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The superiority of angiotensin receptor-neprilysin inhibitor (ARNI) over angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin receptor blocker (ARB) has not been reassessed after the publication of recent trials that did not find clinical benefits. Therefore, we performed an updated network meta-analysis comparing the efficacy and safety of ARNI, ACE-I, ARB, and placebo in heart failure with reduced ejection fraction. We included randomized clinical trials that compared ARNI, ARB, ACE-I, and placebo in heart failure with reduced ejection fraction. We extracted prespecified efficacy end points and produced network estimates, p scores, and surface under the cumulative ranking curve scores using frequentist and Bayesian network meta-analysis approaches. A total of 28 randomized controlled trials including 47,407 patients were included. ARNI was associated with lower risk of all-cause mortality (relative risk [RR] 0.81, 95% confidence interval [CI] 0.68 to 0.96), cardiac death (RR 0.79, 95% CI 0.64 to 0.99), and major adverse cardiac events (MACEs; RR 0.83, 95% CI 0.72 to 0.97) but higher risk of hypotension (RR 1.46, 95% CI 1.02 to 2.10) than ARB. ARNI was associated with lower risk of MACE (RR 0.85, 95% CI 0.74 to 0.97), but higher risk of hypotension (RR 1.69, 95% CI 1.27 to 2.24) compared with ACE-I. P scores and surface under the cumulative ranking curve scores demonstrated superiority of ARNI over ARB and ACE-I in all-cause mortality, cardiac death, MACE, and hospitalization for heart failure. In conclusion, ARNI was associated with improved clinical outcomes, except for higher risk of hypotension, compared with ARB and ACE-I., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The effect of preoperative atrial fibrillation (AF) on clinical outcomes after left ventricular assist device (LVAD) implantation remains uncertain. We sought to conduct a meta-analysis to assess the safety and efficacy of LVAD implantation in AF patients. Medline and Scopus were searched for studies that assessed the effect of preoperative AF on clinical outcomes in patients who underwent LVAD implantation. Outcomes of interest included all-cause mortality, thromboembolic events, and bleeding. Estimates were combined using random effects model to calculate risk ratios (RRs) with 95% confidence intervals. In this meta-analysis of 7 studies including 5,658 patients, preoperative AF was not associated with increased risk of all-cause mortality at 30 days (RR = 0.84 [0.51, 1.37]; p = 0.49; I 2  = 0%), 6 months (RR = 1.17 [0.96, 1.14]; p = 0.11; I 2  = 21%), 1 year (RR = 1.16 [0.84, 1.60]; p = 0.37; I 2  = 53%) and 2 years (RR = 1.14 [0.96, 1.36]; p = 0.12; I 2  = 23%). Preoperative AF did not increase the risk of thromboembolism (RR = 0.86 [0.38, 1.92]; p = 0.71; I 2  = 26%), pump thrombosis (RR = 1.22 [0.88, 1.68]; p = 0.23; I 2  = 49%), stroke (RR = 1.02 [0.87, 1.19]; p = 0.79; I 2  = 11%), or major bleeding (RR = 0.86 [0.38, 1.92]; p = 0.71; I 2  = 26%) after LVAD implantation. However, AF was associated with significantly increased risk of gastro-intestinal bleeding in patients receiving LVADs (RR = 1.27 [1.05, 1.55]; p = 0.014; I 2  = 0%). In conclusion, this meta-analysis reports a significantly increased risk of gastrointestinal (GI) bleeding in LVADs recipients having concomitant AF. However, AF had no significant effect on all-cause mortality, stroke, or thromboembolic events in these patients. Further well-conducted studies are needed to validate these results., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Although echocardiography is usually diagnostic of cardiac tamponade, it may not be readily available at the point-of-care. We sought to develop and validate a measurement of respirophasic variation in the amplitude of pulse oximetry plethysmographic waveforms as a diagnostic tool for cardiac tamponade. Pulse oximetry plethysmographic waveforms were recorded, and the ratio of maximum-to-minimum measured amplitude of these waveforms from one respiratory cycle was calculated by blinded observers. Ratios from 3 consecutive respiratory cycles were then averaged to derive an "oximetry paradoxus" ratio. Cardiac tamponade was independently confirmed or excluded according to a "blinded" objective interpretation of echocardiography or right heart catheterization. Seventy four subjects were enrolled (51% men; mean age 54 ± 15 years); 19 of whom had cardiac tamponade. Oximetry paradoxus area under the curve for diagnosis of cardiac tamponade was 0.90 (95% confidence interval, 0.84 to 0.97); its diagnostic performance was superior to sphygmomanometer-measured pulsus paradoxus (area under the curve difference = 0.16, p = 0.022). In a derivation cohort (n = 37; tamponade, 9 cases), 3 diagnostic oximetry paradoxus thresholds were identified and validated in an independent validation cohort (n = 37; tamponade, 10 cases): 1.2 (100% sensitivity, 44% specificity), 1.5 (80% sensitivity, 81% specificity), and 1.7 (80% sensitivity, 89% specificity). Furthermore, oximetry paradoxus was significantly reduced after draining pericardial fluid. In conclusion, we defined and validated oximetry paradoxus as a simple and ubiquitous point-of-care test to diagnose cardiac tamponade using respirophasic changes in pulse plethysmography waveforms. This test can aid in identifying patients with cardiac tamponade, thus expediting confirmatory testing and life-saving treatment., (Copyright © 2018. Published by Elsevier Inc.)

