Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation - COAPT

Contribution To Literature:

Highlighted text has been updated as of July 20, 2023.

The COAPT trial showed that transcatheter mitral valve approximation using the MitraClip on a background of maximally tolerated GDMT was superior to GDMT alone in reducing HF hospitalization and mortality at 5 years in symptomatic HF patients with grade 3-4+ MR.

Description:

The goal of the trial was to assess the safety and efficacy of transcatheter mitral leaflet approximation using MitraClip among symptomatic heart failure (HF) patients with secondary mitral regurgitation (MR).

Study Design

Patients with HF and grade 3-4+ MR who remained symptomatic despite maximally tolerated guideline-directed medical therapy (GDMT) were randomized to MitraClip + GDMT (n = 302) vs. GDMT alone (n = 312). This trial had an open-label design.

  • Total number of enrollees: 614
  • Duration of follow-up: 24 months
  • Mean patient age: 72 years
  • Percentage female: 37%

Inclusion criteria:

  • Ischemic or nonischemic cardiomyopathy with left ventricular ejection fraction (LVEF) 20%-50% and LV end-systolic dimension (LVESD) ≤70 mm
  • Moderate-to-severe (3+) or severe (4+) secondary MR confirmed by an independent echocardiographic core laboratory prior to enrollment (US American Society of Echocardiography criteria)
  • New York Heart Association (NYHA) functional class II-IVa (ambulatory) despite a stable maximally tolerated GDMT regimen and cardiac resynchronization therapy (CRT) (if appropriate), per societal guidelines
  • Patient has had ≥1 HF hospitalization within 12 months and/or a B-type natriuretic peptide (BNP) ≥300 pg/ml or a NT-proBNP ≥1500 pg/ml 
  • Not appropriate for mitral valve surgery by local heart team assessment
  • Interventional cardiologist believes secondary MR can be successfully treated by the MitraClip

Exclusion criteria:

  • American College of Cardiology/American Heart Association stage D HF, hemodynamic instability, or cardiogenic shock 
  • Untreated clinically significant coronary artery disease requiring revascularization
  • Chronic obstructive pulmonary disease (COPD) requiring continuous home oxygen or chronic oral steroid use 
  • Severe pulmonary hypertension or moderate or severe right ventricular dysfunction 
  • Aortic or tricuspid valve disease requiring surgery or transcatheter intervention
  • Mitral valve orifice area <4.0 cm2 by site-assessed transthoracic echocardiography
  • Life expectancy <12 months due to noncardiac conditions     

Other salient features/characteristics:

  • Prior myocardial infarction: 51%, prior percutaneous coronary intervention: 46%, prior coronary artery bypass grafting: 40%, COPD: 23%
  • Society of Thoracic Surgeons Predicted Risk of Mortality score (STS PROM) for replacement: 8.1%, ≥8%: 42%
  • High surgical risk: 69%
  • Ischemic HF: 61%
  • HF hospitalization within 1 year: 57%
  • Prior CRT: 36%
  • Echo (mean): effective regurgitant orifice area (EROA): 0.41 cm2, LVESD: 53 mm, LV end-diastolic dimension: 62 mm, LVEF: 31.3%, tricuspid regurgitation ≥2+: 16%
  • Beta-blockers: 91%, angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker/angiotensin receptor–neprilysin inhibitor: 66%, mineralocorticoid receptor antagonist: 50%

Principal Findings:

The primary effectiveness endpoint, HF hospitalization at 24 months for MitraClip + GDMT vs. GDMT, was 35.8% vs. 67.9% (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.40-0.70, p < 0.001). The primary safety endpoint, freedom from device-related complications at 12 months, was 96.6% for MitraClip (p < 0.001).

