If you are a non-surgical centre looking to undertake Primary Percutaneous Coronary Intervention (PPCI), support and guidance are available. You are encouraged to reach out for assistance with planning, protocols, governance arrangements, or collaboration with surgical centres.

For advice and support, please contact:
BCIS Non-Surgical Centre Representative:

Abhishek Kumarabhishekkumar@nhs.net

Evidence-based recommendations on intravascular lithotripsy to treat calcified coronary arteries during percutaneous coronary intervention. This involves using ultrasound shockwaves to break up hard deposits in the arteries, to allow blood to flow more freely.

LSA guidance evaluates categories of technologies that are already in widespread use within the NHS. It assesses whether price variations between technologies in a category are justified by differences in innovation, clinical effectiveness and patient benefits. This will support NHS commissioners, procurement teams and healthcare professionals to choose technologies that maximise clinical effectiveness and value for money.

BCIS are pleased to announce that the new PCI guidelines have now been published in ICR3 and can be accessed using the following link: PCI in the UK: Recommendations of the BCIS | ICR Journal. A great deal of work, involving many cardiologists, has gone into producing this document. We hope these updated guidelines will be a useful reference for hospitals across the country. PCI in the UK has been one of the success stories of the NHS and we hope these updated guidelines provide an updated  framework for safe and effective coronary intervention.

Best Wishes,

Gerald Clesham, Hon Sec

 

 

BCIS literature review

March 2025

Authors: Dr. Richard Jabbour, Dr. Claudia Cosgrove, Dr. Natalia Briceno

VALVULAR HEART DISEASE

 

EARLY TAVR

Treatment of severe aortic stenosis without symptoms

 

Rationale:

• The purpose of the study was to determine whether transcatheter aortic valve implantation (versus routine clinical monitoring) was beneficial in patients with severe asymptomatic aortic stenosis (stage C aortic stenosis).

 

Publication date:

• gov number, NCT03042104
• Généreux P, et al; EARLY TAVR Trial Investigators. Transcatheter Aortic-Valve Replacement for Asymptomatic Severe Aortic Stenosis. N Engl J Med. 2025 Jan 16;392(3):217-227.

 

Study Design

• International
• Randomized 1:1
• Parallel
• Open label
• A total of 901 patients underwent randomization; 455 patients were assigned to TAVI and 446 to clinical surveillance.

 

Trial Info:

• 901 Patients included (1578 screened)
• Duration of follow-up: median 3.8 years
• Mean patient age: 75.8 years
• Median STS 1.8%
• 6% low surgical risk
• 30% female
• TAVI valve used: balloon expandable (SAPIEN 3 / SAPIEN 3 ultra)

Inclusion criteria:

• 65 years of age or older
• Severe aortic stenosis
• Patient asymptomatic (negative ETT or physician assessment if unable to perform stress test).
• LV ejection fraction ≥ 50%
• Society of Thoracic Surgeons (STS) risk score ≤ 10

 

Selected exclusion criteria:

• Patient is symptomatic
• Patient has any concomitant valvular, aortic, coronary artery disease requiring surgery making AVR a Class I indication.
• Native aortic annulus size unsuitable for sizes 20, 23, 26, or 29 mm THV
• Iliofemoral vessel characteristics that would preclude safe placement of the introducer sheath.
• Left ventricular outflow tract calcification that would increase the risk of annular rupture or significant paravalvular leak post TAVR
• Evidence of an acute myocardial infarction ≤ 30 days before randomization
• Aortic valve is unicuspid, bicuspid with unfavourable features for TAVR, or is non-calcified
• Severe aortic regurgitation (>3+)
• Severe mitral regurgitation (>3+) or ≥ moderate mitral stenosis
• Pre-existing mechanical or bioprosthetic valve in any position
• Cardiac imaging evidence of intracardiac mass, thrombus or vegetation
• Inability to tolerate or condition precluding treatment with anti-thrombotic therapy
• Stroke or transient ischemic attack within 90 days of randomization
• Renal insufficiency and/or renal replacement therapy
• Active bacterial endocarditis within 180 days of randomization
• Severe lung disease or currently on home oxygen
• Severe pulmonary hypertension
• History of cirrhosis or any active liver disease
• Significant frailty as determined by the Heart Team
• Significant abdominal or thoracic aortic disease that would preclude safe passage of the delivery system
• BMI >50 kg/m2
• Estimated life expectancy <24 months

 

Primary Endpoint:

Major adverse cardiac events: All-cause death, all stroke, and unplanned cardiovascular hospitalization at 2 years

 

Results:

• Primary end-point event: 122 patients (26.8%) in the TAVI group vs 202 patients (45.3%) in the clinical surveillance group (hazard ratio, 0.50; CI 0.40 to 0.63; P<0.001).
• All cause death: 8.4% TAVI vs 9.2% clinical surveillance (not significant)
• Stroke: 4.2% TAVI vs 6.7% clinical surveillance (not significant)
• Unplanned hospitalization for cardiovascular causes: 20.9% TAVI vs 41.7% clinical surveillance (HR 0.43; CI, 0.33-0.55)
• During a median follow-up of 3.8 years, 87% of patients in the clinical surveillance group underwent aortic-valve replacement.
• There were no differences in procedure-related adverse events between patients in the TAVI group and those in the clinical surveillance group who underwent aortic-valve replacement. No patients in either group died of CV causes within 30 days.
• Stroke incidence at 30 days: 0.9% TAVI vs 1.8% control group (converted to aortic valve replacement)

 

Limitations

• Unblinded trial driven by endpoint susceptible to bias
• No surgical arm in trial
• In real world practice ETT is often difficult to adopt in practice due to severe AS
• 87% of patients underwent TAVI in the control arm making it difficult to ascertain a true comparison between groups

 

Conclusions

• Among patients with asymptomatic severe aortic stenosis, a strategy of early TAVI was superior to clinical surveillance in reducing the incidence of death, stroke, or unplanned hospitalization for cardiovascular causes.
• The endpoint of the trial was driven by unplanned TAVR, a component which would be susceptible to bias in this unblinded trial
• Two surgical trials – RECOVERY and AVATAR also found early SAVR were beneficial, but these trials contained relatively small numbers of patients and were therefore underpowered to detect true differences between groups in hard endpoints.
• Notably, 87% of patients effectively received an aortic valve replacement in the clinical surveillance arm
• In young patients with asymptomatic severe AS, the issues regarding long term durability and risks of long-term PPM insertion remain
• There were no differences in death or stroke between groups which indicates that current practice may not change significantly based on these results.

 

TAVR UNLOAD

Treatment of moderate aortic stenosis without symptoms

Rationale:

• The purpose of the study was to explore whether transcatheter aortic valve implantation (SAPIEN 3 THV) was beneficial (compared with clinical surveillance / guideline-directed medical therapy) in patients with moderate stage B aortic stenosis and chronic systolic heart failure.

 

Publication date:

• gov number:NCT02661451
• Van Mieghem NM et al. Transcatheter Aortic Valve Replacement in Patients With Systolic Heart Failure and Moderate Aortic Stenosis: TAVR UNLOAD.J Am Coll Cardiol. 2024 Oct 22:S0735-1097(24)09960-1

 

Study Design

• Randomized, open label
• Parallel
• Investigator initiated
• International
• Enrolment period Jan 2017 – Dec 2022

 

Trial Information

178 Patients with chronic systolic heart failure and moderate aortic stenosis (stage B aortic stenosis) were randomized to TAVI with a balloon-expandable valve (n = 89) vs. clinical surveillance (n = 89).

• Total number of patients: 178
• Duration of follow-up: 23 months
• Mean patient age: 77 years
• Percentage female: 21%
• 6% NYHA III/IV
• Mean aortic valve area (baseline or dobutamine stress): 1.2 cm²in the TAVI group vs. 1.3 cm² in the clinical surveillance group
• Mean aortic valve gradient (baseline or dobutamine stress): 21.9 mmHg in the TAVI group vs. 21.9 mmHg in the clinical surveillance group

 

Inclusion criteria:

• Left ventricular (LV) ejection fraction (EF) < 50% at rest on appropriate guideline-directed medical therapy
• Heart Failure with NYHA class ≥ 2
• Moderate aortic stenosis (typically mean trans-aortic gradient (MG) ≥ 20 mmHg and < 40 mmHg at rest and aortic valve area (AVA) > 1.0 cm2 and ≤1.5 cm2 (or AVA < 1.0 cm2 but indexed AVA > 0.6 cm2) at rest)
• Anatomically suitable for transfemoral TAVR with the SAPIEN 3 or SAPIEN 3 Ultra THV

 

Exclusion criteria

• LVEF < 20% or persistent need for intravenous inotropic support
• Hospitalization for acute decompensated HF within 2 weeks prior to randomization
• Cardiac resynchronization therapy (CRT) device implantation within 1 month prior to randomization
• Coronary artery revascularization (PCI or CABG) within 1 month prior to randomization
• In need and suitable for revascularization per heart team consensus
• Severe aortic and/or mitral regurgitation
• Congenital unicuspid or congenital bicuspid aortic valve
• Concomitant non-aortic valvular disease with a formal indication for valve surgery per established guidelines (ESC/ACC/AHA)
• Previous aortic valve replacement (mechanical or bioprosthetic)
• Severe RV dysfunction
• Previous stroke with permanent disability (modified Rankin score ≥ 2)
• Severe lung disease as indicated by FEV1 <30% predicted or need for chronic daytime supplemental oxygen therapy
• Severe chronic kidney disease: glomerular filtration rate (GFR) < 30 mL/min by MDRD or need for renal replacement therapy
• Gastrointestinal (GI) bleeding within the past 3 months
• Liver cirrhosis Child-Pugh C
• Active systemic infection, including active endocarditis

Primary endpoint

• The primary endpoint was the hierarchical occurrence (win ratio) of:
• all-cause death
• disabling stroke
• disease-related hospitalizations and heart failure equivalents
• change from baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary Score analysed using the win ratio.

Results:

• At the longest follow-up, TAVI resulted in 47.6%-win pairs vs. 36.6% in the clinical surveillance group (p = 0.14).
• At 1-year follow-up, TAVR resulted in 48.0%-win pairs vs. 30.9% in the clinical surveillance group (p = 0.032). This was driven by QoL: Mean change in KCCQ at 1 year: 12.8 in the TAVI group vs. 3.2 in the clinical surveillance group (p = 0.018)
• At the longest follow-up, mean change in KCCQ: 10.9 in the TAVR group vs. 6.1 in the clinical surveillance group (p = 0.20)
• No patients died in TAVI group at 30 days, 1 (1.1%) disabling stroke).
• In the clinical surveillance group, 43% underwent TAVI at a median of 12 months (q1-q3 6-20months). 92% had progression to severe AS.