The impact of physical inactivity on heart failure (HF) mortality is unclear. We analyzed data from the HF Adherence and Retention Trial (HART) which enrolled 902 patients with New York Heart Association class II/III HF, with preserved or reduced ejection fraction, who were followed for 36 months. On the basis of mean self-reported weekly exercise duration, patients were classified into inactive (0 min/week) and active (≥1 min/week) groups and then propensity score matched according to 34 baseline covariates in 1:2 ratio. Sedentary activity was determined according to self-reported daily television screen time (<2, 2 to 4, >4 h/day). The primary outcome was all-cause death. Secondary outcomes were cardiac death and HF hospitalization. There were 196 inactive patients, of whom 171 were propensity matched to 342 active patients. Physical inactivity was associated with greater risk of all-cause death (hazard ratio [HR] 2.01, confidence interval [CI] 1.47 to 3.00; p <0.001) and cardiac death (HR 2.01, CI 1.28 to 3.17; p = 0.002) but no significant difference in HF hospitalization (p = 0.548). Modest exercise (1 to 89 min/week) was associated with a significant reduction in the rate of death (p = 0.003) and cardiac death (p = 0.050). Independent of exercise duration and baseline covariates, television screen time (>4 vs <2 h/day) was associated with all-cause death (HR 1.65, CI 1.10 to 2.48; p = 0.016; incremental chi-square = 6.05; p = 0.049). In conclusion, in patients with symptomatic chronic HF, physical inactivity is associated with higher all-cause and cardiac mortality. Failure to exercise and television screen time are additive in their effects on mortality. Even modest exercise was associated with survival benefit., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Coronary artery disease (CAD) is a major cause of systolic heart failure (HF). Identifying CAD as a cause of systolic HF has prognostic and treatment implications. Whether all patients with systolic HF of unclear etiology should undergo coronary angiography has been controversial. We sought to derive and validate a clinical prediction rule to exclude CAD as a cause of systolic HF. A derivation cohort was formed of consecutive patients who had undergone coronary angiography with a primary diagnosis of systolic HF of unclear etiology (ejection fraction <50%). Using multivariate logistic regression analysis, we derived a prediction rule for severe CAD (≥50% diameter stenosis in the left main, 3-vessel CAD, and 2-vessel CAD involving the proximal left anterior descending artery). The diagnostic performance of the defined prediction rule was prospectively validated in a separate cohort recruited from 2 institutions. Of the 124 patients in the derivation cohort, 27% had CAD, including 15% with severe CAD. The independent predictors of severe CAD included diabetes (odds ratio 5.1, p = 0.005), electrocardiographic Q waves or left bundle branch block (odds ratio 3.8, p = 0.02), and ≥2 nondiabetes risk factors: age (men ≥55 or women ≥65 years), dyslipidemia, hypertension, and tobacco use (odds ratio 4.8, p = 0.02). A prediction rule of having ≥1 independent predictor identified 97% of the patients with CAD and 100% of the patients with severe CAD. In the prospective validation cohort of 143 patients, the prediction rule had 98% sensitivity and 18% specificity for CAD but 100% sensitivity for severe CAD. In conclusion, a simple clinical prediction rule can accurately identify patients with CAD and eliminate the need for angiography in a substantial proportion of patients with systolic HF, with potentially significant cost savings and risk avoidance., (Copyright © 2013 Elsevier Inc. All rights reserved.)