Influence of sex on mortality in hospitalized patients with congestive heart failure and preserved or depressed systolic function

INTRODUCTION AND OBJECTIVES: There is some controversy about the impact of sex on mortality in patients with heart failure. Moreover, little is known about its influence on prognosis in patients with preserved systolic function. The objective of this study was to investigate the influence of sex on survival in patients with heart failure, including subgroups with preserved or depressed left ventricular ejection fraction (LVEF). PATIENTS AND METHOD: The study included 1252 patients (767 male, 61.3%) who were admitted with heart failure to the cardiology department of a tertiary hospital. The median follow-up period was 2.3 years, with the mortality rate rising to 41% after 12 years of follow-up. A LVEF less than 50% was observed in 60.2% of patients. Female patients were older (73.4 +/- 10.0 years vs 66.8 +/- 11.9 years; P < .001), a higher proportion had preserved systolic function (52.2% vs 31.9%; P < .001), and fewer had ischemic cardiopathy (44.1% vs 53.2%; P < .001). RESULTS. In the group as a whole, the influence of sex on prognosis did not reach statistical significance: the hazard ratio in males compared with females was 1.253 (95%CI, 0.978-1.605; P = .074). In addition, no influence of sex on survival was observed in subgroups with preserved or depressed systolic function. CONCLUSIONS: In a large cohort, we did not observe any influence of sex on mortality in hospitalized patients with heart failure, either in the group as a whole or in subgroups with preserved or depressed left ventricular systolic function, despite a tendency towards higher mortality in males.     

Mortality rates and modes of death in heart failure patients with reduced versus preserved systolic function

Background

There are conflicting reports regarding the characteristics and mortality rates of heart failure patients with preserved (HFPSF) vs. reduced systolic left ventricular function (SHF).

Methods

We evaluated the clinical profiles, mortality rates and modes of death in 481 consecutive symptomatic heart failure patients. In 317(66%) patients LVEF was < 40% (SHF), and in 164(34%) LVEF ≥ 40% (HFPSF).

Results

Compared to the HFPSF group, SHF patients were predominantly younger males with ischemic etiology and less cardiovascular comorbidities such as obesity, hypertension, diabetes mellitus and atrial fibrillation. Over a mean follow-up period of 2 years, 148(31%) patients died. Overall mortality was similar between the two groups: 53(32%) HFPSF patients and 95(30%) SHF patients died (p = 0.6), even after adjusting for baseline variables, including age, gender and comorbidities (hazard ratio 1.09; 95% confidence interval 0.74-1.61; p = 0.67). In contrast to the similar mortality rates, the modes of death were different. SHF patients had higher death rates due to pump failure compared to the HFPSF group {32/95(34%) vs. 9/53(17%) patients, p = 0.03}. A trend towards higher rate of non-cardiac death was observed in HFPSF group {33/53(62%) patients vs. 45/95(47%) patients, respectively, p = 0.08}. The prevalence of arrhythmic death was similar in both groups {17/95(18%) vs. 10/53(19%) patients, p = 0.9}.

Conclusions

Although the characteristics of HFPSF and SHF patients are distinctively different, the mortality rates are similar. The mode of death is different among the two groups of patients, as pump failure death is significantly higher in SHF patients, while non-cardiac mortality is more prevalent in HFPSF patients.     

Nifedipine in severely hypertensive patients with congestive heart failure and preserved ventricular systolic function

Nifedipine was used successfully in nine patients with refractory hypertension and left ventricular hypertrophy who had symptoms of congestive heart failure despite preserved left ventricular systolic function. The administration of 10 or 20 mg of nifedipine resulted in an acute decline in BP, from 211 +/- 8/105 +/- 6 mm Hg to 153 +/- 9/78 +/- 5 mm Hg. Six patients received nifedipine and one patient received long-term verapamil therapy (mean follow-up, 16 +/- 4 weeks). In addition to sustained BP control, signs and symptoms of congestive heart failure were greatly improved in all patients treated long term with calcium channel antagonists. No adverse reactions were reported, but a short duration of action limited their usefulness in some patients. Nifedipine seems to be particularly beneficial in this subgroup of severe hypertensive patients with heart failure presumably due to diastolic stiffness of the left ventricle.     

