Temporal trends in characteristics, treatment, and outcomes of heart failure in octogenarians over two decades.

INTRODUCTION AND OBJECTIVES: Octogenarians represent the most rapidly expanding population segment in Europe. The prevalence of heart failure (HF) in this group exceeds 10%. We assessed changes in clinical characteristics, therapy, and 1-year outcomes over 2 decades in chronic HF outpatients aged ≥ 80 years enrolled in a nationwide cardiology registry. METHODS: We included 2520 octogenarians with baseline echocardiographic ejection fraction measurements and available 1-year follow-up, who were recruited at 138 HF outpatient clinics (21% of national hospitals with cardiology units), across 3 enrolment periods (1999-2005, 2006-2011, 2012-2018). RESULTS: At recruitment, over the 3 study periods, there was an increase in age, body mass index, ejection fraction, the prevalence of obesity, diabetes, dyslipidemia, pre-existing hypertension, and atrial fibrillation history. The proportion of patients with preserved ejection fraction rose from 19.4% to 32.7% (P for trend <.0001). Markers of advanced disease became less prevalent. Prescription of beta-blockers and mineralocorticoid receptor antagonists increased over time. During the 1-year follow-up, 308 patients died (12.2%) and 360 (14.3%) were admitted for cardiovascular causes; overall, 591 (23.5%) met the combined primary endpoint of all-cause mortality or cardiovascular hospitalization. On adjusted multivariable analysis, enrolment in 2006 to 2011 (HR, 0.70; 95%CI, 0.55-0.90; P=.004) and 2012 to 2018 (HR, 0.61; 95%CI, 0.47-0.79; P=.0002) carried a lower risk of the primary outcome than recruitment in 1999 to 2005. CONCLUSIONS: Among octogenarians, over 2 decades, risk factor prevalence increased, management strategies improved, and survival remained stable, but the proportion hospitalized for cardiovascular causes declined. Despite increasing clinical complexity, in cardiology settings the burden of hospitalizations in the oldest old with chronic HF is declining.

Age-related changes in clinical characteristics and outcomes of chronic heart failure outpatients in a cardiology setting. A report from the Italian Network on Heart Failure.

AIMS: Ageing and comorbidities are increasing frailty/complexity of heart failure (HF) patients globally. We assessed evolving trends over two decades according to patients' age and time of recruitment in a nationwide cardiology setting in Italy. METHODS AND RESULTS: Chronic HF outpatients recruited between 1999 and 2018 (N = 14,823) were divided into 3 cohorts: 1999-2005 (N = 5404); 2006-2011 (N = 3971); 2012-2018 (N = 5448). We analyzed temporal changes in clinical characteristics, therapies, and outcome (1-year all-cause mortality/cardiovascular hospitalization), overall and by age group: <65 (n = 5465); 65-79 (n = 6838); ≥80 (n = 2520) years old. Across enrolment epochs, comorbidities (atrial fibrillation, hypertension, obesity) increased by both epoch/age groups (p < 0.001), whereas the prevalence of ischemic etiology declined among patients ≥65 years (p = 0.05). Accordingly, the preserved LVEF phenotype (HFpEF) increased in all age categories (p < 0.001) over time. Moreover, the use of betablockers, mineralocorticoid-receptor antagonists and loop-diuretics rose by enrolment epoch in all age groups (p < 0.05). In parallel with these epidemiologic/treatment changes, age-adjusted survival free from cardiovascular hospitalization improved over time (p < 0.0001). However, divergent trends in the end-point components were apparent according to age groups: mortality decreased in patients<80 years, although hospitalizations remained stable in the youngest group, while subjects ≥65 years were less likely to be admitted for cardiovascular causes (all p < 0.005). CONCLUSIONS: Over two decades in a cardiology outpatient setting, the prevalence of comorbid HFpEF increased in all age categories. Mortality improved among patients<80 years and cardiovascular hospitalizations decreased in patients≥65 years. These findings point to the value of cardiologist' input in the management of adult chronic HF patients at all ages.

Treatment with inotropes and related prognosis in acute heart failure: contemporary data from the Italian Network on Heart Failure (IN-HF) Outcome registry.

