136 for angiography vs. £4510 for angiography + FFR; p=0.137) nor the median quality of life using the visual analog scale of the EuroQol EQ-5D-5L (75 vs. 75; p=0.88). The number of clinical events were death (5 vs. 8), stroke (3 vs. 4), MI (23 vs. 22), and unplanned revascularization (26 vs. 33) with a composite hierarchical event rate of 8.7% for angiography versus 9.5% for angiography + FFR (p=0.64). The study thus concluded that routine FFR at the stage of diagnostic angiography is not associated with reduction in cost or improvement in quality of life.

Alirocumab has favourable effects on plaque composition

Effect of alirocumab added to high-intensity statin therapy on coronary atherosclerosis in patients with acute myocardial infraction. The PACMAN-AMI randomized clinical trial.

JAMA 2022; 327:1771-81

PCSK inhibitors have been shown to result in significant reductions in LDL-C and improve clinical outcomes in patients with recent ACS. The PACMAN-AMI trial examined whether the addition of alirocumab to high-intensity statin therapy affected coronary atherosclerotic plaques in the non-infracted related arteries. Following PCU of the culprit lesion in the infarct related artery (IRA), eligible patients underwent intracoronary imaging of the non-IRA with OCT, IVUS and NIRS, and then randomized in a 1:1 fashion to receive either 150mg alirocumab (n=148) or placebo (n=152) biweekly via subcutaneous injection for 52 weeks.  Both groups also received rosuvastatin 20mg daily. Main inclusion criteria were age ≥ 18 years, successful PCI of the culprit vessel (STEMI=53%, NSTEMI=47%), suitability for intracoronary imaging with angiographic stenosis between 20-50% in the proximal segments of two non-IRAs, and LDL-C at baseline ≥ 125 mg/dl if not on a statin for 4 weeks prior to presentation or ≥ 70mg/dl if on a stable dose of a statin. Key exclusion criteria were left main or three vessel disease, history of CABG, severe chronic kidney or liver disease, and known statin intolerance. The mean age was 58 years, 18% were female, 10% were diabetic, and mean LDL-C was 152.4 mg/dl. At 12 months, the primary endpoint of change in mean percent atheroma volume from baseline for alirocumab was greater than placebo -2.13% vs. -0.92% (p<0.001). Mean change in maximum lipid core burden index within 4 mm was −79.42 with alirocumab vs. −37.60 with placebo (difference, −41.24; 95% CI: −70.71 to −11.77; p= 0.006). Mean change in minimal fibrous cap thickness was 62.67μm with alirocumab vs. 33.19μm with placebo (difference, 29.65μm; 95% CI: 11.75-47.55; p=0.001). Adverse events occurred in 70.7% of patients treated with alirocumab vs. 72.8% of patients receiving placebo. The change in LDL-C from baseline was -131.2 mg/dl in the alirocumab group vs. -76.5 mg/dl in the placebo group (p<0.001).

Valvular Heart Disease

Embolic protection remains a challenge

Cerebral embolic protection during transcatheter aortic valve replacement. NEJM 2022 Online

Embolization of biological material from either the aortic valve and/or the aorta may cause a periprocedural stroke in 2-2.5% of patients undergoing TAVI. The Sentinel cerebral embolic protection device (CEP) has been shown to be safe and effective in capturing debris in 99% of patients but the reduction in new cerebral lesion volume was not significant. The PROTECTED TAVR trial was a prospective, postmarket, multicentre, randomized, controlled trial designed to evaluate the efficacy of the Sentinal CEP in reducing stroke within 72 hours of transfemoral TAVI or before discharge. Stroke was defined as an acute episode of a focal or global neurologic dysfunction caused by vascular injury to the brain, spinal cord, or retina leading to haemorrhage or infarction. Disabling stroke, death, transient ischemic attack, delirium, major or minor vascular complications at the CEP access site, and acute kidney injury were also assessed.  Patients (n=3000) were eligible if they had AS and were scheduled to undergo transfemoral TAVI using a commercially available device. Patients were excluded if they had left common carotid or brachiocephalic artery stenosis >70% or the anatomical structure was unfavourable for placement of the CEP device. The mean age was 78.9±7.8 years, mean STS score 3.4±2.7, 40% were female, history of CVA/TIA was present in 8%, 8% had bicuspid AS, 3% had valve-in-valve procedure, a balloon expandable device was used in 64%, and duration of follow-up was 72 hours. The primary outcome was similar in the CEP and control groups (2.3% vs. 2.9%; difference -0.6 percentage points; 95% CI: -1.7 to 0.5; p=0.30). The rates of secondary outcomes for CEP and control groups were disabling stoke (0.5% vs. 1.3%; p<0.05), all-cause mortality (0.5% vs. 0.3%), stroke/TIA/delirium (3.1% vs. 3.7%), and acute kidney injury (0.5% vs. 0.5%).

Potential additional mechanism for stroke in TAVI patients

Cerebral microbleeds during transcatheter aortic valve replacement: a prospective magnetic resonance imaging cohort.

Circ 2022; 146:383-397

Cerebral microbleeds (CMBs) are frequently observed in elderly people and yet their clinical significance remains uncertain. The incidence of new CMBs and factors contributing to their formation in patients undergoing TAVI has not been previously examined. The current study prospectively examined a cohort of 84 patients with severe aortic stenosis that were referred for TAVI. Mean age was 80.9±5.7 years and 53% were female. On preprocedural MRI, 26% of the patients had at least 1 CMBs whilst following TAVI, new CMBs was observed in 23% of patients. In univariate analysis, a previous history of bleeding (p=0.01), higher total dose of heparin (p=0.02), a prolonged procedure (p=0.03), no protamine reversal (p=0.04), higher final ACT (p=0.05), lower final von Willebrand factor high molecular weight: multimer ratio (p=0.007) and lower final closure time with ADP (p=0.02) were associated with the occurrence of new postprocedural CMBs. In multivariate analysis, a prolonged procedure for every 5 minutes of fluoroscopy time (p=0.02) and postprocedural acquired von Willebrand factor defect for every lower 0.1 unit of high molecular weight: ratio (p=0.004) were independently associated with the occurrence of new postprocedural CMBs. Of note, new CMBs were not associated with changes in neurological outcome or quality of life at 6 months follow-up.

UK TAVI provides additional support for TAVI in the lower risk surgical patients

Effect of transcatheter aortic valve implantation vs surgical aortic valve replacement on all-cause mortality in patients with aortic stenosis. A randomized clinical trial.

JAMA 2022; 327:1875-1887

TAVI in intermediate and low-risk patients is being increasingly supported by data from randomized clinical trials. The UK TAVI trial examined whether TAVI was noninferior to SAVR in 913 patients (TAVI=458, SAVR=458) aged 70 years or older with severe symptomatic AS and moderately increased operative risk due to age or comorbidity. Key exclusion criteria were life expectancy < 1-year, previous AVR or TAVI, technically unsuitable for TAVI or SAVR, CAD for which surgical revascularization was required, primary aortic regurgitation, and severe mitral regurgitation. Other salient features included mean LV ejection fraction=5.7%, transfemoral access=92%, conscious sedation during TAVI=70%, 45% received the Sapien 3 valve, 14% Evolut/Evolut R, and 10% Lotus. The primary outcome was all-cause mortality at 1 year. There were 36 secondary outcomes including duration of hospital stay, major bleeding, vascular complications, requirement for a pacemaker, and aortic regurgitation. The median age was 81 years, 46% were female, median STS score was 2.6%, and 99.9% completed follow-up. At 1-year, mortality was 4.6% in the TAVI group and 6.6% in the surgical group (adjusted absolute risk difference of -2.0%; 1-sided 97.5% CI: −∞ to 1.2%; p < .001 for noninferiority). Of the 30 prespecified secondary outcomes, 24 showed no significant difference at 1 year. TAVI was associated with shorter hospital stay (median of 3 days vs. 8 days). TAVI was also associated with significantly lower bleeding complications (7.2% vs. 20.2%; HR: 0.33; 95% CI: 0.24-0.45) but significantly more vascular complications (10.3% vs. 2.4%; HR: 4.42; 95% CI: 2.54-7.71), pacemaker implantation (14.2% vs. 7.3%; HR: 2.05; 95% CI: 1.43-2.94), and mild (38.3% vs. 11.7%) or moderate (2.3% vs. 0.6%) aortic regurgitation. The rates of stroke were similar in the TAVI and SAVR groups (2.3% vs. 0.6%).

Expanding techniques for treating severe TR

6-Month outcomes of the TricValve sytem in patients with tricuspid regurgitation: the TRICUS EURO study.

JACC Cardiol Interv 2022; 15:1366-77

Bicaval valve implantation (CAVI) has emerged as a novel transcatheter strategy for indirectly treating the systemic manifestation of severe tricuspid regurgitation (TR) in patients ineligible for cardiac surgery or edge-to-edge repair. The Tricvalve system consists of 2 self-expanding valves designed for the SVC and IVC premounted in a 27.5-F delivery system. Caval anchoring is based on stent design, radial force, and the degree of oversizing. The TRICUS EURO study was a nonblind, nonrandomized, single arm, multicenter, prospective trial of 35 patients with symptomatic severe TR (grade ≥3 in a 5-grade classification) despite optimal medical therapy and NYHA functional class III or IV. The main exclusion criteria included severe right ventricular dysfunction, severe pulmonary hypertension (PAP≥65mmHg) and/or significant renal dysfunction (defined as serum creatinine >3mg/dl). The primary endpoint was quality of life (QoL) improvement measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) and NYHA functional class improvement at 6-month follow-up. The mean age was 76 ± 6.8 years, 83% were female, 20% were diabetic, and the overall EuroSCORE II was 5.8 ± 4.2. At 30 days, procedural success was 94%, with no procedural death or conversion to surgery. At 6 months, patients had a significant improvement in QoL from 42.01 ± 22.3 to 59.7 ± 23.6 (p=0.004) correlating with a significant improvement in NYHA class with 79.4% of patients noted to be in class I or II (p=0.0006). The rates of 6-month all-cause mortality and heart failure hospitalization were 8.5% and 20% respectively. There were 6 cases of major bleeding and 2 were access site related. The study represents the first comprehensive short-term analysis of a dedicated CAVI system and longer-term data are required to assess clinical benefits and haemodynamic effects upon the pulmonary and right heart status.

Miscellaneous

Hydration remains key for renal protection

Study evaluating the use of RenalGuard to protect patients at high risk of AKI. JACC 2022; 15:1639-48

Contrast-induced nephropathy (CIN) may occur in 2-7% of patients undergoing angiographic procedures. A variety of measures including hydration with sodium bicarbonate, N-acetylcysteine, and hemofiltration have been examined in randomized trials but no measure except adequate intravenous (IV) hydration and minimal contrast use have been shown to be effective strategies. The RenalGuard system (RG) is a device that delivers real-time isotonic IV hydration matched with frusemide-induced diuresis allowing hydration and contrast clearance thus preventing fluid overload and volume depletion. The STRENGTH study examined the superiority of RG over standard practice (considering the ESC guidelines including IV and oral hydration, the dose of contrast medium and staged procedure if necessary) in 259 patients with moderate to severe chronic kidney disease (estimated GFR 15-40 ml/min/m²) requiring complex coronary, structural, or peripheral procedures with an expected contrast injection of at least 3x the estimated GFR. The primary endpoint was the occurrence of CIN, defined as an increase in serum creatinine ≥ 0.3mg/dl and/or an increase of 25% of basal value at around day 3 or the requirement for dialysis within 5 days after the procedure. Secondary endpoints included a change in serum creatinine value and GFR at 12 months, % of patients on temporary or chronic haemodialysis at 12 months, and MACCEs. In the whole population, the mean age was 79 years, 50% were male, baseline GFR was 32ml/min/1.73m², 48% underwent PCI, 34% structural intervention (TAVI and LAA closure), and 18% peripheral intervention. The mean amount of contrast use was similar in both groups (116ml in the RG group vs. 104ml in the control group; p=0.26). The total fluid intake was higher in the RG group (6196ml vs. 1407ml; p<0.0001). The primary endpoint was similar in the RG and control groups (15.9% vs. 13.9%; difference=2.4; 95% CI:-7.1-12; p=0.62). At 12 months, there were no significant differences between the two groups. The rate of MACCEs were also similar at a median of 342 days (20.5% in RG group vs. 22.2% in the control group).

