ACC.19: Trials on Valvular Heart Disease
1. PARTNER 3 (Placement of Aortic Transcatheter Valves 3)
Presented by Martin Leon, MD, and Michael Mack, MD
Is transcatheter aortic valve replacement (TAVR) using a balloon expandable valve non-inferior to surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS) who are at low surgical risk?
- 1,000 low surgical-risk patients (Society of Thoracic Surgeons [STS] < 4%) underwent 1:1 randomization to receive TAVR (SAPIEN 3 valve [Edwards Lifesciences; Irvine, CA]) or SAVR.
- Follow-up occurred at 30 days and 6 months and is planned annually through 10 years.
- Primary outcome was non-hierarchical composite all-cause mortality, stroke, or cardiovascular rehospitalization at 1 year post-procedure.
- Inclusion criteria follow:
- Low surgical risk (STS < 4%)
- Aortic valve area ≤1.0 cm2 or aortic valve area index ≤0.6 cm2/m2
- Aortic valve peak velocity ≥4.0 m/s or mean gradient ≥40 mmHg and
- New York Heart Association Class ≥ II or
- abnormal exercise stress test or
- left ventricular ejection fraction (LVEF) <50%
- Primary statistical analysis was non-inferiority (margin 6%) followed by superiority (if non-inferiority met, using two-sided alpha = 0.05).
- Analysis cohort was the as-treated cohort.
- 503 patients randomized to TAVR and 497 patients to SAVR.
- The final cohort from intention-to-treat to as-treated: TAVR = 496, SAVR = 454.
- Baseline characteristics were not different except for the proportion of patients with New York Heart Association Class III or IV: 31.3% in TAVR versus 23.8% in SAVR.
- Median length of stay was 3 days in TAVR versus 7 days in SAVR (p < 0.001).
- Discharge to home/selfcare occurred in 96% of TAVR group versus 73.1% of SAVR group.
- In-hospital mortality occurred in 0.4% of TAVR versus 0.9% of SAVR.
- At 1 year, the primary endpoint occurred in 8.5% of the TAVR group versus 15.1% of the SAVR group, hazard ratio (HR) 0.54 (95% confidence interval [CI] 0.37, 0.79) meeting non-inferiority (p < 0.001) and superiority (p = 0.001). Similar findings were observed in the intention-to-treat sensitivity analysis.
- All-cause mortality at 1 year was 1.0% in TAVR versus 2.5% in SAVR, HR 0.41 (95% CI 0.14, 1.17), p = 0.09.
- All stroke at 1 year occurred 3.1% of the SAVR group versus 1.2% of the TAVR group.
- Moderate or more paravalvular regurgitation at 1 year occurred in 0.6% of TAVR versus 0.5% of SAVR, p = 1.00.
- In patients with severe symptomatic AS who are at a low surgical risk, TAVR reduced the primary endpoint of death, stroke, or rehospitalization by 46% at 1 year.
- The trial suggests that TAVR should be the preferred strategy in low-surgical-risk patients with severe AS. However, long-term outcomes are needed. The trial committee plans to follow randomized patients up to 10 years.
- Notable patients who were excluded from this trial were those with bicuspid aortic valve (BAV), complex coronary disease, and severe multivalve disease.
2. Evolut Low Risk (Evolut Surgical Replacement and Transcatheter Aortic Valve Implantation in Low Risk Patients)
Presented by Michael Reardon, MD
Is TAVR using a self-expandable valve non-inferior to SAVR in patients who are at low surgical risk?
- 1,468 patients were randomized. In the intention-to-treat analysis, 734 patients had SAVR and 734 had TAVR.
- Mean STS risk score was 1.9 ± 0.7 in both groups.
- Primary endpoint was a composite of death or disabling stroke at 24 months, using Bayesian methods.
- Primary endpoint was met, TAVR (outcome 5.3%) was non-inferior to SAVR (outcome 6.7%), difference of -1.4 percentage points; 95% Bayesian credible interval for difference was -4.9 to 2.1, posterior probability >0.999.
