Cardiology

Packer, M. (2016). “Kicking the tyres of a heart failure trial: Physician response to the approval of sacubitril/valsartan in the USA.” Eur J Heart Fail: 2016 Aug [Epub ahead of print].

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Angiotensin receptor-neprilysin inhibition has been shown to be superior to target doses of an ACE inhibitor in reducing the risk of cardiovascular death and clinical disease progression in patients with chronic heart failure and a reduced EF. Nevertheless, although sacubitril/valsartan has been available in the USA for a year, uptake of the drug by practitioners has been slow, in part because of misconceptions about the pivotal trial that demonstrated its efficacy in heart failure (PARADIGM-HF). This review addresses questions that have been raised in the USA about the design of the trial as well as the patients who were studied, the replicability and applicability of the results, and the safety of neprilysin inhibition. The totality of evidence indicates that the PARADIGM-HF trial used an appropriate comparator; enrolled patients typical of those seen in the community with mild to moderate symptoms; yielded highly persuasive and replicable results; and demonstrated benefits that are applicable to patients taking subtarget doses of ACE inhibitors and ARBs. Regulatory review in the USA concluded that the established advantages of sacubitril/valsartan on cardiovascular death and disease progression outweighed hypothetical uncertainties about the long-term effects of neprilysin inhibition in patients who might not have survived without the drug. Accordingly, both the new US and European Society of Cardiology heart failure guidelines recommend sacubitril/valsartan as the preferred approach to inhibiting the renin-angiotensin system in patients with chronic heart failure who are currently receiving an ACE inhibitor or ARB.

Baber, U., M. E. Farkouh, Y. Arbel, P. Muntner, G. Dangas, M. J. Mack, T. H. Hamza, R. Mehran and V. Fuster (2016). “Comparative efficacy of coronary artery bypass surgery vs. Percutaneous coronary intervention in patients with diabetes and multivessel coronary artery disease with or without chronic kidney disease.” Eur Heart J: 2016 Aug [Epub ahead of print].

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BACKGROUND: The optimal method of coronary revascularization among patients with diabetes mellitus (DM) and multivessel coronary artery disease (CAD) complicated by chronic kidney disease (CKD) remains unknown. PURPOSE: To examine the impact of coronary artery bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) on cardiovascular outcomes in patients with diabetes with and without CKD. METHODS: We conducted an ‘as-treated’ subgroup analysis of the FREEDOM trial to examine the therapeutic efficacy of CABG vs. PCI among patients with DM stratified by the presence (n = 451) or absence (n = 1392) of CKD. We defined CKD as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2. Baseline characteristics and clinical outcomes were compared between PCI and CABG groups within each CKD stratum. The primary endpoint was the composite occurrence of all-cause death, stroke or myocardial infarction [major adverse cardiovascular and cerebrovascular events (MACCE)]. Event rates were estimated at 5 years using the Kaplan-Meier approach and hazard ratios (HRs) for CABG (vs. PCI) were generated using Cox regression. RESULTS: Patients with CKD (mean eGFR 47 mL/min/1.73m2) were older and more often female compared to those without renal impairment. Over a median follow-up of 3.8 years, the effect of CABG on MACCE was consistent among those with CKD (26.0% vs. 35.6%; HR [95% CI]: 0.73 [0.50-1.05]) and without CKD (16.2% vs. 23.6%; HR [95% CI)]: 0.76 [0.58-1.00]) with no evidence of interaction (pint = 0.83). Stroke rates were non-significantly higher with CABG whereas rates of MI and repeat revascularization were significantly reduced with CABG in both groups. CONCLUSIONS: Compared to PCI, the effects of CABG on long-term risks for MACCE observed in the FREEDOM trial are preserved among patients with mild to moderate CKD.

