Cardiology

K, C. B., E. Mejia-Lopez, P. McCullough, K. Breathett, J. L. Kennedy, J. Tallaj, J. Bergin, S. Pamboukian, M. Abuannadi and S. Mazimba (2017). “Clinical impact of changes in hemodynamic indices of contractile function during treatment of acute decompensated heart failure.” J Card Fail: 2017 Jul [Epub ahead of print].

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BACKGROUND: The objective was to determine the impact of improving right ventricular versus left ventricular stroke work indices (RVSWI v. LVSWI) during therapy for acute decompensated heart failure (ADHF). METHODS AND RESULTS: Cox proportional hazards regression and logistic regression was used to analyze key factors associated with outcomes in 175 patients (age 56.7 +/- 13.6 years, 29.1% female) with hemodynamic data from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial. In this cohort, 28.6% and 69.7%, respectively, experienced the outcomes of death, transplant, or ventricular assist device (DVADTX) and DVADTX or HF rehospitalization (DVADTXHF) during 6 months of follow-up. Increasing RVSWI (DeltaRVSWI) from baseline to discharge was associated with a decrease in DVADTXHF (HR 0.923 [95% CI 0.871-0.979] per 0.1 mmHg*L/m2 increase); however, increasing LVSWI (DeltaLVSWI) only had a non-significant association with decreased DVADTXHF (P=0.11) In a multivariable model, patients with DeltaRVSWI

Packer, M. (2017). “Why has a run-in period been a design element in most landmark clinical trials? Analysis of the critical role of run-in periods in drug development.” J Card Fail: 2017 Jul [Epub ahead of print].

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Prior exposure to one of the randomized treatments has been a routine design element of large-scale trials in patients at high cardiovascular risk. A run-in feature has allowed our trials to be more realistic; it has strengthened their ability to estimate the true treatment effect, and it has never undermined the validity of a trial’s findings. Those who suggest that run-in periods distort the results of large-scale trials should become more familiar with our history of drug development and our standards of clinical practice. Physicians use run-in periods every day in real life, and trialists have used run-in periods for decades to reliably establish the role of new cardiovascular drugs. Those who reflexively criticize the trials because of their inclusion of a run-in period need to carefully re-examine how medicine is practiced and how it advances.

Lima, B., O. Dur, J. Chuang, T. Chamogeorgakis, D. J. Farrar, K. S. Sundareswaran, J. Felius, S. M. Joseph, S. A. Hall and G. V. Gonzalez-Stawinski (2017). “Novel cardiac coordinate modeling system for three-dimensional quantification of inflow cannula malposition of heartmate ii lvads.” Asaio j: 1-16.

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Optimal function of left ventricular assist devices (LVADs) depends on proper alignment of the inflow cannula (IC). Quantitative guidelines for IC angulation are lacking because of variation in cardiac geometry and difficulty in analyzing three-dimensional (3D) cannula orientation relative to the left ventricle (LV). Based on contrast-enhanced computed tomography images from five normal and five clinically malpositioned IC cases in patients with HeartMate II LVADs, we developed a method for 3D quantification of IC malpositioning. Using Mimics image software (Materialise, Leuven, Belgium), the native heart, major arteries, and LVAD were segmented to create patient-specific 3D models, allowing LV cavity volume and long-axis length to be measured directly. The deviation of the IC was quantified in a cylindrical coordinate system at the IC insertion point relative to the mitral valve and septum, and IC occlusion was assessed by the distance between cannula inlet and the proximal endocardium. Compared with normal cases, patients with malpositioned pumps had shorter LV length (p = 0.03) and reduced pump pocket depth (p = 0.009). Malpositioned pumps may experience greater obstruction by the nearby myocardium. This quantitative 3D modeling tool may help identify different modes of pump malalignment and migration and may facilitate preoperative planning and minimally invasive approaches via virtual LVAD implantation.

Baron, S. J., S. V. Arnold, K. Wang, E. A. Magnuson, K. Chinnakondepali, R. Makkar, H. C. Herrmann, S. Kodali, V. H. Thourani, S. Kapadia, L. Svensson, D. L. Brown, M. J. Mack, C. R. Smith, M. B. Leon and D. J. Cohen (2017). “Health status benefits of transcatheter vs surgical aortic valve replacement in patients with severe aortic stenosis at intermediate surgical risk: Results from the partner 2 randomized clinical trial.” JAMA Cardiol: 2017 Jun [Epub ahead of print].

