Cardiology

Grover, F. L., S. Vemulapalli, J. D. Carroll, F. H. Edwards, M. J. Mack, V. H. Thourani, R. G. Brindis, D. M. Shahian, C. E. Ruiz, J. P. Jacobs, G. Hanzel, J. E. Bavaria, E. M. Tuzcu, E. D. Peterson, S. Fitzgerald, M. Kourtis, J. Michaels, B. Christensen, W. F. Seward, K. Hewitt and D. R. Holmes, Jr. (2016). “2016 annual report of the society of thoracic surgeons/american college of cardiology transcatheter valve therapy registry.” J Am Coll Cardiol: 2016 Dec [Epub ahead of print].

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BACKGROUND: The STS/ACC Transcatheter Valve Therapy (TVT) Registry captures all procedures with Food and Drug Administration (FDA) approved transcatheter valve devices performed in the United States and is mandated as a condition of reimbursement by a Centers for Medicaid and Medicare Services (CMS) OBJECTIVES: This annual report focuses on patient characteristics, trends, and outcomes of transcatheter aortic and mitral valve catheter-based valve procedures in the United States. METHODS: Data for all patients receiving commercially approved devices from 2012 through December 31, 2015 are entered in the TVT Registry. RESULTS: The 54,782 TAVR patients demonstrated decreases in expected risk of 30-day operative mortality (STS PROM) 7% to 6% and TAVR PROM (TVT PROM) 4% to 3% (both p<.0001) from 2012 to 2015. Observed in-hospital mortality decreased from 5.7% to 2.9% and one-year mortality decreased from 25.8% to 21.6. However, 30-day post procedure pacemaker insertion increased from 8.8% in 2013 to 12.0% in 2015. The 2,556 patients who underwent TMC in 2015 were similar to 2013-14 patients with hospital mortality of 2% with mitral regurgitation reduced to gradient /= 2 in 87% of patients (p<.0001). The 349 patients who underwent MViV and MViR procedures were high risk with, an STS PROM for MVR of 11%. The observed hospital mortality was 7.2% and 30-day post procedure was 8.5%. SUMMARY: The TVT Registry is an innovative registry that that monitors quality, patient safety and trends for these rapidly evolving new technologies. CONDENSED ABSTRACT: The STS/ACC TVT Registry captures all Food and Drug Administration (FDA) approved transcatheter valve devices preformed in the United States and is mandated as a condition for reimbursement by the Centers for Medicare Services. TAVR patients' expected risks of mortality and actual in-hospital mortality decreased. Transcatheter mitral clip procedures had a low mortality with reduced in mitral regurgitation to grade /= 2 in 87%. Mitral valve in valve or valve in ring patients were high risk for mortality, but actual hospital mortality was lower. The TVT Registry is an innovative registry that monitors quality, safety and trends of these evolving technologies.

Nadruz, W., Jr., B. L. Claggett, J. J. McMurray, M. Packer, M. R. Zile, J. L. Rouleau, A. S. Desai, K. Swedberg, M. Lefkowitz, V. C. Shi, M. F. Prescott and S. D. Solomon (2016). “Impact of body mass index on the accuracy of n-terminal pro-brain natriuretic peptide and brain natriuretic peptide for predicting outcomes in patients with chronic heart failure and reduced ejection fraction: Insights from the paradigm-hf study (prospective comparison of arni with acei to determine impact on global mortality and morbidity in heart failure trial).” Circulation 134(22): 1785-1787.

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The design and primary results of the PARADIGM-HF trial have been previously described.5 The patients randomized in the trial (n=8399) were required to have a plasma BNP ≥150 pg/mL or an NT-proBNP ≥600 pg/mL or, if they were hospitalized for HF within the previous 12 months, a BNP ≥100 pg/mL or an NT-proBNP ≥400 pg/ mL. The present study included patients with available BMI data and who had BNP and NT-proBNP locally measured at the time of screening (n=8217). It considered the primary outcome of the PARADIGM-HF trial, the composite of death from cardiovascular causes or a first hospitalization for HF, as the study outcome. The patients were categorized into 4 groups according to BMI: <25.0 (nonoverweight/obese; n=2536); 25.0 to 29.9 (overweight; n=3116); 30.0 to 34.9 (obese; n=1694); and ≥35.0 kg/m2 (moderately/severely obese; n=871). BNP and NT-proBNP were divided into quartiles within the whole studied population. The trial was approved by the ethics committee at each participating institution, and all the patients provided written informed consent.

Packer, M. (2016). “Development and evolution of a hierarchical clinical composite end point for the evaluation of drugs and devices for acute and chronic heart failure: A 20-year perspective.” Circulation 134(21): 1664-1678.

