Baylor Heart and Vascular Institute

Packer, M., J. J. V. McMurray, H. Krum, W. Kiowski, B. M. Massie, A. Caspi, C. M. Pratt, M. C. Petrie, D. DeMets, I. Kobrin, S. Roux and K. Swedberg (2017). “Long-term effect of endothelin receptor antagonism with bosentan on the morbidity and mortality of patients with severe chronic heart failure: Primary results of the enable trials.” JACC Heart Fail 5(5): 317-326.

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OBJECTIVES: The objective of this clinical trial was to evaluate the long-term effect of endothelin receptor antagonism with bosentan on the morbidity and mortality of patients with severe chronic heart failure. BACKGROUND: Endothelin may play a role in heart failure, but short-term clinical trials with endothelin receptor antagonists have reported disappointing results. Long-term trials are lacking. METHODS: In 2 identical double-blind trials, we randomly assigned 1,613 patients with New York Heart Association functional class IIIb to IV heart failure and an ejection fraction <35% to receive placebo or bosentan (target dose 125 mg twice daily) for a median of 1.5 years. The primary outcome for each trial was clinical status at 9 months (assessed by the hierarchical clinical composite); the primary outcome across the 2 trials was death from any cause or hospitalization for heart failure. RESULTS: Bosentan did not influence clinical status at 9 months in either trial (p = 0.928 and p = 0.263). In addition, 321 patients in the placebo group and 312 patients in the bosentan group died or were hospitalized for heart failure (hazard ratio [HR]: 1.01; 95% confidence interval [CI]: 0.86 to 1.18; p = 0.90). The bosentan group experienced fluid retention within the first 2 to 4 weeks, as evidenced by increased peripheral edema, weight gain, decreases in hemoglobin, and an increased risk of hospitalization for heart failure, despite intensification of background diuretics. During follow-up, 173 patients died in the placebo group and 160 patients died in the bosentan group (HR: 0.94; 95% CI: 0.75 to 1.16). About 10% of the bosentan group showed meaningful increases in hepatic transaminases, but none had acute or chronic liver failure. CONCLUSIONS: Bosentan did not improve the clinical course or natural history of patients with severe chronic heart failure and but caused early and important fluid retention.

Blanke, P., J. K. Park, P. Grayburn, C. Naoum, K. Ong, K. Kohli, B. L. Norgaard, J. G. Webb, J. Popma, D. Boshell, P. Sorajja, D. Muller and J. Leipsic (2017). “Left ventricular access point determination for a coaxial approach to the mitral annular landing zone in transcatheter mitral valve replacement.” J Cardiovasc Comput Tomogr: Apr [Epub ahead of print].

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INTRODUCTION: To facilitate coaxial device deployment in transcatheter mitral valve replacement (TMVR), a coaxial approach to the mitral annular plane is needed. We sought to establish a method to determine an ‘orthogonal’ left ventricular (LV) access point for transapical TMVR and to quantitatively characterize its location in patients with severe mitral regurgitation using cardiac computed tomography. METHODS: Cardiac CT data sets of 54 patients with moderate-severe mitral regurgitation evaluated for potential TMVR were analyzed. The D-shaped mitral annular contour was segmented and a 2-dimensional annular plane was derived, allowing for subsequent definition of the perpendicularly oriented mitral annular trajectory. The ‘orthogonal’ LV access point was defined as the transection point of mitral trajectory with the LV epicardial surface. The location of the access point was quantified by its epicardial distance from the true apex and by the rotational offset from a 3-chamber view. RESULTS: LV access points orthogonal to the mitral annular plane were most frequently located in the anterolateral (n = 22, 40.7%) and anterior (n = 16, 29.6%), less frequently anteroseptal (n = 6, 11.1%) and inferolateral (n = 5, 9.3%) ventricular segment; none inferior or inferoseptal. The mean distance to the LV apex was 17.6 +/- 7.7 mm. The mean forward rotational offset from the 3-chamber view was 96.4 +/- 43.4 degrees , relating to a mean forward rotational offset of 6.4 +/- 43.4 degrees in regard to a hypothetical, secondary 90 degrees x-plane view. No significant difference between patients with degenerative mitral valve disease or functional mitral regurgitation was observed. CONCLUSION: The location of the LV access point that provides an orthogonal trajectory to the mitral annular plane exhibits relevant inter-individual variability. It is commonly not identical with the true apex, and frequently localized in the anterolateral or anterior ventricular segments.

Farber, A. J., K. Suarez, K. Slicker, C. D. Patel, B. Pope, R. Kowal and J. B. Michel (2017). “Frequency of troponin testing in inpatient versus outpatient settings.” Am J Cardiol 119(8): 1153-1155.

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Troponin elevation is required to diagnose acute myocardial infarction (AMI), yet elevated values are often encountered in noncardiac disease states. We evaluated inpatient (IP) and outpatient (OP) encounters at 14 hospitals in calendar year 2014 and found that troponin assays were performed during 12% of all OP visits and 29% of all IP visits: 82,853 encounters in all. We employed an expert panel to estimate the likelihood of AMI based on primary International Statistical Classification of Diseases and Related Health Problems, 9th edition diagnoses. We compared IP and OP testing, finding that AMI would not be expected in most IP encounters. Sepsis was the most common diagnosis associated with IP troponin testing. We found an association between troponin testing in patients with sepsis and utilization of electrocardiography, echocardiography, and cardiac catheterization. Our data indicate that troponin testing has expanded beyond patient populations in whom AMI might be expected.

Rosenthal, R. L. (2017). “Electronic stethoscope for coronary stenosis detection.” Am J Med 130(5): e225.

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I read with interest the report by Azimpour et al1 on the ability of an electronic stethoscope to detect turbulent diastolic flow in coronary arteries associated with coronary stenosis by the use of a signal processing algorithm. Instead of the “gold standard” of percentage coronary stenosis they adopt as the reference standard, it would be more physiologically pertinent to explore the relationship to fractional flow reserve or some other similar measure of trans-stenotic flow gradient, such as the instantaneous wave-free ratio.

Packer, M. (2017). “Response by packer to letter regarding article, “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 135(15): e892-e893.

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The hierarchical clinical composite end point (HCCE) was developed to address 2 important goals in the analysis of clinical trial data: (1) to minimize the bias inherent in the censoring of important adverse events when the primary end point was focused entirely on a patient benefit, and (2) to expand the range of responses when the primary end point was focused entirely on the risk of an adverse event. Over the past 20 years, the hierarchical clinical composite has succeeded with respect to both goals, and yet, as I described in my article,1 the HCCE still has important limitations and remains a work in progress.