Cardiology

Anker, S.D., Butler, J., Filippatos, G., Khan, M.S., Marx, N., Lam, C.S.P., Schnaidt, S., Ofstad, A.P., Brueckmann, M., Jamal, W., Bocchi, E., Ponikowski, P., Perrone, S.V., Januzzi, J.L., Verma, S., Böhm, M., Ferreira, J.P., Pocock, S.J., Zannad, F. and Packer, M. (2020). “Effect of Empagliflozin on Cardiovascular and Renal Outcomes in Patients With Heart Failure by Baseline Diabetes Status – Results from the EMPEROR-Reduced Trial.” Circulation Nov 29. [Epub ahead of print.].

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Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve outcomes in patients with heart failure with reduced ejection fraction, but additional information is needed about whether glycemic status influences the magnitude of their benefits on heart failure and renal events. Methods: Patients with class II-IV heart failure and a left ventricular ejection fraction ≤40% were randomized to receive empagliflozin (10 mg daily) or placebo in addition to recommended therapy. We prespecified a comparison of the effect of empagliflozin in patients with and without diabetes. Results: Of the 3730 patients enrolled, 1856 (50%) had diabetes, 1268 (34%) had prediabetes (HbA1c 5.7-6.4%), and 606 (16%) had normoglycemia (HbA1c <5.7%). The risks of the primary outcome (cardiovascular death or hospitalization for heart failure), total hospitalizations for heart failure, and adverse renal outcomes were higher in patients with diabetes, but were similar between patients with prediabetes and normoglycemia. Empagliflozin reduced the risk of the primary outcome in patients with and without diabetes (hazard ratio 0.72 [95% CI 0.60-0.87] and 0.78 [95% CI 0.64-0.97], respectively, interaction P =0.57). Patients with and without diabetes also did not differ with respect to the effect of empagliflozin on total hospitalizations for heart failure, on the decline in estimated glomerular filtration rate over time, and on the risk of serious adverse renal outcomes. Among these endpoints, the effects of the drug did not differ in patients with prediabetes or normoglycemia. When analyzed as a continuous variable, baseline HbA1c did not significantly modify the benefits of empagliflozin on the primary outcome (P-interaction=0.40). Empagliflozin did not lower HbA1c in patients with prediabetes or normoglycemia and was not associated with increased risk of hypoglycemia. Conclusions: In the EMPEROR-Reduced trial, empagliflozin significantly improved cardiovascular and renal outcomes in patients with heart failure and a reduced ejection fraction, independent of baseline diabetes status and across the continuum of HbA1c.

Rahimi, G., Tecson, K.M., Elsaid, O. and McCullough, P.A. (2020). “Role of Ischemic Heart Disease in Major Adverse Renal and Cardiac Events Among Individuals with Heart Failure with Preserved Ejection Fraction (From the TOPCAT Trial).” Am J Cardiol Dec 3;S0002-9149(20)31296-0. [Epub ahead of print.].

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Despite improvements in the prognosis of patients with heart failure with reduced ejection fraction (HFrEF), established therapy for heart failure patients with preserved ejection fraction (HFpEF) is lacking. Additionally, ischemic heart disease adversely impacts the clinical course of HFrEF patients; however, its role in HFpEF is not fully understood. We conducted a post hoc analysis of propensity score matched patients from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial to compare HFpEF patients with versus without myocardial ischemia in terms of major adverse renal and/or cardiac events (MARCE). Of 3445 participants, the prevalence of ischemia was 59%. For this analysis, we included 1747 ischemic patients and 1207 propensity matched non-ischemic patients. Ischemia was associated with a 20% increased risk (HR=1.20, 95% CI=1.042-1.382, p-value=0.0112) of MARCE in adjusted analyses. Other important predictors of MARCE were diabetes (HR=1.60, 95% CI=1.38-1.87, p <0.0001), dyslipidemia (HR=1.30, 95% CI=1.10-1.52, p=0.001) and smoking (HR=1.33, 95% CI=1.04-1.69, p= 0.0197). Revascularization was not significantly associated with MARCE in the subgroup of ischemic HFpEF patients. Future work is warranted to develop tailored interventions for patients with both HFpEF and ischemic heart disease to mitigate the risk of MARCE .

Elsaid, O., McCullough, P.A., Tecson, K.M., Williams, R.S. and Yoon, A. (2020). “Ventricular Fibrillation Storm in Coronavirus 2019.” Am J Cardiol 135: 177-180.

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Cardiac arrhythmia is a known manifestation of novel coronavirus 2019 (COVID-19) infection. Herein, we describe the clinical course of an otherwise healthy patient who experienced persistent ventricular tachycardia and fibrillation which is believed to be directly related to inflammation, as opposed to acute myocardial injury or medications that can prolong the QT interval.

McCullough, P.A. (2020). “Favipiravir and the Need for Early Ambulatory Treatment of SARS-CoV-2 Infection (COVID-19).” Antimicrob Agents Chemother 64(12).

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It is becoming increasingly clear that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), like most human viral infections, will require multiple drugs in combination to treat COVID-19 illness. In this issue of the Journal, Doi and colleagues describe successful treatment of patients with early COVID-19 with favipiravir, an oral polymerase inhibitor, to rapidly and substantially clear SARS-CoV-2 from nasal secretions irrespective if it was started relatively early or later within the first week of infection. These data support the concept that favipiravir could be paired with at least one more off-target antiviral agent (doxycycline, azithromycin, or ivermectin) followed by corticosteroids and antithrombotics to prevent COVID-19 hospitalization and death in those over age 50 and/or those with one or more comorbidities. Clinical trials and advanced practice should immediately pivot to combination/sequential drug therapy for ambulatory COVID-19 illness.

Barker, C.M., Cork, D.P., McCullough, P.A., Mehta, H.S., Houten, J.V., Gunnarsson, C., Mollenkopf, S. and Verta, P. (2020). “Healthcare utilization in clinically significant tricuspid regurgitation patients with and without heart failure.” J Comp Eff Res Nov 11. [Epub ahead of print.].

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Aim: This study evaluated how the presence of right-sided heart disease (RSHD), other valve disease (OVD) and heart failure (HF) impacts healthcare utilization in patients with tricuspid valve disease (tricuspid regurgitation [TR]). Materials & methods: Of the 33,686 patients with TR: 6618 (19.6%) had TR-only; 8952 (26.6%) had TR with HF; 12,367 (36.7%) had TR with OVD but no HF; and 5749 (17.1%) had TR with RSHD only. Results: The presence of RSHD, OVD or HF in patients with TR was independently associated with increased annualized hospitalizations, hospital days and costs relative to patients with TR alone. Conclusion: All three co-morbidities were associated with increased healthcare utilization, with HF showing the greatest impact across all measures.