- All-cause mortality occurred in 0.5% of TAVR versus 1.3% of SAVR (95% CI -1.9, 0.2)
- At 30 days, TAVR group had less disabling stroke (0.5% vs. 1.7%), acute kidney injury (2.4% vs. 7.5%), atrial fibrillation (7.7% vs. 35.4%), and bleeding complications (2.4% vs. 7.5%) and SAVR had less need for pacemaker implantation (6.1% in SAVR vs. 17.4% in TAVR).
- TAVR in low surgical-risk patients with severe AS was non-inferior for all-cause mortality and disabling stroke and had fewer complications except for the need for a pacemaker.
- Longer-term follow-up is needed. However, data are reassuring that TAVR performance compared with SAVR is independent of surgical risk.
3. COAPT-QoL (Health Status After Transcatheter Mitral Valve Repair in Patients With Heart Failure and Secondary Mitral Regurgitation)
Presented by Suzanne V. Arnold, MD, MHA
What are the early and late health status outcomes of MitraClip (Abbott; Abbott Park, IL) versus standard care in patients with secondary mitral regurgitation (MR)?
- COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) was a multi-center, open-label randomized controlled trial of patients with heart failure (HF) and 3+/4+ secondary MR who remained symptomatic despite optimal medical therapy.
- Patient reported health status assessed at 1, 6, 12, and 24 months using the following:
- Kansas City Cardiomyopathy Questionnaire (KCCQ)
- SF-36 Physical and Mental Summary Scores
- Primary outcome was KCCQ-overall summary score (KCCQ-OS) over 24 months.
- Main statistical analysis was done using piecewise linear regression (patients who died of HF had their KCCQ-OS imputed to the worst observed value).
- Baseline health status was not different between both groups (KCCQ-OS was 53.2 ± 22.8 in the MitraClip group vs. 51.6 ± 23.3 in the standard-of-care group).
- Over 24 months, there was a 12.8-point difference in the KCCQ-OS in favor of the MitraClip group (p < 0.001).This benefit was true for all domains of the KCCQ (physical limitations, quality of life, total symptoms, and social limitations).
- At 24 months, MitraClip had substantial benefit in terms of symptoms, functional status, and quality of life.
- COAPT had strict criteria for optimal therapy and inclusion of patients in the trial. Whether these findings will be replicated in routine clinical care is yet to be evaluated.
4. Echocardiographic Outcomes From the COAPT Trial
Presented by Federico M. Asch, MD
- What are the echocardiographic MR grading criteria utilized in COAPT for screening and post-MitraClip?
- What are the echocardiographic characteristics of the COAPT population?
- What are the serial echocardiographic outcomes in the COAPT trial?
- What are the baseline echocardiographic predictors of clinical outcomes (responders and non-responders to MitraClip)?
- Transthoracic echocardiography was done at baseline and 1, 6, 12, 18, and 24 months during the trial (designed to continue to 5 years).
- The severity of MR (being 3+ or 4+) was graded using 3 criteria:
- Effective regurgitant orifice area (EROA) ≥0.3 cm2 or pulmonary vein systolic flow reversal (n = 570 or 85.7% of patients)
- EROA of 0.2 to <0.3 cm2 with one of the following: regurgitant volume ≥45 ml/beat, regurgitant fraction ≥40%, or vena contracta ≥0.5 cm (n = 70 or 10% of patients)
- EROA not measured or <0.2 but other supporting criteria present (n = 25 or 3.8% of patients)
- Baseline echocardiographic characteristics were not different between both groups.
- Left ventricular end diastolic volume increased a mean of 54.9 ml in the medical therapy group versus 13.8 ml in the MitraClip group, p < 0.05.
- LVEF declined in both groups (-8.3% in medical therapy group vs. -7.5% in the MitraClip arm).
- At 24 months, 99% of the patients in the MitraClip arm had mild (77.2%) or moderate (21.9%) MR compared with 43.4% (15.8% mild, 27.6% moderate) of the medical therapy group, p < 0.001.