Long-term survival in patients hospitalized with congestive heart failure: relation to preserved and reduced left ventricular systolic function.

AIMS: The purpose of this study was to evaluate the influence of left ventricular systolic function on the survival in a large consecutive cohort of patients hospitalized with congestive heart failure and to determine how left ventricular systolic function interacts with co-morbid conditions in terms of prognosis. METHODS AND RESULTS: Analysis of survival data from 5491 patients admitted for new or worsening heart failure to 34 departments of cardiology or internal medicine in Denmark from 1993-1996 was carried out. A standardized echocardiogram was available for 95% of the patients, and left ventricular systolic function was estimated using wall motion index score. Follow-up time was 5-8 years. Patients with preserved systolic function were older, more frequently female, and had less evidence of ischemia than patients with systolic dysfunction. After 1 year, 24% of the patients had died. Low wall motion index was a potent independent predictor of death (risk ratio for one unit increase, 0.60 (0.56-0.64)), and was of greater prognostic significance in younger patients and patients with a history of myocardial ischemia. However, even in patients with preserved systolic function, mortality was high (1 year mortality, 19%). CONCLUSION: In hospitalized heart failure patients, particularly in younger patients with ischemic heart disease, mortality risk is inversely related to left ventricular systolic function.     

Treatment of heart failure with preserved systolic function

Heart failure is a major public health problem. Heart failure with preserved systolic function (HF-PSF) is a common form, which is difficult to diagnose. Results of recent studies show that HF-PSF has a poor prognosis, with an annual survival rate similar to that of heart failure with left ventricular systolic dysfunction. Despite these findings, the therapeutic management of HF-PSF is not clearly defined. We will discuss in this review of the literature the current therapeutic management of HF-PSF, including the role of precipitating factors such as hypertension, myocardial ischaemia and supraventricular arrhythmias, and the main results of epidemiological registries and randomized controlled clinical trials in this disease. Only four large therapeutic trials have assessed the impact of different classes of drugs (digoxin, angiotensin II converting enzyme inhibitors, angiotensin II receptors type I blockers and beta-blockers) on morbidity and mortality in HF-PSF. Results of these trials are disappointing. Apart from the beta-blockers, the other three classes of drugs did not show benefit on the outcome of the disease. Moreover, the results of the beta-blocker trial are controversial as a mixed population of heart failure with and without preserved systolic function was studied. Finally, the current therapeutic management of patients with HF-PSF is still based on our pathophysiological knowledge: education, low salt diet, diuretics, slowing heart rate and controlling triggering factors. Other large randomized controlled multicenter trials, which may help us in the understanding of HF-PSP and its therapeutic management, are ongoing.     

Comparison of African-American patients with systolic heart failure versus preserved ejection fraction

Evidence exists for race-specific differences in the cause and natural history of heart failure (HF). These differences may have important treatment implications, but relatively limited data on African-Americans exist. A cohort of 89 African-American patients admitted to an urban teaching hospital with diagnoses of HF was examined. Most patients had systolic HF (71%), and the remainder had HF with preserved ejection fractions (EFs). Patients with HF with preserved EFs tended to be generally older (67 vs 57 years, p = 0.01) and were more likely to be women (69% vs 42%, p = 0.02). There were no significant differences between patients with systolic HF and those with HF with preserved EFs in the prevalence of coronary artery disease (23%), diabetes mellitus (44%), or chronic obstructive pulmonary disease (38%). Gastrointestinal bleeding and anemia were significant contributors to admission in patients with preserved EFs, with baseline hematocrits being significantly lower (34.9 vs 38.3, p = 0.01). On discharge, patients with HF with preserved EFs were less likely to be prescribed angiotensin-converting enzyme inhibitors than patients with systolic HF (65% vs 83%, p = 0.08) or diuretics (58% vs 82.%, p = 0.03). In conclusion, differences exist in African-American patients who present with HF; optimal therapeutic approaches will require a better understanding of their underlying pathophysiology.     