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Importance: In patients with severe aortic stenosis (AS) at intermediate surgical risk, treatment with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) results in similar 2-year survival. The effect of TAVR vs SAVR on health status in patients at intermediate surgical risk is unknown. Objective: To compare health-related quality of life among intermediate-risk patients with severe AS treated with either TAVR or SAVR. Design, Setting, and Participants: Between December 2011 and November 2013, 2032 intermediate-risk patients with severe AS were randomized to TAVR with the Sapien XT valve or SAVR in the Placement of Aortic Transcatheter Valve 2 Trial and were followed up for 2 years. Data analysis was conducted between March 1, 2016, to April 30, 2017. Main Outcomes and Measures: Health status was assessed at baseline, 1 month, 1 year, and 2 years using the Kansas City Cardiomyopathy Questionnaire (KCCQ) (23 items covering physical function, social function, symptoms, self-efficacy and knowledge, and quality of life on a 0- to 100-point scale; higher scores indicate better quality of life), Medical Outcomes Study Short Form-36 (36 items covering 8 dimensions of health status as well as physical and mental summary scores; higher scores represent better health status), and EuroQOL-5D (assesses 5 dimensions of general health on a 3-level scale, with utility scores ranging from 0 [death] to 1 [ideal health]). Analysis of covariance was used to examine changes in health status over time, adjusting for baseline status. Results: Of the 2032 randomized patients, baseline health status was available for 1833 individuals (950 TAVR, 883 SAVR) who formed the primary analytic cohort. A total of 1006 (54.9%) of the population were men; mean (SD) age was 81.4 (6.8) years. Over 2 years, both TAVR and SAVR were associated with significant improvements in both disease specific (16-22 points on the KCCQ-OS scale) and generic health status (3.9-5.1 points on the SF-36 physical summary scale). At 1 month, TAVR was associated with better health status than SAVR, but this difference was restricted to patients treated via transfemoral access (mean difference in the KCCQ overall summary [KCCQ-OS] score, 14.1 points; 95% CI, 11.7 to 16.4; P < .01) and was not seen in patients treated via transthoracic access (mean difference in KCCQ-OS, 3.5 points; 95% CI, -1.4 to 8.4; P < .01 for interaction). There were no significant differences between TAVR and SAVR in any health status measures at 1 or 2 years. Conclusions and Relevance: Among intermediate-risk patients with severe AS, health status improved significantly with both TAVR and SAVR through 2 years of follow up. Early health status improvement was greater with TAVR, but only among patients treated via transfemoral access. Longer term follow-up is needed to assess the durability of quality-of-life improvement with TAVR vs SAVR in this population.

Kotecha, D., M. D. Flather, D. G. Altman, J. Holmes, G. Rosano, J. Wikstrand, M. Packer, A. J. S. Coats, L. Manzano, M. Bohm, D. J. van Veldhuisen, B. Andersson, H. Wedel, T. G. von Lueder, A. S. Rigby, A. Hjalmarson, J. Kjekshus and J. G. F. Cleland (2017). “Heart rate and rhythm and the benefit of beta-blockers in patients with heart failure.” J Am Coll Cardiol 69(24): 2885-2896.

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BACKGROUND: The relationship between mortality and heart rate remains unclear for patients with heart failure with reduced ejection fraction in either sinus rhythm or atrial fibrillation (AF). OBJECTIVES: This analysis explored the prognostic importance of heart rate in patients with heart failure with reduced ejection fraction in randomized controlled trials comparing beta-blockers and placebo. METHODS: The Beta-Blockers in Heart Failure Collaborative Group performed a meta-analysis of harmonized individual patient data from 11 double-blind randomized controlled trials. The primary outcome was all-cause mortality, analyzed with Cox proportional hazard ratios (HR) modeling heart rate measured at baseline and approximately 6 months post-randomization. RESULTS: A higher heart rate at baseline was associated with greater all-cause mortality for patients in sinus rhythm (n = 14,166; adjusted HR: 1.11 per 10 beats/min; 95% confidence interval [CI]: 1.07 to 1.15; p < 0.0001) but not in AF (n = 3,034; HR: 1.03 per 10 beats/min; 95% CI: 0.97 to 1.08; p = 0.38). Beta-blockers reduced ventricular rate by 12 beats/min in both sinus rhythm and AF. Mortality was lower for patients in sinus rhythm randomized to beta-blockers (HR: 0.73 vs. placebo; 95% CI: 0.67 to 0.79; p < 0.001), regardless of baseline heart rate (interaction p = 0.35). Beta-blockers had no effect on mortality in patients with AF (HR: 0.96, 95% CI: 0.81 to 1.12; p = 0.58) at any heart rate (interaction p = 0.48). A lower achieved resting heart rate, irrespective of treatment, was associated with better prognosis only for patients in sinus rhythm (HR: 1.16 per 10 beats/min increase, 95% CI: 1.11 to 1.22; p < 0.0001). CONCLUSIONS: Regardless of pre-treatment heart rate, beta-blockers reduce mortality in patients with heart failure with reduced ejection fraction in sinus rhythm. Achieving a lower heart rate is associated with better prognosis, but only for those in sinus rhythm.