Cardiology

Sherwood, M. W., S. Vemulapalli, J. K. Harrison, D. Dai, A. N. Vora, M. J. Mack, D. R. Holmes, J. S. Rumsfeld, D. J. Cohen, V. H. Thourani, A. Kirtane and E. D. Peterson (2018). “Variation in post-TAVR antiplatelet therapy utilization and associated outcomes: Insights from the STS/ACC TVT Registry.” Am Heart J 204: 9-16.

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BACKGROUND: Dual antiplatelet therapy (DAPT) is recommended following transcatheter aortic valve replacement (TAVR); however, the optimal antiplatelet strategy is undefined, and little is known about practice patterns. We aimed to describe contemporary practice patterns of antiplatelet therapy and their relationship to outcomes post-TAVR. METHODS: The population was derived from the National Cardiovascular Data Registry, Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry with Center for Medical Services linkage for 1-year outcomes from October 1, 2011 to June 30,2016. The primary outcome measured was DAPT use in patients without anticoagulation. Secondary outcomes included death, major bleeding, myocardial infarction (MI), and stroke at 1year. RESULTS: Overall, 16,694 patients underwent transfemoral TAVR at 444 hospitals and were discharged without anticoagulation. Among these, 13,546 (81.1%) patients were discharged on DAPT, whereas 3,148 patients (18.9%) were discharged on monotherapy. Patients discharged on DAPT versus monotherapy were similar in age, sex, and most comorbid illnesses but had higher rates of coronary artery disease (64.6% vs 52.3%; P<.01) and peripheral artery disease (25.2% vs 22.3%; P<.01). Hospital prescribing patterns varied significantly (median frequency of DAPT 85.7%, interquartile range 94.1%-74.2%). DAPT (vs monotherapy) patients had a similar mortality risk at 1year (adjusted hazard ratio 0.92, 95% CI 0.81-1.05), significantly higher risk for major bleeding (1.48, 1.10-1.99), and similar hazard for stroke (1.04, 0.83-1.31) and MI (1.00, 0.72-1.39). CONCLUSIONS: In the United States, most patients were discharged on DAPT following TAVR. Practice patterns varied significantly among hospitals. Patients discharged with DAPT had a similar adjusted risk of mortality, stroke, and MI compared to antiplatelet monotherapy, although risk for bleeding was significantly higher. Future investigation is needed to define the optimal antiplatelet therapy for patients undergoing TAVR.

Shahian, D. M., T. G. Gleason, R. J. Shemin, J. D. Carroll and M. J. Mack (2018). “TAVR 2.0: Collaborating to Measure, Assure, and Advance Quality.” Ann Thorac Surg Aug 1. [Epub ahead of print].

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The 2018 TAVR Multisociety Expert Consensus Systems of Care Document is a substantial enhancement of the previous 2012 document, reflecting our continually improving understanding of the requirements for safe and effective use of this technology. Mandatory participation in the TVT registry, direct measures of quality, volume thresholds to assure adequate experience and sample sizes for quality measures, and consistent involvement of MDT’s are critical to the ongoing evolution of transcatheter aortic valve therapy; they are also a paradigm for similar new initiatives in the future. Finally, the Multisociety Writing Committee strongly supports continuation of the TAVR NCD to assure that gains made during the successful initial introduction of this technology are maintained. (Excerpt from unpaginated advanced text; no abstract available.)

Packer, M. and D. W. Kitzman (2018). “Obesity-Related Heart Failure With a Preserved Ejection Fraction: The Mechanistic Rationale for Combining Inhibitors of Aldosterone, Neprilysin, and Sodium-Glucose Cotransporter-2.” JACC Heart Fail 6(8): 633-639.

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Obesity-related heart failure with a preserved ejection fraction (HFpEF) is an important phenotype prevalent in the community, especially in people with metabolic disorders (e.g., dyslipidemia, diabetes). These individuals exhibit a marked expansion of plasma volume, but ventricular distensibility is limited, most likely as a result of cardiac microvascular rarefaction acting in concert with myocardial and pericardial fibrosis. Consequently, the increase in plasma volume causes a disproportionate increase in cardiac filling pressures, leading to heart failure, even though systolic ejection is not impaired. The features of this syndrome appear to be related (in part) to the overproduction of adipocyte-derived cell-signaling molecules, including aldosterone and neprilysin. The resulting sodium retention and plasma volume expansion is exacerbated by their mutual actions to promote cardiac and systemic inflammation and fibrosis. Inhibitors of aldosterone, neprilysin, and the sodium-glucose transporter-2 (SGLT2) can ameliorate the plasma volume expansion and pro-inflammatory and profibrotic pathways, potentially opposing the action of diverse adipocytokines. All 3 classes of drugs can reduce the quantity of visceral adipose tissue and ameliorate its abnormal biological properties. This mechanistic framework is supported by the results of large-scale randomized trials with mineralocorticoid receptor antagonists and SGLT2 inhibitors and is being further tested in an ongoing large-scale trial of neprilysin inhibition. The promise of using mineralocorticoid receptor antagonists, neprilysin inhibitors, and SGLT2 inhibitors (alone or in combination) in the management of obesity-related HFpEF suggests that physicians might finally have a phenotype of HFpEF that they can understand and treat.

Packer, M. (2018). “Obesity-Associated Heart Failure as a Theoretical Target for Treatment With Mineralocorticoid Receptor Antagonists.” JAMA Cardiol Jul 25. [Epub ahead of print].

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Importance: Despite their clinical benefits, mineralocorticoid receptor antagonists are greatly underprescribed by most practitioners who treat patients with chronic heart failure. A novel approach to encouraging the use of these drugs is to enhance awareness about the intimate link between aldosterone and obesity. Observations: There is a strong association between abdominal obesity and circulating levels of aldosterone, and markers of abdominal obesity identify patients most likely to benefit from mineralocorticoid receptor antagonism. In a trial of patients with heart failure and a reduced ejection fraction, patients with an increased waist circumference exhibited an approximately 50% reduction in the risk of a primary end point. The magnitude of benefit was more than twice as great in patients with abdominal obesity than in those with a normal waist circumference, and patients with abdominal obesity tolerated treatment better than nonobese patients. Similarly, in a trial of patients with heart failure and a preserved ejection fraction, those who were most likely to have abdominal obesity (identified by their level of natriuretic peptides) were most likely to demonstrate a benefit of treatment with spironolactone, exhibiting an approximately 80% reduction in the risk of a primary end point (based on a small number of events). Conclusions and Relevance: Although these analyses are post hoc, their concordance and strong biological foundation suggests that abdominal obesity may identify patients who respond most favorably to mineralocorticoid receptor antagonism. Given the easy availability of its measurement, targeting patients with an increased waist circumference could enhance the adoption of these important drugs for the treatment of chronic heart failure in clinical practice.

Gaudino, M., M. J. Mack and D. P. Taggart (2018). “Additional arterial conduits in coronary artery bypass surgery: Finally coming of age.” J Thorac Cardiovasc Surg 156(2): 541-543.

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At 50 years, CABG has entered a mature phase. It is now time to clarify the effect of procedural characteristics on clinical outcomes and to define the most appropriate strategy for each individual patient. Observational data have intrinsic biases and should only be considered hypothesis-generating. Randomized trials remain the only way to solve the conundrum of arterial grafts. International collaboration will be key to the success of this process. (Excerpt from text, p. 543; no abstract available.)