- Regarding MR grading, proximal isovelocity surface area and hemodynamics after MitraClip have major limitations. Color Doppler, pulmonary vein flow, and vena contracta are the most available and reliable methods.
- In patients with HF and 3+ or 4+ secondary MR, transcatheter mitral valve repair with MitraClip provided substantial death and HF benefits in all echocardiographic subgroups, regardless of degree of left ventricular dysfunction, left ventricular dimensions, pulmonary hypertension, severity of tricuspid regurgitation or individual MR parameters (all responders).
- Baseline LVEF, tricuspid regurgitation, and MR severity predicted poor outcomes in patients with HF treated with guideline-directed medical therapy alone, but not after MR was corrected by MitraClip.
- Right ventricular systolic pressure was the only independent echocardiographic predictor of poor outcomes after MitraClip and guideline-directed medical therapy treatments.
MitraClip appears to be an excellent option to treat secondary MR across all echocardiographic subgroups.
5. POET (Partial Oral Treatment of Endocarditis)
Presented by Henning Bundgaard, MD
In stabilized patients with infective endocarditis, can oral antibiotics have similar efficacy and safety compared with continued intravenous (IV) antibiotics?
- POET is a nationwide, non-inferiority randomized study including all Danish heart hospitals.
- A specific plan for oral antibiotics was developed for this study and compared with using the European Society of Cardiology guidelines for IV antibiotics.
- Specific inclusion criteria follow:
- Left-sided endocarditis based on the modified Duke criteria caused by streptococci or enterococcus faecalis or staphylococcus aureus or coagulase-negative staphylococci
- ≥10 days of IV antibiotic treatment and ≥1 week after valve surgery
- Tempurature <38.0 °C (<100.4 °F) >2 days
- C-reactive protein dropped to ≤25% of peak value or <20 mg/L
- White blood cell count <15 x 109/L
- No sign of abscess formation by transesophageal echocardiography ≤48 hours of randomization
- Follow-up for all participants was at 6 months, and then longer-term follow-up occurred with a range of 10-85 months.
- Primary endpoint was a composite endpoint at 6 months of all-cause mortality, unplanned cardiac surgery, embolic event confirmed by imaging, or relapse of bacteraemia with the primary pathogen.
- 400 patients randomized to oral (n = 201) versus IV (n = 199) groups.
- Distribution of pathogens in IV versus oral groups: streptococcus (52.3% vs. 45.8%), E. faecalis (23.1% vs. 25.4%), S. aureus (20.1% vs. 23.4%), and coagulase-negative staph (5% vs. 6.6%).
- The primary outome at 6 months occurred in 12.1% of the IV group versus 9.0% of the oral group, difference of 3.1% (95% CI, -3.4% - 9.6%, p = 0.40), which met the prespecified non-inferiority criteria.
- For longer-term follow-up, median follow-up was 3.5 years (interquartile range 2.3-5.1). The composite primary outcome occured in 26.4% of the oral group versus 38.2% of the IV group (HR 0.64; 95% CI 0.45, 0.91). This difference was mainly driven by a difference in all-cause mortality: 16.4% in the oral group versus 27.1% in the IV group (p = 0.009).
- Median length of stay in the IV group was 19 days (14-25) versus 3 days (1-10) in the oral group.
Results are reassuring for efficacy and safety of oral antibiotics in infective endocarditis. Authors estimate that 50% of cases of infective endocarditis in Denmark may be candidates for partial oral antibiotic regimen similar to the trial design.
6. Outcomes of Transcatheter Aortic Valve Replacement With Balloon-Expandable Sapien3 Valve in Bicuspid Aortic Stenosis: An Analysis of the STS/ACC TVT Registry
Presented by Raj Makkar, MD
What are the outcomes of TAVR with balloon-expandable SAPIEN 3 valve (Edwards Lifesciences; Irvine, CA) in native bicuspid versus tri-leaflet aortic valve stenosis in the STS/ACC TVT Registry?
