Cardiology

Solomon, S. D., M. Vaduganathan, L. C. B, M. Packer, M. Zile, K. Swedberg, J. Rouleau, A. P. M, A. Desai, H. L. L, L. Kober, I. Anand, N. Sweitzer, G. Linssen, B. Merkely, J. Luis Arango, D. Vinereanu, C. H. Chen, M. Senni, A. Sibulo, S. Boytsov, V. Shi, A. Rizkala, M. Lefkowitz and J. J. V. McMurray (2020). “Sacubitril/Valsartan Across the Spectrum of Ejection Fraction in Heart Failure.” Circulation 141(5): 352-361.

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BACKGROUND: While disease-modifying therapies exist for heart failure (HF) with reduced left ventricular ejection fraction (LVEF), few options are available for patients in the higher range of LVEF (>40%). Sacubitril/valsartan has been compared with a renin-angiotensin-aldosterone-system inhibitor alone in 2 similarly designed clinical trials of patients with reduced and preserved LVEF, permitting examination of its effects across the full spectrum of LVEF. METHODS: We combined data from PARADIGM-HF (LVEF eligibility/=45%; n=4796) in a prespecified pooled analysis. We divided randomized patients into LVEF categories: 22.5% to 32.5% (n=3987), >32.5% to 42.5% (n=3143), > 42.5% to 52.5% (n=1427), > 52.5% to 62.5% (n=2166), and >62.5% (n=1202). We assessed time to first cardiovascular death and HF hospitalization, its components, and total heart failure hospitlizations, all-cause mortality, and noncardiovascular mortality. Incidence rates and treatment effects were examined across categories of LVEF. RESULTS: Among 13 195 randomized patients, we observed lower rates of cardiovascular death and HF hospitalization, but similar rates of noncardiovascular death, among patients in the highest versus the lowest groups. Overall sacubitril/valsartan was superior to renin-angiotensin-aldosterone-system inhibition for first cardiovascular death or heart failure hospitalization (Hazard Ratio [HR] 0.84 [95% CI, 0.78-0.90]), cardiovascular death (HR 0.84 [95% CI, 0.76-0.92]), heart failure hospitalization (HR 0.84 [95% CI, 0.77-0.91]), and all-cause mortality (HR 0.88 [95% CI, 0.81-0.96]). The effect of sacubitril/valsartan was modified by LVEF (treatment-by-continuous LVEF interaction P=0.02), and benefit appeared to be present for individuals with EF primarily below the normal range, although the treatment benefit for cardiovascular death diminished at a lower ejection fraction. We observed effect modification by LVEF on the efficacy of sacubitril/valsartan in both men and women with respect to composite total HF hospitalizations and cardiovascular death, although women derived benefit to higher ejection fractions. CONCLUSIONS: The therapeutic effects of sacubitril/valsartan, compared with a renin-angiotensin-aldosterone-system inhibitor alone, vary by LVEF with treatment benefits, particularly for heart failure hospitalization, that appear to extend to patients with heart failure and mildly reduced ejection fraction. These therapeutic benefits appeared to extend to a higher LVEF range in women compared with men. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov. Unique identifiers: NCT01920711 (PARAGON-HF), NCT01035255 (PARADIGM-HF).

Simpson, J., P. S. Jhund, L. H. Lund, S. Padmanabhan, B. L. Claggett, L. Shen, M. C. Petrie, W. T. Abraham, A. S. Desai, K. Dickstein, L. Kober, M. Packer, J. L. Rouleau, G. Mueller-Velten, S. D. Solomon, K. Swedberg, M. R. Zile and J. J. V. McMurray (2020). “Prognostic Models Derived in PARADIGM-HF and Validated in ATMOSPHERE and the Swedish Heart Failure Registry to Predict Mortality and Morbidity in Chronic Heart Failure.” JAMA Cardiol Jan 29. [Epub ahead of print].

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Importance: Accurate prediction of risk of death or hospitalizations in patients with heart failure (HF) may allow physicians to explore how more accurate decisions regarding appropriateness and timing of disease-modifying treatments, advanced therapies, or the need for end-of-life care can be made. Objective: To develop and validate a prognostic model for patients with HF. Design, Setting, and Participants: Multivariable analyses were performed in a stepwise fashion. Harrell C statistic was used to assess the discriminative ability. The derivation cohort was Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF) participants. The models were validated using the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure Trial (ATMOSPHERE) study and in the Swedish Heart Failure Registry (SwedeHF). A total of 8399 participants enrolled in PARADIGM-HF. Data were analyzed between June 2016 and June 2018. Main Outcomes and Measures: Cardiovascular death, all-cause mortality, and the composite of cardiovascular death or HF hospitalization at both 1 and 2 years. Results: Complete baseline clinical data were available for 8011 patients in PARADIGM-HF. The mean (SD) age of participants was 64 (11.4) years, 78.2% were men (n = 6567 of 8011), and 70.6% were New York Heart Association class II (n = 5919 of 8011). During a mean follow-up of 27 months, 1546 patients died, and 2031 had a cardiovascular death or HF hospitalization. The common variables were: male sex, race/ethnicity (black or Asian), region (Central Europe or Latin America), HF duration of more than 5 years, New York Heart Association class III/ IV, left ventricular ejection fraction, diabetes mellitus, beta-blocker use at baseline, and allocation to sacubitril/valsartan. Ranked by chi2, N-terminal pro brain natriuretic peptide was the single most powerful independent predictor of each outcome. The C statistic at 1 and 2 years was 0.74 (95% CI, 0.71-0.76) and 0.71 (95% CI, 0.70-0.73) for the primary composite end point, 0.73 (95% CI, 0.71-0.75) and 0.71 (95% CI, 0.69-0.73) for cardiovascular death, and 0.71 (95% CI, 0.69-0.74) and 0.70 (95% CI, 0.67-0.74) for all-cause death, respectively. When validated in ATMOSPHERE, the C statistic at 1 and 2 years was 0.71 (95% CI, 0.69-0.72) and 0.70 (95% CI, 0.68-0.71) for the primary composite end point, 0.71 (95% CI, 0.69-0.74) and 0.70 (95% CI, 0.69-0.72) for cardiovascular death, and 0.71 (95% CI, 0.69-0.74) and 0.70 (95% CI, 0.68-0.72) for all-cause death, respectively. An online calculator was created to allow calculation of an individual’s risk (http://www.predict-hf.com). Conclusions and Relevance: Predictive models performed well and were developed and externally validated in large cohorts of geographically representative patients, comprehensively characterized with clinical and laboratory data including natriuretic peptides, who were receiving contemporary evidence-based treatment.

