Differential prognostic impact of resting heart rate in older compared with younger patients with chronic heart failure--insights from TIME-CHF.

BACKGROUND: There is little information regarding the prognostic role of resting heart rate (HR) in older compared with younger patients with chronic heart failure (HF). METHODS AND RESULTS: In patients enrolled in the Trial of Intensified Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) with sinus rhythm, effects of baseline HR (≥70 vs <70 beats/min [bpm]) on 18-month outcomes were compared between older (≥75 years; n = 186) and younger (<75 years; n = 141) patients. Older patients with lower (61 ± 6 bpm) and higher (83 ± 9 bpm) HR had similar left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and survival and HF hospitalization-free survival. In contrast, younger patients with higher HR (81 ± 7 bpm) had higher NT-proBNP and NYHA functional class, lower LVEF, and a higher risk of death (hazard ratio 4.01 [95% confidence interval (CI) 1.17 -13.69]; P = .02) and death or HF hospitalization (hazard ratio 2.35 [95% CI 1.01-5.50]; P = .04) than those with lower HR (62 ± 5 bpm), with the association between higher HR and survival remaining significant after adjustment for NYHA functional class, LVEF, and NT-proBNP. CONCLUSIONS: In contrast to HF patients aged <75 years, we found no association between HR and worse outcomes in HF patients aged ≥75 years.

End-of-life preferences of elderly patients with chronic heart failure.

AIMS: Elderly heart failure (HF) patients are assumed to prefer improved quality of life over longevity, but sufficient data are lacking. Therefore, we assessed the willingness to trade survival time for quality-of-life (QoL) and the preferences for resuscitation. METHODS AND RESULTS: At baseline and after 12 and 18 months, 622 HF patients aged ≥60 years (77 ± 8 years, 74% NYHA-class ≥III) participating in the Trial of Intensified vs. standard Medical therapy in Elderly patients with Congestive Heart Failure had prospective evaluation of end-of-life preferences by answering trade-off questions (willingness to accept a shorter life span in return for living without symptoms) and preferences for resuscitation if necessary. The time trade-off question was answered by 555 patients (89%), 74% of whom were not willing to trade survival time for improved QoL. This proportion increased over time (Month 12: 85%, Month 18: 87%, P < 0.001). In multivariable analysis, willingness to trade survival time increased with age, female sex, a reduced Duke Activity Status Index, Geriatric Depression Score, and history of gout, exercise intolerance, constipation and oedema, but even combining these variables did not result in reliable prediction. Of 603 (97%) patients expressing their resuscitation preference, 51% wished resuscitation, 39% did not, and 10% were undecided, with little changes over time. In 430 patients resuscitation orders were known; they differed from patients' preferences 32% of the time. End-of-life preferences were not correlated to 18-month outcome. CONCLUSION: Elderly HF patients are willing to address their end-of-life preferences. The majority prefers longevity over QoL and half wished resuscitation if necessary. Prediction of individual preferences was inaccurate.

Preoperative smoking cessation program in patients undergoing intermediate to high-risk surgery: a randomized, single-blinded, controlled, superiority trial.

BACKGROUND: At present, effectively implementing smoking cessation programs in the health care system constitutes a major challenge. A unique opportunity to initiate smoking cessation focuses on smokers scheduled for surgery. These patients are not only highly motivated to quit smoking but also likely to benefit from a reduction in postoperative complications which may translate into a decrease of costs. Nevertheless, surgical patients are not routinely informed about the benefits of preoperative smoking cessation. Potential reasons for this missed opportunity may be the lack of time and training of surgeons and anaesthesiologists. We therefore aim to analyse the impact of a preoperative high-intensity smoking cessation intervention on surgical complications up to a 90-day postoperative period in patients of various surgical disciplines. The hypothesis is that a preoperative smoking cessation program improves outcomes in smokers undergoing intermediate to high-risk surgery. METHODS: The present study is a single-centre, randomized trial with two parallel groups of smokers scheduled for surgery comparing surgery alone and surgery with preoperative smoking cessation. We plan to randomize 251 patients. The primary objective is to compare complications between patients with an institutional multifaceted smoking cessation intervention starting 4 weeks before surgery compared to patients in the advice-only group (control group) within a 90-day postoperative period. The primary endpoint is the Comprehensive Complication Index (CCI®) within 90 days of surgery. Secondary outcomes include the length of hospital stay, cost of care, quality of life, smoking abstinence, and reduction in nicotine consumption. DISCUSSION: The hypothesis is that a preoperative smoking cessation program improves outcomes in smokers undergoing surgery. TRIAL REGISTRATION: BASEC #2021-02004; ClinicalTrials.gov: NCT05192837 . Registered on January 14, 2022.

Predictors of early readmission or death in elderly patients with heart failure.

BACKGROUND: Contemporary heart failure (HF) patients are elderly and have a high rate of early rehospitalization or death, resulting in a high burden for both the patients and the health care system. Prior studies were focused on younger and less well-characterized patients. We aimed to identify predictors of early hospital readmission and death in elderly patients with HF. METHODS: Patients with chronic HF taking part in the TIME-CHF study (n = 614, age 77 +/- 8 years, 41% female, left ventricular ejection fraction 35% +/- 13%) were evaluated with respect to predictors of hospital readmission or death 30 and 90 days after inclusion. Demographic, clinical, laboratory, echocardiographic, and social variables were obtained at baseline and included in a multivariable logistic regression analysis to identify predictors of early events. RESULTS: The rate of hospital readmission or death was high at 30 (11%) and 90 days (26%). The reason for hospitalization was HF in 33%, other cardiovascular in 32%, and noncardiovascular in 45% of the cases, respectively. Predictors of readmission or death at 30 days were angina, lower systolic blood pressure, anemia, more extensive edema, higher creatinine levels, and dry cough; and at 90 days were coronary artery disease, prior pacemaker implantation, high jugular venous pressure, pulmonary rales, prior abdominal surgery, older age, and depressive symptoms. CONCLUSIONS: Early hospital readmission or death was frequent among elderly HF patients. A very large proportion of readmissions were due to noncardiovascular causes. In addition to clinical signs of HF, comorbidities are important predictors of early events in elderly HF patients.