Secondary outcomes for MitraClip + GDMT vs. GDMT:

  • All-cause mortality: 29.1% vs. 46.1%, HR 0.62, 95% CI 0.46-0.82, p < 0.001
  • Death or HF hospitalization: 45.7% vs. 67.9%, p < 0.001
  • Cardiovascular death: 29.1% vs. 46.1%, p < 0.001
  • Stroke: 4.4% vs. 5.1%, p = 0.93
  • LV assist device (LVAD) or heart transplant: 4.4% vs. 9.5%, p = 0.01
  • Mean change in LV end-diastolic volume (LVEDV) at 1 year compared with baseline: -3.7 vs. 17.1 mm
  • MR severity ≤2% at 24 months: 99.1% vs. 43.4%, p < 0.001
  • MR severity improved by ≥2 grades: 84.1% vs. 15.9%, p < 0.0001
  • Tricuspid regurgitation severity worsened: 17.7% vs. 16.1%, p = 0.34

On echo subanalysis, it appeared that PISA and hemodynamics after MitraClip had limitations, while color Doppler, pulmonary vein flow, and vena contracta were more reliable to assess residual MR.

Quality-of-life (QoL) subanalysis:

  • Mean Kansas City Cardiomyopathy Questionnaire (KCCQ)-OS (overall summary) at baseline for MitraClip + GDMT vs. GDMT: 53.2 vs. 51.6; mean KCCQ-QoL: 45.2 vs. 44.7
  • At 24 months, mean KCCQ-OS: 70.9 vs. 61.2, p < 0.01; mean KCCQ-QoL: 71.6 vs. 58.5, p < 0.05
  • Alive and moderately improved at 24 months: 36.4% vs. 16.6%, p < 0.001
  • Alive and substantially improved at 24 months: 29.1% vs. 11.7%, p < 0.001

Three-year outcomes: At 2 years, patients in the GDMT arm could cross over to the MitraClip arm if needed. As a result, total crossover was 18.6% (majority between 2 and 3 years). For the primary results, on ITT, there was still a profound benefit of MitraClip + GDMT over GDMT (annualized rates 35.5% vs. 68.8%, HR 0.49, 95% CI 0.37-0.63, p < 0.001). Benefit of MitraClip on mortality was preserved (42.8% vs. 55.5%, p = 0.001). Among the MitraClip patients, progressive HF requiring LVAD or heart transplant occurred in an additional 3.6% of patients (total 7.4%). Among the patients who crossed over, first HF hospitalization at 1 year was lower (13.8%), and the curves for the other clinical endpoints were more similar to the MitraClip arm than to the GDMT only arm, suggesting that benefit noted for the original MitraClip arm could be replicated in the control arm with MitraClip implantation (crossover).

Echo parameters: The beneficial effect of transcatheter mitral valve replacement compared with GDMT alone was consistent in all echocardiographic subgroups, independent of the severity of LV dysfunction, LV dilatation, pulmonary hypertension, severity of tricuspid regurgitation, or individual MR characteristics. At 12 months, LVEF decreased (-5.6% vs. -12.8%, p = 0.048) and the LV volumes progressively increased (LV end-systolic dimension: 0.15 vs. 0.43, p = 0.02) in both groups compared with baseline, but less so with MitraClip.

Cost-effectiveness analysis: A patient-level economic analysis was performed combining data from COAPT and from a medical center for follow-up costs. The mean cost for the transcatheter mitral valve repair (TMVr) procedure was $35,755 (excluding physician fees), of which $30,628 was attributable to the cost of devices used in the procedure. After including ancillary costs and physician costs, the total cost of the index hospitalization was $48,198. Follow-up medical care costs were reduced by $11,690 per patient with TMVr vs. GDMT (95% CI -$20,714 to -$3,010; p = 0.018). However, when combined with the upfront cost of the initial TMVr admission, cumulative 2-year costs remained significantly higher with TMVr ($73,416 vs. $38,345; mean difference $35,072; 95% CI $26,370 to $44,085; p < 0.001). Under the base case scenario (benefits of MitraClip decreased between years 2 and 5, with no difference at 5 years), life expectancy was projected to be 6.12 years and 4.63 years for the MitraClip and GDMT groups, respectively. Based on these lifetime projections, the incremental cost-effectiveness ratio (ICER) for MitraClip vs. GDMT was $55,600/quality-adjusted life-year (QALY).

Health status changes: (n = 551; patients alive at 30 days) At least moderate improvement (≥10% increase in KCCQ-OS) was 58% for TMVr vs. 26% for GDMT. Early improvement in KCCQ-OS was inversely associated with the risk of death or HF hospitalization between 1 month and 2 years (p < 0.001). Every 10-point increase in KCCQ-OS from baseline to 1 month was associated with a 14% lower hazard of death or HF hospitalization during follow-up (HR 0.86, 95% CI 0.81-0.92, p < 0.001).