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Traditional approaches to the assessment of new treatments for heart failure have generally evaluated individual components of the syndrome at fixed points in time or have relied on surrogate physiological measures that are poorly correlated with the clinical status of patients. Conventional time-to-event trials that focus on morbidity and mortality represent an important methodological advance, but they generally assign undue weight to clinical events of less importance and are insensitive to difference in functional capacity among individuals who do not experience a clinical event during follow-up. Twenty years ago, a hierarchical clinical composite was developed to address these limitations; it aims to assess the clinical course of patients as a physician would in practice by combining a symptomatic assessment of the patient at each visit with an evaluation of the clinical stability of the patient between visits. The composite does not generate a numeric score by summing arbitrarily assigned weights to certain symptoms or events; instead, the composite ranks relevant measures and outcomes according to clinical priority. In doing so, the clinical composite minimizes the biases created by noncompleting patients in the assessment of symptoms or exercise tolerance while expanding the range of patients who contribute to the treatment difference in a typical morbidity and mortality trial. When applied appropriately, the hierarchical clinical composite end point has reliably distinguished effective from ineffective treatments. The composite may have particular advantages in the evaluation of new devices and transcatheter interventions in chronic heart failure and of new drugs for acute heart failure. Recent modifications enhance its discriminant characteristics and its ability to accurately assess the efficacy of novel interventions for heart failure.

McCullough, P. A., T. Ball, K. M. Cox and M. D. Assar (2016). “Use of oral anticoagulation in the management of atrial fibrillation in patients with esrd: Pro.” Clin J Am Soc Nephrol 11(11): 2079-2084.

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Warfarin has had a thin margin of benefit over risk for the prevention of stroke and systemic embolism in patients with ESRD because of higher bleeding risks and complications of therapy. The successful use of warfarin has been dependent on the selection of patients with nonvalvular atrial fibrillation at relatively high risk of stroke and systemic embolism and lower risks of bleeding over the course of therapy. Without such selection strategies, broad use of warfarin has not proven to be beneficial to the broad population of patients with ESRD and nonvalvular atrial fibrillation. In a recent meta-analysis of use of warfarin in patients with nonvalvular atrial fibrillation and ESRD, warfarin had no effect on the risks of stroke (hazard ratio, 1.12; 95% confidence interval, 0.69 to 1.82; P=0.65) or mortality (hazard ratio, 0.96; 95% confidence interval, 0.81 to 1.13; P=0.60) but was associated with increased risk of major bleeding (hazard ratio, 1.30; 95% confidence interval, 1.08 to 1.56; P<0.01). In pivotal trials, novel oral anticoagulants were generally at least equal to warfarin for efficacy and safety in nonvalvular atrial fibrillation and mild to moderate renal impairment. Clinical data for ESRD are limited, because pivotal trials excluded such patients. Given the very high risk of stroke and systemic embolism and the early evidence of acceptable safety profiles of novel oral anticoagulants, we think that patients with ESRD should be considered for treatment with chronic anticoagulation provided that there is an acceptable bleeding profile. Apixaban is currently indicated in ESRD for this application and may be preferable to warfarin given the body of evidence for warfarin and its difficulty of use and attendant adverse events.

Packer, M., R. Holcomb, W. T. Abraham, S. Anker, K. Dickstein, G. Filippatos, H. Krum, A. P. Maggioni, J. J. McMurray, A. Mebazaa, C. O’Connor, F. Peacock, P. Ponikowski, F. Ruschitzka, D. J. van Veldhuisen and J. Holzmeister (2016). “Rationale for and design of the true-ahf trial: The effects of ularitide on the short-term clinical course and long-term mortality of patients with acute heart failure.” Eur J Heart Fail: 2016 Nov [Epub ahead of print].

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The TRUE-AHF is a randomized, double-blind, parallel-group, placebo-controlled trial which is evaluating the effects of a 48-h infusion of ularitide (15 ng/kg/min) on the short- and long-term clinical course of patients with acute heart failure. Noteworthy features of the study include the early enrolment of patients following their initial clinical presentation (within 12 h), and entry blood pressure criteria and thresholds for the adjustment of drug infusion rates, which aim to minimize the risk of hypotension. The trial has two primary endpoints: (i) cardiovascular mortality during long-term follow-up; and (ii) the clinical course of patients during their index hospitalization. Cardiovascular mortality is evaluated in this event-driven trial by following all randomized patients for the occurrence of death until the end of the entire study without truncation at an arbitrarily determined early time point. The clinical course during the index hospitalization is evaluated using the hierarchical clinical composite endpoint, which combines information regarding changes in symptoms and the occurrence of in-hospital worsening heart failure events and death into a single ranked metric that captures interval clinical events and minimizes the likelihood of missing data and confounding due to intensification of background therapy. The design of the TRUE-AHF trial capitalizes on lessons learned from earlier trials and aims to evaluate definitively the potential benefit of ularitide in patients with acute heart failure.