Dear stakeholder

Launch of Acute Aortic Dissection Pathway Toolkit

We are pleased to let you know that we have launched NHS England and NHS Improvement’s new Acute Aortic Dissection (AAD) Pathway Toolkit. This consists of three separate documents which you will find attached. These are:
– Acute Aortic Dissection Toolkit Final Version 20220314
– 45.2a AAD Toolkit Interaction pdf
– 45.2b AAD Self-Assessment Questionnaire

The toolkit aims to improve patient outcomes through optimising the pathway from the point of diagnosis to definitive care and is underpinned by 7 key principles.

The toolkit has been developed as part of the work programme of the Vascular and Cardiac Clinical Reference Groups and is one of the products of the Cardiac Pathway Improvement Programme (CPIP). It is primarily a resource for those delivering cardiac services and is not intended to be a patient-facing resource, however we are very grateful for the range of patient groups and people with experience of acute aortic dissection who have supported its development, alongside clinical experts. The toolkit will be housed on the FutureNHS platform – an online workspace for NHS staff.

Kind regards,

Tarana Akther (she / her)
Project Manager 
Specialised Commissioning, Service Transformation Programme
NHS England and NHS Improvement

BCIS R&D Group Literature Review

September 2022

Prepared by Michael Mahmoudi, Paul Morris and Natalia Briceno
Edited by Michael Mahmoudi

Coronary Artery Disease

No need for routine non-invasive stress testing post-PCI

Routine functional testing or standard care in high-risk patients after PCI. NEJM 2022; 387:905-915

The optimal follow-up strategy for patients undergoing coronary revascularization who have high-risk characteristics is variable. Some studies have shown that functional testing is widely used in clinical practice with more than half of all such patients having had functional testing within 2 years of revascularization. The POST-PCI investigators conducted a randomized superiority trial to compare an active follow-up strategy of routine functional testing (nuclear stress testing, stress echocardiography, Exercise electrocardiography) examined whether a follow-up strategy that includes functional testing improved clinical outcomes. Patients (n=1706) who had undergone successful PCI with DES, bioresorbable scaffolds, or drug-coated balloon (for ISR) who had at least one high-risk anatomical feature (left main disease, bifurcation disease, ostial disease, CTO, multivessel disease warranting PCI of at least two vessels, a restenotic lesion, lesion length > 30mm or a lesion warranting a stent length of > 32mm, and bypass graft disease) or clinical characteristics (diabetes mellitus, chronic renal disease defined as serum creatinine ≥ 177 mmol/l or long-term haemodialysis, and enzyme positive ACS) were enrolled to a strategy of routine functional testing (n=849) at 1 year post PCI or standard care alone (n=857). Patients underwent routine follow-up at 6, 12, 18, and 24 months. The primary endpoint was a composite of MACE defined as death from any cause, MI, or hospitalization for unstable angina at 2 years. The mean age was 64.7±10.3, 79.5% were men, 21% had left main disease, 43.5% had bifurcation disease, 69.8% had multivessel disease, 70.1% had a diffuse long lesion, 38.7% had diabetes, 19.4% had an ACS, 96.4% were treated with DES, the mean number of stents per patient was 2.0, the mean stent length was 57mm, FFR was measured in 35.7% of the patients, and intravascular imaging was used in 74.4%. At 2 years, the primary endpoint was similar in the functional testing and standard care groups (5.5% vs. 6.0%; HR: 0.9; 95% CI: 0.61-1.35; p=0.62). There were no between-group differences with respect to the components of the primary outcome. At 2 years, invasive angiography had been undertaken in 12.3% of the functional testing group and 9.3% of the standard care group (p=0.62) had undergone invasive angiography. The rates of revascularization were also similar in the two groups (8.1% vs. 5.8%; p>0.05).

Reviving a failing heart with PCI

Percutaneous revascularization for ischemic ventricular dysfunction.

NEJM 2022 Online

The benefits of coronary revascularization in patients with significant left ventricular systolic dysfunction remains uncertain. A survival benefit in patients undergoing CABG in this population became apparent only after 10 years in the STICH trial. The REVIVED investigators examined whether coronary revascularization with PCI in addition to guideline directed optimal medical therapy (OMT) (n=347) as compared to OMT alone (n=353) improved event-free survival in patients with left ventricular ejection fraction (LVEF) ≤ 35%, extensive coronary artery disease (BCIS jeopardy score ≥ 6) and myocardial viability in at least four dysfunctional segments amenable to revascularization with PCI. The primary composite outcome was death from any cause or hospitalization for heart failure over a minimum follow-up period of 24 months. The major secondary outcomes were LVEF at 6 and 12 months, KCCQ overall summary score, the score on the EQ-5D-5L score, and NYHA functional class. The two groups were well matched for baseline characteristics. Median age was 70 years, 88% were men, 77% had NYHA class I/II, and 67% had no angina. The primary outcome occurred in 37.2% of the PCI plus OMT group and 38% of the OMT group (HR, 0.99; 95% CI: 0.78-1.27; p=0.96). The rates of death (31.7% vs. 32.6%; HR, 0.98; 95% CI: 0.75-1.27) and hospitalization for heart failure (14.7% vs. 15.3%; HR, 0.97; 95% CI: 0.66-1.43) were similar in the PCI plus OMT and OMT groups. The LVEF was similar in the two groups at 6 months (mean difference, -1.6 percentage points; 95% CI: -3.7-0.5) and at 12 months (mean difference; 0.9 percentage points; 95% CI: -1.7-3.4). Quality of life scores at 6 and 12 months favoured the PCI group but this difference diminished at 24 months. Of note, approximately 50% of the patients had 2V CAD and a median of two lesions and vessels were treated per patient which may be out of proportion to the extent of LV dysfunction. Other salient features include lack of description of the severity of stenoses, physiological assessment of the lesion, and lack of correlation of stenosis with previous ischemic/viability testing.

Secure compliance with the polypill

Polypill strategy in secondary cardiovascular prevention.

NEJM 2022; 387:967-977

Noncompliance with guideline directed optimal medical therapy is a frequently observed challenge faced by patients and healthcare providers. This is often associated with adverse clinical outcomes particularly in patients at the highest risk of adverse clinical events. A polypill strategy has been shown to improve compliance and lower cardiovascular event rates in trials of primary prevention.  The SECURE trial was a randomized phase 3 trial designed to assess the efficacy of a polypill strategy, as compared with standard care, with respect to major cardiovascular outcomes (defined as CV death, nonfatal type 1 MI, nonfatal ischemic stroke, or urgent revascularization) in patients older than 75 years of age or at least 65 years of age with at least one of the following risk factors: diabetes mellitus, mild or moderate renal disease defined as creatinine clearance 30-60 ml/min/1.73m² of body surface area, previous MI, previous coronary revascularization (PCI or CABG), or previous stroke. All patients had to have had a history of type 1 MI within the previous 6 months. The polypill contained any of three formulations Polypill AAR40-a single pill containing aspirin 100mg, ramipril 2.5, 5, or 10mg, and atorvastatin 40mg. The dose of the atorvastatin could be reduced to 20mg on clinical grounds in which case the Polypill AAR20 was used (same as AAR40 but reduced dose of atorvastatin at 20mg). In patients who were not on ramipril at baseline, treatment was commenced at 2.5mg; in those who were already on an ACE inhibitor, treatment was commenced at the equivalent dose of ramipril with the aim of reaching 10mg. Follow-up was undertaken at 6, 12, 18, 24, 36, and 48 months. At 6 and 24 months, adherence was checked using the eight-item Morisky Medication Adherence Scale. A total of 2499 patients were randomized (polypill=1258, standard care=1241). The median time between the index MI and randomization was 8 days. The mean age was 76±6.6 years, 31% were female, 77.9% had hypertension, 57.4% had diabetes, 51.3% had a history of smoking, mean systolic blood pressure was 129.1±17.7, and mean LDL was 89.2±37.2. Most patients in the polypill group (91.7%) received the 40mg formulation of atorvastatin as compared to 40.4% in the standard care group. 98.7% of patients in the standard care group received aspirin and 95.1% received an additional antiplatelet agent as compared to 94% in the polypill group. The primary endpoint was lower in the polypill group (9.5% vs. 12.7%; HR: 0.76; 95% CI; 0.60-0.96; p=0.02). All components of the composite outcome except for urgent revascularization were reduced in a consistent manner. The secondary outcome of CV death, MI, or stroke was also lower in the polypill group (8.2% vs. 11.7%; HR: 0.70; 95% CI: 0.54-0.90); p=0.005). All-cause mortality was similar in both groups (9.3% vs. 9.5%; p=0.79). Adherence was higher in the polypill group both at 6 months (70.6% vs. 62.7%; RR: 1.13; 95% CI: 1.06-1.20) and 24 months (74.1% vs. 63.2%; RR: 1.17; 95% CI: 1.10-1.25).

Routine pressure wire assessment not supported by RIPCORD-2

Routine pressure wire assessment versus conventional angiography in the management of patients with coronary artery disease: The RIPCORD 2 trial.

Circ 2022 Online

FFR-guided PCI has been shown to be associated lower resource utilization and improved clinical outcomes compared with angiography guidance alone. The value of FFR of all major coronary vessels at the time diagnostic angiography has not been established. The RIPCORD 2 trial was an 1100 patient prospective, multicentre, randomized trial that compared a strategy of coronary angiography alone versus coronary angiography + routine FFR assessment of all epicardial vessels of sufficient size amenable to revascularization to determine whether the latter strategy was associated with more effective resource utilization, improved quality of life, and better clinical outcome. In the angiography + FFR group, the median number of vessels examined was 4. There were no differences in the median hospital costs between the two groups (£4136 for angiography vs. £4510 for angiography + FFR; p=0.137) nor the median quality of life using the visual analog scale of the EuroQol EQ-5D-5L (75 vs. 75; p=0.88). The number of clinical events were death (5 vs. 8), stroke (3 vs. 4), MI (23 vs. 22), and unplanned revascularization (26 vs. 33) with a composite hierarchical event rate of 8.7% for angiography versus 9.5% for angiography + FFR (p=0.64). The study thus concluded that routine FFR at the stage of diagnostic angiography is not associated with reduction in cost or improvement in quality of life.

Alirocumab has favourable effects on plaque composition

Effect of alirocumab added to high-intensity statin therapy on coronary atherosclerosis in patients with acute myocardial infraction. The PACMAN-AMI randomized clinical trial.

JAMA 2022; 327:1771-81

PCSK inhibitors have been shown to result in significant reductions in LDL-C and improve clinical outcomes in patients with recent ACS. The PACMAN-AMI trial examined whether the addition of alirocumab to high-intensity statin therapy affected coronary atherosclerotic plaques in the non-infracted related arteries. Following PCU of the culprit lesion in the infarct related artery (IRA), eligible patients underwent intracoronary imaging of the non-IRA with OCT, IVUS and NIRS, and then randomized in a 1:1 fashion to receive either 150mg alirocumab (n=148) or placebo (n=152) biweekly via subcutaneous injection for 52 weeks.  Both groups also received rosuvastatin 20mg daily. Main inclusion criteria were age ≥ 18 years, successful PCI of the culprit vessel (STEMI=53%, NSTEMI=47%), suitability for intracoronary imaging with angiographic stenosis between 20-50% in the proximal segments of two non-IRAs, and LDL-C at baseline ≥ 125 mg/dl if not on a statin for 4 weeks prior to presentation or ≥ 70mg/dl if on a stable dose of a statin. Key exclusion criteria were left main or three vessel disease, history of CABG, severe chronic kidney or liver disease, and known statin intolerance. The mean age was 58 years, 18% were female, 10% were diabetic, and mean LDL-C was 152.4 mg/dl. At 12 months, the primary endpoint of change in mean percent atheroma volume from baseline for alirocumab was greater than placebo -2.13% vs. -0.92% (p<0.001). Mean change in maximum lipid core burden index within 4 mm was −79.42 with alirocumab vs. −37.60 with placebo (difference, −41.24; 95% CI: −70.71 to −11.77; p= 0.006). Mean change in minimal fibrous cap thickness was 62.67μm with alirocumab vs. 33.19μm with placebo (difference, 29.65μm; 95% CI: 11.75-47.55; p=0.001). Adverse events occurred in 70.7% of patients treated with alirocumab vs. 72.8% of patients receiving placebo. The change in LDL-C from baseline was -131.2 mg/dl in the alirocumab group vs. -76.5 mg/dl in the placebo group (p<0.001).