Predictors of response: Responders were defined as those who were alive without HF hospitalization and had an improvement of 5-<20 points on the KCCQ-OS scale. Super-responders were those who had no HF hospitalization and ≤20-point improvements on the KCCQ-OS scale. Comparing super-responders and nonresponders, only treatment assignment (GDMT alone compared with MitraClip: odds ratio [OR] 3.40, 95% CI 1.97-5.90, p < 0.0001), serum creatinine (per 1 mg/dl: OR 0.66, 95% CI 0.47-0.93, p = 0.018), and KCCQ-OS score (per 5 points: OR 0.86, 95% CI 0.80-0.91, p < 0.0001) were statistically significant. Comparing responders and nonresponders, only treatment assignment (GDMT alone compared with MitraClip: OR 1.72, 95% CI 1.02-2.92, p < 0.043) was statistically significant. Super-responders were more likely to have residual ≤1+ MR at 30 days, and both super-responders and responders had a significant decrease in estimated right ventricular systolic pressure at 30 days.

NYHA class: NYHA functional class II: 39.2%; NYHA class III: 52.5%; ambulatory NYHA functional class IV: 8.3%. Rates of death or HF-related hospitalization were progressively higher with increasing NYHA functional class. Compared with GDMT alone, MitraClip implantation resulted in lower 2-year rates of death or HF-related hospitalization consistently in patients in NYHA functional class II (39.7% vs. 63.7%; HR 0.54, 95% CI 0.37-0.77), NYHA functional class III (46.6% vs. 65.5%; HR 0.60, 95% CI 0.45-0.82), and NYHA functional class IV (66.7% vs. 85.2%; HR 0.55, 95% CI 0.28-1.10; p interaction = 0.86).

Impact of pulmonary hypertension (n = 528 [86%]): Pulmonary artery systolic pressure (PASP) ≥50 mm Hg was noted in 34.8% of patients. These patients were more frequently male, had history of type 2 diabetes mellitus, anemia, higher NT-proBNP, and higher STS scores. Two-year rates of death or HF hospitalization were higher among patients with pulmonary hypertension than those without (68.8% vs. 49.1%, p = 0.002). Rates of death or HF hospitalization were reduced by transcatheter mitral valve repair (TMVr) versus GDMT alone, irrespective of baseline PASP (p for interaction = 0.45). TMVr reduced PASP from baseline to 30 days to a greater extent than GDMT alone (adjusted least squares mean: –4.0 vs. –0.9 mm Hg; p = 0.006).

Effect of age: Median age was 74 years. Primary endpoint was similar for MitraClip + GDMT vs. GDMT among patients aged <74 years (37.3% vs. 64.5%) and ≥74 years (51.7% vs. 69.6%); p for interaction = 0.1. Benefit in reducing HF hospitalization was reduced among elderly patients (HR 0.67, 95% CI 0.48-0.93) compared with younger patients (HR 0.37, 95% CI 0.25-0.55); p for interaction = 0.03.

Impact of renal dysfunction: Moderate chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] 30-60): 53.3%, severe CKD (eGFR <30): 23.8%; end-stage renal disease (ESRD): 6.1%. Worse baseline renal function was associated with higher rates of all-cause death or HF hospitalization at 24 months both in patients treated with both therapies. Treatment with the MitraClip was beneficial across all three renal function groups in reducing the composite outcome of all-cause death or HF hospitalization (p interaction = 0.62) as well as death (p interaction = 0.24). New-onset ESRD for MitraClip + GDMT vs. GDMT: 2.9% vs. 8.1% (p = 0.008); new renal replacement therapy: 2.5% vs. 7.4% (p = 0.011).