McCullough, P. A., E. Bennett-Guerrero, L. S. Chawla, T. Beaver, R. L. Mehta, B. A. Molitoris, A. Eldred, G. Ball, H. J. Lee, M. T. Houser and S. Khan (2016). “Abt-719 for the prevention of acute kidney injury in patients undergoing high-risk cardiac surgery: A randomized phase 2b clinical trial.” J Am Heart Assoc 5(8): 1-11.

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BACKGROUND: Patients undergoing cardiac surgeries with cardiopulmonary bypass (on-pump) have a high risk for acute kidney injury (AKI). We tested ABT-719, a novel alpha-melanocyte-stimulating hormone analog, for prevention of AKI in postoperative cardiac surgery patients. METHODS AND RESULTS: This phase 2b randomized, double-blind, placebo-controlled trial included adult patients with stable renal function undergoing high-risk on-pump cardiac surgery in the United States and Denmark. Participants received placebo (n=61) or cumulative ABT-719 doses of 800 (n=59), 1600 (n=61), or 2100 mug/kg (n=59). Primary outcome was development of AKI based on Acute Kidney Injury Network (AKIN) criteria, measured utilizing preoperative creatinine value and maximum value within 48 hours and urine output within the first 42 hours postsurgery. Secondary outcomes included incidence of AKI based on maximal changes from baseline in novel AKI biomarkers over a 72-hour period after clamp release and length of intensive care unit stays through 90 days postsurgery. A total of 65.5%, 62.7%, and 69.6% of patients in the 800-, 1600-, and 2100-mug/kg groups, respectively, developed AKI (stages 1, 2, and 3 combined) versus 65.5% in the placebo group (for each pair-wise comparison with placebo, P=0.966, 0.815, and 0.605, respectively). Adverse events occurred at a similar rate in all treatment groups. CONCLUSIONS: ABT-719 treatment did not lower AKI incidence using AKIN criteria, influence the elevations of novel biomarkers, or change 90-day outcomes in patients after cardiac surgery.

Cedars, A. and A. R. Opotowsky (2016). “Sustaining happiness in adult congenital heart disease.” World J Pediatr Congenit Heart Surg 7(5): 635-637.

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Patients with ACHD appear to have a distinct psychological adaptation to their lifelong heart disease. Although there is some inconsistency in the results of published studies, most data indicate that QOL among patients with ACHD is similar to the healthy general population, with the exception of the physical functioning domain.3 Furthermore, despite marked variability in objectively measured physical capacity between lesions,4 QOL in ACHD is not clearly related to lesion severity or complexity.3,5 This phenomenon appears to be consistent between countries with dramatically different health-care systems.6 The present study by Steele et al in a group of patients with CHD of high complexity provides further evidence for this observation. The apparent mental resilience among patients with ACHD is in stark contrast to adults with acquired heart failure (HF) in whom QOL is notably impaired compared to healthy controls.7 Although the reasons for preserved QOL in ACHD remain unknown, it has been proposed that patients with ACHD have a unique ‘‘sense of coherence.’’8 This concept, first introduced by Aaron Antonovsky as a metric of individual optimism and sense of control, may insulate patients with ACHD against health-related stressors.9

Packer, M. (2016). “Heart failure’s dark secret: Does anyone really care about optimal medical therapy?” Circulation 134(9): 629-631.

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Today, most heart failure physicians focus on devices and transplantation; hospital-based management teams devoted only to achieving optimal medical therapy are scarce. The financial demands on heart failure specialists are enormous. A viable business plan can no longer be based on the misguided hope that payers will reimburse generously for prescriptions of digitalis and diuretics; in contrast, cardiac procedures generate meaningful revenues. A growing advocacy now encourages the use of ventricular assist devices in ambulatory patients on the basis of the dual misconceptions that the hazards are readily managed and that the clinical responses to medical therapy are poor. The biases in favor of performing procedures are so great that a National Institutes of Health–sponsored randomized trial comparing left ventricular assistance and optimal medical therapy in ambulatory patients was closed because of slow recruitment.