Valvular Heart Disease

Embolic protection remains a challenge

Cerebral embolic protection during transcatheter aortic valve replacement. NEJM 2022 Online

Embolization of biological material from either the aortic valve and/or the aorta may cause a periprocedural stroke in 2-2.5% of patients undergoing TAVI. The Sentinel cerebral embolic protection device (CEP) has been shown to be safe and effective in capturing debris in 99% of patients but the reduction in new cerebral lesion volume was not significant. The PROTECTED TAVR trial was a prospective, postmarket, multicentre, randomized, controlled trial designed to evaluate the efficacy of the Sentinal CEP in reducing stroke within 72 hours of transfemoral TAVI or before discharge. Stroke was defined as an acute episode of a focal or global neurologic dysfunction caused by vascular injury to the brain, spinal cord, or retina leading to haemorrhage or infarction. Disabling stroke, death, transient ischemic attack, delirium, major or minor vascular complications at the CEP access site, and acute kidney injury were also assessed.  Patients (n=3000) were eligible if they had AS and were scheduled to undergo transfemoral TAVI using a commercially available device. Patients were excluded if they had left common carotid or brachiocephalic artery stenosis >70% or the anatomical structure was unfavourable for placement of the CEP device. The mean age was 78.9±7.8 years, mean STS score 3.4±2.7, 40% were female, history of CVA/TIA was present in 8%, 8% had bicuspid AS, 3% had valve-in-valve procedure, a balloon expandable device was used in 64%, and duration of follow-up was 72 hours. The primary outcome was similar in the CEP and control groups (2.3% vs. 2.9%; difference -0.6 percentage points; 95% CI: -1.7 to 0.5; p=0.30). The rates of secondary outcomes for CEP and control groups were disabling stoke (0.5% vs. 1.3%; p<0.05), all-cause mortality (0.5% vs. 0.3%), stroke/TIA/delirium (3.1% vs. 3.7%), and acute kidney injury (0.5% vs. 0.5%).

Potential additional mechanism for stroke in TAVI patients

Cerebral microbleeds during transcatheter aortic valve replacement: a prospective magnetic resonance imaging cohort.

Circ 2022; 146:383-397

Cerebral microbleeds (CMBs) are frequently observed in elderly people and yet their clinical significance remains uncertain. The incidence of new CMBs and factors contributing to their formation in patients undergoing TAVI has not been previously examined. The current study prospectively examined a cohort of 84 patients with severe aortic stenosis that were referred for TAVI. Mean age was 80.9±5.7 years and 53% were female. On preprocedural MRI, 26% of the patients had at least 1 CMBs whilst following TAVI, new CMBs was observed in 23% of patients. In univariate analysis, a previous history of bleeding (p=0.01), higher total dose of heparin (p=0.02), a prolonged procedure (p=0.03), no protamine reversal (p=0.04), higher final ACT (p=0.05), lower final von Willebrand factor high molecular weight: multimer ratio (p=0.007) and lower final closure time with ADP (p=0.02) were associated with the occurrence of new postprocedural CMBs. In multivariate analysis, a prolonged procedure for every 5 minutes of fluoroscopy time (p=0.02) and postprocedural acquired von Willebrand factor defect for every lower 0.1 unit of high molecular weight: ratio (p=0.004) were independently associated with the occurrence of new postprocedural CMBs. Of note, new CMBs were not associated with changes in neurological outcome or quality of life at 6 months follow-up.

UK TAVI provides additional support for TAVI in the lower risk surgical patients

Effect of transcatheter aortic valve implantation vs surgical aortic valve replacement on all-cause mortality in patients with aortic stenosis. A randomized clinical trial.

JAMA 2022; 327:1875-1887

TAVI in intermediate and low-risk patients is being increasingly supported by data from randomized clinical trials. The UK TAVI trial examined whether TAVI was noninferior to SAVR in 913 patients (TAVI=458, SAVR=458) aged 70 years or older with severe symptomatic AS and moderately increased operative risk due to age or comorbidity. Key exclusion criteria were life expectancy < 1-year, previous AVR or TAVI, technically unsuitable for TAVI or SAVR, CAD for which surgical revascularization was required, primary aortic regurgitation, and severe mitral regurgitation. Other salient features included mean LV ejection fraction=5.7%, transfemoral access=92%, conscious sedation during TAVI=70%, 45% received the Sapien 3 valve, 14% Evolut/Evolut R, and 10% Lotus. The primary outcome was all-cause mortality at 1 year. There were 36 secondary outcomes including duration of hospital stay, major bleeding, vascular complications, requirement for a pacemaker, and aortic regurgitation. The median age was 81 years, 46% were female, median STS score was 2.6%, and 99.9% completed follow-up. At 1-year, mortality was 4.6% in the TAVI group and 6.6% in the surgical group (adjusted absolute risk difference of -2.0%; 1-sided 97.5% CI: −∞ to 1.2%; p < .001 for noninferiority). Of the 30 prespecified secondary outcomes, 24 showed no significant difference at 1 year. TAVI was associated with shorter hospital stay (median of 3 days vs. 8 days). TAVI was also associated with significantly lower bleeding complications (7.2% vs. 20.2%; HR: 0.33; 95% CI: 0.24-0.45) but significantly more vascular complications (10.3% vs. 2.4%; HR: 4.42; 95% CI: 2.54-7.71), pacemaker implantation (14.2% vs. 7.3%; HR: 2.05; 95% CI: 1.43-2.94), and mild (38.3% vs. 11.7%) or moderate (2.3% vs. 0.6%) aortic regurgitation. The rates of stroke were similar in the TAVI and SAVR groups (2.3% vs. 0.6%).

Expanding techniques for treating severe TR

6-Month outcomes of the TricValve sytem in patients with tricuspid regurgitation: the TRICUS EURO study.

JACC Cardiol Interv 2022; 15:1366-77

Bicaval valve implantation (CAVI) has emerged as a novel transcatheter strategy for indirectly treating the systemic manifestation of severe tricuspid regurgitation (TR) in patients ineligible for cardiac surgery or edge-to-edge repair. The Tricvalve system consists of 2 self-expanding valves designed for the SVC and IVC premounted in a 27.5-F delivery system. Caval anchoring is based on stent design, radial force, and the degree of oversizing. The TRICUS EURO study was a nonblind, nonrandomized, single arm, multicenter, prospective trial of 35 patients with symptomatic severe TR (grade ≥3 in a 5-grade classification) despite optimal medical therapy and NYHA functional class III or IV. The main exclusion criteria included severe right ventricular dysfunction, severe pulmonary hypertension (PAP≥65mmHg) and/or significant renal dysfunction (defined as serum creatinine >3mg/dl). The primary endpoint was quality of life (QoL) improvement measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) and NYHA functional class improvement at 6-month follow-up. The mean age was 76 ± 6.8 years, 83% were female, 20% were diabetic, and the overall EuroSCORE II was 5.8 ± 4.2. At 30 days, procedural success was 94%, with no procedural death or conversion to surgery. At 6 months, patients had a significant improvement in QoL from 42.01 ± 22.3 to 59.7 ± 23.6 (p=0.004) correlating with a significant improvement in NYHA class with 79.4% of patients noted to be in class I or II (p=0.0006). The rates of 6-month all-cause mortality and heart failure hospitalization were 8.5% and 20% respectively. There were 6 cases of major bleeding and 2 were access site related. The study represents the first comprehensive short-term analysis of a dedicated CAVI system and longer-term data are required to assess clinical benefits and haemodynamic effects upon the pulmonary and right heart status.

Miscellaneous

Hydration remains key for renal protection

Study evaluating the use of RenalGuard to protect patients at high risk of AKI. JACC 2022; 15:1639-48

Contrast-induced nephropathy (CIN) may occur in 2-7% of patients undergoing angiographic procedures. A variety of measures including hydration with sodium bicarbonate, N-acetylcysteine, and hemofiltration have been examined in randomized trials but no measure except adequate intravenous (IV) hydration and minimal contrast use have been shown to be effective strategies. The RenalGuard system (RG) is a device that delivers real-time isotonic IV hydration matched with frusemide-induced diuresis allowing hydration and contrast clearance thus preventing fluid overload and volume depletion. The STRENGTH study examined the superiority of RG over standard practice (considering the ESC guidelines including IV and oral hydration, the dose of contrast medium and staged procedure if necessary) in 259 patients with moderate to severe chronic kidney disease (estimated GFR 15-40 ml/min/m²) requiring complex coronary, structural, or peripheral procedures with an expected contrast injection of at least 3x the estimated GFR. The primary endpoint was the occurrence of CIN, defined as an increase in serum creatinine ≥ 0.3mg/dl and/or an increase of 25% of basal value at around day 3 or the requirement for dialysis within 5 days after the procedure. Secondary endpoints included a change in serum creatinine value and GFR at 12 months, % of patients on temporary or chronic haemodialysis at 12 months, and MACCEs. In the whole population, the mean age was 79 years, 50% were male, baseline GFR was 32ml/min/1.73m², 48% underwent PCI, 34% structural intervention (TAVI and LAA closure), and 18% peripheral intervention. The mean amount of contrast use was similar in both groups (116ml in the RG group vs. 104ml in the control group; p=0.26). The total fluid intake was higher in the RG group (6196ml vs. 1407ml; p<0.0001). The primary endpoint was similar in the RG and control groups (15.9% vs. 13.9%; difference=2.4; 95% CI:-7.1-12; p=0.62). At 12 months, there were no significant differences between the two groups. The rate of MACCEs were also similar at a median of 342 days (20.5% in RG group vs. 22.2% in the control group).

BCIS R&D Group Literature Review

September 2022

Prepared by Michael Mahmoudi, Paul Morris and Natalia Briceno
Edited by Michael Mahmoudi

Coronary Artery Disease

No need for routine non-invasive stress testing post-PCI

Routine functional testing or standard care in high-risk patients after PCI. NEJM 2022; 387:905-915

The optimal follow-up strategy for patients undergoing coronary revascularization who have high-risk characteristics is variable. Some studies have shown that functional testing is widely used in clinical practice with more than half of all such patients having had functional testing within 2 years of revascularization. The POST-PCI investigators conducted a randomized superiority trial to compare an active follow-up strategy of routine functional testing (nuclear stress testing, stress echocardiography, Exercise electrocardiography) examined whether a follow-up strategy that includes functional testing improved clinical outcomes. Patients (n=1706) who had undergone successful PCI with DES, bioresorbable scaffolds, or drug-coated balloon (for ISR) who had at least one high-risk anatomical feature (left main disease, bifurcation disease, ostial disease, CTO, multivessel disease warranting PCI of at least two vessels, a restenotic lesion, lesion length > 30mm or a lesion warranting a stent length of > 32mm, and bypass graft disease) or clinical characteristics (diabetes mellitus, chronic renal disease defined as serum creatinine ≥ 177 mmol/l or long-term haemodialysis, and enzyme positive ACS) were enrolled to a strategy of routine functional testing (n=849) at 1 year post PCI or standard care alone (n=857). Patients underwent routine follow-up at 6, 12, 18, and 24 months. The primary endpoint was a composite of MACE defined as death from any cause, MI, or hospitalization for unstable angina at 2 years. The mean age was 64.7±10.3, 79.5% were men, 21% had left main disease, 43.5% had bifurcation disease, 69.8% had multivessel disease, 70.1% had a diffuse long lesion, 38.7% had diabetes, 19.4% had an ACS, 96.4% were treated with DES, the mean number of stents per patient was 2.0, the mean stent length was 57mm, FFR was measured in 35.7% of the patients, and intravascular imaging was used in 74.4%. At 2 years, the primary endpoint was similar in the functional testing and standard care groups (5.5% vs. 6.0%; HR: 0.9; 95% CI: 0.61-1.35; p=0.62). There were no between-group differences with respect to the components of the primary outcome. At 2 years, invasive angiography had been undertaken in 12.3% of the functional testing group and 9.3% of the standard care group (p=0.62) had undergone invasive angiography. The rates of revascularization were also similar in the two groups (8.1% vs. 5.8%; p>0.05).

Reviving a failing heart with PCI

Percutaneous revascularization for ischemic ventricular dysfunction.