Hospitalizations: At 2 years, all-cause hospitalization for MitraClip + GDMT vs. GDMT alone: 68.6% vs. 80.7% (p = 0.004); CV hospitalization: 50.2% vs. 66.8% (p < 0.0001); HF hospitalization: 34.8% vs. 56.4% (p < 0.0001). Total all-cause hospitalization: 102.3/100 patient-year (P-Y) vs. 143.3/100 P-Y (p < 0.0001); fatal all-cause hospitalizations: 7.8 vs. 14.5/100 P-Y (p = 0.002); total CV hospitalizations: 54.9 vs. 88.0/100 P-Y (p < 0.0001); CV non-HF hospitalization: 20.0% vs. 22.1% (p = 0.50).

Five-year follow-up: 87% completed 5-year follow-up. Primary effectiveness endpoint (HF hospitalization) for MitraClip + GDMT vs. GDMT: 61% vs. 83%, HR 0.49, 95% CI 0.40-0.61; 33.1% vs. 57.2%/year. Majority of difference was within first 36 months; no difference between years 3-5 on landmark analysis. Death or HF hospitalization: 73.6% vs. 91.5%, HR 0.53, 95% CI 0.44-0.64. All-cause mortality: 57.3% vs. 67.2%, HR 0.72, 95% CI 0.58-0.89. MR ≤2+ at 5 years on core-lab assessment (n = 103): 94.7% vs. 91.3%. Unplanned mitral valve intervention or surgery: 4.5% vs. 52.0% (crossover to MitraClip in GDMT only arm: 48.7%); LVAD or heart transplant: 9.5% vs. 12.4%, p > 0.05. Single-leaflet device attachment in MitraClip arm: 0.7%.

Ventricular remodeling: Change in left ventricular end-diastolic volume index (LVEDVi) at 6 months compared with baseline for MitraClip + GDMT vs. GDMT: -8.8 vs. -7.9 ml/m2 (p = 0.76); change in LVESVi at 6 months compared with baseline for MitraClip + GDMT vs. GDMT: -3.1 vs. -6.0 ml/m2 (p = 0.22). Among all patients, a greater decrease in LVEDVi at 6 months was not associated with a greater reduction in death or HF between 6 months and 2 years (adjusted HR 0.94, 95% CI 0.87-1.02, p = 0.12), or all-cause mortality between 6 months and 2 years (HR 0.92, 95% CI 0.84-1.02, p = 0.11). There was a lower risk of CV death between 6 months and 2 years (adjusted HR 0.90 per 10 ml/m2 decrease, 95% CI 0.81-1.00, p = 0.04). No difference in these clinical outcomes was observed for changes in LVESVi at 6 months. The treatment benefits of transcatheter edge-to-edge repair (TEER) were not significant regardless of the degree of LV remodeling at 6 months.

Cerebrovascular events (CVEs): Within 30 days of randomization for MitraClip + GDMT vs. GDMT: 0.7% vs. 0% (p = 0.15). At 4 years, stroke or transient ischemic attack (TIA): 12.3% vs. 10.2% (p = 0.91). Stroke: 10.5% vs. 8.7% (p = 0.87). An interaction was observed among those on baseline anticoagulation. MitraClip compared with GDMT alone was associated with a reduced risk of CVEs among patients with anticoagulation (adjusted HR 0.24, 95% CI 0.08-0.73) compared with an increased risk of CVEs in patients without anticoagulation (adjusted HR 2.27, 95% CI 1.08-4.81; p interaction = 0.001).

Interpretation:

The results of this landmark trial indicate that transcatheter mitral valve approximation using the MitraClip on a background of maximally tolerated GDMT was superior to GDMT alone in reducing HF hospitalization and mortality in symptomatic HF patients with grade 3-4+ MR. Improvements were also observed in LV dimensions, renal outcomes, hospitalizations (primarily related to HF, both fatal and nonfatal), and patient symptoms. Significant improvements were noted in QoL measurements starting at 1 month and sustained out to 5 years. The device had excellent safety. There was a high rate of crossover after 2 years from GDMT to the MitraClip arm. Benefits were sustained among elderly patients, although benefit in HFH was greater among younger patients compared with older patients.

In the overall cohort, changes in LV dimensions at 6 months on echocardiogram were seen in both arms. Directionally, favorable remodeling appeared to have a positive impact on outcomes between 6 months and 2 years in both arms, but only the association between CV death and change in LVEDVi was statistically significant. The beneficial impact of TEER + GDMT over GDMT alone at 2 years did not appear to be driven by more favorable remodeling with TEER. At 4 years, stroke/TIA rates were similar between MitraClip + GDMT vs. GDMT alone.