 

Limitations

• Small number of patients
• Underpowered to detected difference in treatment groups
• Trial stopped early due to issues with recruitment / funding
• Lack of sham control may have influenced the quality-of-life findings
• Study only performed with balloon-expandable (Sapien) valve

 

Conclusion:

•   TAVI was not superior to clinical surveillance with guideline directed medical therapy for the primary hierarchical composite endpoint in patients with moderate AS and heart failure with reduced ejection fraction at a median follow up of 23 months
• Performing TAVI in moderate aortic stenosis was however safe and may lead to improvements in quality of life
• When analysis was restricted to 1 year of follow-up, TAVI was associated with an improvement in the composite of clinical events and quality of life. This was driven by QoL with an improvement in KCCQ compared with clinical surveillance.
• The trial was relatively small and underpowered to detect a difference in hard endpoints between groups
• In the clinical surveillance group, 43% underwent TAVI at a median of 12 months. 92% had progression to severe AS.
• Further data is eagerly awaited: For example, the PROGRESS (NCT04889872) and EXPAND II (NCT05149755) trials are exploring the efficacy of TAVI (balloon-expandable and self-expanding devices) in patients with moderate AS.

 

CORONARY ARTERY DISEASE

 

DCB-BIF trial 

DCB use in side branches

Rationale:

• The aim of the trial was to evaluate whether a strategy of treating a pinched side branch during provisional stenting with a drug coated balloon improves outcomes as compared with a non-compliant balloon, in patients with simple, true coronary bifurcations.

 

Publication:

• Gao, X, Tian, N, Kan, J. et al. Drug-Coated Balloon Angioplasty of the Side Branch During Provisional Stenting: The Multicenter Randomized DCB-BIF Trial. JACC. 2025 Jan, 85 (1) 1–15. https://doi.org/10.1016/j.jacc.2024.08.067

 

Study Design

• International (22 centres; China, Italy, Indonesia, Republic of Korea)
• Randomized 1:1 stratified by diabetes, initial presentations and sites.
• Treatment allocation masked to all except for physician and staff in the cardiac catheterization laboratory.

 

Trial Information

• 784 patients included (1231 screened)
• Duration of follow-up: 12 months
• Paclitaxel coated balloon used
• Mean patient age: 65 years
• 3% female
• 6% had diabetes
• 1% had Median 1,1,1 bifurcation lesions
• Crossover from 1 stent to 2 stent strategy occurred in 3.3% of the DCB arm and 3.8% in the NCB group.
• Distal left mains made up 15.2% of cases enrolled.

 

Procedure:

• Provisional stenting according to the EBC recommendations
• SB pre dilatation not recommended
• Stenting of MV was followed by proximal optimisation technique (POT)
• Randomisation in cases where ostial SB diameter stenosis ≥70%
• In DCB group, 1:1 non-compliant balloon NCB) used to dilate ostium, with sufficient predilatation defined as less than or equal to 50% residual stenosis. Then DCB inflated for 60 seconds. Following DCB, kissing balloon inflation performed with 2 NCBs and re POT performed. Indications for SB rescue stenting included Type C dissection or TIMI flow grad less than 3.
• In NCB group, all steps the same except that a DCB was not used.

 

Inclusion criteria:

• Patients aged 18 or over
• Presentation with silent ischaemia, stable or unstable angina or acute myocardial infarction older than one week from onset of chest pain to admission.
• Target lesion simple and true bifurcation (Median 1,1,1; Medina 1,0,1; Medina 0,1,1). With reference vessel diameter greater than or equal to 2.5mm, baseline diameter stenosis greater than or equal to 50%, side branch lesion length less than 10mm, successful recanalization of CTO in other MV or SB before enrolment, ostial SB stenosis greater than or equal to 70% after stenting MV.

 

Selected exclusion criteria:

• Allergy to study balloon, stent or protocol required concomitant medications
• Intolerance to DAPT
• Life expectancy less than 12 months
• Pregnancy or breast feeding
• Re stenotic lesion
• Severe calcification requiring rotational atherectomy
• Haemodynamic instability.

 

Primary Endpoint:

• Major adverse cardiac events at 12 months following the procedure, encompassing cardiac death, target vessel MI or clinically driven target-lesion revascularisation.

 

Results:

• Baseline characteristics well matched between groups.
• Luminal gain was slightly higher in SB in the DCB arm (p=0.041) as assessed by quantitative coronary analysis.
• Kissing balloon inflation after dilating SB was performed in fewer patients in NCB arm (p=0.001).
• Complete revascularisation was achieved in a similar proportion of patients in both arms.
• QFR post MV stenting was significant in side branch, which improved following treatment to side branch.
• Primary end point: Occurred in 49 patients in NCB group as compared with 28 patients in DCB group (Kaplan-Meier rate: 12.5% vs 7.2%; HR: 0.56;95% CI: 0.35-0.88; P= 0.013).
• Risk of spontaneous MI higher in NCB group (p=0.029) leading to a higher rate of target vessel MI in NCB group (p=0.009).
• No difference in secondary outcomes of al cause death, cardiac death, periprocedural MI, MACE without periprocedural MI, clinically driven TLR or stent thrombosis.

 

Limitations 

• Treatment allocation unblinded to the operators
• Results may not be applicable to sirolimus coated balloons.
• Overall low rates of patients presenting with myocardial infarction, so may not be able to extrapolate results to this group of patients
• Complex bifurcation lesions and those with calcium were excluded
• Overall comparable but low rates of intra coronary imaging use
• Lower rate of KBI in NCB group
• Females underrepresented.

 

Conclusions

• First randomised trail evaluating the use of DCBs for treating side branch stenoses following MV stenting in true bifurcation lesions.
• Combination of main vessel stenting and DCB treatment to the side branch led to fewer MACE at 12 months, driven by fewer target vessel myocardial infarctions.
• No difference in cardiac death, all cause death, or stent thrombosis were observed.
• Results consistent with smaller PEPCAD-V study.
• No reduction in target lesion revascularisation, suggesting the observed increase in myocardial infarctions may not have been deemed clinically significant to warrant re study or revascularisation.

  

 

The CLEAR trial: Colchcine in Acute Myocardial Infarction 

Rationale:

• There has been a lot on interest in anti-inflammatory therapeutics in coronary artery disease, given the role that inflammation is thought to have in the development of atherosclerosis. Given prior conflicting data, the aim of this study was to evaluate the effects of colchicine in patients following a myocardial infarction.

 

Publication:

• Jolly et al; CLEAR Investigators. Colchicine in Acute Myocardial Infarction. N Engl J Med. 2025 Feb 13;392(7):633-642.

 

Study Design

• International multicentre RCT
• Prospective
• Double blind
• 2 by 2 factorial design
• Patients randomly assigned to receive either colchicine or placebo and spironolactone or placebo in a 1:1:1:1 allocation. Results of the spironolactone arm are reported elsewhere.
• Randomisation stratified according to trial centre and type of myocardial infarction.
• Time to event analyses were performed

 

Trial Information

• 7062 patients enrolled (across 104 centres in 14 countries)
• 3528 patients assigned to receive colchicine, 3534 to receive placebo.
• Median follow up 3 years
• Mean age 61 years
• 20% females enrolled
• 9% had previous MI, 10% had prior PCI
• 5% had diabetes
• 1% presented with STEMI, 4.9% had NSTEMI
• C reactive protein levels and safety also assessed
• Trial drugs colchicine 0.5mg, spironolactone 25mg and placebo
• Initially weight-based dosage of colchicine, but swapped to once a day give higher than average discontinuation
• 9% of patients in colchicine group discontinued the trial regimen

 

Inclusion criteria:

• STEMI who underwent PCI or NSTEMI who had undergone PCI and had one or more of the following risk factors: an LVEF no more than 45%, diabetes mellitus, multi vessel coronary artery disease, prior MI or age greater than 60
• Patients enrolled within 72 hours of PCI

 

Selected exclusion criteria:

• Age ≤18years
• Pregnancy or breastfeeding
• Hypotension
• Diarrhoea
• Allergy to everolimus
• Unable to take DAPT

 

Primary Endpoint:

• Primary efficacy outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, stroke or unplanned ischaemia driven coronary revascularisation.

 

Results:

• Primary outcome occurred in 9.1% of patients in colchicine group, as compared with 9.3% in the placebo group (hazard ratio, 0.99; 95% CI, 0.85 to 1.16; P=0.93).
• There was no difference in death from cardiovascular causes, recurrent MI or stroke (hazard ratio, 0.98; 95% CI, 0.82 to 1.17)
• Death from non-cardiovascular causes occurred in 1.3% of patients in the colchicine group and 1.9% in the placebo group (hazard ratio, 0.68; 95% CI, 0.46 to 0.99)
• Primary outcome was consistent across all pre specified subgroups (age, sex, presence of diabetes, degree of coronary disease, renal function, presentation) aside from dosing. In those patients weighing less than 70kg who received BD dosing had fewer events.
• There was no difference in serious adverse events. More patients reported diarrhoea in the colchicine group (p<0.001). There was no difference in infections between groups.

 

Limitations 

• Women underrepresented.
• High rate of treatment discontinuation (in one quarter of patients in treatment arm)
• Twice daily colchicine was not evaluated.

 

Conclusions

• In patients presenting with STEMI or high risk NSTEMI, treatment with the anti-inflammatory colchicine did not reduce the incidence of death from cardiovascular causes, recurrent myocardial infarction, stroke or unplanned ischaemia-driven coronary revascularisation at a median of 3 years.
• There was no difference in secondary end points
• No difference in serious adverse events, however, increase in reported diarrhoea in colchicine arm
• These results contrast with the previous COLCOT trial, which enrolled 4745 patients within 30 days of AMI and compared colchicine with placebo. This trial demonstrated that colchicine reduced the primary outcome of a composite of death from CV causes, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina leading to coronary revascularisation. More recent trials evaluating colchicine in patients post stroke have had similar neutral outcomes like this trial. Whilst it is unclear why there is a lack of consistency in results, the most recent trials have also been neutral.
• There is an ongoing need to assess therapeutics that impact different parts of the inflammatory pathways in large clinical trials.

 

NICOR publishes 2025 National Cardiac Audit Programme (NCAP) Annual Report

We are delighted to share with you the 2025 National Cardiac Audit Programme (NCAP) Annual Report, the annual summary report for patients, carers and the public and the 10 interactive clinical domain summary reports.

Covering the 12 months from 1 April 2023 to 31 March 2024, this year’s report provides evidence that the landscape of cardiovascular disease is evolving. There are clear examples of good practice across the NHS, however challenges and pressures persist – including in cardiovascular services. In some regions, waiting lists for elective cardiovascular treatments are growing longer, urgent admissions face delays, and care inequalities and variances remain a significant concern.

The NCAP analyses combined with inputs from clinical colleagues, patients, and carers, have provide accessible insights into the performance of cardiovascular services, highlighting both successes and areas where improvements can be made.

Thank all our colleagues, community representative group members and stakeholders for their continued support and contribution. Particularly our clinical colleagues, their supporting audit and clerical teams, and their hospital management teams for ensuring that important data are collected and sent to NICOR. We hope our annual reports put these data into context.

The annual report is accompanied by 10 interactive sub-specialty clinical reports that offer detailed, domain-level analyses. These interactive tools enable users to:

• drill down into the performance of different regions and individual hospitals
• focus on specific areas of interest to better understand local trends and outcomes.

These reports can be found on the NICOR website.

Understanding the continued pressures on hospitals and their clinical teams, we are most grateful for your continuing hard work and contributions to the NCAP.