NEJM 2022 Online

The benefits of coronary revascularization in patients with significant left ventricular systolic dysfunction remains uncertain. A survival benefit in patients undergoing CABG in this population became apparent only after 10 years in the STICH trial. The REVIVED investigators examined whether coronary revascularization with PCI in addition to guideline directed optimal medical therapy (OMT) (n=347) as compared to OMT alone (n=353) improved event-free survival in patients with left ventricular ejection fraction (LVEF) ≤ 35%, extensive coronary artery disease (BCIS jeopardy score ≥ 6) and myocardial viability in at least four dysfunctional segments amenable to revascularization with PCI. The primary composite outcome was death from any cause or hospitalization for heart failure over a minimum follow-up period of 24 months. The major secondary outcomes were LVEF at 6 and 12 months, KCCQ overall summary score, the score on the EQ-5D-5L score, and NYHA functional class. The two groups were well matched for baseline characteristics. Median age was 70 years, 88% were men, 77% had NYHA class I/II, and 67% had no angina. The primary outcome occurred in 37.2% of the PCI plus OMT group and 38% of the OMT group (HR, 0.99; 95% CI: 0.78-1.27; p=0.96). The rates of death (31.7% vs. 32.6%; HR, 0.98; 95% CI: 0.75-1.27) and hospitalization for heart failure (14.7% vs. 15.3%; HR, 0.97; 95% CI: 0.66-1.43) were similar in the PCI plus OMT and OMT groups. The LVEF was similar in the two groups at 6 months (mean difference, -1.6 percentage points; 95% CI: -3.7-0.5) and at 12 months (mean difference; 0.9 percentage points; 95% CI: -1.7-3.4). Quality of life scores at 6 and 12 months favoured the PCI group but this difference diminished at 24 months. Of note, approximately 50% of the patients had 2V CAD and a median of two lesions and vessels were treated per patient which may be out of proportion to the extent of LV dysfunction. Other salient features include lack of description of the severity of stenoses, physiological assessment of the lesion, and lack of correlation of stenosis with previous ischemic/viability testing.

Secure compliance with the polypill

Polypill strategy in secondary cardiovascular prevention.

NEJM 2022; 387:967-977

Noncompliance with guideline directed optimal medical therapy is a frequently observed challenge faced by patients and healthcare providers. This is often associated with adverse clinical outcomes particularly in patients at the highest risk of adverse clinical events. A polypill strategy has been shown to improve compliance and lower cardiovascular event rates in trials of primary prevention.  The SECURE trial was a randomized phase 3 trial designed to assess the efficacy of a polypill strategy, as compared with standard care, with respect to major cardiovascular outcomes (defined as CV death, nonfatal type 1 MI, nonfatal ischemic stroke, or urgent revascularization) in patients older than 75 years of age or at least 65 years of age with at least one of the following risk factors: diabetes mellitus, mild or moderate renal disease defined as creatinine clearance 30-60 ml/min/1.73m² of body surface area, previous MI, previous coronary revascularization (PCI or CABG), or previous stroke. All patients had to have had a history of type 1 MI within the previous 6 months. The polypill contained any of three formulations Polypill AAR40-a single pill containing aspirin 100mg, ramipril 2.5, 5, or 10mg, and atorvastatin 40mg. The dose of the atorvastatin could be reduced to 20mg on clinical grounds in which case the Polypill AAR20 was used (same as AAR40 but reduced dose of atorvastatin at 20mg). In patients who were not on ramipril at baseline, treatment was commenced at 2.5mg; in those who were already on an ACE inhibitor, treatment was commenced at the equivalent dose of ramipril with the aim of reaching 10mg. Follow-up was undertaken at 6, 12, 18, 24, 36, and 48 months. At 6 and 24 months, adherence was checked using the eight-item Morisky Medication Adherence Scale. A total of 2499 patients were randomized (polypill=1258, standard care=1241). The median time between the index MI and randomization was 8 days. The mean age was 76±6.6 years, 31% were female, 77.9% had hypertension, 57.4% had diabetes, 51.3% had a history of smoking, mean systolic blood pressure was 129.1±17.7, and mean LDL was 89.2±37.2. Most patients in the polypill group (91.7%) received the 40mg formulation of atorvastatin as compared to 40.4% in the standard care group. 98.7% of patients in the standard care group received aspirin and 95.1% received an additional antiplatelet agent as compared to 94% in the polypill group. The primary endpoint was lower in the polypill group (9.5% vs. 12.7%; HR: 0.76; 95% CI; 0.60-0.96; p=0.02). All components of the composite outcome except for urgent revascularization were reduced in a consistent manner. The secondary outcome of CV death, MI, or stroke was also lower in the polypill group (8.2% vs. 11.7%; HR: 0.70; 95% CI: 0.54-0.90); p=0.005). All-cause mortality was similar in both groups (9.3% vs. 9.5%; p=0.79). Adherence was higher in the polypill group both at 6 months (70.6% vs. 62.7%; RR: 1.13; 95% CI: 1.06-1.20) and 24 months (74.1% vs. 63.2%; RR: 1.17; 95% CI: 1.10-1.25).

Routine pressure wire assessment not supported by RIPCORD-2

Routine pressure wire assessment versus conventional angiography in the management of patients with coronary artery disease: The RIPCORD 2 trial.

Circ 2022 Online

FFR-guided PCI has been shown to be associated lower resource utilization and improved clinical outcomes compared with angiography guidance alone. The value of FFR of all major coronary vessels at the time diagnostic angiography has not been established. The RIPCORD 2 trial was an 1100 patient prospective, multicentre, randomized trial that compared a strategy of coronary angiography alone versus coronary angiography + routine FFR assessment of all epicardial vessels of sufficient size amenable to revascularization to determine whether the latter strategy was associated with more effective resource utilization, improved quality of life, and better clinical outcome. In the angiography + FFR group, the median number of vessels examined was 4. There were no differences in the median hospital costs between the two groups (£4136 for angiography vs. £4510 for angiography + FFR; p=0.137) nor the median quality of life using the visual analog scale of the EuroQol EQ-5D-5L (75 vs. 75; p=0.88). The number of clinical events were death (5 vs. 8), stroke (3 vs. 4), MI (23 vs. 22), and unplanned revascularization (26 vs. 33) with a composite hierarchical event rate of 8.7% for angiography versus 9.5% for angiography + FFR (p=0.64). The study thus concluded that routine FFR at the stage of diagnostic angiography is not associated with reduction in cost or improvement in quality of life.

Alirocumab has favourable effects on plaque composition

Effect of alirocumab added to high-intensity statin therapy on coronary atherosclerosis in patients with acute myocardial infraction. The PACMAN-AMI randomized clinical trial.

JAMA 2022; 327:1771-81

PCSK inhibitors have been shown to result in significant reductions in LDL-C and improve clinical outcomes in patients with recent ACS. The PACMAN-AMI trial examined whether the addition of alirocumab to high-intensity statin therapy affected coronary atherosclerotic plaques in the non-infracted related arteries. Following PCU of the culprit lesion in the infarct related artery (IRA), eligible patients underwent intracoronary imaging of the non-IRA with OCT, IVUS and NIRS, and then randomized in a 1:1 fashion to receive either 150mg alirocumab (n=148) or placebo (n=152) biweekly via subcutaneous injection for 52 weeks.  Both groups also received rosuvastatin 20mg daily. Main inclusion criteria were age ≥ 18 years, successful PCI of the culprit vessel (STEMI=53%, NSTEMI=47%), suitability for intracoronary imaging with angiographic stenosis between 20-50% in the proximal segments of two non-IRAs, and LDL-C at baseline ≥ 125 mg/dl if not on a statin for 4 weeks prior to presentation or ≥ 70mg/dl if on a stable dose of a statin. Key exclusion criteria were left main or three vessel disease, history of CABG, severe chronic kidney or liver disease, and known statin intolerance. The mean age was 58 years, 18% were female, 10% were diabetic, and mean LDL-C was 152.4 mg/dl. At 12 months, the primary endpoint of change in mean percent atheroma volume from baseline for alirocumab was greater than placebo -2.13% vs. -0.92% (p<0.001). Mean change in maximum lipid core burden index within 4 mm was −79.42 with alirocumab vs. −37.60 with placebo (difference, −41.24; 95% CI: −70.71 to −11.77; p= 0.006). Mean change in minimal fibrous cap thickness was 62.67μm with alirocumab vs. 33.19μm with placebo (difference, 29.65μm; 95% CI: 11.75-47.55; p=0.001). Adverse events occurred in 70.7% of patients treated with alirocumab vs. 72.8% of patients receiving placebo. The change in LDL-C from baseline was -131.2 mg/dl in the alirocumab group vs. -76.5 mg/dl in the placebo group (p<0.001).

Valvular Heart Disease

Embolic protection remains a challenge

Cerebral embolic protection during transcatheter aortic valve replacement. NEJM 2022 Online

Embolization of biological material from either the aortic valve and/or the aorta may cause a periprocedural stroke in 2-2.5% of patients undergoing TAVI. The Sentinel cerebral embolic protection device (CEP) has been shown to be safe and effective in capturing debris in 99% of patients but the reduction in new cerebral lesion volume was not significant. The PROTECTED TAVR trial was a prospective, postmarket, multicentre, randomized, controlled trial designed to evaluate the efficacy of the Sentinal CEP in reducing stroke within 72 hours of transfemoral TAVI or before discharge. Stroke was defined as an acute episode of a focal or global neurologic dysfunction caused by vascular injury to the brain, spinal cord, or retina leading to haemorrhage or infarction. Disabling stroke, death, transient ischemic attack, delirium, major or minor vascular complications at the CEP access site, and acute kidney injury were also assessed.  Patients (n=3000) were eligible if they had AS and were scheduled to undergo transfemoral TAVI using a commercially available device. Patients were excluded if they had left common carotid or brachiocephalic artery stenosis >70% or the anatomical structure was unfavourable for placement of the CEP device. The mean age was 78.9±7.8 years, mean STS score 3.4±2.7, 40% were female, history of CVA/TIA was present in 8%, 8% had bicuspid AS, 3% had valve-in-valve procedure, a balloon expandable device was used in 64%, and duration of follow-up was 72 hours. The primary outcome was similar in the CEP and control groups (2.3% vs. 2.9%; difference -0.6 percentage points; 95% CI: -1.7 to 0.5; p=0.30). The rates of secondary outcomes for CEP and control groups were disabling stoke (0.5% vs. 1.3%; p<0.05), all-cause mortality (0.5% vs. 0.3%), stroke/TIA/delirium (3.1% vs. 3.7%), and acute kidney injury (0.5% vs. 0.5%).

Potential additional mechanism for stroke in TAVI patients

Cerebral microbleeds during transcatheter aortic valve replacement: a prospective magnetic resonance imaging cohort.

Circ 2022; 146:383-397

Cerebral microbleeds (CMBs) are frequently observed in elderly people and yet their clinical significance remains uncertain. The incidence of new CMBs and factors contributing to their formation in patients undergoing TAVI has not been previously examined. The current study prospectively examined a cohort of 84 patients with severe aortic stenosis that were referred for TAVI. Mean age was 80.9±5.7 years and 53% were female. On preprocedural MRI, 26% of the patients had at least 1 CMBs whilst following TAVI, new CMBs was observed in 23% of patients. In univariate analysis, a previous history of bleeding (p=0.01), higher total dose of heparin (p=0.02), a prolonged procedure (p=0.03), no protamine reversal (p=0.04), higher final ACT (p=0.05), lower final von Willebrand factor high molecular weight: multimer ratio (p=0.007) and lower final closure time with ADP (p=0.02) were associated with the occurrence of new postprocedural CMBs. In multivariate analysis, a prolonged procedure for every 5 minutes of fluoroscopy time (p=0.02) and postprocedural acquired von Willebrand factor defect for every lower 0.1 unit of high molecular weight: ratio (p=0.004) were independently associated with the occurrence of new postprocedural CMBs. Of note, new CMBs were not associated with changes in neurological outcome or quality of life at 6 months follow-up.

UK TAVI provides additional support for TAVI in the lower risk surgical patients

Effect of transcatheter aortic valve implantation vs surgical aortic valve replacement on all-cause mortality in patients with aortic stenosis. A randomized clinical trial.