BACKGROUND: In the recent Italian Network on Heart Failure (IN-HF) Outcome registry, including 1,855 patients with acute heart failure (AHF), we reviewed the use of inotropes and their prognostic implication on in-hospital and 12-month mortality. METHODS: IN-HF Outcome is a prospective, multicenter, observational, study involving 61 Italian cardiology centers. AHF patients have been enrolled over a 2-year period and followed-up for 1 year. Inotropes were used in 360 patients (19.4%). RESULTS: Patients who received inotropes had a more severe clinical and hemodynamic profile than those who did not and exhibited a significantly higher rate of in-hospital (21.4% vs 2.7%, p < 0.01) and 1-year (50.6% vs 17.7%, p < 0.01) mortality. At entry, systolic blood pressure (SBP) was ≤ 110 mm Hg in 58%, 111 to 130 mm Hg in 24.5%, and > 130 mm Hg in 17.5%. Multivariable analyses showed use of inotropes was the strongest predictor of all-cause death. These data were confirmed by propensity score analyses. According to SBP at entry, the 2 groups with SBP > 110 mm Hg who took inotropes, despite a more favorable clinical profile, exhibited a similar worse prognosis, particularly at 1 year: 56.3% (≤ 110 mm Hg), 43.7% (111-130 mm Hg), and 40.3% (>130 mm Hg) vs 17.7%. CONCLUSIONS: Inotropes were used in nearly 20% of the patient admitted for AHF, and this treatment was associated with a short-term to medium-term poor prognosis. An inappropriate use of inotropes in patients with normal to high SBP, and presumably preserved cardiac output, may have significantly contributed to affect the all-group outcome.

n-3PUFA and Holter-derived autonomic variables in patients with heart failure: data from the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca (GISSI-HF) Holter substudy.

BACKGROUND: n-3 Polyunsaturated fatty acid (n-3PUFA) supplementation in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca (GISSI-HF) study reduced total mortality in patients with heart failure (HF), but the mechanism of action is still debated. The hypothesis of the present GISSI-HF substudy was that n-3PUFA may have beneficial effects on cardiac autonomic control. OBJECTIVE: To evaluate the effect of 1 g/day of n-3PUFA vs placebo on heart rate variability variables, deceleration capacity, and turbulence slope. METHODS: The GISSI-HF study enrolled patients with HF of any cause and severity. Twenty-four-hour (range 16-24 hours) Holter recordings were performed and analyzed in 388 patients at baseline, 3 months, and 12 months. Baseline characteristics were compared by using the χ(2) test, t test, or nonparametric Wilcoxon 2-sample test. Changes over time were tested by using the analysis of covariance adjusted by baseline values. RESULTS: At baseline, 36% of the patients were older than 70 years, 82% were men, 92% presented a left ventricular ejection fraction<40%, and 80% were in New York Heart Association class II. An increase in mean RR interval, standard deviation of all normal-to-normal RR intervals, very low frequency power (all P<.05), and turbulence slope (P = .05) was observed after 3 months in the n-3PUFA group compared to the placebo group, independently of the frequency of dietary fish consumption or beta-blocker treatment. These differences between study groups were no longer statistically significant at 12 months. A per-protocol analysis in patients compliant with study treatment showed similar results. CONCLUSIONS: n-3PUFA supplementation partially restored autonomic modulation in patients with chronic HF; this effect was maximal after 3 months of treatment.

QT variability index on 24-hour Holter independently predicts mortality in patients with heart failure: analysis of Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca (GISSI-HF) trial.