Sengupta, A., S. Zaid, N. Kamioka, J. Terre, M. Miyasaka, S. A. Hirji, M. Hensey, N. Geloo, G. Petrossian, N. Robinson, E. Sarin, L. Ryan, S. H. Yoon, C. W. Tan, O. K. Khalique, S. K. Kodali, T. Kaneko, P. B. Shah, S. C. Wong, A. Salemi, K. Sharma, J. A. Kozina, M. A. Szerlip, C. W. Don, S. Gafoor, M. Zhang, Z. Newhart, S. R. Kapadia, S. L. Mick, A. Krishnaswamy, A. Kini, H. Ahmad, S. L. Lansman, M. J. Mack, J. G. Webb, V. Babaliaros, V. H. Thourani, R. R. Makkar, M. B. Leon, I. George and G. H. L. Tang (2020). “Mid-Term Outcomes of Transcatheter Aortic Valve Replacement in Extremely Large Annuli With Edwards SAPIEN 3 Valve.” JACC Cardiovasc Interv 13(2): 210-216.

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OBJECTIVES: The aim of this study was to report the 1-year results of transcatheter aortic valve replacement (TAVR) with the Edwards SAPIEN 3 (S3) valve in extremely large annuli. BACKGROUND: Favorable 30-day outcomes of S3 TAVR in annuli >683 mm(2) have previously been reported. Pacemaker implantation rates were acceptable, and a larger left ventricular outflow tract and more eccentric annular anatomy were associated with increasing paravalvular leak. METHODS: From December 2013 to December 2018, 105 patients across 15 centers with mean area 721.3 +/- 36.1 mm(2) (range 683.5 to 852.0 mm(2)) underwent TAVR using an S3 device. Clinical, anatomic, and procedural characteristics were analyzed. One-year survival and echocardiographic follow-up were reached in 94.3% and 82.1% of patients, respectively. Valve Academic Research Consortium-2 30-day and 1-year outcomes were reported. RESULTS: The mean age was 76.9 +/- 10.4 years, and Society of Thoracic Surgeons predicted risk score averaged 5.2 +/- 3.4%. One-year overall mortality and stroke rates were 18.2% and 2.4%, respectively. Quality-of-life index improved from baseline to 30 days and at 1 year (p < 0.001 for both). Mild paravalvular aortic regurgitation occurred in 21.7% of patients, while moderate or greater paravalvular aortic regurgitation occurred in 4.3%. Mild and moderate or severe transvalvular aortic regurgitation occurred in 11.6% and 0%, respectively. Valve gradients remained stable at 1 year. CONCLUSIONS: S3 TAVR in annular areas >683 mm(2) is feasible, with favorable mid-term outcomes.

Roberts, W. C. and A. T. Kietzman (2020). “Severe Eosinophilic Myocarditis in the Portion of Left Ventricular Wall Excised to Insert a Left Ventricular Assist Device for Severe Heart Failure.” Am J Cardiol 125(2): 264-269.

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Described herein are 3 adults in whom histologic study of the left ventricular myocardium excised (“LV core”) to insert a left ventricular assist device (LVAD) disclosed severe acute myocarditis and the inflammatory cells included numerous eosinophils (eosinophilic myocarditis). Examination of the clinical records disclosed elevated absolute eosinophil counts at the time of insertion of the LVAD and the counts rapidly (<30 days) returned to normal after the operation. Because of the numerous medications that each patient was taking at the time of LVAD insertion, identification of a specific initiating medication as its cause was not possible. Of the 3 patients, 2 had idiopathic-dilated cardiomyopathy and 1 had ischemic cardiomyopathy and each had had heart failure for years. The eosinophilic myocarditis in these 3 patients appears to have been transient and superimposed on the earlier cardiomyopathy.

Roberts, W. C. and O. S. Khan (2020). “Massive Cardiomegaly (>1000 g Heart) and Obesity.” Am J Cardiol 125(2): 277-281.

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Described herein are certain clinical and morphologic findings in 9 patients who at necropsy had hearts weighing >1000 g, a weight approximately 3 times normal. With the exception of 2 patients with hypertrophic cardiomyopathy, the common finding in the remaining 7 patients was obesity. None had valvular heart disease, the previously described major cause of massive cardiomegaly. Thus, obesity needs to be added to the causes of massive cardiomegaly, a cause not previously recognized. Electrocardiograms in 4 patients disclosed high total 12-lead QRS voltage on the electrocardiogram in only one despite the massive cardiomegaly.