JAMA 2022; 327:1875-1887

TAVI in intermediate and low-risk patients is being increasingly supported by data from randomized clinical trials. The UK TAVI trial examined whether TAVI was noninferior to SAVR in 913 patients (TAVI=458, SAVR=458) aged 70 years or older with severe symptomatic AS and moderately increased operative risk due to age or comorbidity. Key exclusion criteria were life expectancy < 1-year, previous AVR or TAVI, technically unsuitable for TAVI or SAVR, CAD for which surgical revascularization was required, primary aortic regurgitation, and severe mitral regurgitation. Other salient features included mean LV ejection fraction=5.7%, transfemoral access=92%, conscious sedation during TAVI=70%, 45% received the Sapien 3 valve, 14% Evolut/Evolut R, and 10% Lotus. The primary outcome was all-cause mortality at 1 year. There were 36 secondary outcomes including duration of hospital stay, major bleeding, vascular complications, requirement for a pacemaker, and aortic regurgitation. The median age was 81 years, 46% were female, median STS score was 2.6%, and 99.9% completed follow-up. At 1-year, mortality was 4.6% in the TAVI group and 6.6% in the surgical group (adjusted absolute risk difference of -2.0%; 1-sided 97.5% CI: −∞ to 1.2%; p < .001 for noninferiority). Of the 30 prespecified secondary outcomes, 24 showed no significant difference at 1 year. TAVI was associated with shorter hospital stay (median of 3 days vs. 8 days). TAVI was also associated with significantly lower bleeding complications (7.2% vs. 20.2%; HR: 0.33; 95% CI: 0.24-0.45) but significantly more vascular complications (10.3% vs. 2.4%; HR: 4.42; 95% CI: 2.54-7.71), pacemaker implantation (14.2% vs. 7.3%; HR: 2.05; 95% CI: 1.43-2.94), and mild (38.3% vs. 11.7%) or moderate (2.3% vs. 0.6%) aortic regurgitation. The rates of stroke were similar in the TAVI and SAVR groups (2.3% vs. 0.6%).

Expanding techniques for treating severe TR

6-Month outcomes of the TricValve sytem in patients with tricuspid regurgitation: the TRICUS EURO study.

JACC Cardiol Interv 2022; 15:1366-77

Bicaval valve implantation (CAVI) has emerged as a novel transcatheter strategy for indirectly treating the systemic manifestation of severe tricuspid regurgitation (TR) in patients ineligible for cardiac surgery or edge-to-edge repair. The Tricvalve system consists of 2 self-expanding valves designed for the SVC and IVC premounted in a 27.5-F delivery system. Caval anchoring is based on stent design, radial force, and the degree of oversizing. The TRICUS EURO study was a nonblind, nonrandomized, single arm, multicenter, prospective trial of 35 patients with symptomatic severe TR (grade ≥3 in a 5-grade classification) despite optimal medical therapy and NYHA functional class III or IV. The main exclusion criteria included severe right ventricular dysfunction, severe pulmonary hypertension (PAP≥65mmHg) and/or significant renal dysfunction (defined as serum creatinine >3mg/dl). The primary endpoint was quality of life (QoL) improvement measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) and NYHA functional class improvement at 6-month follow-up. The mean age was 76 ± 6.8 years, 83% were female, 20% were diabetic, and the overall EuroSCORE II was 5.8 ± 4.2. At 30 days, procedural success was 94%, with no procedural death or conversion to surgery. At 6 months, patients had a significant improvement in QoL from 42.01 ± 22.3 to 59.7 ± 23.6 (p=0.004) correlating with a significant improvement in NYHA class with 79.4% of patients noted to be in class I or II (p=0.0006). The rates of 6-month all-cause mortality and heart failure hospitalization were 8.5% and 20% respectively. There were 6 cases of major bleeding and 2 were access site related. The study represents the first comprehensive short-term analysis of a dedicated CAVI system and longer-term data are required to assess clinical benefits and haemodynamic effects upon the pulmonary and right heart status.

Miscellaneous

Hydration remains key for renal protection

Study evaluating the use of RenalGuard to protect patients at high risk of AKI. JACC 2022; 15:1639-48

Contrast-induced nephropathy (CIN) may occur in 2-7% of patients undergoing angiographic procedures. A variety of measures including hydration with sodium bicarbonate, N-acetylcysteine, and hemofiltration have been examined in randomized trials but no measure except adequate intravenous (IV) hydration and minimal contrast use have been shown to be effective strategies. The RenalGuard system (RG) is a device that delivers real-time isotonic IV hydration matched with frusemide-induced diuresis allowing hydration and contrast clearance thus preventing fluid overload and volume depletion. The STRENGTH study examined the superiority of RG over standard practice (considering the ESC guidelines including IV and oral hydration, the dose of contrast medium and staged procedure if necessary) in 259 patients with moderate to severe chronic kidney disease (estimated GFR 15-40 ml/min/m²) requiring complex coronary, structural, or peripheral procedures with an expected contrast injection of at least 3x the estimated GFR. The primary endpoint was the occurrence of CIN, defined as an increase in serum creatinine ≥ 0.3mg/dl and/or an increase of 25% of basal value at around day 3 or the requirement for dialysis within 5 days after the procedure. Secondary endpoints included a change in serum creatinine value and GFR at 12 months, % of patients on temporary or chronic haemodialysis at 12 months, and MACCEs. In the whole population, the mean age was 79 years, 50% were male, baseline GFR was 32ml/min/1.73m², 48% underwent PCI, 34% structural intervention (TAVI and LAA closure), and 18% peripheral intervention. The mean amount of contrast use was similar in both groups (116ml in the RG group vs. 104ml in the control group; p=0.26). The total fluid intake was higher in the RG group (6196ml vs. 1407ml; p<0.0001). The primary endpoint was similar in the RG and control groups (15.9% vs. 13.9%; difference=2.4; 95% CI:-7.1-12; p=0.62). At 12 months, there were no significant differences between the two groups. The rate of MACCEs were also similar at a median of 342 days (20.5% in RG group vs. 22.2% in the control group).

BCIS R&D Group Literature Review

September 2022

Prepared by Michael Mahmoudi, Paul Morris and Natalia Briceno
Edited by Michael Mahmoudi

Coronary Artery Disease

No need for routine non-invasive stress testing post-PCI

Routine functional testing or standard care in high-risk patients after PCI. NEJM 2022; 387:905-915

The optimal follow-up strategy for patients undergoing coronary revascularization who have high-risk characteristics is variable. Some studies have shown that functional testing is widely used in clinical practice with more than half of all such patients having had functional testing within 2 years of revascularization. The POST-PCI investigators conducted a randomized superiority trial to compare an active follow-up strategy of routine functional testing (nuclear stress testing, stress echocardiography, Exercise electrocardiography) examined whether a follow-up strategy that includes functional testing improved clinical outcomes. Patients (n=1706) who had undergone successful PCI with DES, bioresorbable scaffolds, or drug-coated balloon (for ISR) who had at least one high-risk anatomical feature (left main disease, bifurcation disease, ostial disease, CTO, multivessel disease warranting PCI of at least two vessels, a restenotic lesion, lesion length > 30mm or a lesion warranting a stent length of > 32mm, and bypass graft disease) or clinical characteristics (diabetes mellitus, chronic renal disease defined as serum creatinine ≥ 177 mmol/l or long-term haemodialysis, and enzyme positive ACS) were enrolled to a strategy of routine functional testing (n=849) at 1 year post PCI or standard care alone (n=857). Patients underwent routine follow-up at 6, 12, 18, and 24 months. The primary endpoint was a composite of MACE defined as death from any cause, MI, or hospitalization for unstable angina at 2 years. The mean age was 64.7±10.3, 79.5% were men, 21% had left main disease, 43.5% had bifurcation disease, 69.8% had multivessel disease, 70.1% had a diffuse long lesion, 38.7% had diabetes, 19.4% had an ACS, 96.4% were treated with DES, the mean number of stents per patient was 2.0, the mean stent length was 57mm, FFR was measured in 35.7% of the patients, and intravascular imaging was used in 74.4%. At 2 years, the primary endpoint was similar in the functional testing and standard care groups (5.5% vs. 6.0%; HR: 0.9; 95% CI: 0.61-1.35; p=0.62). There were no between-group differences with respect to the components of the primary outcome. At 2 years, invasive angiography had been undertaken in 12.3% of the functional testing group and 9.3% of the standard care group (p=0.62) had undergone invasive angiography. The rates of revascularization were also similar in the two groups (8.1% vs. 5.8%; p>0.05).

Reviving a failing heart with PCI

Percutaneous revascularization for ischemic ventricular dysfunction.

NEJM 2022 Online

The benefits of coronary revascularization in patients with significant left ventricular systolic dysfunction remains uncertain. A survival benefit in patients undergoing CABG in this population became apparent only after 10 years in the STICH trial. The REVIVED investigators examined whether coronary revascularization with PCI in addition to guideline directed optimal medical therapy (OMT) (n=347) as compared to OMT alone (n=353) improved event-free survival in patients with left ventricular ejection fraction (LVEF) ≤ 35%, extensive coronary artery disease (BCIS jeopardy score ≥ 6) and myocardial viability in at least four dysfunctional segments amenable to revascularization with PCI. The primary composite outcome was death from any cause or hospitalization for heart failure over a minimum follow-up period of 24 months. The major secondary outcomes were LVEF at 6 and 12 months, KCCQ overall summary score, the score on the EQ-5D-5L score, and NYHA functional class. The two groups were well matched for baseline characteristics. Median age was 70 years, 88% were men, 77% had NYHA class I/II, and 67% had no angina. The primary outcome occurred in 37.2% of the PCI plus OMT group and 38% of the OMT group (HR, 0.99; 95% CI: 0.78-1.27; p=0.96). The rates of death (31.7% vs. 32.6%; HR, 0.98; 95% CI: 0.75-1.27) and hospitalization for heart failure (14.7% vs. 15.3%; HR, 0.97; 95% CI: 0.66-1.43) were similar in the PCI plus OMT and OMT groups. The LVEF was similar in the two groups at 6 months (mean difference, -1.6 percentage points; 95% CI: -3.7-0.5) and at 12 months (mean difference; 0.9 percentage points; 95% CI: -1.7-3.4). Quality of life scores at 6 and 12 months favoured the PCI group but this difference diminished at 24 months. Of note, approximately 50% of the patients had 2V CAD and a median of two lesions and vessels were treated per patient which may be out of proportion to the extent of LV dysfunction. Other salient features include lack of description of the severity of stenoses, physiological assessment of the lesion, and lack of correlation of stenosis with previous ischemic/viability testing.

Secure compliance with the polypill

Polypill strategy in secondary cardiovascular prevention.

NEJM 2022; 387:967-977

Noncompliance with guideline directed optimal medical therapy is a frequently observed challenge faced by patients and healthcare providers. This is often associated with adverse clinical outcomes particularly in patients at the highest risk of adverse clinical events. A polypill strategy has been shown to improve compliance and lower cardiovascular event rates in trials of primary prevention.  The SECURE trial was a randomized phase 3 trial designed to assess the efficacy of a polypill strategy, as compared with standard care, with respect to major cardiovascular outcomes (defined as CV death, nonfatal type 1 MI, nonfatal ischemic stroke, or urgent revascularization) in patients older than 75 years of age or at least 65 years of age with at least one of the following risk factors: diabetes mellitus, mild or moderate renal disease defined as creatinine clearance 30-60 ml/min/1.73m² of body surface area, previous MI, previous coronary revascularization (PCI or CABG), or previous stroke. All patients had to have had a history of type 1 MI within the previous 6 months. The polypill contained any of three formulations Polypill AAR40-a single pill containing aspirin 100mg, ramipril 2.5, 5, or 10mg, and atorvastatin 40mg. The dose of the atorvastatin could be reduced to 20mg on clinical grounds in which case the Polypill AAR20 was used (same as AAR40 but reduced dose of atorvastatin at 20mg). In patients who were not on ramipril at baseline, treatment was commenced at 2.5mg; in those who were already on an ACE inhibitor, treatment was commenced at the equivalent dose of ramipril with the aim of reaching 10mg. Follow-up was undertaken at 6, 12, 18, 24, 36, and 48 months. At 6 and 24 months, adherence was checked using the eight-item Morisky Medication Adherence Scale. A total of 2499 patients were randomized (polypill=1258, standard care=1241). The median time between the index MI and randomization was 8 days. The mean age was 76±6.6 years, 31% were female, 77.9% had hypertension, 57.4% had diabetes, 51.3% had a history of smoking, mean systolic blood pressure was 129.1±17.7, and mean LDL was 89.2±37.2. Most patients in the polypill group (91.7%) received the 40mg formulation of atorvastatin as compared to 40.4% in the standard care group. 98.7% of patients in the standard care group received aspirin and 95.1% received an additional antiplatelet agent as compared to 94% in the polypill group. The primary endpoint was lower in the polypill group (9.5% vs. 12.7%; HR: 0.76; 95% CI; 0.60-0.96; p=0.02). All components of the composite outcome except for urgent revascularization were reduced in a consistent manner. The secondary outcome of CV death, MI, or stroke was also lower in the polypill group (8.2% vs. 11.7%; HR: 0.70; 95% CI: 0.54-0.90); p=0.005). All-cause mortality was similar in both groups (9.3% vs. 9.5%; p=0.79). Adherence was higher in the polypill group both at 6 months (70.6% vs. 62.7%; RR: 1.13; 95% CI: 1.06-1.20) and 24 months (74.1% vs. 63.2%; RR: 1.17; 95% CI: 1.10-1.25).