We also invite you to contribute your comments, feedback, queries, or suggestions for future reports. Please NICOR: nicor.auditenquiries@nhs.net.

The introduction of Primary Percutaneous Coronary Intervention (PPCI) has seen a significant growth in the out of hours workload for interventional cardiologists. Very few medical specialties require the immediate return of senior medical staff to hospital on a 24/7 basis, where they are required to perform complex procedures in often very sick patients. This pattern of work is very disruptive to family life and involves regular sleep disturbance. Interventional cardiology risks becoming an unpopular specialty.

There is a perception that the time has come for a review of the working arrangements for consultant interventional cardiologists in the UK. The purpose of this document is to review the traditional arrangements and outline other options that are available under the current NHS consultant contract.

 

 

BCIS literature review

December 2024

Authors: Dr. Richard Jabbour, Dr. Claudia Cosgrove, Dr. Natalia Briceno

 

CORONARY ARTERY DISEASE

SENIOR-RITA trial

Invasive treatment in older adults with NSTEMI

 

Rationale: This study sought to determine whether a conservative approach, with medical therapy, or invasive coronary angiography with revascularisation was better in older patients (>75 years) presenting with NSTEMI.

 

Publication: Invasive Treatment Strategy for Older Patients with Myocardial Infarction. Kunadian et al. NEJM 2024 Nov 7;391(18):1673-1684.

 

Study design

• Multicentre (48 UK sites)
• Patients >75 years old presenting with NSTEMI
• Exclusions: STEMI, unstable angina, cardiogenic shock, life expectancy <1 year, deemed unable to undergo coronary angiography
• Randomised 1:1 (conservative management vs invasive management)
• Both arms received medical therapy including aspirin, P2Y12 inhibitor, statin, beta-blocker and ACE-inhibitor
• Primary outcome was a composite of death from cardiovascular causes or nonfatal myocardial infarction

 

Study population

• 1518 patients; mean age 82 years; 45% female
• 32% frail (Fried Frailty Index); 60% cognitive impairment (MoCA)
• Median follow up 4.1 years
• In Invasive arm: 90% underwent angiography, 50% received revascularisation (PCI in 47%, CABG in 3%)

 

Results

• Primary event occurred in 193 (25.6%) of invasive strategy arm, vs 201 (26.3%) of conservative arm (HR 0.94; 95% CI 0.77 to 1.14; P = 0.53).
• There was 25% relative reduction in the occurrence of non-fatal MI in the invasive group vs. the conservative group.
• There were fewer patients who underwent subsequent coronary angiography (5.6% vs. 24.2%) and revascularisation procedures (3.9% vs. 13.7%) in the invasive-strategy group than in the conservative-strategy group.
• In patients undergoing angiography: radial access in 89%;
• Procedural complications <1%
• TIA (2.4 % vs. 1.2%) and BARC bleeding (8.2% vs. 6.4%) in invasive strategy vs. conservative group.

 

Interpretation and clinical application

• Routine invasive angiography and revascularisation in addition to medical therapy, appears to offer no significant mortality benefit over medical therapy alone in patients older than 75 years presenting with NSTEMI.
• When invasive angiography was performed, in older, frail patients, rates of bleeding and procedural complications in this study were low.

 

Limitations

• Only 1 in 5 eligible patients were enrolled. 65% of patients excluded based on physician’s clinical decision underwent invasive procedure (likely clinician bias towards invasive management). However, in the screening log, patients randomised and those not randomised had similar baseline characteristics strengthening the generalisability of this study.

 

EARTH-STEMI meta-analysis

Complete revascularisation in older adults

 

Rationale: Current guidelines recommend complete revascularisation of non-culprit arteries in patients presenting with STEMI. However, older patients were underrepresented in the landmark trials on which these guidelines are based on. The aim of this meta-analysis was to evaluate whether complete revascularisation in older STEMI patients has a positive impact on long term clinical outcomes.

 

Publication reference: Campo et al. Complete Versus Culprit-Only Revascularization in Older Patients With ST-Segment-Elevation Myocardial Infarction: An Individual Patient Meta-Analysis. Circulation. 2024 Nov 5;150(19):1508-1516.

 

Study Design

• Individual patient meta-analysis
• 7 randomised controlled trials included that compared complete revascularisation with culprit only (COMPLETE, Compare-Acute, CvLPRIT, DANAMI-3-PRIMULTI, FIRE, Full-REVASC, and a study by Hamza et al)
• Follow up ranged from 6 months to a maximum of 6.2 years.

 

Inclusion criteria:

• Age ≥ 75 years
• Clinical presentation as STEMI
• Successful treatment of culprit lesion
• Multivessel disease with at least one non-culprit lesion in a different vessel (angiographic or FFR guided)

 

Outcomes:

• Primary end point: composite of death, myocardial infarction or ischaemic driven complete revascularisation.
• Secondary end points: composite of cardiovascular death or myocardial infarction, individual components of composite outcomes. Safety endpoints including stroke, stent thrombosis, major bleeding and contrast induced kidney injury.

 

Trial Population:

• 1733 patients were included in this meta-analysis (917 in culprit only, 816 in complete group); Median age was 79 (77-83) years.
• 15% of patients in this study were older than 85 years of age.
• Baseline and procedural characteristics were similar, except for female sex (higher proportion of females in the culprit only group).
• 77% of the patients in the complete arm received PCI of non-culprit lesion within index hospitalization.
• Treatment of no culprit lesions physiology guided in 57%

Results:

• There was a numerically lower number of patients experiencing a primary outcome in the complete revascularisation group at the longest follow up, which did not reach statistical significance (HR 0.83, 95% CI 0.69-1.01).
• When censoring the follow up at each year, complete revascularisation demonstrated a significant reduction of the primary outcome at four years.
• Cardiovascular death or myocardial infarction was significantly lower in patients randomised to complete revascularisation at the longest follow up (HR 0.76, 95% CI 0.58-0.99).
• Ischaemia driven revascularisation was significantly lower in the complete revascularisation group.

 

Interpretation and clinical implications:

• Whilst there was a signal of benefit of the primary outcome at the longest follow up, this was only significant when follow up was censored to four years, suggesting that this early benefit may not be sustained at longer term follow up.
• Ischaemia driven revascularisation was lower in the complete group, but bias may have had an impact given the open label trials included.
• These results can be used to aid discussions with regards to management of older patients presenting with STEMI and multi-vessel disease.
• It is important to continue to assess each patient individually, balancing the pros and cons of complete revascularisation, taking into account frailty, co-morbidities and coronary artery disease complexity alongside procedural risk.

 

Limitations:

• Over 85’s underrepresented.
• Variation in length of follow up across studies included.
• Most trials included did not stratify the randomisation by age.
• Trials enrolled patients spanning a large time frame, with potential bias introduced with changes in techniques and device.

 

REC-CAGEFREE I

Drug coated balloons in native disease

 

Rationale: Drug coated balloons (DCB) are used in routine practice for both treatment of de novo small vessel coronary artery disease and in stent restenosis. However, it remains unclear whether the theoretical benefits of DCB translate into comparable clinical outcomes in larger coronary arteries. The aim of this trial was to assess the non-inferiority of DCB as compared with DES in non-complex de novo coronary artery disease regardless of vessel size in both acute coronary (including STEMI) and chronic coronary syndromes.

 

Publication reference: Gao et al. Drug-coated balloon angioplasty with rescue stenting versus intended stenting for the treatment of patients with de novo coronary artery lesions (REC-CAGEFREE I): an open-label, randomised, non-inferiority trial. Lancet. 2024 Sep 14;404(10457):1040-1050.

 

Study Design

• 43 centres in China
• Randomized 1:1 (Swide DCB (paclitaxel and iopromide) versus Firebird 2 DES (sirolimus eluting DES with cobalt chromium alloy platform, 86 μm thick struts, durable polymer)
• Non-inferiority, open label
• Pre specified total length of follow up 10 years, 2 year follow up data presented
• Intention to treat analysis performed

 

Inclusion criteria:

• Patients aged 18 years or older
• Requiring PCI for acute or chronic coronary syndromes
• De novo non-complex target lesions regardless of vessel size
• Successful and satisfactory pre dilatation (no type D, E or F dissection, TIMI 3 flow, no residual stenosis greater than 30% or more, no serious complications)

 

Key Exclusion criteria:

•  Cardiogenic shock
•  Revascularisation for in stent restenosis

 

Outcomes:

• Primary end point: device orientated composite endpoint-DoCE (composite of cardiovascular death, target myocardial infarction (TV-MI) and clinically and physiologically indicated TLF at 24 months.
• Secondary end points were rates of DoCE at 1 month and 12 months, rates of individual components of DoCE, a patient orientated composite endpoint (all death, any stroke, any MI and any revascularisation) and individual components, target vessel failure, clinically and physiologically indicated target vessel revascularisation, BARC bleeding, device or vessel thrombosis.

 

Trial Population:

• 2902 potentially eligible, with 2272 undergoing successful predilatation and enrolment (78.3%)
• 106 out of 1133 randomised to the DCB group underwent rescue stenting (9.4%)
• 48.4% of cases enrolled involved small vessel disease (diameter  <3mm).
• Median age 62 years; 69.3% male; All patients of Chinese ethnicity
• 2529 lesions treated in the 2272 patients, of which 50.7% in the LAD
• 64.5% of lesions treated with cutting or scoring balloons, with no difference is use of these balloons between groups.
• Imaging performed in approximately one in ten patients.
• No signficant differences in baseline characteristics

 

Results:

• At 24 months, DoCE occurred in 6,4% of 1133 patients in DCB group and 3.4% of 1139 In the DES group, with a difference of 3.04% in cumulative event rate (P _{non-inferiority} =0.65), driven mainly by an increased rate of clinically or physiologically driven TLR.
• Peri procedural MI rates and major bleeding were similar in both groups.
• Vessel size exhibited a significant treatment by subgroup interaction, with a signal that DCB had greater benefit in reducing the primary outcome in small vessel coronary artery disease.

 

Interpretation and clinical implications:

• This is the first randomised study of DCB vs. DES in de novo coronary disease regardless of vessel size.
• In low complexity lesions regardless of vessel size, DES remains to DCB.
• In 1/5^th of patients, predilatation is unsuccessful requiring DES implantation
• For now, routine use of DCB should be limited to small vessel de novo disease and in stent re-stenosis.
• DES should remain the preferred treatment for de novo large vessel coronary artery disease.

 

Limitations:

• Single blinded open label, therefore could introduce bias in assessing outcomes.
• All patients of Chinese ethnicity, therefore results may not be translatable.
• Trial investigated a paclitaxel coated balloon, and therefore the results cannot be extrapolated to sirolimus coated balloons.

 

 

INTRVASCULAR IMAGING

OCCUPI

OCT-guided vs angiography-guided PCI in ‘complex’ lesions

 

Rationale: There is a growing body of evidence to suggest that intracoronary imaging guidance in PCI results in improved clinical outcomes, particularly in certain lesion subsets. However, the results of RCTs to date have been mixed. This study sought to determine the clinical benefits of OCT-guided vs angiography-guided PCI in ‘complex’ lesions.