BACKGROUND: Increased temporal variability of repolarization, as reflected by QT interval variability measured over 10-15 minutes, predicted spontaneous ventricular arrhythmias and death in implantable cardioverter-defibrillator patients in mild to moderate heart failure (HF). OBJECTIVE: The purpose of this study was to test our hypothesis that increased mean QT variability over 24 hours would be associated with increased cardiovascular (CV) mortality in a heterogeneous HF population. METHODS: The Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure trial prospectively enrolled subjects with HF of any cause. Twenty-four-hour Holter recordings from 268 subjects were analyzed using a template-matching, semiautomatic algorithm to measure QT and heart rate time series in sequential 5-minute epochs over 24 hours. The QT variability index (QTVI) was expressed as the log ratio of the normalized QT variance over normalized heart rate variance. Total and CV mortality were assessed as a function of continuous and dichotomous QTVI (>-0.84) in univariate and multivariable Cox proportional hazards models, adjusting for significant clinical predictors. RESULTS: After a median of 47 months, there were 53 deaths, of which 44 were from CV causes. A significant association with the outcome was found for QTVI both as continuous and dichotomous variables after adjustment for clinical covariates (age >70, New York Heart Association class III-IV, left ventricular ejection fraction, nonsustained ventricular tachycardia, creatinine): QTVI hazard ratio (HR) 4.0 (confidence interval [CI] 1.8-88; P = .008) for total and 4.4 (CI 1.9-10.1; P = .0006) for CV mortality; QTVI >-0.84 HR 2.0 (CI 1.1-3.6; P = .02) for total and 2.1 (CI 1.1-3.8; P = .02) for CV mortality. CONCLUSION: Increased repolarization lability, as reflected in QTVI measured over 24 hours, is associated with increased risk for total and CV mortality in a heterogeneous population with chronic HF.

Age-dependent prognostic significance of atrial fibrillation in outpatients with chronic heart failure: data from the Italian Network on Congestive Heart Failure Registry.

OBJECTIVES: The role of atrial fibrillation (AF) in older patients with heart failure (HF) is controversial because many variables seem to influence their outcome. We investigated the predictivity of AF in 3 age groups of outpatients with HF. METHODS: We analyzed 8,178 outpatients enrolled in the Italian Network on Congestive Heart Failure Registry with HF diagnosed according to the European Society of Cardiology criteria. A trained cardiologist established the diagnosis of AF and HF at the entry visit at each center. We stratified the population into 3 age groups, as follows: group A, < or =65 years; group B, 66-75 years, and group C, >75 years. RESULTS: Group A was composed of 4,261 patients, 683 with AF (16.0%); in group B there were 2,651 patients, 638 with AF (24.1%), and group C was composed of 1,266 patients, 412 with AF (32.5%). The 1-year mortality rate was higher in AF patients in all groups. In a multivariate model, AF remained an independent risk factor for death in groups A and B, but not in group C [group A: hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.10-1.81; group B: HR 1.29, 95% CI 1.00-1.67; group C: HR 1.05, 95% CI 0.78-1.43]. CONCLUSION: The prevalence of AF increased with age and was associated with a higher mortality rate. However, AF independently predicted all-cause mortality only in patients aged < or =75 years.

24-hour QT variability in heart failure.

BACKGROUND: Previous studies have shown that increased temporal variability of repolarization, as reflected by QT interval variability measured for 10 minutes, predicted spontaneous ventricular arrhythmias in implantable cardioverter defribrillator patients, but it is unclear how these measures perform in 24-hour recordings. METHODS: Twenty-four-hour digital Holter recordings from 372 subjects with chronic heart failure enrolled in Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca, (GISSI) Heart Failure study were analyzed using a template-matching, semiautomatic algorithm to measure QT and heart rate time series in sequential 5-minute epochs for 24 hours. QT variability was expressed as normalized QT variance (QTVN) or as the log ratio of the QTVN over normalized heart rate variance (QT variability index, or QTVI). RESULTS: A pronounced diurnal variation was seen in both QTVI and QTVN. Both were lowest in the midnight to 6 am time frame and increased throughout the day, peaking at noon to 6 pm, then decreasing 6 pm to midnight. For QTVI, all 4 time points were significantly different (P < .0001). QT variability index correlated with heart rate (r = 0.38, P < .0001) and was significantly higher for those in higher New York Heart Association (NYHA) classes (r = 0.22, P = .0003). Normalized QT variance did not correlate with heart rate or NYHA but correlated negatively with serum potassium (r = -0.22, P = .0002) and manifested the greatest increase during midmorning hours. CONCLUSIONS: Repolarization lability as reflected in QT variability has a pronounced diurnal variation and increases significantly after 6 am, the time of greatest arrhythmic risk. QT variability for 24 hours might improve risk prediction in chronic heart failure patients and should be tested in appropriate trials.