Routine pressure wire assessment not supported by RIPCORD-2

Routine pressure wire assessment versus conventional angiography in the management of patients with coronary artery disease: The RIPCORD 2 trial.

Circ 2022 Online

FFR-guided PCI has been shown to be associated lower resource utilization and improved clinical outcomes compared with angiography guidance alone. The value of FFR of all major coronary vessels at the time diagnostic angiography has not been established. The RIPCORD 2 trial was an 1100 patient prospective, multicentre, randomized trial that compared a strategy of coronary angiography alone versus coronary angiography + routine FFR assessment of all epicardial vessels of sufficient size amenable to revascularization to determine whether the latter strategy was associated with more effective resource utilization, improved quality of life, and better clinical outcome. In the angiography + FFR group, the median number of vessels examined was 4. There were no differences in the median hospital costs between the two groups (£4136 for angiography vs. £4510 for angiography + FFR; p=0.137) nor the median quality of life using the visual analog scale of the EuroQol EQ-5D-5L (75 vs. 75; p=0.88). The number of clinical events were death (5 vs. 8), stroke (3 vs. 4), MI (23 vs. 22), and unplanned revascularization (26 vs. 33) with a composite hierarchical event rate of 8.7% for angiography versus 9.5% for angiography + FFR (p=0.64). The study thus concluded that routine FFR at the stage of diagnostic angiography is not associated with reduction in cost or improvement in quality of life.

Alirocumab has favourable effects on plaque composition

Effect of alirocumab added to high-intensity statin therapy on coronary atherosclerosis in patients with acute myocardial infraction. The PACMAN-AMI randomized clinical trial.

JAMA 2022; 327:1771-81

PCSK inhibitors have been shown to result in significant reductions in LDL-C and improve clinical outcomes in patients with recent ACS. The PACMAN-AMI trial examined whether the addition of alirocumab to high-intensity statin therapy affected coronary atherosclerotic plaques in the non-infracted related arteries. Following PCU of the culprit lesion in the infarct related artery (IRA), eligible patients underwent intracoronary imaging of the non-IRA with OCT, IVUS and NIRS, and then randomized in a 1:1 fashion to receive either 150mg alirocumab (n=148) or placebo (n=152) biweekly via subcutaneous injection for 52 weeks.  Both groups also received rosuvastatin 20mg daily. Main inclusion criteria were age ≥ 18 years, successful PCI of the culprit vessel (STEMI=53%, NSTEMI=47%), suitability for intracoronary imaging with angiographic stenosis between 20-50% in the proximal segments of two non-IRAs, and LDL-C at baseline ≥ 125 mg/dl if not on a statin for 4 weeks prior to presentation or ≥ 70mg/dl if on a stable dose of a statin. Key exclusion criteria were left main or three vessel disease, history of CABG, severe chronic kidney or liver disease, and known statin intolerance. The mean age was 58 years, 18% were female, 10% were diabetic, and mean LDL-C was 152.4 mg/dl. At 12 months, the primary endpoint of change in mean percent atheroma volume from baseline for alirocumab was greater than placebo -2.13% vs. -0.92% (p<0.001). Mean change in maximum lipid core burden index within 4 mm was −79.42 with alirocumab vs. −37.60 with placebo (difference, −41.24; 95% CI: −70.71 to −11.77; p= 0.006). Mean change in minimal fibrous cap thickness was 62.67μm with alirocumab vs. 33.19μm with placebo (difference, 29.65μm; 95% CI: 11.75-47.55; p=0.001). Adverse events occurred in 70.7% of patients treated with alirocumab vs. 72.8% of patients receiving placebo. The change in LDL-C from baseline was -131.2 mg/dl in the alirocumab group vs. -76.5 mg/dl in the placebo group (p<0.001).

Valvular Heart Disease

Embolic protection remains a challenge

Cerebral embolic protection during transcatheter aortic valve replacement. NEJM 2022 Online

Embolization of biological material from either the aortic valve and/or the aorta may cause a periprocedural stroke in 2-2.5% of patients undergoing TAVI. The Sentinel cerebral embolic protection device (CEP) has been shown to be safe and effective in capturing debris in 99% of patients but the reduction in new cerebral lesion volume was not significant. The PROTECTED TAVR trial was a prospective, postmarket, multicentre, randomized, controlled trial designed to evaluate the efficacy of the Sentinal CEP in reducing stroke within 72 hours of transfemoral TAVI or before discharge. Stroke was defined as an acute episode of a focal or global neurologic dysfunction caused by vascular injury to the brain, spinal cord, or retina leading to haemorrhage or infarction. Disabling stroke, death, transient ischemic attack, delirium, major or minor vascular complications at the CEP access site, and acute kidney injury were also assessed.  Patients (n=3000) were eligible if they had AS and were scheduled to undergo transfemoral TAVI using a commercially available device. Patients were excluded if they had left common carotid or brachiocephalic artery stenosis >70% or the anatomical structure was unfavourable for placement of the CEP device. The mean age was 78.9±7.8 years, mean STS score 3.4±2.7, 40% were female, history of CVA/TIA was present in 8%, 8% had bicuspid AS, 3% had valve-in-valve procedure, a balloon expandable device was used in 64%, and duration of follow-up was 72 hours. The primary outcome was similar in the CEP and control groups (2.3% vs. 2.9%; difference -0.6 percentage points; 95% CI: -1.7 to 0.5; p=0.30). The rates of secondary outcomes for CEP and control groups were disabling stoke (0.5% vs. 1.3%; p<0.05), all-cause mortality (0.5% vs. 0.3%), stroke/TIA/delirium (3.1% vs. 3.7%), and acute kidney injury (0.5% vs. 0.5%).

Potential additional mechanism for stroke in TAVI patients

Cerebral microbleeds during transcatheter aortic valve replacement: a prospective magnetic resonance imaging cohort.

Circ 2022; 146:383-397

Cerebral microbleeds (CMBs) are frequently observed in elderly people and yet their clinical significance remains uncertain. The incidence of new CMBs and factors contributing to their formation in patients undergoing TAVI has not been previously examined. The current study prospectively examined a cohort of 84 patients with severe aortic stenosis that were referred for TAVI. Mean age was 80.9±5.7 years and 53% were female. On preprocedural MRI, 26% of the patients had at least 1 CMBs whilst following TAVI, new CMBs was observed in 23% of patients. In univariate analysis, a previous history of bleeding (p=0.01), higher total dose of heparin (p=0.02), a prolonged procedure (p=0.03), no protamine reversal (p=0.04), higher final ACT (p=0.05), lower final von Willebrand factor high molecular weight: multimer ratio (p=0.007) and lower final closure time with ADP (p=0.02) were associated with the occurrence of new postprocedural CMBs. In multivariate analysis, a prolonged procedure for every 5 minutes of fluoroscopy time (p=0.02) and postprocedural acquired von Willebrand factor defect for every lower 0.1 unit of high molecular weight: ratio (p=0.004) were independently associated with the occurrence of new postprocedural CMBs. Of note, new CMBs were not associated with changes in neurological outcome or quality of life at 6 months follow-up.

UK TAVI provides additional support for TAVI in the lower risk surgical patients

Effect of transcatheter aortic valve implantation vs surgical aortic valve replacement on all-cause mortality in patients with aortic stenosis. A randomized clinical trial.

JAMA 2022; 327:1875-1887

TAVI in intermediate and low-risk patients is being increasingly supported by data from randomized clinical trials. The UK TAVI trial examined whether TAVI was noninferior to SAVR in 913 patients (TAVI=458, SAVR=458) aged 70 years or older with severe symptomatic AS and moderately increased operative risk due to age or comorbidity. Key exclusion criteria were life expectancy < 1-year, previous AVR or TAVI, technically unsuitable for TAVI or SAVR, CAD for which surgical revascularization was required, primary aortic regurgitation, and severe mitral regurgitation. Other salient features included mean LV ejection fraction=5.7%, transfemoral access=92%, conscious sedation during TAVI=70%, 45% received the Sapien 3 valve, 14% Evolut/Evolut R, and 10% Lotus. The primary outcome was all-cause mortality at 1 year. There were 36 secondary outcomes including duration of hospital stay, major bleeding, vascular complications, requirement for a pacemaker, and aortic regurgitation. The median age was 81 years, 46% were female, median STS score was 2.6%, and 99.9% completed follow-up. At 1-year, mortality was 4.6% in the TAVI group and 6.6% in the surgical group (adjusted absolute risk difference of -2.0%; 1-sided 97.5% CI: −∞ to 1.2%; p < .001 for noninferiority). Of the 30 prespecified secondary outcomes, 24 showed no significant difference at 1 year. TAVI was associated with shorter hospital stay (median of 3 days vs. 8 days). TAVI was also associated with significantly lower bleeding complications (7.2% vs. 20.2%; HR: 0.33; 95% CI: 0.24-0.45) but significantly more vascular complications (10.3% vs. 2.4%; HR: 4.42; 95% CI: 2.54-7.71), pacemaker implantation (14.2% vs. 7.3%; HR: 2.05; 95% CI: 1.43-2.94), and mild (38.3% vs. 11.7%) or moderate (2.3% vs. 0.6%) aortic regurgitation. The rates of stroke were similar in the TAVI and SAVR groups (2.3% vs. 0.6%).

Expanding techniques for treating severe TR

6-Month outcomes of the TricValve sytem in patients with tricuspid regurgitation: the TRICUS EURO study.

JACC Cardiol Interv 2022; 15:1366-77

Bicaval valve implantation (CAVI) has emerged as a novel transcatheter strategy for indirectly treating the systemic manifestation of severe tricuspid regurgitation (TR) in patients ineligible for cardiac surgery or edge-to-edge repair. The Tricvalve system consists of 2 self-expanding valves designed for the SVC and IVC premounted in a 27.5-F delivery system. Caval anchoring is based on stent design, radial force, and the degree of oversizing. The TRICUS EURO study was a nonblind, nonrandomized, single arm, multicenter, prospective trial of 35 patients with symptomatic severe TR (grade ≥3 in a 5-grade classification) despite optimal medical therapy and NYHA functional class III or IV. The main exclusion criteria included severe right ventricular dysfunction, severe pulmonary hypertension (PAP≥65mmHg) and/or significant renal dysfunction (defined as serum creatinine >3mg/dl). The primary endpoint was quality of life (QoL) improvement measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) and NYHA functional class improvement at 6-month follow-up. The mean age was 76 ± 6.8 years, 83% were female, 20% were diabetic, and the overall EuroSCORE II was 5.8 ± 4.2. At 30 days, procedural success was 94%, with no procedural death or conversion to surgery. At 6 months, patients had a significant improvement in QoL from 42.01 ± 22.3 to 59.7 ± 23.6 (p=0.004) correlating with a significant improvement in NYHA class with 79.4% of patients noted to be in class I or II (p=0.0006). The rates of 6-month all-cause mortality and heart failure hospitalization were 8.5% and 20% respectively. There were 6 cases of major bleeding and 2 were access site related. The study represents the first comprehensive short-term analysis of a dedicated CAVI system and longer-term data are required to assess clinical benefits and haemodynamic effects upon the pulmonary and right heart status.