 

Publication: Optical coherence tomography-guided versus angiography-guided percutaneous coronary intervention for patients with complex lesions (OCCUPI): an investigator-initiated, multicentre, randomised, open-label, superiority trial in South Korea. Hong et al, Lancet, 2024 Sep 14;404(10457):1029-1039.

 

Study design

• Multicentre (20 sites in South Korea)
• Patients undergoing PCI with DES of ‘complex’ lesions*
• Randomised 1:1 (OCT vs. angio guidance)
• In OCT group: OCT performed pre-stent, and ‘recommended’ post stent.
• Open label.
• Primary outcome: MACE (cardiac death, MI, stent thrombosis, ischaemia-driven TLR) at 1 year

 

*Complex lesions defined as: acute MI, CTO, Long lesion (expected stent length ≥28 mm), Calcified lesions, Bifurcation, Unprotected LMS, Small vessel <2.5mm, Intracoronary thrombus visible on angiography, Stent thrombosis, In-stent restenosis, Bypass graft lesions

 

Study population

• 1604 patients
• 80% male, 20% female; Median age 64 years
• 33% with diabetes
• 99% patients completed 1 year follow up

 

Results

• Primary endpoint (MACE) occurred in 37 (5%) in the OCT arm and 59 (7%) in the angio arm. HR 0·62 (95% CI 0·41–0·93); p=0·023.
• Significantly lower rates of spontaneous MI (7 (1%) with OCT vs 19 (2%) with angio) and ischaemia-driven TVR (12 (2%) with OCT and 33 (4%) with angio.
• 545 (71%) of patients met all 3 criteria for ‘stent optimisation’.
• Patients with stent optimisation had significantly lower rates of the primary outcome (16 [3%] of 545 vs 19 [9%] of 222).
• Patients with suboptimal results on OCT had no significant difference in primary outcome compared to angiographic guidance.
• Stroke, bleeding, CIN not significantly different between groups.
• Procedural time greater by 10 min with OCT than angiographic guidance, (53 min vs. 43min).

Interpretation and clinical application

• In patients undergoing PCI with DES for a wide range of lesion subsets, OCT guidance, when used to achieve optimal mechanical stent results, is associated with a lower incidence of MACE at 1 year.
• No apparent detriment to using OCT in terms of procedural time or renal injury.

 

Limitations

• Relatively short follow up period for assessment of restenosis.
• Modest effect.

 

 

VALVULAR HEART DISEASE

NOTION 3 Trial

Role of PCI in patients with obstructive CAD undergoing TAVI

 

Rationale: The purpose of the trial was to analyse whether percutaneous coronary intervention (PCI) or conservative therapy was effective in patients in who had obstructive coronary artery disease underwent transcatheter aortic valve implantation (TAVI).

 

Publication date: NOTION-3. Lønborg J et al. PCI in Patients Undergoing Transcatheter Aortic-Valve Implantation. N Engl J Med. 2024 Dec;391(23):2189-00.

 

Study Design

• International
• Randomized 1:1
• Parallel
• Open label

Patients with symptomatic severe aortic stenosis with obstructive coronary artery disease in at least one vessel were randomized to PCI (n = 227) vs. conservative therapy (n = 228).  PCI was ideally recommended to be performed prior to TAVI but was allowed during or within 2 days post TAVI.

 

Trial information:

• 455 Patients included.
• Duration of follow-up: median 2 years
• Mean patient age: 82 years
• Median STS 3%
• Percentage female: 32% (PCI) vs. 33% (conservative)
• Percentage with diabetes: 26% (PCI) vs 27% (Conservative)
• Median LVEF 60% (PCI) vs 60% (conservative)

 

Inclusion criteria:

• Symptomatic severe aortic stenosis assessed by Heart Team and selected for TAVI
• At least one vessel (≥2.5 mm) with obstructive coronary artery disease, defined as fractional flow reserve ≤0.80 or ≥90% angiographic stenosis

 

Exclusion criteria:

• Previous tissue AVR
• Limited life expectancy <1 year
• Severe renal failure – eGFR <20
• Recent acute coronary syndrome within 14 days
• Left main coronary artery stenosis

 

Characteristics:

• PCI prior to TAVI: 74%; PCI at the same time as TAVI: 17%; PCI post TAVI: 9%
• Balloon-expandable valve: 40%.
• Complete Revascularisation achieved 89%

Primary Endpoint: Major adverse cardiac events: a composite of all-cause mortality, myocardial infarction, or urgent revascularization

 

Principal Findings: The primary outcome was 26% in the PCI group vs. 36% in the conservative therapy group (p = 0.04).

 

Secondary outcomes:

• All-cause mortality: 23% (PCI) vs. 27% (conservative)
• MI: 7% (PCI) vs. 14% (conservative)
• Urgent revascularisation: 2% (PCI) vs. 11% (conservative)
• Major bleeding: 11% (PCI) vs. 10% (conservative)

 

Limitations

• Small sample size and therefore underpowered for hard end points
• Patients with recent ACS and left main disease excluded
• Unblinded outcome may have influenced unplanned revascularisation
• Patients with a recent acute coronary syndrome and left main coronary-artery stenosis were not included
• The enrolment period occurred over the course of 5 years during which the technical aspects of TAVI and PCI, and the medical treatment as well as patient selection for TAVI evolved.

 

Conclusions

• The trial found that in patients with obstructive coronary artery disease undergoing TAVI, there was a reduction in major adverse cardiovascular events in those who underwent PCI prior or around the time of the TAVI procedure driven by a reduction in myocardial infarction and urgent revascularisation.
• This contrasts with the ACTIVATION trial which did not find a net benefit and was halted early due to futility. NOTION 3 included more patients and had a longer follow-up.
• The ongoing COMPLETE TAVR trial is also assessing this hypothesis.
• The decision to perform PCI prior to TAVI should consider the disease complexity, coronary artery location, age, patient comorbidities and symptoms. This should also be balanced with the patient’s bleeding risk.

 

Limitations:

• It should be noted that the median number of physiologically significant lesions per patient was low (n=1), the SYNTAX score was also low (median 9), and few patients therefore had multivessel disease.

 

RESHAPE HF 2 Trial

Mitral edge-edge repair in moderate to severe MR and heart failure

 

Rationale: To assess the safety and efficacy of mitral edge-to-edge repair (MitraClip System) with optimal medical therapy in symptomatic heart failure (NYHA class II- IV) patients with co-existent secondary moderate to severe mitral regurgitation. Registry data has indicated that a relatively high proportion of patients undergoing TEER contemporarily actually have moderate rather than severe HR (44% moderate from registry data). Accordingly, the RESHAPE-HF2 trial assessed moderate to severe MR and the effectiveness of TEER on top of optimal medical therapy (OMT).

 

Publication date: Anker SD, et al. Transcatheter Valve Repair in Heart Failure with Moderate to Severe Mitral Regurgitation. N Engl J Med. 2024 Nov 14;391(19):1799-1809.

 

Study Design

• International (30 sites, 9 countries)
• Randomised 1:1 TEER + OMT vs OMT alone
• Parallel assignment; Open label

 

Patients with HF and grade 3-4 MR who remained symptomatic despite optimal medical therapy were randomized to M-TEER with MitraClip + OMT (n=250) vs. OMT alone (n=255).

 

Trial Information

• Total number of patients: 505 (250 patients device group; 255 control)
• Duration of follow-up: 24 months (mean 18.8 months)

 

Inclusion criteria:

• Signs and symptoms of HF (NYHA class II-IV) despite optimal medical therapy.
• Left ventricular ejection fraction (LVEF) of 20-50%.
• Moderate-to-severe (3+) or severe (4+) secondary (functional) MR.
• Minimum of one documented hospitalization (acute care admission or emergency room visit) for heart failure within 12 months preceding randomization OR values of 300 pg/mL for BNP or 1000 pg/mL for NT-proBNP after optimal medical and/or device management within 90 days preceding randomization.

 

Exclusion criteria:

• Predominantly degenerative MR (primary).
• Mitral surgery recommended as preferred treatment option.
• Renal replacement therapy.
• Any percutaneous cardiovascular intervention, carotid surgery, cardiovascular surgery, or atrial fibrillation ablation within 90 days prior to randomization.

 

Baseline Characteristics

• Prior myocardial infarction: 57.6% device group vs. 52.9% control group
• Prior PCI: 47.2% device vs. 49.0% control
• Prior coronary artery bypass grafting (CABG): 27.6% device vs. 25.1% control
• Ischemic HF: 64.8% device vs. 65.5% control
• HF hospitalization within 1 year: 66% device vs. 65.9% control
• Median NT-proBNP: 2651 device vs. 2816 control
• Median EF 32% device group vs. 31% control

 

Primary Outcome measures:

• Composite rate of recurrent heart failure hospitalizations and cardiovascular (CV) death within 24 months.
• Rate of total (first and recurrent) HF hospitalizations within 24 months.
• Change in quality of life (overall KCCQ-OS score) from baseline to 12 months.

 

Principal Findings:

• The primary endpoint: MitraClip + OMT vs. OMT, was 37.0 vs. 58.9 events per 100 patient-years (p = 0.002).
• First or recurrent HF hospitalization: 26.9 vs. 46.6 events per 100 patient-years (p = 0.002).
• Mean change from baseline in KCCQ-OS: 21.6±9 (TEER+OMT) vs. 8± 24.5 (OMT) (p < 0.001).
• MR ≤2+ at 12 months: 90.4% (TEER + OMT) vs. 36.1% (OMT) (p < 0.001).

 

Conclusion:

• MitraClip therapy on top of OMT was found to be beneficial and trial met the composite primary endpoint of first / recurrent HF hospitalisation and all-cause mortality at 24 months.
• The benefit was primarily due to a reduction in HF hospitalization since there was no reduction in all-cause death observed.
• TEER was associated with greater improvements in QoL score (KCCQ-OS).

 

Limitations:

• Unblinded nature may have introduced bias, especially regarding QoL assessments

 

The report covers the 12 months from 1 April 2022 to 31 March 2023 and explores what could be potentially important post-pandemic shifts in the demand for cardiovascular services, how these are provided, and the variability experienced in different locations. NCAP now includes 11 cardiovascular audits and registries, eight of which provide results to this 2024 report.

The National Cardiac Audit Programme (NCAP) aims to drive quality improvement (QI) in the design and delivery of cardiovascular services. This 2024 NCAP report covers quality of care outcome measures across seven cardiovascular domains. Each of these sub-specialty audits is concerned with a particular area of cardiovascular disease (CVD) treatment.

The National Institute for Cardiovascular Outcomes Research (NICOR) is now part of the NHS Arden & Greater East Midlands Commissioning Support Unit and is commissioned directly by NHS England and NHS Wales (GIG Cymru) to run NCAP.

BCIS R&D Group Literature Review

April 2024

Prepared by Michael Mahmoudi and Natalia Briceno

Edited by Michael Mahmoudi

 

Coronary Artery Disease

What next for iFR guided PCI?

Instantaneous wave free ration vs. fractional flow reserve and 5-year mortality: iFR SWEDEHEART and DEFINE FLAIR.