Early readmission of elderly patients with congestive heart failure

Repetitive hospitalizations are a major health problem in elderly patients with chronic disease, accounting for up to one fourth of all inpatient Medicare expenditures. Congestive heart failure, one of the most common indications for hospitalization in the elderly, is also associated with a high incidence of early rehospitalization, but variables identifying patients at increased risk and an analysis of potentially remediable factors contributing to readmission have not previously been reported. We prospectively evaluated 161 patients 70 years or older that had been hospitalized with documented congestive heart failure. Hospital mortality was 13% (n = 21). Among patients discharged alive, 66 (47%) were readmitted within 90 days. Recurrent heart failure was the most common cause for readmission, occurring in 38 patients (57%). Other cardiac disorders accounted for five readmissions (8%), and noncardiac illness led to readmission in 21 cases (32%). Factors predictive of an increased probability of readmission included a prior history of heart failure, four or more admissions within the preceding 8 years, and heart failure precipitated by an acute myocardial infarction or uncontrolled hypertension (all P less than .05). Using subjective criteria, 25 first readmissions (38%) were judged possibly preventable, and 10 (15%) were judged probably preventable. Factors contributing to preventable readmissions included noncompliance with medications (15%) or diet (18%), inadequate discharge planning (15%) or follow-up (20%), failed social support system (21%), and failure to seek medical attention promptly when symptoms recurred (20%). Thus, early rehospitalization in elderly patients with congestive heart failure may be preventable in up to 50% of cases, identification of high risk patients is possible shortly after admission, and further study of nonpharmacologic interventions designed to reduce readmission frequency is justified.     

Correlates and outcomes of preserved left ventricular systolic function among older adults hospitalized with heart failure

Background Heart failure (HF) in older adults is often associated with preserved left ventricular systolic function (LVSF). The objective of this retrospective follow-up study was to determine the correlates and outcomes of preserved LVSF among older adults hospitalized with HF. Methods We studied older Medicare beneficiaries hospitalized with HF (n = 1091) who had documented LVSF evaluation (n = 438). LVSF was defined as preserved if left ventricular ejection fraction was ≥40%. The Fisher exact test and the Student t test were used to compare baseline characteristics between patients with preserved versus those with impaired LVSF. Multivariate logistic regression analysis was used to determine the correlates of preserved LVSF. Cox proportional hazards analyses were used to determine the associations between LVSF and both 4-year mortality rates and 6-month readmission rates and the associations between angiotensin-converting enzyme (ACE) inhibitor use and 4-year mortality rates, separately, in patients with preserved and impaired LVSF. Results Of the 438 patients, 200 (46%) had preserved LVSF. Women were more likely to have preserved LVSF (odds ratio [OR] = 2.44, 95% CI 1.57-3.81) than men. Preserved LVSF was associated with lower 4-year mortality rates (adjusted hazards ratio [HR] = 0.67, 95% CI 0.52-0.86) but not with 6-month readmission rates (adjusted HR = 0.66, 95% CI 0.41-1.09). The use of ACE inhibitors was associated with lower 4-year mortality rates in patients with impaired LVSF (adjusted HR = 0.61, 95% CI 0.43-0.86) but not in those with preserved LVSF (HR = 0.96, 95% CI 0.65-1.42). Conclusions Among older adults hospitalized with HF, preserved LVSF was common among women and was associated with significantly higher morbidity and mortality rates, which were unaffected by treatment with ACE inhibitors. (Am Heart J 2002;144:365-72.)     