- 2,726 patients with BAV versus 79,096 patients with tri-leaflet aortic valve (TAV).
- BAV patients were younger with lower STS risk score.
- A 1:1 propensity matching was done using 25 variables. This resulted in a 1:1 matched cohort of 2,691 patients in the BAV group and 2,691 patients in the TAV group.
- The matched cohort had no differences in baseline characteristics.
- Primary endpoint was mortality and stroke at 30 days and 1 year.
- Outcomes were obtained from linked Centers for Medicare and Medicaid Services claims data.
- Mean annular size was 25.1 ± 3.2 mm in BAV versus 24.6 ± 3.0 mm in TAV, p < 0.0001.
- 35.2% of BAV patients required a 29 mm valve compared with 26.4% of TAV, p < 0.001.
- Procedural outcomes had similar success rate of about 96.5%. Conversion to surgery occurred in 0.9% of BAV versus 0.4% of TAV, p = 0.03. Annular rupture occurred in 0.3% of BAV versus 0.0% of TAV, p = 0.02.
- At 30 days, all-cause mortality, life-threatening bleeding, major vascular complications, and aortic valve reintervention were not different. However, all strokes were higher in BAV (2.4%) compared with TAV (1.6%), p = 0.02, and rate of pacemaker implantation was higher in BAV (9.1%) versus TAV (7.5%), p = 0.03.
- At 1 year, in the unadjusted analysis, all-cause mortality was 10.4% in the BAV group versus 14.4% in the TAV group (HR 0.75; 95% CI 0.65, 0.87), p < 0.001.
- In the matched cohort, 1-year mortality was 10.5% in BAV versus 12.0% in TAV (HR 0.9; 95% CI 0.73, 1.10), p = 0.31.
- Stroke and paravalvular leak were not different at 1 year between BAV versus TAV in the matched cohort.
It is clear that the outcomes of TAVR in BAV are improving when compared to prior observational studies. However, there are fundamental differences in the characteristics of patients with BAV and TAV. With the prevalence of BAV in the general population, a randomized trial of SAVR versus TAVR in BAV may be needed.
Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Diabetes and Cardiometabolic Disease, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Valvular Heart Disease, Atrial Fibrillation/Supraventricular Arrhythmias, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Cardiac Surgery and VHD, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Heart Transplant, Mechanical Circulatory Support, Interventions and Imaging, Interventions and Structural Heart Disease, Echocardiography/Ultrasound, Mitral Regurgitation
Keywords: ACC Annual Scientific Session, ACC19, Aortic Valve Insufficiency, Aortic Valve Stenosis, Aspirin, Atrial Fibrillation, Cardiac Surgical Procedures, Geriatrics, Heart Failure, Heart Valve Diseases, Heart Valve Prosthesis, Pacemaker, Artificial, Stroke, Transcatheter Aortic Valve Replacement, Vascular Diseases, Acute Kidney Injury, Aortic Valve Stenosis, Atrial Fibrillation, Cardiac Surgical Procedures, Geriatrics, Heart Failure, Heart Valve Diseases, Heart Valve Prosthesis, Pacemaker, Artificial, Stroke, Transcatheter Aortic Valve Replacement, Vascular Diseases, Adrenergic beta-Antagonists, Cardiac Surgical Procedures, Cardiomyopathies, Coronary Artery Bypass, Echocardiography, Geriatrics, Heart-Assist Devices, Heart Failure, Heart Transplantation, Heart Valve Diseases, Mitral Valve Insufficiency, Myocardial Infarction, Myocardial Ischemia, Natriuretic Peptide, Brain, Percutaneous Coronary Intervention, Pulmonary Disease, Chronic Obstructive, Stroke, Stroke Volume, Administration, Oral, Anti-Bacterial Agents, Bacteremia, Cardiac Surgical Procedures, Endocarditis, Endocarditis, Bacterial, Enterococcus, Enterococcus faecalis, Heart Valve Diseases, Primary Prevention, Staphylococcal Infections, Staphylococcus aureus, Streptococcus, Treatment Outcome
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