EHJ 2023; 44:4376-4384

The landmark iFR-SWEDEHEART and DEFINE-FLAIR studies demonstrated that at 1-year follow-up, iFR guided coronary revascularization was non-inferior to FFR guided revascularization in term of MACE. A 1-year meta-analysis of both studies found increased risk of a combination of death and revascularization in the iFR group. The current study examined the 5-year results of both studies in a study-level meta-analysis. In a total population of 4511 patients, 76% were male, 71% had hypertension, 27% had diabetes, 72% had chronic coronary syndrome, 53% had single vessel disease, 71% had type A or B lesions, average iFR was 0.91±0.1 and average FFR was 0.83±0.1. In both studies, the proportion of examined/treated lesions in the LAD was highest (iFR-SWEDEHEART=48% and DEFINE-FLAIR=53%). Revascularization was more commonly undertaken in the FFR group than in the iFR group (55% vs. 50%; p=0.008). PCI was the most common mode of revascularization. The composite endpoint occurred more frequently in the iFR group (HR 1.18; 95% CI:1.04-1.34; p=0.12). All-cause mortality was significantly higher in the iFR group (HR 1.34; 95% CI: 1.08-1.67; p=0.0074). There were no differences in the rate of MI (HR 1.02; 95% CI: 0.80-1.32; p=0.85) and unplanned revascularization (HR0.99; 95% CI: 0.83-1.19; p=0.94). Although the underlying reasons for the excess mortality observed in this meta-analysis are likely to be multifactorial, one potential explanation may be the iFR/FFR discordance which has been previously reported in such studies as the CONTRAST study involving lesions in the LMS and proximal LAD which theoretically could be extended to proximal lesions in a large RCA or LCX. Revascularization of the LMS/proximal LAD are associated with prognostic significance and deferral of such lesions may be associated with a higher mortality. In the current analysis, LAD lesions constituted half of the patient population in both studies and the number of revascularized patients was higher in the FFR group.

 PCI reduces angina!

A placebo-controlled trial of percutaneous coronary intervention for stable angina.

NEJM 2023; 389:2319-2330

The overall impact of PCI in reducing the symptom of angina in patients with stable CAD has at times been controversial. The ORBITA-2 trial was designed to address this uncertainty in 301 patients with stable angina who were not receiving any antianginal medication. Patients were eligible for enrolment if they were suitable for PCI, had angina, anatomical evidence of severe stenosis upon invasive angiography or CTCA, and evidence of ischaemia on non-invasive imaging or FFR/iFR. Key exclusion criteria were age >85 years, recent ACS, previous CABG, significant LMS disease, CTO, severe valvular heart disease, severe LV systolic dysfunction, severe respiratory disease, and life expectancy < 2 years. At enrolment, antianginal medications were stopped, and dual antiplatelet and statin therapy were initiated. Patients were instructed to use a dedicated smartphone application to report the presence or absence of angina daily. Patients completed the SAQ, EQ-5D-5L, a modified ETT, underwent dobutamine stress echocardiography, and the CCS class was assessed. Patients then entered a 2-week pre-randomization symptom assessment phase and proceeded to randomization if they reported at least one episode of angina. Asymptomatic patients were withdrawn from the trial. Suitable patients were then randomised to either PCI (n=151) or a placebo sham procedure (n=150). In the PCI group, complete revascularization of the target was mandated. In patients with multivessel disease, all the vessels were treated during the index procedure. Patients in the placebo arm remined sedated without any intervention for at least 15 minutes. The primary endpoint was the angina symptom score and an ordinal clinical outcome of scale of health status associated with angina. Mean age was 64 years, 21% were female, CCS angina severity was class I in 4%, class II in 58%, and Class III in 39%. The vessels involved were LAD in 55%, RCA in 22%, left Cx in 9%, and branch vessels in 14%. The median FFR was 0.63 and the median iFR was 0.78. At 12 weeks follow-up, the mean angina symptom score was 2.9 in the PCI group and 5.6 in the placebo group (OR 2.21; 95% CI interval: 1.41-3.47; p<0.001). One patient in the placebo group had unacceptable angina leading to unblinding. ACS occurred in 4 patients in the PCI group and in 6 patients in the placebo group. Salient features include short duration of follow-up and small sample size. In summary, ORBITA 2 has shown that PCI results in greater improvements in anginal frequency and exercise time compared with a sham procedure.

CTCA should be considered as first line investigation in CABG patients.

Computed tomography cardiac angiography before invasive coronary angiography in patients with previous bypass surgery: the BYPASS-CTCA trial. Circulation 2023; 148:1371-1380

The clinical benefits of CT cardiac angiography (CTCA) in patients with previous CABG who are undergoing invasive angiography (ICA) are uncertain. The BYPASS-CTCA trial examined whether a strategy of CTCA prior to ICA was associated with improvements in procedural duration of ICA, patient satisfaction, and the incidence contrast nephropathy in 688 patients. Key inclusion criteria were patients ≥ 18 years of age with previous CABG requiring ICA, stable angina, and NSTEMI. Exclusion criteria included STEMI, severe kidney disease, inability to tolerate beta-blocker, and contrast allergy. Mean age was 69±10.4 years, 15.7% were female, 58.4% were white, 85.3% were hypertensive, and 53.8% were diabetic, and the median time from CABG to ICA was 12 years. At a median follow-up of 1 year, the procedure duration was shorter in the CT+ICA group (18.6 minutes vs. 39.5 minutes; p<0.001), patient satisfaction score was greater (1.49 vs. 2.54; p<0.001), and the incidence of contrast nephropathy was lower (3.4% vs. 27.9%; p<0.001). Procedural complications, defined as MI, stroke, or bleeding was also lower in the CT+ICA group (2.3% vs. 10.8%; p<0.001). In summary, in patients with previous CABG requiring ICA, a strategy of CTCA prior to ICA is associated with improved clinical safety and patient satisfaction.

Bypass graft failure is more common than we think.

Graft failure after coronary artery bypass grafting and its association with patient characteristics and clinical events: a pooled individual patient data analysis of clinical trials with imaging follow-up.

Circulation 2023; 148:1305-1315

Coronary artery bypass grafting (CABG) has been shown to improve mortality and revascularization rates across the whole spectrum of coronary artery disease. The rate of graft failure, its implications, and factors associated with graft failure has not been examined in contemporary clinical practice. The current study is a pooled individual patient data from seven trials including 4413 patients with systematic CABG graft imaging to examine the incidence of graft failure and its association with clinical risk factors. The primary outcome was a composite of MI or repeat revascularization occurring after CABG and before imaging. The association between graft failure and MI, repeat revascularization, and all-cause mortality occurring after imaging was also examined. Mean age was 64.4±9.1 years, 17.6% were female, 37.6% were diabetic, 26% had previous MI, 4.8% had chronic kidney disease, 24.3% had off-pump CABG, mean number of grafts was 3.04±1, and 5.6% had bilateral internal thoracic artery graft. The median clinical follow-up time was 2.07 years. The median time to imaging was 1.02 years. There were 1487 (33.7%) patients with graft failure. On a graft level, the overall graft failure rate was 16.6%; individual conduit failure rate was 9.7% for the left internal thoracic artery, 13.8% for the radial artery, 19.7% for SVGs, and 23% for the right internal thoracic artery. In the patient-level analysis, female gender and the total number of grafts were associated with graft failure, whereas LAD target was inversely related associated with it. In the graft-level analysis, age, female gender, and smoking were directly associated with graft failure whereas LAD target and use of statins were inversely associated with it. The primary outcome of MI or repeat revascularization before imaging occurred in 3.8% of patients and occurred more frequently in patients with graft failure compared with patients without graft failure (8% vs. 1.7%; p<0.001). Graft failure was independently associated with the primary outcome (aOR 3.98; 95% CI: 3.54-4.47; p<0.001). Death from any cause after imaging occurred significantly more commonly in patients with graft failure (11% vs. 2.1%; aOR 2.79; 95% CI: 2.01-3.89; p<0.001). The association of graft failure with the primary outcome was consistent across all subgroups and was significantly stronger in patients who received < 3 grafts. Graft failure was associated with an increased risk of the primary outcome regardless of whether the target vessel was the LAD or a non-LAD vessel. In summary, graft failure remains a common challenge and is associated with adverse clinical outcomes.

Image guided PCI must be considered standard of care.

Comparison of intravascular imaging, functional, or angiographically guided coronary intervention.

JACC 2023; 82:2167-76

The limitations of angiography guided PCI have been well established as have the benefits of image guided (IVUS/OCT) and functionally guided (FFR/iFR/resting full-cycle ratio/diastolic hyperaemia-free ratio/quantitative flow ratio). The current manuscript performed a network meta-analysis of randomized controlled trials (RCTs) and examined the outcomes with intravascular imaging-guided, functionally guided, and angiography guided PCI. The primary outcome was trial-defined MACE, which was defined predominantly as a composite of CV death, MI, and TLR. The secondary outcomes were all-cause death, CV death, MI, stent thrombosis, and TLR. A total of 32 eligible RCTs were identified including 22,684 results. The mean follow-up ranged from 6 months to 5 years. Both intravascular -guided PCI (RR: 0.72; 95% CI: 0.62-0.82) and functionally guided PCI (RR: 0.81; 95% CI: 0.69-0.96) were associated with reduced MACE as compared to angiography guided PCI. There was no difference in MACE between intravascular and functionally guided PCI (RR: 0.88; 95% CI: 0.72-1.07). The three groups had similar outcomes regarding all-cause death. Intravascular guided PCI was associated with reduced CV death compared with angiography guided PCI (RR: 0.56; 95% CI: 0.42-0.75). There was no significant difference in CV death between intravascular imaging and functionally guided PCI (RR: 0.74; 95% CI: 0.48-1.13). As compared to angiography guided PCI, both intravascular guided (RR: 0.81; 95% 0.66-0.99) and functionally guided PCI were associated with reduced rates of MI (RR: 0.78; 95% CI: 0.63-0.96). MI rates did not vary with intravascular or functionally guided PCI. As compared to angiography guided PCI, intravascular image guided PCI was associated reduced rates of stent thrombosis (RR: 0.48; 95% CI: 0.31-0.73), reduced TLR (RR: 0.75; 95% CI: 0.57-0.99). Among the 3 strategies, intravascular guided PCI was ranked first for reducing MACE, CV death, stent thrombosis, and TLR.

Be aware of transfusing MI patients with anaemia.