Neurohumoral pathways in heart failure with preserved systolic function

Other than natriuretic peptides, neurohumoral markers have not been studied adequately in heart failure with preserved systolic function. There is little evidence of chronic activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, as in heart failure with reduced systolic function. These and other neurohumoral pathways may, however, become excessively stimulated by exercise and during episodes of acute decompensation. Blood natriuretic peptide concentrations are chronically elevated in patients with heart failure and preserved systolic function but not to the same extent as in patients with reduced systolic function. The role of neurohumoral antagonists in the treatment of heart failure and preserved systolic function has yet to be fully investigated.     

Central sleep apnea is a predictor of cardiac readmission in hospitalized patients with systolic heart failure

BackgroundHospitalized heart failure patients have a high readmission rate. We sought to determine the independent risk due to central sleep apnea (CSA) of readmission in patients with systolic heart failure (SHF).Methods and ResultsThis was a prospective observational cohort study of hospitalized patients with SHF. Patients underwent sleep studies during their hospitalization and were followed for 6 months to determine their rate of cardiac readmissions; 784 consecutive patients were included; 165 patients had CSA and 139 had no sleep-disordered breathing (SDB); the remainder had obstructive sleep apnea (OSA). The rate ratio for 6 months' cardiac readmissions was 1.53 (95% confidence interval 1.1–2.2; P = .03) in CSA patients compared with no SDB. This rate ratio was adjusted for systolic function, type of cardiomyopathy, age, weight, sex, diabetes, coronary disease, length of stay, admission sodium, creatinine, hemoglobin, blood pressure, and discharge medications. Severe OSA was also an independent predictor of readmissions with an adjusted rate ratio of 1.49 (P = .04).ConclusionIn this first evaluation of the impact of SDB on cardiac readmissions in heart failure, CSA was an independent risk factor for 6 months' cardiac readmissions. The effect size of CSA exceeded that of all known predictors of heart failure readmissions.     

Heart rate predicts mortality in patients with heart failure and preserved systolic function

BackgroundElevated resting heart rates have been associated with increased mortality and morbidity in patients with heart failure and decreased left ventricular ejection fraction (EF). It is unclear, though, if this association applies to those with heart failure and preserved EF.Methods and ResultsWe determined outcome for 685 consecutive patients with a prior diagnosis of heart failure and a preserved EF (>50%) documented on echocardiography at 1 of 3 laboratories. Patients with non-sinus rhythm were excluded from the analysis. We determined adjusted mortality rates at 1 year after the echocardiogram. The mean age of the cohort was 70 ± 11 years. Of the 685 included patients, 87% had a history of hypertension, 50% had diabetes, and the mean EF was 60% ± 6%. All-cause mortality at 1 year was significantly lower in the group with heart rate below 60 beats/min (10%) when compared with the group with heart rates between 60 and 70 beats/min (18%), 71–90 beats/min (20%), and >90 beats/min (35%) (P < .0001). After adjustment for patient history, demographics, laboratory values, and echocardiographic findings, the hazard ratios for total mortality (relative to a heart rate of <60) were 1.26 (95% CI, 0.88–1.80) for HR 60–69, 1.47 (95% CI, 1.02–2.07) for HR 70–90, and 2.00 (95% CI, 1.31–3.04) for HR>90 (P = .01 across all groups).ConclusionsThese data suggest that an elevated resting heart rate is a marker for increased mortality in patients with heart failure and preserved systolic function. Heart rate may be useful in these patients for improved cardiovascular risk assessment.     