All operators in this trial were experienced in the use of MitraClip. These results come on the heels of the recently published MITRA-FR trial, which did not show a benefit in this patient population. Possible reasons for differences include enrollment of patients with more severe MR (EROA >30 in COAPT vs. >20 in MITRA-FR) and less dilated ventricles (LVEDV 101 vs. 135, respectively). Procedural complications and success in reducing MR were also higher in the COAPT trial. These are truly landmark findings and will likely have a significant impact on the management of patients with secondary MR.

The cost-effectiveness analysis suggests higher costs with MitraClip compared with GDMT (mean difference approximately $35,000 over 2 years), with ICER analysis suggesting intermediate cost-effectiveness of MitraClip + GDMT over GDMT alone. This further underscores the need to carefully identify the patients most likely to benefit from MitraClip among patients with HF and MR.

References:

Vincent F, Redfors B, Kotinkaduwa LN, et al. Cerebrovascular Events After Transcatheter Edge-to-Edge Repair and Guideline-Directed Medical Therapy in the COAPT Trial. JACC Cardiovasc Interv 2023;16:1448-59.

Editorial Comment: Praz F, Vahanian A. Stroke After Mitral TEER: A Grain of Sand in the Stapler? JACC Cardiovasc Interv 2023;16:1460-2.

Stone GW, Abraham WT, Lindenfeld J, et al., on behalf of the COAPT Investigators. Five-Year Follow-up After Transcatheter Repair of Secondary Mitral Regurgitation. N Engl J Med 2023;388:2037-48.

Editorial: McMurray JJ, Metra M. Transcatheter Repair of Secondary Mitral Regurgitation. N Engl J Med 2023;388:2097-8.

Lindman BR, Asch FM, Grayburn PA, et al. Ventricular Remodeling and Outcomes After Mitral Transcatheter Edge-to-Edge Repair in Heart Failure: The COAPT Trial. JACC Cardiovasc Interv 2023;16:1160-72.

Editorial Comment: Kreidel F, Frank D, Bartko P, et al. Paradoxes Continued: Treatment of Secondary MR and Impact on Ventricular Remodeling. JACC Cardiovasc Interv 2023;16:1173-5.

Presented by Dr. Gregg W. Stone at the American College of Cardiology Annual Scientific Session (ACC.23/WCC), New Orleans, LA, March 5, 2023.

Giustino G, Camaj A, Kapadia SR, et al. Hospitalizations and Mortality in Patients With Secondary Mitral Regurgitation and Heart Failure: COAPT Trial. J Am Coll Cardiol 2022;80:1857-68.

Editorial Comment: Carabello BA. Secondary Mitral Regurgitation: It Is Still the Ventricle. J Am Coll Cardiol 2022;80:1869-70.

Song C, Madhavan MV, Lindenfeld J, et al. Age-Related Outcomes After Transcatheter Mitral Valve Repair in Patients With Heart Failure: Analysis From COAPT. JACC Cardiovasc Interv 2022;15:397-407.

Editorial Comment: Praz F, Vahanian A. TEER Gives Years to Life and Life to Years to Elderly Patients With SMR. JACC Cardiovasc Interv 2022;15:408-10.

Beohar N, Ailawadi G, Kotinkaduwa LN, et al. Impact of baseline renal dysfunction on cardiac outcomes and end-stage renal disease in heart failure patients with mitral regurgitation: the COAPT trial. Eur Heart J 2022;43:1639-48.

Ben-Yehuda O, Shahim B, Chen S, et al. Pulmonary Hypertension in Transcatheter Mitral Valve Repair for Secondary Mitral Regurgitation: The COAPT Trial. J Am Coll Cardiol 2020;76:2595-606.

Editorial Comment: Implications of Elevated Pulmonary Artery Pressure for Transcatheter Mitral Repair: Time for Comprehensive Hemodynamic Investigation. J Am Coll Cardiol 2020;76:2607-10.

Giustino G, Lindenfeld J, Abraham WT, et al. NYHA Functional Classification and Outcomes After Transcatheter Mitral Valve Repair in Heart Failure: The COAPT Trial. JACC Cardiovasc Interv 2020;13:2317-28.