Restrictive or liberal transfusion strategy in myocardial infarction and anaemia. NEJM 2023; 389:2446-2456

The safety and efficacy of blood transfusion in anaemic patients presenting with an acute MI remains uncertain. Blood transfusion should, in theory, improve oxygen delivery to the ischaemic myocardium and reduce the risk of reinfarction and death or potentially increase the risk of heart failure from fluid overload & thrombosis from increased blood viscosity. The MINT trial was designed to address whether a strategy of restrictive or liberal transfusion in such patients were associated with differences in the risk of death or MI. A total of 3,506 patients presenting with STEMI or NSTEMI with a haemoglobin (Hb) level <10 g/dL were enrolled. Key exclusion criteria included uncontrolled bleeding, patients receiving palliative therapy, or patients scheduled for cardiac surgery. In the restrictive-strategy group, transfusion was permitted but not essential in patients with Hb<8 g/dL but was recommended in patients with Hb<7 g/dL or when anginal symptoms persisted despite OMT. In the liberal-strategy group, one unit of packed RBC was given post randomization and RBC were given to maintain the Hb>10 g/dL until hospital discharge or 30 days. The primary outcome was a composite of MI or death from any cause up to 30 days after randomization. The secondary outcomes were the individual components of the primary outcome and the composite outcome of death, MI, ischaemia driven unscheduled coronary revascularization, or hospital readmission for any ischaemic cardiac condition within 30 days. Mean age was 72.1 years, 45.5% were women, approximately 33% had a previous history of MI and PCI, 30% had a history of heart failure, 81% presented with NSTEMI, mean Hb was 8.6 g/dL, and median creatinine was 124 mmol/L. The mean Hb level was lower in the restrictive-strategy group by 1.3 g/dL (95% CI: 1.2-1.4) on day 1 and lower by 1.6 g/dL on day 3 (95% CI: 1.5-1.7). The total number of transfused RBC was 3.5x fold greater in the liberal strategy-group (4325 units vs. 1237 units). The mean number of transfused RBC was also greater in the liberal-strategy group (2.5±2.3 vs. 0.7±1.6). The primary outcome was similar in the restrictive-strategy and liberal-strategy group (16.9% vs. 14.5%; RR: 1.15; 95% CI: 0.99-1.34; p=0.07). At 30 days, the rates of the secondary outcomes in the restrictive-strategy and liberal-strategy groups were death (9.9% vs. 8.3%; RR: 1.19; 95% CI: 0.96-1.47), MI (8.5% vs. 7.2%; RR: 1.19; 95% CI: 0.94-1.49), death, MI, revascularization, or hospitalization (19.6% vs. 17.4%; RR: 1.13; 95% CI: 0.98-1.29). Of note, cardiac death was more common in the restrictive-strategy group (5.5% vs. 3.2%; RR:1.74; 95% CI: 1.26-2.40). The risk of other clinical outcomes was similar.

Biodegradable polymer is superior to durable polymer.

Long-term outcomes with biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents in ST-segment elevation myocardial infarction: 5-year follow-up of the BIOSTEMI randomised superiority trial.

Lancet 2023; 402:1979-1990

BIOSTEMI Extended Survival (ES) evaluates the 5-year follow up data from the BIOSTEMI study, which was an investigator led, single blinded, randomised superiority trial comparing a biodegradable polymer sirolimus eluting stent (Orsiro, Biotronik) with a durable polymer everolimus eluting stent (Xience Alpine, Abbott) in STEMI patients. A biodegradable polymer and thinner struts have been developed with the aim of reducing vessel wall injury with subsequent reduction in inflammatory response and neointimal hyperplasia. The original trial population consisted of 1300 patients presenting including 1622 lesions randomised 1:1 to a biodegradable polymer versus a durable polymer DES. Included in the analysis were 407 patients recruited to the BIOSCIENCE randomised controlled trial who presented with STEMI, and the investigators used Bayesian statistical methods whereby superiority was demonstrated if the Bayesian posterior probability for a rate ratio (RR) of less than 1 was greater than 0.975. Data at 2 years reported superiority of the biodegradable polymer stent, with a reduction in the primary endpoint of target lesion failure (components of cardiac death, target vessel myocardial infarction or clinically indicated target lesion revascularization at 5 years). However, the question remained whether these benefits held once the polymer had fully degraded, which was around or after the 2-year time point. At 5 years, data was available for 85% of patients. There were no significant differences in baseline characteristics aside from a higher rate of total vessel occlusion in the durable polymer group. Target lesion failure occurred in 8% of patients treated in the biodegradable polymer DES and in 11% of patients treated with the durable polymer DES (Bayesian posterior probability for superiority of 0.988), driven by reduced rates of clinically indicated target lesion revascularisation (3.1% versus 5.4%). There were no significant differences in the stent size used, which may have had an influence as the smaller stent sizes in the biodegradable polymer DES have thinner struts. It is interesting that the reduction in target lesion failure has only been observed in the STEMI population, but not in an all-comer population. What was also interesting is that the event curves separated early, and the difference was sustained. The question is why this biodegradable polymer stent platform performs better, and whether that relates to a more biocompatible stent design in the setting of a pro inflammatory state during an acute infarct. Whether this difference observed is due to the polymer itself, the type of drug or the strut design is unclear. One piece of data that is missing and would have been insightful is the use of intra coronary imaging between groups as any differences in use may have had an impact on the outcome. Although the results may not be as impactful as historical trials comparing bare-metal and second- generation DES, there is a signal that stent design may need to be tailored to differing populations.

ARREST does not support transfer to dedicated cardiac centres in OOHCA.

Expedited transfer to a cardiac centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomized clinical trial.

Lancet 2023; 402:1329-1337

Despite technological advances in management of post cardiac arrest patients, including targeted temperature management and multi-organ support including mechanical circulatory support (MCS), out of hospital cardiac arrest (OHCA) is associated with significant mortality. At present in the absence of ST elevation myocardial infarction, patients sustaining an OHCA are transported by the ambulance to the nearest A&E department.  Whether a pathway where OHCA patients are transferred directly to a heart attack or cardiac arrest centre (with the facility for emergent angiography, access to MCS and specialist cardiac intensive care support) improves outcomes is unknown. The ARREST trial was a UK delivered prospective multicentre randomised superiority trial where patients were randomised 1:1 by the London Ambulance Service to either transfer to one of 7 cardiac arrest centres or the closest emergency department (one of 32 centres) in London. Main exclusions to note included a clear non cardiac cause for arrest and patients with STEMI. The primary endpoint was all cause mortality at 30 days. The trial population included a total of 822 patients with majority being male. A cardiac cause for OOHCA was found in 63% of the cardiac arrest centre group and 59% in the standard care group. Time taken to reach the assigned hospital was 7 minutes longer in the standard care group. As expected, there was a higher proportion of patients receiving haemodynamic, renal and ventilatory support, alongside higher invasive coronary angiography rates in the cardiac arrest centre group. Downtimes were similar between groups. 30-day all-cause mortality was no different between groups, both at 63% (unadjusted RR for survival 1·00; 95% CI: 0·90-1·11; p=0·96; risk difference 0·2%; 95% CI: 6·5-6·8). Neurological outcomes were similar at discharge. A sub-group analysis suggested that those under the age of 57 appeared to do better being taken to a cardiac arrest centre, with the converse in those between the ages of 57 and 71. There did not appear to be a differential treatment affect when stratified according to presenting arrest rhythm. ARREST is another neutral trial in this field and adds to the growing body of evidence that advanced therapeutics may not lead to better clinical outcomes. Instead, effective CPR, timely defibrillation, remain the cornerstone of treatment for OOHCA patients.

MIRACLE₂ outperforms downtime in OOHCA patients.

MIRACLE₂ score compared with downtime and current selection criterion for invasive cardiovascular therapies after OHCA.

JACC Intev 2023; 16:2439-2450

The MIRACLE₂ score is emerging as an important tool to assess futility and aid selection of patients for further advanced therapies who present following an out of hospital cardiac arrest (OHCA). This study assessed the effect of downtime on the primary endpoint of poor neurological outcome in a European multi-centre cardiac arrest registry, and to compare it with the performance of the MIRACLE₂ score. The investigators also modelled the use of the MIRACLE₂ score as compared with current RCT recruitment criteria for resuscitated cardiac arrest (downtime), to assess its utility in guiding future RCT recruitment. 1259 patients from the EURCAR registry were recruited across 6 European heart attack centres. The inclusion criteria for the registry included patients with a confirmed cardiac cause or highly suspicious for a cardiac cause for their arrest. Exclusion for this study were those patients with a GCS of 15/15, those with no documented GCS and those with no documented zero or low flow times. Out of the cohort, 8.1% of patients had a downtime greater than 60 minutes, with a poor neurological outcome (as defined by a cerebral performance category of 3 (severe disability), 4 (persistent coma), or 5 (death)). Out of these patients, 84.3% of patients died, and 91.1% of patients had poor neurological outcome. In those with downtime less than 30minutes, poor neurological outcome occurred in 41.8%, with an overall morality of 30.3%. Majority of patients were male (77.9%) with an average age of 62.9 years. A large proportion of patients (76.8%) had an initial shockable rhythm and 47.1% had SCAI cardiogenic shock classification of C to E. Overall hospital mortality was 43.9% and poor neurological outcome occurred in 56.3%. The median downtime was 25 minutes. Those patients with a downtime of greater than 30 minutes were more likely to have an unwitnessed cardiac arrest, less likely to have an initial shockable rhythm and were more likely to require adrenaline. Those with a longer downtime were more likely to be in SCAI CS C to E. Downtime had less of an impact on the primary outcome when patients were stratified by their MIRACLE₂ score, seen both in those with a low MIRACLE₂ score (where even those patients with a downtime of greater than 60 minutes had a lower rate of poor neurological outcome) and those with a high MIRACLE₂ (where a shorter downtime had less of an effect on outcome). In a multi variable analysis, the MIRACLE₂ score demonstrated the strongest association with outcome as compared with total downtime and its components. Finally, when modelled for exclusion from study recruitment, a MIRACLE₂ score ³5 had the highest positive predictive value (0.92) when compared with exclusion criteria for CULPRIT-SHOCK (0.80), EURO-SHOCK (0.74) and ECLS-SHOCK (0.81), p<0.001. This study appears to suggest that the duration of downtime is a poor discriminator of neurological outcome, and that the MIRACLE₂ score that incorporates detailed presenting characteristics increases the predictive value.

Growing evidence for DEB use.

Drug-coated balloon angioplasty for de-novo lesions on the left anterior descending artery.

Circ Cardiovasc Intv 2023; 16:e013232

Drug coated balloons (DCBs) have been shown to be efficacious in the treatment of in stent re-stenosis and in de-novo small vessel disease, but data on their outcomes in the treatment of large vessel disease is sparse. Theoretically, DCBs would allow either complete avoidance or reduction in the length of metal implanted, whilst potentially mitigating the risk of future restenosis, particularly in long and diffuse disease. The authors in their retrospective analysis sought to assess the impact of DCB use in de-novo disease in the LAD. They retrospectively included all consecutive patients undergoing PCI involving DCBs in the LAD between 2018 and 2022, compared with consecutive patients receiving DES between 2010 and 2018 from two Italian centres. Exclusion criteria were those patients that received short stents <23mm in length and in stent re stenosis. A mixture of different DCBs were used with differing anti-proliferative drugs and delivery systems. Bail out stenting occurred in around 30% of DCB cases, and patients who received a hybrid approach (DCB and DES) were included in the DCB group. The primary endpoint was incidence of target lesion failure, which was a composite of cardiac death, target vessel myocardial infarction and target lesion revascularization. Propensity scoring matching was performed to reduce the impact of confounders, resulting in 139 matched pairs. In the DCBs recruitment period, 147 patients underwent DCB PCI in de-novo lesions in the LAD. 701 patients undergoing DES PCI were included in the analysis. In terms of the baseline characteristics, the DCB group had a higher proportion of prior PCI and multi vessel disease. Patients in the DES group were more likely to have LV systolic dysfunction and proximal LAD treated. The length of vessel treated was higher in the DCB group. Only 29.2% of the DCB group received DCB alone. Bail out stenting occurred in around 30.2% of cases due to flow limiting dissections. IVUS was more likely to be used in the DCB group. In the original population, there was no difference in the 2-year incidence of target lesion failure. Following propensity score matching, the DCB group had lower rates of target lesion failure (HR, 0.2; 95% CI: 0.07–0.58; p=0.003), target lesion revascularisation (HR, 0.24; 95% CI: 0.08–0.72; p=0.011), and target vessel failure (HR, 0.39; 95% CI: 0.19–0.83; p=0.014). In both the unmatched and matched data sets for both target lesion failure and target lesion revascularization the Kaplan-Meier curve for DCB had an incremental increase just over 6 months then the rates plateau. There were no significant adverse events with DCB use with small residual dissections not resulting in any safety signals. Salient features include observational nature of the study; DES patients were enrolled across a longer and earlier time period, and lack of distinction between clinically driven versus non-clinically driven revascularization.

