Cardiology

Stone, G. W., N. J. Weissman and M. J. Mack (2019). “Transcatheter Mitral-Valve Repair in Patients with Heart Failure. Reply.” N Engl J Med 380(20): 1980-1981.

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The authors reply: Crestanello et al. question the apparently low forward stroke volume calculated from the total left ventricular stroke volume, which was determined by applying Simpson’s method to two-dimensional biplane echocardiographic measurements and using an assumed regurgitant volume. The actual mean forward stroke volume in the COAPT trial as measured with Doppler was 51 ml, and the regurgitant volume as measured with the use of the PISA (proximal isovelocity surface area) method was 59 ml, values that are consistent with severe mitral regurgitation. There are several reasons for the discrepancies from Crestanello’s theoretical extrapolation, in which two-dimensional and Doppler data are combined, the most important being the substantial underestimation of left ventricular volume (and stroke volume), as determined by two-dimensional echocardiography with the use of Simpson’s rule, especially in patients with dilated ventricles, such as those enrolled in the COAPT trial. Drake et al. posit that a lack of imaging guidance resulted in a high rate of recurrence of mitral regurgitation after surgical repair with a downsized annuloplasty ring in the trial conducted by the Cardiothoracic Surgical Trials Network. That trial used detailed echocardiographic analysis to gauge patient suitability for inclusion. A post hoc subanalysis defined the anatomical features shown on echocardiography that were predictive of a durable surgical repair. Ongoing, detailed echocardiographic analyses in the COAPT trial will further delineate the anatomical features that predict favorable outcomes after transcatheter mitral-leaflet approximation. We do agree that image-guided assessment is essential to the identification of a responder population and that in the future it may direct patient-specific intervention (leaflet repair, annuloplasty, or valve replacement). What Garbi and Lancellotti term valvular heart failure secondary to mitral regurgitation, Grayburn et al. designate as disproportionate mitral regurgitation and Carabello calls tertiary mitral regurgitation. Regardless of the nomenclature, we agree that relative to the MITRA-FR trial, the COAPT trial investigators enrolled a greater proportion of patients in whom prognosis was dictated more by the severity of mitral regurgitation than by the degree of left ventricular dysfunction — a major reason why patients in the COAPT trial, but not those in the MITRA-FR trial, benefited from transcatheter mitral-valve repair. We further agree that reduction in left atrial pressure (and volume) was probably responsible for many of the clinical benefits associated with transcatheter mitral-valve repair in the COAPT trial. Mitral-valve replacement offers the potential for greater reduction in mitral regurgitation than transcatheter mitral-valve repair. Whether the procedure will provide sufficiently greater clinical effectiveness warranting a potentially more complex and complicated procedure is uncertain and can only be addressed by means of adequately powered randomized trials. Finally, Kalavrouziotis et al. are incorrect in stating that enrollment in the COAPT trial was “supervised” by the sponsor. Rather, investigators at each site determined whether screened patients met prespecified enrollment criteria, a determination that was then confirmed by a physician-led, sponsor-independent, central eligibility committee and echocardiographic core laboratory. We believe that practitioner fidelity to the inclusion and exclusion criteria used in the COAPT trial should lead to duplication of our results in the real world. (Text of authors’ reply to several letters in the same issue of NEJM; see also authors’ original article, Stone, G. W., J. Lindenfeld, W. T. Abraham, S. Kar, D. S. Lim, J. M. Mishell, B. Whisenant, P. A. Grayburn, M. Rinaldi, S. R. Kapadia, V. Rajagopal, I. J. Sarembock, A. Brieke, S. O. Marx, D. J. Cohen, N. J. Weissman and M. J. Mack (2018). “Transcatheter Mitral-Valve Repair in Patients with Heart Failure.” N Engl J Med 379(24): 2307-2318.)

Webb, J. G., D. J. Murdoch, M. C. Alu, A. Cheung, A. Crowley, D. Dvir, H. C. Herrmann, S. K. Kodali, J. Leipsic, D. C. Miller, P. Pibarot, R. M. Suri, D. Wood, M. B. Leon and M. J. Mack (2019). “3-Year Outcomes After Valve-in-Valve Transcatheter Aortic Valve Replacement for Degenerated Bioprostheses: The PARTNER 2 Registry.” J Am Coll Cardiol 73(21): 2647-2655.