Miscellaneous

Hydration remains key for renal protection

Study evaluating the use of RenalGuard to protect patients at high risk of AKI. JACC 2022; 15:1639-48

Contrast-induced nephropathy (CIN) may occur in 2-7% of patients undergoing angiographic procedures. A variety of measures including hydration with sodium bicarbonate, N-acetylcysteine, and hemofiltration have been examined in randomized trials but no measure except adequate intravenous (IV) hydration and minimal contrast use have been shown to be effective strategies. The RenalGuard system (RG) is a device that delivers real-time isotonic IV hydration matched with frusemide-induced diuresis allowing hydration and contrast clearance thus preventing fluid overload and volume depletion. The STRENGTH study examined the superiority of RG over standard practice (considering the ESC guidelines including IV and oral hydration, the dose of contrast medium and staged procedure if necessary) in 259 patients with moderate to severe chronic kidney disease (estimated GFR 15-40 ml/min/m²) requiring complex coronary, structural, or peripheral procedures with an expected contrast injection of at least 3x the estimated GFR. The primary endpoint was the occurrence of CIN, defined as an increase in serum creatinine ≥ 0.3mg/dl and/or an increase of 25% of basal value at around day 3 or the requirement for dialysis within 5 days after the procedure. Secondary endpoints included a change in serum creatinine value and GFR at 12 months, % of patients on temporary or chronic haemodialysis at 12 months, and MACCEs. In the whole population, the mean age was 79 years, 50% were male, baseline GFR was 32ml/min/1.73m², 48% underwent PCI, 34% structural intervention (TAVI and LAA closure), and 18% peripheral intervention. The mean amount of contrast use was similar in both groups (116ml in the RG group vs. 104ml in the control group; p=0.26). The total fluid intake was higher in the RG group (6196ml vs. 1407ml; p<0.0001). The primary endpoint was similar in the RG and control groups (15.9% vs. 13.9%; difference=2.4; 95% CI:-7.1-12; p=0.62). At 12 months, there were no significant differences between the two groups. The rate of MACCEs were also similar at a median of 342 days (20.5% in RG group vs. 22.2% in the control group).

BCIS R&D Group

Literature Review May 2020

Prepared by: Michael Mahmoudi, Julian Gunn, Paul Morris & Aung Myat

Edited by Michael Mahmoudi

STABLE CAD & ACS

Is there a role for revascularization in stable angina?

Invasive or conservative strategy for stable coronary artery disease?

NEJM 2020; 382:1395-1407

The preferred contemporary approach to the management of stable angina is not well defined. Two strategies are commonly used: (a) guideline based medical therapy including antianginal drugs as well as disease modifying agents and (b) an invasive strategy consisting of coronary angiography followed by PCI or CABG plus medical therapy.  The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial tested whether an initial invasive strategy would result in better outcomes than a conservative strategy in 5179 patients with stable angina and moderate or severe myocardial ischemia with regards to the primary endpoint of death from cardiovascular causes, MI, or hospitalization for unstable angina, heart failure, resuscitated cardiac arrest. Key exclusion criteria were GFR < 30, recent ACS, unprotected left main stenosis of at least 50%, LV ejection fraction < 35%, NYHA class III or IV heart failure, and “unacceptable angina” despite the use of medical therapy. The majority of patients also underwent CTCA at screening to confirm the presence of obstructive CAD and exclude left main disease. At 6 months, the cumulative event rate was 5.3% in the invasive strategy group and 3.4% in the conservative strategy group (difference 1.9 percentage points; 95% CI: 0.8-3.0); at 5 years, the cumulative event rates were also similar (16.4% vs. 18.2%; difference -1.8 percentage points; 95% CI: -4.7-1.0). The difference in outcomes was driven by results for MI and those results depended on the definition used in the analysis. Of note, patients in the invasive strategy reported fewer angina symptoms than patients in the conservative group although the magnitude of this benefit depended on angina frequency at baseline with 35% having no angina at baseline. The Kaplan-Meier curves showed a trend for a greater number of MI (predominantly procedural) in the invasive strategy group during the first 6 months of the trial but as the trial proceeded the curves crossed and more MI (predominantly spontaneous) occurred in the conservative group. Finally, at 4 years, the cumulative incidence of death from cardiovascular causes or MI based on the primary definition was higher in the conservative strategy group  (13.9% vs. 11.7%). It is possible that ISCHEMIA ended before a substantial difference in favour of the invasive strategy emerged.

Should morphine be replaced by another analgesic agent in ACS patients?

Morphine and cardiovascular outcomes among patients with non-ST-segment elevation acute coronary syndromes undergoing coronary angiography.

JACC 2020; 75:289-300

Morphine is routinely utilised in the management of acute chest pain in patients presenting with ACS. From a pharmacological perspective, morphine and other opiates delay gastric emptying thus compromising intestinal absorption of P2Y₁₂ inhibitors. A number of small studies have demonstrated that morphine reduced active metabolite exposure and antiplatelet effects of clopidogrel, prasugrel, and ticagrelor in stable patients post ACS, in acute MI, and during elective PCI. The current study was designed to explore the association between morphine and ischemic events in 5,438 patients treated with clopidogrel in the context of non-ST-segment elevation ACS in the EARLY-ACS trial. Patients that were not treated with clopidogrel (n=3,462) were used as negative controls. At 96 hours, morphine use was associated with higher rates of the composite endpoint of death, MI, recurrent ischemia, or thrombotic bailout (OR: 1.40; 95% CI: 1.04-1.87; p=0.026). There was a trend for higher rates of death or MI at 30 days (OR: 1.29; 95% CI: 0.98-1.70; p=0.072). The results question a routine strategy of routine morphine use in ACS patients or delaying the administration of clopidogrel loading dose until the time of PCI when the effects of morphine may have subsided.

Antiplatelet therapy in elderly patients presenting with NSTEMI

Clopidogrel versus ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation acute coronary syndrome (POPular AGE): the randomised, open-label non-inferiority trial.

Lancet 2020;395:1374-81

Landmark trials such as PLATO and TRITON-TIMI 38  have demonstrated the advantage of a more potent antiplatelet effect from ticagrelor or prasugrel versus clopidogrel. The elderly who are often at high risk from thrombotic and bleeding events have been underrepresented in such trials. Investigators from the Netherlands randomised 1002 patients aged ≥70 presenting with NSTE-ACS 1:1 to clopidogrel versus ticagrelor or prasugrel along with standard therapy for 12 months. There were two co-primary endpoints. The safety endpoint was any bleeding requiring medical intervention, defined as PLATO major or minor bleeding. The net clinical benefit outcome was a composite of all-cause death, MI, stroke and PLATO major or minor bleeding. The median age was 77 (IQR 73-81) in the clopidogrel arm (n=500) and 77 (IQR 73-82) in the ticagrelor arm (n=502). There were 64% men and 36% women recruited. Given the open-label construct of the trial, 95% (475/502) of those in the prasugrel/ticagrelor cohort were prescribed ticagrelor. This was to be expected given the contraindications and cautionary advice associated with prasugrel in those ≥75 years old. The primary bleeding endpoint was significantly lower in the clopidogrel arm (HR 0.71, 95% CI 0.54-0.94; p=0.02 for superiority). The net clinical benefit endpoint satisfied the non-inferiority threshold in the clopidogrel arm (absolute risk difference -4%, 95% CI -10.0-1.4; p=0.03) but not for superiority (HR 0.82, 95% CI 0.66-1.03; p=0.11). In essence, treatment with clopidogrel in elderly NSTE-ACS patients resulted in lower bleeding events but not at the cost of greater thrombotic events. The trial was not powered to test for differences in mortality. One of the most important findings of the study was the rate of study drug discontinuation. Only 53% of patients completed their 12-month course of ticagrelor compared to 78% in the clopidogrel cohort, predominantly due to bleeding, dyspnoea and need for chronic oral anticoagulation.

ONYX ONE supports shorter DAPT duration

Polymer-based or Polymer-free Stents in Patients at High Bleeding Risk.

NEJM 2020; 382:1208-18

The optimal duration of dual antiplatelet therapy particularly in patients at high bleeding risk who undergo PCI has not been determined. The ONYX ONE trial compared the polymer-based zotarolimus-eluting stent (ZES) (Resolute Onyx; Medtronic; n=1,003) with the polymer-free umirolimus-coated stent (UCS) (Biofreedom; BioSensors; n=993) in patients undergoing PCI and who were deemed at high-bleeding risk. After PCI, patients were treated with 1 month of DAPT, followed by single antiplatelet therapy. The primary outcome was death from cardiac causes, MI, or stent thrombosis. The secondary outcome was target lesion failure, a composite of death from cardiac causes, target vessel MI, or clinically indicated target lesion revascularization. Both outcomes were powered for noninferiority. At 1 year, the primary outcome occurred in 17.1% in the ZES group and 16.9% in the UCS group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI: 3.5; noninferiority margin, 4.1; p=0.01 for noninferiority). The secondary outcome occurred in 17.6% of the ZES group and 17.4% of the UCS group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI: 3.5; noninferiority margin, 4.4; p=0.007 for noninferiority). Important limitations of the trial included its single-blind nature, noninferiority testing of the primary and secondary outcomes, and lack of a control group taking DAPT for a longer duration.

PHYSIOLOGY & IMAGING

Invasive physiology use remains  modest in stable CAD

Utilization and outcomes of measuring fractional flow reserve in patients with stable ischemic heart disease.

JACC 2020; 75:409-19

FFR/iFR guided revascularization is considered the gold standard for invasive assessment of ischemia. Despite evidence from clinical trials and recommendations from the American and European societies FFR/iFR use remains limited with large differences between countries and health systems. The current study sought to evaluate contemporary, real-world patterns of FFR use and its effect on outcomes in patients with stable ischemic heart disease and angiographically intermediate disease (40% to 69% stenosis by visual assessment. A total of 17,989 patients were identified through the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program. Over a period of 8 years (2009-2017), the rate of FFR use gradually increased from 14.8% to 18.5% in patients with intermediate lesions, and from 44% to 75% in patients undergoing PCI. One-year mortality was significantly lower in the FFR group (2.8% vs. 5.9%; p<0.001). After adjustment for patient, site-level, and procedural factors, FFR-guided revascularization was associated with a 43% lower risk of mortality at 1 year compared with angiography-only revascularization.

IVUS a MUST for left main PCI

Intravascular Imaging and 12-Month Mortality After Unprotected Left Main Stem PCI. An Analysis From the British Cardiovascular Intervention Society Database.

JACC Cardiovasc Interv 2020; 13:346-57

Despite intravascular imaging being shown to improve PCI outcomes in both randomized trials and registries, its use to optimise PCI remains limited. The current study has utilised the UK National PCI Audit to explore temporal changes in and implications of the use of IVUS for unprotected LM PCI in 11,264 patients. Imaging guidance significantly increased from 30.2% of procedures in 2007 to 50.2% in 2014. The factors associated with imaging use included stable angina presentation (OR: 1.2; 95% CI :1.15-1.25; p<0.001), bifurcation LM disease (OR: 1.22; 95% CI: 1.14-1.30; p<0.001), previous PCI (OR: 1.32; 95% CI: 1.22-1.32; p<0.001).  After propensity scoring was performed to adjust for baseline imbalances between groups, imaging guidance was strongly associated with a lower rate of coronary complications, fewer in-hospital major adverse cardiovascular events, and 46% and 34% reductions in 30-day and 12-month mortality respectively. Greater mortality reductions were observed with higher operator LM PCI volume. In logistic regression modelling, imaging use was associated with improved 12-month survival.

CATHETER BASED VALVULAR INTERVENTION

Self-expandable or balloon-expandable TAVI?

Balloon-Expandable Versus Self-Expanding Transcatheter Aortic Valve Replacement. A propensity-Matched Comparison from the FRANCE-TAVI Registry.

Circ 2020; 141:243-59

There are very few randomized head-to-head trials comparing the balloon with the self-expanding transcatheter aortic valve replacement devices. Despite the inherent differences in expansion mode, stent frame, and leaflet characteristics between the device types, which translate into some differences in hemodynamic function, paravalvular sealing, and periprocedural complications have been considered comparable. The FRANCE-TAVI  nationwide registry of 12,141 patients undergoing balloon-expandable (Edwards, n=8,038) or self-expandable (Medtronic, n=4,103) has reported on ≥ moderate paravalvular regurgitation, in-hospital mortality, and 2-year all-cause mortality. In propensity-matched analyses, the self-expandable cohort had higher rates of ≥ moderate paravalvular regurgitation (15.5% vs. 8.3%; RR: 1.9; 95% CI: 1.63-2.22; p<0.0001) and in-hospital mortality (5.6% vs. 4.2%; RR:1.34; 95% CI: 1.07-1.66; p=0.01). 2-year mortality was also higher in the self-expandable group (29.8% vs. 26.6%; HR: 1.17; 95% CI: 1.06-1.29; p=0.003).