Grayburn PA, Sannino A, Cohen DJ, et al. Predictors of Clinical Response to Transcatheter Reduction of Secondary Mitral Regurgitation: The COAPT Trial. J Am Coll Cardiol 2020;76:1007-14.

Editorial Comment: Hahn RT. Super-Responders and Nonresponders in the COAPT Trial: Not as Simple as Clip or No Clip. J Am Coll Cardiol 2020;76:1015-17.

Arnold SV, Stone GW, Mack MJ, et al., on behalf of the COAPT Investigators. Health Status Changes and Outcomes in Patients With Heart Failure and Mitral Regurgitation: From COAPT. J Am Coll Cardiol 2020;75:2099-106.

Editorial Comment: Meinertz T, Münzel T. Kansas City Cardiomyopathy Quality Score Indicates Sustained Health Status Improvement in Patients After TMVr. J Am Coll Cardiol 2020;75:2107-9.

Baron SJ, Wang K, Arnold SV, et al., on behalf of the COAPT Investigators. Cost-Effectiveness of Transcatheter Mitral Valve Repair Versus Medical Therapy in Patients With Heart Failure and Secondary Mitral Regurgitation: Results From the COAPT Trial. Circulation 2019;140:1881-91.

Cost-effectiveness analysis: Presented by Dr. Suzanne J. Baron at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2019), San Francisco, CA, September 29, 2019.

Three-year outcomes: Presented by Dr. Michael J. Mack at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2019), San Francisco, CA, September 28, 2019.

Asch FM, Grayburn PA, Siegel RJ, et al., on behalf of the COAPT Investigators. Transcatheter Mitral Valve Replacement in Patients With Heart Failure and Secondary Mitral Regurgitation: From COAPT Trial. J Am Coll Cardiol 2019;74:2969-79.

Arnold SV, Chinnakondepalli KM, Spertus JA, et al., on behalf of the COAPT Investigators. Health Status After Transcatheter Mitral-Valve Repair in Heart Failure and Secondary Mitral Regurgitation: COAPT Trial. J Am Coll Cardiol 2019;73:2123-32.

Editorial Comment: Iung B, Messika-Zeitoun D. Transcatheter Mitral Valve Repair in Secondary MR: New Findings and New Challenges. J Am Coll Cardiol 2019;73:2133-4.

COAPT: Presented by Dr. Federico M. Asch at the American College of Cardiology Annual Scientific Session (ACC 2019), New Orleans, LA, March 17, 2019.

COAPT QoL Subanalysis: Presented by Dr. Suzanne Arnold at the American College of Cardiology Annual Scientific Session (ACC 2019), New Orleans, LA, March 17, 2019.

Stone GW, Lindenfeld JA, Abraham WT, et al., on behalf of the COAPT Investigators. Transcatheter Mitral-Valve Repair in Patients With Heart Failure. N Engl J Med 2018;379:2307-18.

Editorial: Nishimura RA, Bonow RO. Percutaneous Repair of Secondary Mitral Regurgitation — A Tale of Two Trials. N Engl J Med 2018;379:2374-6.

Presented by Dr. Gregg W. Stone at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2018), San Diego, CA, September 23, 2018.

Clinical Topics: Anticoagulation Management, Cardiac Surgery, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Valvular Heart Disease, Aortic Surgery, 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: ACC23, ACC Annual Scientific Session, ACC19, Anticoagulants, TCT18, Transcatheter Cardiovascular Therapeutics, Adrenergic beta-Antagonists, Cardiac Surgical Procedures, Cardiomyopathies, Coronary Artery Bypass, Echocardiography, Geriatrics, Heart-Assist Devices, Heart Failure, Heart Transplantation, Heart Valve Diseases, Ischemic Attack, Transient, Mitral Valve Insufficiency, Myocardial Infarction, Myocardial Ischemia, Natriuretic Peptide, Brain, Percutaneous Coronary Intervention, Pulmonary Disease, Chronic Obstructive, Renal Insufficiency, Chronic, Stroke, Stroke Volume, TCT19, Transcatheter Cardiovascular Therapeutics


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