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BACKGROUND: Transcatheter aortic valve replacement (TAVR) for degenerated surgical bioprosthetic aortic valves is associated with favorable early outcomes. However, little is known about the durability and longer-term outcomes associated with this therapy. OBJECTIVES: The aim of this study was to examine late outcomes after valve-in-valve TAVR. METHODS: Patients with symptomatic degeneration of surgical aortic bioprostheses at high risk (>/=50% major morbidity or mortality) for reoperative surgery were prospectively enrolled in the multicenter PARTNER (Placement of Aortic Transcatheter Valves) 2 valve-in-valve and continued access registries. Three-year clinical and echocardiographic follow-up was obtained. RESULTS: Valve-in-valve procedures were performed in 365 patients. The mean age was 78.9 +/- 10.2 years, and the mean Society of Thoracic Surgeons score was 9.1 +/- 4.7%. At 3 years, the overall Kaplan-Meier estimate of all-cause mortality was 32.7%. Aortic valve re-replacement was required in 1.9%. Mean transaortic gradient was 35.0 mm Hg at baseline, decreasing to 17.8 mm Hg at 30-day follow-up and 16.6 mm Hg at 3-year follow-up. Baseline effective orifice area was 0.93 cm(2), increasing to 1.13 and 1.15 cm(2) at 30 days and 3 years, respectively. Moderate to severe aortic regurgitation was reduced from 45.1% at pre-TAVR baseline to 2.5% at 3 years. Importantly, moderate or severe mitral and tricuspid regurgitation also decreased (33.7% vs. 8.6% [p < 0.0001] and 29.7% vs. 18.8% [p = 0.002], respectively). Baseline left ventricular ejection fraction was 50.7%, increasing to 54.7% at 3 years (p < 0.0001), while left ventricular mass index was 136.4 g/m(2), decreasing to 109.1 g/m(2) at 3 years (p < 0.0001). New York Heart Association functional class improved, with 90.4% in class III or IV at baseline and 14.1% at 3 years (p < 0.0001), and Kansas City Cardiomyopathy Questionnaire overall score increased (43.1 to 73.1; p < 0.0001). CONCLUSIONS: At 3-year follow-up, TAVR for bioprosthetic aortic valve failure was associated with favorable survival, sustained improved hemodynamic status, and excellent functional and quality-of-life outcomes. (The PARTNER II Trial: Placement of Aortic Transcatheter Valves II - PARTNER II - Nested Registry 3/Valve-in-Valve [PII NR3/ViV]; NCT03225001).

Thakkar, S. J., P. A. Grayburn, S. A. Hall and W. C. Roberts (2019). “Orthotopic Heart Transplantation for Ankylosing Spondylitis Masquerading as Nonischemic Cardiomyopathy.” Am J Cardiol 123(10): 1732-1735.

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Described herein is a 48-year-old man who underwent orthotopic heart transplantation because of severe heart failure considered clinically due to idiopathic dilated cardiomyopathy, but examination of the operatively excised native heart disclosed classic features of ankylosing spondylitis. Orthotopic heart transplantation for this condition has not been reported previously.

Roberts, W. C., L. C. Jameson, A. Bahmani, C. S. Roberts, A. E. Rafael and S. A. Hall (2019). “Morphological and Functional Characteristics of the Right Ventricle Functioning as a Systemic Ventricle for Decades After an Atrial Switch Procedure for Complete Transposition of the Great Arteries.” Am J Cardiol 123(11): 1863-1867.

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Described herein are certain clinical and cardiac morphologic findings in 4 adults with complete transposition of the great arteries who underwent the Mustard procedure in the newborn period or in childhood and each lived >30 years thereafter before either having orthotopic heart transplantation (3 patients) or dying while awaiting orthotopic heart transplantation. Compared with the wall of the left ventricle, the wall of the right ventricle (the systemic one) was much thicker, the myofibers much larger, and either grossly-visible or microscopic-sized scars were present in its wall. Additionally, some intramural coronary arteries in the right ventricular wall were numerous, large, had thick walls, and often narrowed lumens. That the Mustard operation provided the necessary time for the right ventricle (the systemic one) to develop to its fullest is a tribute to this procedure.

Qamer, S. Z., A. Malik, E. Bayoumi, P. H. Lam, S. Singh, M. Packer, I. E. Kanonidis, C. J. Morgan, A. Abdelmawgoud, R. M. Allman, G. C. Fonarow and A. Ahmed (2019). “Digoxin Use and Outcomes in Patients with Heart Failure with Reduced Ejection Fraction.” Am J Med May 28. [Epub ahead of print].

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BACKGROUND: Heart failure is a leading cause for hospital readmission. Digoxin use may lower this risk in patients with heart failure with reduced ejection fraction (HFrEF), but data on contemporary patients receiving other evidence-based therapies are lacking. METHODS: Of the 11,900 patients with HFrEF (ejection fraction less-than-or-equal-to 45%) in Medicare-linked OPTIMIZE-HF, 8401 were not on digoxin, of whom 1571 received discharge prescriptions for digoxin. We matched 1531 of these patients with 1531 not receiving digoxin by propensity scores for digoxin use. The matched cohort (n=3062; mean age, 76years; 44% women; 14% African American) was balanced on 52 baseline characteristics. We assembled a second matched cohort of 2850 patients after excluding those with estimated glomerular filtration rate<15ml/min/1.73m(2) and heart rate<60 beats/min. Hazard ratios (HR) and 95% confidence intervals (CI) for digoxin-associated outcomes were estimated in the matched cohorts. RESULTS: Among the 3062 matched patients, digoxin use was associated with a significantly lower risk of heart failure readmission at 30days (HR, 0.74; 95% CI, 0.59-0.93), 1year (HR, 0.81; 95% CI, 0.72-0.92) and 6years (HR, 0.90; 95% CI 0.81-0.99). The association with all-cause readmission was significant at 1 and 6years but not 30days. There was no association with mortality. Similar associations were observed among the 2850 matched patients without bradycardia or renal insufficiency. CONCLUSIONS: Among hospitalized older patients with HFrEF receiving contemporary treatments for heart failure, digoxin use is associated with a lower risk of hospital readmission, but not all-cause mortality.