The evolution of self-expandable TAVI

Three Generations of Self-Expanding Transcatheter Aortic Valves. A Report From the STS/ACC TVT Registry.

JACC Cardiovasc Interv 2020; 13:170-79

The ever-increasing improvements in transcatheter technology has advanced TAVI to equivalency or superiority to SAVR in multiple studies across the spectrum of surgical risk. The current report focuses on real-world data from the Society of Thoracic Surgeons/American College of Cardiology TVT Registry for patients undergoing TAVI with CoreValve, Evolut R, or Evolut PRO valves for the treatment of tricuspid aortic stenosis between January 2014 to September 2017. The valves analysed included the 23, 26, and 29mm sizes. Propensity matching was performed using the Evolut PRO group as the reference. In 18,874 patients undergoing TAVI, 5,514 patients received the CoreValve, 11, 295 Evolut R, and 2,065 Evolut PRO. At 30-days, there were fewer patients with more than mild AR for the unmatched (7.8% CoreValve, 5.2% Evolut R and 2.8% Evolut PRO; p<0.001) and matched populations (8.3% CoreValve, 5.4% Evolut R and 3.4% Evolut PRO; p=0.03). The mean aortic valve gradients at 30 days in the matched populations were <8 mmHg for all three valves (7.3 mmHg CoreValve, 7.5 mmHg Evolut R, and 7.2 mmHg Evolut PRO).

PARTNER-2 at 5 years

Five-Year Outcomes of Transcatheter or Surgical Aortic-Valve Replacement.

NEJM 2020; 382:799-809

To be established as first line therapy for the treatment of symptomatic, severe aortic stenosis, TAVI must prove to be as effective as SAVR in the long term. The PARTNER 2 cohort A trial involved 2,032 patients who were stratified according to intended transfemoral or transthoracic access and randomly assigned to undergo TAVR with the balloon-expandable SAPIENT XT valve or SAVR. TAVR was found to be noninferior to SAVR with regards to the primary outcome of death from any cause or disabling stroke at 2 years. The investigators have now confirmed that at 5 years, there was no difference in the incidence of death or disabling stroke between TAVI and SAVR (47.9% vs. 43.4%; HR: 1.09; 95% CI 0.95-1.25). A landmark analysis of events occurring between 2 and 5 years after the procedure showed a divergence of event rates in favour of surgery (HR: 1.27; 95% CI: 1.06-1.53). This late increase in risk with TAVR has also been reported with the self-expanding TAVI valve. Other salient findings included greater paravalvular regurgitation in the TAVI group, patients in the TAVI group had nearly three times as many valve-related hospitalizations and required 21 aortic valve reinterventions as compared to 6 in the surgery group.

Optimal antithrombotic therapy in TAVI patients

Anticoagulation with or without clopidogrel after transcatheter aortic-valve implantation.

NEJM 2020; 382:1696-1707

Bleeding risk is particularly relevant in patients undergoing TAVI, especially those receiving oral anticoagulation, given the typical age of the patients, the frequent presence of comorbidities, and the use of large-bore access catheters. Expert opinion has indicated that administration of clopidogrel may reduce the risk of stroke and other embolic complications that are due in part to thrombus formation on the bioprosthetic valves. The POPular TAVI trial (cohort B) tested the hypothesis that in patients receiving anticoagulation, the use of oral anticoagulants alone would be safer (n=157) than oral anticoagulants plus 3 months of clopidogrel (n=156). The two coprimary endpoints of the trial were all bleeding and non-procedural related bleeding within 12 months after TAVI. Bleeding was lower in the anticoagulation only group (21.7% vs. 34.6%; RR: 0.63; 95% CI: 0.43-0.90; p=0.01). Most bleeding events were at the access site. Non-procedural related bleeding was also lower in the anticoagulation only group (21.7% vs. 34%; RR: 0.64; 95% CI: 0.44-0.92; p=0.02). Important limitations of the study included the definitions used in the trial with bleeding occurring during TAVI or the index hospitalization being defined as non-procedure related even if it occurred at the access site. Details regarding baseline and procedural characteristics, including aspirin use, the specific direct-acting oral anticoagulant used by patients, and how often oral anticoagulants were withheld periprocedurally, are lacking.

TAVI for bicuspid aortic valve disease

Outcomes of Transcatheter Aortic Valve Replacement in Patients with Bicuspid Aortic Valve Disease. A Report from the Society of Thoracic Surgeons/American College of Cardiology Valve Therapy Registry.

Circ 2020; 141:1071-79

Patients with bicuspid aortic valve stenosis (BAVS) have been excluded from pivotal TAVI trials. The aim of the current study was to compare the outcomes of TAVI in patients with BAVS and tricuspid aortic valve stenosis (TAVS). There were 170,959 eligible procedures in the Society of Thoracic Surgeons/American College of Cardiology Valve Therapy Registry. Of these, 5,412 TAVI procedures were performed in patients with BAVS, including 3,705 with current generation devices. As compared to patients with TAVS, patients with BAVS were younger and had a lower STS score. With current generation devices, device success was 96.3%, and the incidence of 2+ AR was 2.7%. A lower 1-year adjusted risk of mortality was observed in patients with BAVS (HR: 0.88; 95% CI: 0.78-0.99) whereas no difference was observed in the 1-year adjusted risk of stroke (HR: 1.14; 95% CI: 0.94-1.39).

MISCELLANEOUS

Evolution of renal denervation for hypertension

Alcohol-Mediated Renal Denervation Using the Peregrine System Infusion Catheter for Treatment of Hypertension.

JACC Cardiovasc Interv 2020; 13:471-84

The success of catheter-based renal denervation for the treatment of hypertension has remained variable. The Peregrine Catheter system has been developed to deliver small doses of pure dehydrated alcohol into the renal periadventitial space to ablate the afferent and efferent sympathetic nerve bundles. The current study examined the safety and efficacy of the infusion of 0.6ml of alcohol in 45 patients with uncontrolled hypertension taking 3 or more antihypertensive medications. Mean 24-hour ambulatory BP reduction at 6 months versus baseline was -11 mmHg for systolic BP and -7 mmHg for diastolic BP. Office systolic BP was reduced by -18/-10 mmHg at 6 months. Antihypertensive medications were reduced in 23% and increased in 5% of patients at 6 months. The primary safety endpoint, defined as the absence of periprocedural major vascular complications, major bleeding, acute kidney injury, or death within 1 month was met in 96% of patients. Two patients developed access site pseudoaneurysms. There were no death or instances of MI, stroke, TIA, or renal artery stenosis. There were two cases of minor vessel dissection that resolved without treatment.

BP control without the pills?

Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial.

Lancet 2020; 395:1444-51

The SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medication. The study randomized 331 patients with office systolic blood pressure of 150-180 mmHg to either renal denervation or a sham procedure. The primary efficacy endpoint was baseline adjusted change in 24-hour systolic BP and the secondary efficacy endpoint was baseline adjusted change in office systolic BP from baseline to 3 months after the procedure. The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0.999 for both. The treatment difference between the two groups for systolic BP was -3.9 mmHg and for office systolic BP  the difference was -6.5 mmHg. There were no major device-related or procedural related safety events up to 3 months after the procedure.

Very late stent outcomes

Stent-Related Adverse Events >1 Year After Percutaneous Coronary Intervention.

JACC 2020; 75:590-604

Many contemporary drug-eluting stent (DES) trials have focused on 1-year outcomes. The frequency and predictors of stent-related major adverse cardiovascular events (MACE) after the first year have not been extensively studied. Individual patient data from patients involved in 19 prospective, randomized metallic stent trials were examined for the frequency and predictors of very-late stent-related events and MACE by stent type. Amongst 25,032 patients, 3718, 7934, and 13380 were treated with bare metal stents (BMS), first generation DES (DES1) and second generation DES (DES2) respectively. MACE rates within 1 year after PCI were progressively lower following treatment with BMS versus DES1 versus DES2 (17.9% vs. 8.2% vs. 5.1% respectively; p<0.0001). Between years 1 and 5, very late MACE occurred in 9.4% of patients including 2.9% cardiac death, 3.1% MI, and 5.1% ischemia driven target lesion revascularization. Very late MACE occurred in 9.7%, 11%, and 8.3% of patients treated with BMS, DES1 and DES2 respectively (p<0.0001), linearly increasing between 1 and 5 years. The use DES1, age, coronary risk factors such as diabetes and smoking, and variables associated with extensive disease (eg. previous revascularization, calcification, multivessel disease) were identified as predictors of very late events.

It’s all about risk factor modification

Modifiable risk factors, cardiovascular disease, and mortality in 155722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study.

Lancet 2020;395:795-808

The Prospective Urban Rural Epidemiology (PURE) study was designed to standardise the prospective measurement of the effects of 14 modifiable risk factors on cardiovascular disease (CVD) and mortality across 21 countries categorised by different socio-economic strata. Between January 2005 to December 2016, investigators recruited 155,722 participants without a prior history of CVD who were then followed up for a median of 9.5 years. Behavioural risk factors were tobacco use, alcohol intake, diet quality, physical activity, and sodium intake. Metabolic risk factors included hypertension, dysglycaemia (or history of diabetes), non-HDL cholesterol, body mass index and waist-to-hip ratio as a surrogate of centripetal obesity. Education was the primary socioeconomic factor of interest. Symptoms of depression was measured as were grip strength and household and ambient air pollution. Important findings included a mean BMI, waist-to-hip ratio, and non-HDL cholesterol greatest in high-income countries, prevalence of hypertension highest in middle-income countries, and diabetes found most often in low-income countries. Tobacco was most strongly associated with CVD, followed by physical activity and poor diet. Hypertension had a stronger association with CVD than diabetes, elevated non-HDL cholesterol and obesity. In the overall cohort, hypertension was the strongest risk factor for CVD, followed by high non-HDL cholesterol, household air pollution, tobacco use, poor diet, low education, abdominal obesity, and diabetes. Elevated non-HDL cholesterol was the largest risk factor for MI, followed by hypertension and smoking.

Simple measures to reduce radiation exposure

Effectiveness of additional x-ray protection devices in reducing scattered radiation in radial intervention: the ESPRESSO randomized trial.

EuroIntervention 2020 Online

The incidence of radiation associated pathology correlates with length of career and the complexity cases undertaken. Radiation protection practice and training varies considerably between different centres and countries. It is remarkable how simple alterations to practice, can reduce dose, not just to the operator but also to the other staff in the lab. Over a career, these measures make a big difference. Modern interventional trends such as increasing patient BMI, and case complexity are all associated with increased operator x-ray dose. The ESPRESSO trial compared three basic radiation protection measures in the context of radial arterial access. The trial randomised 600 patients undergoing radial access intervention, prospectively, to ‘Shield only’ – a 60*76 cm, 0.5mm Pb, ceiling mounted Mavig shield, ‘Shield + curtain’ – as above, plus an attached 0.5 Pb curtain underhanging the shield, and ‘Shield + curtain + drape’ – as above, plus a 75*40 cm 0.5 Pb drape positioned over the waist. The drape was custom made and covered the patient’s lower abdomen and groin area.  All strategies were all used alongside standard lead apron and thyroid collar. Outcome measures were the radiation dose to the first and second operator and the patient with analysis on an intention to treat basis. There was a mixture of interventional cases including PCI (in 53%), diagnostic studies, left ventriculography and a small percentage of right heart catheterisation and even biopsy.  No cases crossed over. Patient and case characteristics were well balanced between groups. There were no between-group differences in screening or procedure time. The key results were no statistically significant differences in patient dose-area product. As compared with group 1 (shield only), group 2 (+ curtain) was associated with non-significant 3% dose reduction for first operator and 17% dose reduction in the second operator. Group 3 (+ curtain and drape) had a significant 19% dose reduction for first operator and 39% reduction for second operator. Most centres will be familiar with the equipment used in groups 1 and 2 but may not utilise the drape over the patient’s waist. This appears to be a particularly inexpensive (reusable) and simple to use strategy associated with considerable benefit in every case performed.