Valvular Heart Disease

New horizon for transcatheter MV intervention.

5-year prospective evaluation of mitral valve-in-valve, valve-in-ring, and valve-in-MAC outcomes. MITRAL trial results.

JACC Intv 2023; 16:2211-2227

Repeat mitral valve surgery is associated with greater morbidity and mortality as compared to the first operation. Transcatheter mitral valve replacement (TMVR), either via the transeptal or transapical route, has emerged as a novel treatment modality for high-risk surgical patients presenting with degenerated bioprostheses, failed surgical repairs with annuloplasty rings, or native mitral valve disease with severe mitral annular calcifications (MAC). The MITRAL (Mitral Implantation of Transcatheter Valves) was a prospective trial that evaluated the safety and efficacy of the SAPIEN 3, and SAPIEN XT transcatheter heart valves (THV) in patients with failed bioprostheses, failed rings, or severe MAC. The two-year outcomes showed survival rates of 93.9% in patients undergoing MViV, 50% in patients undergoing MViR, and 60.7% in patients undergoing ViMAC. There was significant improvement in functional class, and valve function remained stable. The current manuscript reports the final 5-year results. Between February 2015 and December 2017, 91 patients underwent TMVR (MViV=30, MViR=30, and ViMAC=31) across 13 sites in the US. The primary end points were clinical effectiveness, THV performance, and a primary safety end point (all-cause mortality). In the MViV group, mean age was 76±10 years, 63% were women, median LVEF was 56%, median baseline neo-LVOT area was 330mm², and mean STS score was 10.2% ± 6.5%. All-cause mortality was 21.4%, 14.3% had had a stroke, 28.6% required hospitalization for heart failure, 3.6% required MV reintervention, 3.6% developed subclinical valve thrombosis due to subtherapeutic INR, and there were no cases of endocarditis. There was a significant improvement in functional status with 94.7% in NYHA class I or II and KCCQ median score 51 at 5 years. The mean MVG (6.6 ± 2.5 mmHg) and estimated PASP (46.1 ± 16.5) at 5 years remained unchanged from year 1. Grade 1+ MR was present in 15.8% and all had no or trace paravalvular MR. In the MViR group, mean age was 72 ± 9 years, 37% were women, median LVEF was 47%, median baseline neo-LVOT area was 440 mm², and mean STS score was 8.7% ± 4.7%. All-cause mortality was 65.5%, 6.9% had had a stroke, 34.5% were hospitalized for heart failure, and there were no new additional cases of mitral valve intervention, valve thrombosis or endocarditis. NYHA class I or II status had fallen from 76.9% at 2 years to 50% at years but KCCQ score remained stable. The mean MVG (5.8 ± 0.1 mmHg) and estimated PASP (43.0 ± 26.9 mmHg) remained unchanged from 2 years. In the ViMAC group, mean age was 75 ± 8 years, 71% were women, median LVEF was 63%, baseline neo-LVOT area was 160mm², and mean STS score was 8.6% ± 8.2%. All-cause mortality was 67.9%, 17.9% had had a stroke, 17.8% required MV reintervention, and 42.9% were hospitalized for heart failure.  One episode of endocarditis was identified at 3 years and 1 more at years. 55.6% of patients were in NYHA class I or II and KCCQ score remained stable at 5 years. The mean MVG (6.7 ± 2.5 mmHg) and PASP (46.3 ± 18.6 mmHg) was unchanged from 1 year. In summary, THVR provides a safe and effective therapy in high-risk surgical risks who require reintervention for a wide range of mitral valve disease.

Growing evidence for TAVI in low-risk patients.

Transcatheter aortic valve replacement in low-risk patients at 5 years.

NEJM 2023; 389:1949-1960

The PARTNER 3 trial has shown that in low-risk patients, TAVR was superior to SAVR in reducing death, stroke, or rehospitalization. The current manuscript reports on the 5-year outcomes of the study. Briefly, the trial randomized a total of 1000 patients to either TAVR using the SAPIEN 3 valve (n=503) or SAVR (n=497). Low-risk was defined as STS risk of 30-day mortality <4%. Mean age of the participants was 73 years, 30% were female, and 31% were diabetic. Key inclusion criteria were symptomatic severe AS and suitability for transfemoral access. Key exclusion criteria included frailty, bicuspid AV, LVEF<30%, MI with 1 month, stroke or TIA within 90 days, concomitant significant MR or MS, concomitant complex CAD, severe lung disease or pulmonary hypertension or BMI exceeding 50 kg/m². The first primary endpoint was a composite of death, stroke, or rehospitalization related to the valve, the procedure, or heart failure. The second primary endpoint was a hierarchical composite that included death, disabling stroke, nondisabling stroke, and number of rehospitalization days analysed with the use of a win ratio analysis. At 5 years, a component of the first primary endpoint occurred 111 of 496 patients in the TAVR group and 117 of 454 patients SAVR group (KM estimates, 22.8% vs. 27.2%; difference -4.3 percentage points; 95% CI: -9.9-1.3; p=0.07). The win ratio for the second primary endpoint was 1.17 (95% CI: 0.90-1.51; p=0.25). The KM estimates for the components of the primary endpoint in the TAVR and SAVR were death (10% vs.  8.2%; p=0.35), stroke (5.8% vs 6.4%; p=0.60) and rehospitalization (13.7% vs. 17.4%; p=0.09). Other parameters in the TAVR and SAVR group included AF (13.7% vs. 42.4%; p<0.5), serious bleeding (10.2% vs 14.8%; p<0.05), valve thrombosis (2.5% 0.2%; p<0.05) repeat aortic valve intervention (2.6% vs. 3.0%; p=0.72), paravalvular regurgitation ≥ mild (20.8% vs. 3.2%; p<0.05) and mean transvalvular gradient (12.8mmHg vs. 11.7mmHg; p<0.001). In summary, in low-risk patients undergoing TAVR or SAVR, there were no significant between-group differences in the two primary composite endpoints.

Bleeding remains a challenge in TAVI patients.

Bleeding in patients undergoing transfemoral transcatheter aortic valve replacement: incidence, trends, clinical outcomes, and predictors.

JACC Intv. 2023; 16:2951-2962

Bleeding remains one of the most common complications associated with TAVR, in part related to pre-existing comorbidities and in-part related to procedural characteristics. The current study examined the incidence, temporal trends, clinical outcomes and predictors of bleeding complications in participants of the CENTER2 study undergoing TAVR between 2007-2022. The CENTER2 study consists of 25,771 patients undergoing TAVR of whom 24,321 underwent transfemoral TAVI. The incidence of 30-day bleeding was available in 23,562 patients (96.9%). All overt bleeding events were defined according to VARC-2 definition. The mean age was 81.5±6.7 years, 56% were women, mean STSPROM was 4.9%, balloon expandable valves were used in 43%, 58% were treated using the newer generation valves, and median follow-up was 365 days. Major bleeding occurred in 6.6% within the first 30 days after TAVR. Of these, 29.4% were classified as life-threatening. Minor bleeding was observed in 4.7%. Rates of major bleeding decreased from 11.5% in 2007-2010 to 5.5% in 2019-2022 (P_trend <0.001). The incidence of minor bleeding did not change significantly from 9.9% in 2007-2010 to 4.3% in 2019-2022 (P_trend=0.75). The incidence of major bleeding within 30 days after TAVR was higher in women (8.0% vs. 5.5%; OR: 1.48; 95% CI: 1.33-1.65; p<0.001). Patients with intermediate and high surgical risk reported higher rates of major bleeding compared to those with low surgical risk (7.1% vs. 6.8% vs. 5.4%; p=0.002). Rates of major bleeding was similar in patients with or without history of atrial fibrillation or in patients with previous history of PCI although minor bleeding was more common in patients with atrial fibrillation (6.0% vs 5.2%; OR: 1.18; 95% CI: 1.03-1.34; p=0.02). Patients with previous history of PVD had higher incidence of major bleeding (9.0% vs. 6.2%; OR: 1.39; 95% CI: 1.20-1.61; p<0.001) and minor bleeding (6.5% vs. 5.3%; OR: 1.24; 95% CI: 1.05-1.47; p=0.01). Dual antiplatelet therapy at baseline was associated with higher rates of 30-day major bleeding compared with single antiplatelet therapy (12.2% vs. 9.1%; OR: 1.40; 95% CI: 1.13-1.72; p=0.002). Patients on oral anticoagulants interrupted before the procedure did not have increased risk of major bleeding as compared to those on antiplatelet therapy. As compared to patients without major bleeding, patients with major bleeding had a higher mortality risk during the first 30 days (14.1% vs. 4.3%; OR: 3.66; 95% CI: 3.11-4.31; p<0.001) and during 1-year follow-up (27.8% vs. 14.5%; HR 1.50; 95% CI: 1.41-1.59; p<0.001). Patients with major bleeding surviving the first 30 days after TAVR remained at increased risk of mortality during the first year (HR: 1.20; 95% CI: 1.08-1.32; p<0.001). Patients with major bleeding had higher rates of other adverse outcomes including major vascular complications (10.9% vs. 0.3%; p<0.001), minor vascular complications (37.9% vs. 6.2%; p<0.001), and a longer hospital stay (9 days vs. 6 days; p<0.001). Access site bleeding represented 70% of major bleeding complications. Other bleeding sites included pericardium, GI, urogenital tract, and intracranial. Multivariate predictors of major bleeding within 30 days after TAVR were female sex, BMI, PVD, and the use of older generation valves.

Two equally effective devices for mTEER.

1-year outcomes from the CLASP IID randomized trial for degenerative mitral regurgitation.

