Background-Patients with chronic heart failure (CHF) have a continuing high mortality. Autonomic dysfunction may play an important role in the pathophysiology of cardiac death in CHF. UK-HEART examined the value of heart rate variability (HRV) measures as independent predictors of death in CHF. Methods and Results-In a prospective study powered for mortality, we recruited 433 outpatients 62Ϯ9.6 years old with CHF (NYHA functional class I to III; mean ejection fraction, 0.41Ϯ0.17). Time-domain HRV indices and conventional prognostic indicators were related to death by multivariate analysis. During 482Ϯ161 days of follow-up, cardiothoracic ratio, SDNN, left ventricular end-systolic diameter, and serum sodium were significant predictors of all-cause mortality.The risk ratio for a 41.2-ms decrease in SDNN was 1.62 (95% CI, 1.16 to 2.44). The annual mortality rate for the study population in SDNN subgroups was 5.5% for Ͼ100 ms, 12.7% for 50 to 100 ms, and 51.4% for Ͻ50 ms. SDNN, creatinine, and serum sodium were related to progressive heart failure death. Cardiothoracic ratio, left ventricular end-diastolic diameter, the presence of nonsustained ventricular tachycardia, and serum potassium were related to sudden cardiac death. A reduction in SDNN was the most powerful predictor of the risk of death due to progressive heart failure. Conclusions-CHF is associated with autonomic dysfunction, which can be quantified by measuring HRV. A reduction in SDNN identifies patients at high risk of death and is a better predictor of death due to progressive heart failure than other conventional clinical measurements. High-risk subgroups identified by this measurement are candidates for additional therapy after prescription of an ACE inhibitor. (Circulation. 1998;98:1510-1516.)

In ambulant outpatients with chronic HF, low serum sodium and SDNN and high serum creatinine identify patients at increased risk of death due to progressive HF.

Background-Therapies for patients with chronic heart failure caused by left ventricular systolic dysfunction have advanced substantially over recent decades. The cumulative effect of these therapies on mortality, mode of death, symptoms, and clinical characteristics has yet to be defined. Methods and Results-This study was a comparison of 2 prospective cohort studies of outpatients with chronic heart failure caused by left ventricular systolic dysfunction performed between 1993 and 1995 (historic cohort: nϭ281) and 2006 and 2009 (contemporary cohort: nϭ357). In the historic cohort, 83% were prescribed angiotensin-converting enzyme inhibitors and 8.5% were prescribed ␤-adrenoceptor antagonists, compared with 89% and 80%, respectively, in the contemporary cohort. Mortality rates over the first year of follow-up declined from 12.5% to 7.8% between eras (Pϭ0.04), and sudden death contributed less to contemporary mortality (33.6% versus 12.7%; PϽ0.001). New York Heart Association class declined between eras (PϽ0.001). QTc dispersion across the chest leads declined from 85 ms (SD, 2) to 34 ms (SD, 1) and left ventricular end-diastolic dimensions declined from 65 mm (SD, 0.6) to 59 mm (SD, 0.5) (both PϽ0.001). Conclusions-Survival has significantly improved in patients with chronic heart failure caused by left ventricular systolic dysfunction over the past 15 years; furthermore, sudden death makes a much smaller contribution to mortality, and noncardiac mortality is a correspondingly greater contribution. This has been accompanied by an improvement in symptoms and some markers of adverse electric and structural left ventricular remodeling. (Circ Heart Fail. 2011;4: 396-403.)