Limited role for fibroblast growth factor 23 in assessing prognosis in heart failure patients: data from the TIME-CHF trial.

AIM: Fibroblast growth factor 23 (FGF23) is an intensively studied biomarker at the crossroads of cardiovascular disease, heart failure (HF) and chronic kidney disease. Independent associations between increasing FGF23 levels and cardiovascular events were found in many, but not all studies. By analysing data from the TIME-CHF cohort, we sought to investigate the prognostic value of FGF23 in an elderly, multimorbid HF patient cohort. We determined differences between intact (iFGF23) and C-terminal FGF23 (cFGF23) regarding their prognostic value and their levels over time in different HF subgroups according to left ventricular ejection fraction (LVEF). METHODS AND RESULTS: In this multicentre trial of 622 patients with symptomatic HF aged ≥60 years, we determined iFGF23 and cFGF23 at baseline, 3, 6 and 12-month follow-up. In unadjusted analyses, cFGF23 significantly predicted all HF-related outcomes at all time points. The predictive value of iFGF23 was less and not statistically significant at baseline. After multivariable adjustments, the association between both cFGF23 and iFGF23 and outcome lost statistical significance apart from cFGF23 at month 3. Overall, patients with preserved and mid-range LVEF had higher levels of iFGF23 and cFGF23 than those with reduced LVEF. Levels decreased significantly during the first 3 months in mid-range and reduced LVEF patients, but did not significantly change over time in those with preserved LVEF. CONCLUSIONS: Fibroblast growth factor 23 is of limited value regarding risk prediction in this elderly HF population. Potentially heterogeneous roles of FGF23 in different LVEF groups deserve further investigation.

BNP-guided vs symptom-guided heart failure therapy: the Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized trial.

CONTEXT: It is uncertain whether intensified heart failure therapy guided by N-terminal brain natriuretic peptide (BNP) is superior to symptom-guided therapy. OBJECTIVE: To compare 18-month outcomes of N-terminal BNP-guided vs symptom-guided heart failure therapy. DESIGN, SETTING, AND PATIENTS: Randomized controlled multicenter Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) of 499 patients aged 60 years or older with systolic heart failure (ejection fraction < or = 45%), New York Heart Association (NYHA) class of II or greater, prior hospitalization for heart failure within 1 year, and N-terminal BNP level of 2 or more times the upper limit of normal. The study had an 18-month follow-up and it was conducted at 15 outpatient centers in Switzerland and Germany between January 2003 and June 2008. INTERVENTION: Uptitration of guideline-based treatments to reduce symptoms to NYHA class of II or less (symptom-guided therapy) and BNP level of 2 times or less the upper limit of normal and symptoms to NYHA class of II or less (BNP-guided therapy). MAIN OUTCOME MEASURES: Primary outcomes were 18-month survival free of all-cause hospitalizations and quality of life as assessed by structured validated questionnaires. RESULTS: Heart failure therapy guided by N-terminal BNP and symptom-guided therapy resulted in similar rates of survival free of all-cause hospitalizations (41% vs 40%, respectively; hazard ratio [HR], 0.91 [95% CI, 0.72-1.14]; P = .39). Patients' quality-of-life metrics improved over 18 months of follow-up but these improvements were similar in both the N-terminal BNP-guided and symptom-guided strategies. Compared with the symptom-guided group, survival free of hospitalization for heart failure, a secondary end point, was higher among those in the N-terminal BNP-guided group (72% vs 62%, respectively; HR, 0.68 [95% CI, 0.50-0.92]; P = .01). Heart failure therapy guided by N-terminal BNP improved outcomes in patients aged 60 to 75 years but not in those aged 75 years or older (P < .02 for interaction) CONCLUSION: Heart failure therapy guided by N-terminal BNP did not improve overall clinical outcomes or quality of life compared with symptom-guided treatment. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN43596477.

Atrial fibrillation: estimated excess rate of stroke due to lacking adherence to guidelines.

QUESTIONS UNDER STUDY: Many patients with atrial fibrillation (AF), risk factors for stroke and no obvious contraindications do not receive oral anticoagulation. Estimations of the increased rate of stroke due to neglected anticoagulation, particularly in an elderly, non-selected population, are unknown. METHODS: Consecutive patients with paroxysmal or permanent atrial fibrillation admitted to the medical or surgical department of our hospital for any reason were studied. Risk factors for stroke and contraindications for anticoagulation were recorded. Estimations of the increased rate of cerebrovascular events due to neglected anticoagulation were based on data of a large meta-analysis. Patients were further stratified into different age and risk groups. RESULTS: 484 patients with a mean age of 75 (12) years were studied, 45% were female. 237 patients had no oral anticoagulation at hospital discharge, despite guideline recommendations. Contraindications for anticoagulation were found in 85 (36%) of these patients, resulting in 152 patients with neglected anticoagulation (31% of all patients with AF). We estimated that, if all those patients would have been treated according to guidelines, 7.4 strokes per year could be prevented in the study population. The estimated rate of preventable events was 4.9%/year (7.4/152). CONCLUSIONS: With better adherence to guidelines for oral anticoagulation in patients with atrial fibrillation and risk factors for stroke, a significant number of strokes could be prevented.