JACC Intv 2023; 16:2803-2816

Mitral transcatheter edge-to-edge repair (mTEER) utilising the PASCAL (Edwards Lifesciences) or the MitraClip device (Abbott Vascular) are now established therapies for patients with severe symptomatic degenerative MR (DMR) who are considered high-risk for conventional cardiac surgery. The CLASP IID trial is the first randomized controlled trial comparing clinical outcomes with the PASCAL system and MitraClip system in prohibitive-surgical risk patients with severe symptomatic DMR. Eligible patients had 3+ or 4+ DMR, were classified as prohibitive-surgical risk by the local heart team and were deemed candidates for mTEER. Patients were randomized either to the PASCAL system (n=204) or MitraClip system (n=96) in a 2:1 ratio. Noninferiority of the PASCAL system compared with the MitraClip system was assessed for the primary and secondary endpoints. The primary safety endpoint was the composite major adverse event (MAE) rate at 30 days comprising CV mortality, stroke, MI< new need for renal replacement therapy, severe bleeding, and non-elective mitral valve intervention (either percutaneous or surgical). The primary effectiveness endpoint was the proportion of patients with MR ≤2+ at 6 months. The secondary effectiveness endpoints were MR ≤2+ and MR ≤1+ rates at 1 year. Additional endpoints at 1-year included functional and quality-of-life outcomes such as 6-minute walk distance, KCCQ score, and EQ-5D-5L visual analog score. Mean age was 81 years, 66% were men, mean STS score was 5.5, 65% were in NYHA class III/IV, and comorbidities were common including AF (57%), cardiomyopathy (19%), renal impairment (38%), and diabetes (19%). Successful implantation rate was 98.5% in the PASCAL and 98.9% in the MitraClip group (p=1.0). The mean number of devices implanted was lower in the PASCAL group (1.4 vs. 1.6; p=0.022). The 30-day composite MAE rate was comparable in the PASCAL and MitraClip group and met the set noninferiority margin (4.6% vs. 5.4%; absolute difference -0.8%). The MAE for the PASCAL group consisted of 1 (0.5%) CV death, 1 (0.5%) stroke, 7 (3.6%) severe bleeding, and 3 (1.5%) non-elective mitral valve reintervention. In the MitraClip group, the 30-day composite MAE consisted of 2 (2.2%) CV death, 1 (1.1%) stroke, 1 (1.1%) MI, 2 (2.2%) severe bleeding, and 1 (1.1%) non-elective mitral valve reintervention. MR ≤2+ at 6 month in the PASCAL and MitraClip group were similar (97.9% vs. 95.7%; absolute difference 2.2%) and met the noninferiority margin. The PASCAL system was noninferior to the MitraClip system with regards to 1-year rates of MR ≤2+ and MR ≤1+. At year, there was no difference between the two groups for other key secondary endpoints including death, stroke, and heart failure hospitalization. The Kaplan-Meier estimates for freedom from MAE at 1 year were similar in the PASCAL and MitraClip group (84.7% vs. 88.3%; p=0.47). Freedom from CV mortality (96.3% vs. 92.6%; p=0.16), heart failure hospitalization (91.9% vs. 96.7%; p=0.14) were similar in the PASCAL and MitraClip group. Significant improvements in functional classification and quality of life were sustained in both treatment groups (p<0.001 for all vs baseline).

Increasing support for mitral transcatheter valve-in-valve intervention.

Cardiac reoperation or transcatheter mitral valve replacement for patients with failed mitral prostheses.

JACC 2024; 83:317-330

The utilization of a bioprosthesis in patients undergoing surgical mitral valve replacement (SMVR) has increased over time from 16.8% in 1996 to 75.8% in 2016. Bioprostheses degenerate over time so that approximately one third of such patient will require intervention over the subsequent 10 years. Transcatheter mitral valve replacement (TMVR) has emerged as an attractive treatment alternative to SMVR but its short and mid-term outcomes and the association between case volume and outcome have not been adequately addressed. The current study addressed this knowledge gap by analysing data from Medicare beneficiaries aged ≥65 years who had undergone either redo SMVR (rSMVR) or TMVR between January 2016 and December 2020. Key exclusion criteria were patients who had undergone concomitant CABG, AVR, and tricuspid valve intervention. The primary endpoint was mid-term (up to 3 years) MACE defined as a composite of all-cause death, heart failure hospitalization, stroke, and reintervention. The secondary endpoint were in-hospital outcomes and individual components MACE. In a population of 4,293 eligible patients, 64% received rSMVR and 36% received TMVR. The median follow-up period was 18 months. Over the study period, the number of rSMVR cases fell (186 cases in Q1 2016 to 125 cases in Q4 2020; p=0.02), whilst the number of TMVR increased (38 cases to 117 cases; p<0.001). Patients who underwent TMVR were older (78 years vs. 73 years; p<0.001), more likely to be female (60% vs. 53.5%; p<0.001) and had a higher Charlson Comorbidity Index score was significantly higher in the TMVR group (5 vs. 6; p<0.001). Independent predictors for undergoing TMVR for a failed mitral bioprosthesis included older age, female sex, prior CABG/PCI, congestive heart failure, COPD, liver disease, dementia, and Charlson Comorbidity Index score ≥5. After propensity score matching, the Kaplan-Meier estimate of patients who received TMVR and rSMVR were similar (44% vs. 44%; p=0.2). On landmark analysis at 6 months, TMVR was associated with a lower risk of MACE in the initial 6 months (aHR: 0.75, 95% CI: 0.63-0.88; p<0.001) but a higher risk of MACE beyond 6 months (aHR: 1.28, 95% CI: 1.04-1.58; p=0.02). Increased procedural volume was associated with decreased risk of mid-term MACE after rSMVR (p=0.001) but not after TMVR (p=0.3). Interestingly, >80% of the institutions performed <10 cases of each procedure during the study period.

Enduring health benefits of tTEER.

Health status after transcatheter tricuspid valve repair in patients with severe tricuspid regurgitation.

JACC 2024; 83:1-13

The TRILUMINATE trial has shown that tricuspid transcatheter edge-to-edge repair (tTEER) is effective in reducing tricuspid regurgitation (TR) in patients with severe symptomatic TR, had no effect on reducing mortality or heart failure hospitalization at 1 year, and improved patient-reported health status as compared to medical therapy. The current manuscript addressed the timing and magnitude of the health status benefits of tTEER. The mean age of the analytic group was 78±7 years, 55% were women, 12% had chronic pulmonary disease, TR was severe in 28%, massive in 19%, and torrential in 51%. Both disease specific and generic health status were impaired at baseline. Mean KCCQ-OS score at baseline was 55.8±23.6, with the lowest domain score being QoL at 48.2±26.3. Mean SF-36 PCS was 35±10and mean SF-36 MCS was 46.9±12.4. In patients randomized to tTEER, the KCCQ-OS score increased by an average of 14.3 points by 1 month. All KCCQ domains improved by 1 month with the largest change occurring in the QoL domain (mean change 19.8 points; 95% CI: 16.7-25 points). Scores on the SF-36 PCS (4.9 points; 95% CI: 3.5-6.1 points) and MCS (2 points; 95% CI: 0.1-3.3 points) also increased at 1 month and were sustained at 1 year. In patients randomized to medical therapy, the KCCQ-OS increased by 4.8 points (95% CI: 2-6.8 points) and was maintained at 1 year. The SF-36 PCS and MCS scores did not change significantly. In patients who survived at 1 month, patients in the tTTER had a greater improvement in the KCCQ-OS as compared to medical therapy alone (mean between group difference 9.4 points; 95% CI: 5.3-13.4; p<0.001) with smaller improvements at 6 6 months (mean between group difference 11.2 points; 95% CI: 7.1-15.4; p<0.001) and 1 year (mean between group difference 10.4 points; 95% CI: 6.3-14.6; p<0.001). As compared to medical therapy, tTEER was associated with greater benefit for each of the KCCQ domains, with the largest improvements being observed for QoL and Social Limitations domains. tTEER was associated with. Modest benefits on the SF-36 PCS at 1 year and no significant benefit on SF-36 MCS. At both 1 month and 1 year, more patients in the tTEER group had improvements in KCCQ-OS scores and fewer patients deteriorated from baseline compared with medical therapy. When combining survival and health status outcomes, more patients in the tTEER group were alive with a large health status improvement at 1 year (41.5% vs. 15.5%; NNT=3.9; 95% CI: 2.8-6.7 points). The tTEER group were also more likely to be alive and well at 1 year (74.8% vs. 45.9%; NNT=3.5; 95% CI: 2.5-5.5). Exploratory analyses indicated that much of the health status benefit of tTEER could be explained by reduction in TR severity and that health status after tTEER was correlated with reduced 1-year mortality and heart failure hospitalization.

A novel therapeutic strategy for severe AS.

Treatment of severe symptomatic aortic valve stenosis using non-invasive ultrasound therapy: a cohort study.

Lancet 2023; 402:2317-2325

TAVI has become the standard of care for patients with severe aortic stenosis who are deemed to have a high surgical risk. However, there is a cohort of patients that are unsuitable for TAVI, either due to significant co-morbidities, lack of vascular access or anatomical position of the coronaries. Non-invasive ultrasound therapy (NIUT) delivered by the Valvesoft device (Cardiawave, Levallois-Perret, France) is a new technology that delivers precise and focused ultrasound pulses at a high acoustic intensity to the aortic valve through the chest wall. It does this with real time ultrasound imaging. The energy delivered by the device acts on calcific tissues, producing dense energetic cavitary bubble clouds which theoretically soften the aortic valve leaflets when the bubbles collapse. A feasibility and safety study has been performed in a swine model confirming that non diseased tissues are not affected, and the investigators report in this article the first in human single arm study of this device. 40 patients were recruited between March 2019 and May 2022 from three centres in France, Serbia and The Netherlands. Patients with severe symptomatic aortic stenosis not deemed suitable for either surgical AVR or TAVI were included. Exclusion criteria were the presence of an implanted electrical device, unstable arrythmia, valve prosthesis in the aortic position, chest deformity and intracardiac thrombus. All patients underwent at least one NIUT session of a maximum of 60 minutes, usually divided into six period of 10 minutes, with periprocedural monitoring including ECG, blood pressure and saturation monitoring. The primary safety endpoint for the study was procedure related death for up to 30 days, and the primary efficacy endpoint was the effect of the device in reducing the mean transaortic pressure and increasing the valve area (AVA). Follow up data was obtained at 6 months. The mean age of patients was 83.5 ±8.4 years with a mean STS score of 5.6% (4±4.4). Two patients had a bicuspid aortic valve.  22 patients had low flow low gradient aortic stenosis, of which 17 had paradoxical low flow low gradient AS. Overall the mean LV ejection fraction was 53% (±10) and the mean peak velocity was 4.1m/s (±0.9).  Out of the 40 patients that underwent NIUT, only one had a serious procedure related adverse event, whereby saturations transiently dropped related to morphine administration with full recovery. Non serious procedure related events included pain and transient but not sustained arrhythmias. There was no procedure related death up to 30 days. 3 patients underwent an additional NIURT procedure. Overall survival at 6 months was 72.5%. No episodes of stroke were reported. A sub study looking at pre procedure and post procedure MRI brains published previously did not demonstrate any new ischaemic intra cerebral lesions. Overall, the AVA increased by 10% (from 0·58cm2[±0·18] to 0·64cm2 [±0·21]; p=0·0088) and the mean pressure gradient decreased by 7% (41·9±20.1 mmHg to 38·8± 17.2 mmHg; p=0·024). There was a reported improvement in NYHA class in 68% of patients at 6 months. Observationally the patients with a bicuspid valve appeared more responsive to treatment. Allowing for the sample size, the study appears to indicate that the therapy may be safe, well tolerated, and improves haemodynamic parameters.