BackgroundAtrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions.Methods and ResultsIn the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS 2 score was 3.5. Over 1.9 years of median follow‐up, 1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677).ConclusionsIn a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.

Ejection fraction (EF) is the most common measure of left ventricular function in patients with heart failure. However, serial measurements of EF are costly and not practical for guiding frequent management decisions. Impedance cardiography (ICG) provides noninvasive hemodynamic measures with proven validity. The purpose of this study was to assess how changes in ICG parameters compared with changes in EF in heart failure subjects enrolled in a comprehensive outpatient management program. Retrospective chart review identified 13 subjects with two sets of paired echocardiography and ICG measurements (before and after treatment in an outpatient heart failure clinic setting). Mean age was 69+/-11 years, etiology was 54% ischemic heart disease, and mean New York Heart Association class was 2.5+/-0.5. The mean time between pre- and posttreatment EF measurements was 198+/-161 days. Changes in cardiac index and systolic time ratio by ICG were compared with changes in EF by echocardiography. From entry to final measurement, mean EF improved 9%+/-13%. Seven (54%) subjects had >5% improvement in EF, three (23%) had >5% decrease, and three had <5% change. Changes in ICG cardiac index and systolic time ratio were highly correlated with changes in EF (0.85, -0.73). ICG may be a practical, reliable, and cost-effective method of monitoring left ventricular function and guiding management decisions.

Angiotensin-converting enzyme inhibitors, beta adrenergic blockers, and nesiritide are pharmacologic agents for heart failure with both short- and long-term neurohormonal and hemodynamic effects. Angiotensin-converting enzyme inhibitors and beta adrenergic blockers reduce morbidity and mortality in chronic heart failure. Higher doses may result in better outcomes than lower doses, but concern about hemodynamic tolerance is a major barrier to the initiation and up-titration of these agents. Nesiritide is a newer neurohormonal agent with proven efficacy and safety for use in decompensated heart failure, but appropriate patient selection has been challenging for clinicians. Like vasodilators, nesiritide may be underutilized in heart failure treatment. Impedance cardiography is a newer, noninvasive monitoring technology that can accurately measure hemodynamic parameters. Impedance cardiography is being used with increasing frequency by clinicians to guide therapy in patients with heart failure and has been proposed in heart failure treatment algorithms. Three case reports are presented to illustrate how hemodynamic data using impedance cardiography can be utilized in the initiation and titration of neurohormonal agents.

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Measurement of systolic BP alone does not reliably indicate the degree of vasoconstriction or vasodilation that exists in patients with CHF. Measurement of SVRI by ICG may help guide determination of need and tolerance for vasodilating medications in CHF.

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