Prevention of readmission in elderly patients with congestive heart failure

Objective: To determine the feasibility and potential impact of a non-pharmacologic multidisciplinary intervention for reducing hospital readmissions in elderly patients with congestive heart failure. Design: Prospective, randomized clinical trial, with 2:1 assignment to the study intervention or usual care. Setting: 550-bed secondary and tertiary care university teaching hospital. Patients and participants: 98 patients ≥70 years of age (mean 79±6 years) admitted with documented congestive heart failure. Interventions: Comprehensive multidisciplinary treatment strategy consisting of intensive teaching by a geriatric cardiac nurse, a detailed review of medications by a geriatric cardiologist with specific recommendations designed to improve medication compliance and reduce side effects, early consultation with social services to facilitate discharge planning, dietary teaching by a hospital dietician, and close follow-up after discharge by home care and the study team. Measurements and main results: All patients were followed for 90 days after initial hospital discharge. The primary study endpoints were rehospitalization within the 90-day interval and the cumulative number of days hospitalized during follow-up. The 90-day readmission rate was 33.3% (21.7%–44.9%) for the patients receiving the study intervention (n=63) compared with 45.7% (29.2–62.2%) for the control patients (n=35). The mean number of days hospitalized was 4.3±1.1 (2.1–6.5) for the treated patients vs. 5.7±2.0 (1.8–9.6) for the usual-care patients. In a prospectively defined subgroup of patients at intermediate risk for readmission (n=61), readmissions were reduced by 42.2% (from 47.6% to 27.5%; p=0.10), and the average number of hospital days during follow-up decreased from 6.7±32 days to 3.2±1.2 days (p=NS). Conclusions: These pilot data suggest that a comprehensive, multidisciplinary approach to reducing repetitive hospitalizations in elderly patients with congestive heart failure may lead to a reduction in readmissions and hospital days, particularly in patients at moderate risk for early rehospitalization. Further evaluation of this treatment strategy, including an assessment of the cost-effectiveness, is warranted. Received from the Geriatric Cardiology Section, Division of Cardiology, Jewish Hospital at Washington University Medical Center, St. Louis, Missouri. Presented in part at the 47th Annual Scientific Meeting of the American Geriatrics Society, May 18, 1990, Atlanta, Georgia. Supported by a Community Research Grant-in-Aid from the American Heart Association, Missouri Affiliate.     

Prognosis in patients with heart failure and preserved left ventricular systolic function.

BACKGROUND: It is recognized that heart failure patients with preserved left ventricular systolic function have better prognosis; nevertheless, there are some studies with conflicting results. Also, there is a paucity of data concerning the prognostic factors in this group of patients. OBJECTIVES: To determine possible variables with prognostic relevance in heart failure patients with preserved left ventricular systolic function (ejection fraction > 40%). METHODS: 157 consecutive ambulatory patients with heart failure were assessed; those patients with ejection fraction > 40% were included in the study (n = 46). All patients were evaluated by clinical interview and physical examination, ECG, echocardiogram (M-mode, 2D and pulsed Doppler of mitral flow), biochemical study and determination of type B natriuretic peptide (BNP). The patients were grouped according to the rhythm presented on ECG: Group I--patients with atrial fibrillation; Group II--patients in sinus rhythm Group II was further subdivided in two groups according to the presence or absence of restrictive left ventricular filling pattern. All patients had a clinical follow-up, with recording of events (death or hospitalization from cardiac cause). The mean follow-up time was 682.2 +/- 55 days. RESULTS: The mean age of the patients was 70.4 +/- 1.2 years; 54.3% were women; mean ejection fraction was 49.6 +/- 1%; mean BNP levels were 202.9 +/- 41.3 pg/ml. Mortality was 19.6% and the combined event death or hospitalization from cardiac cause) occurred in 26.1% of the patients. Among the clinical, demographic, biochemical, echocardiographic and neurohumoral parameters, only BNP levels had prognostic significance in the whole population. In Group II patients, BNP levels, heart rate and restrictive left ventricular filling pattern were identified as having prognostic significance. Kaplan-Meyer curve analysis showed that both BNP and restrictive left ventricular filling pattern seemed to be important prognostic markers. CONCLUSIONS: This preliminary study suggests thar neurohumoral activity (determined by plasma BNP levels) and a restrictive ventricular filling pattern may be important factors in prognostic stratification of heart failure patients with preserved left ventricular systolic function.     

The epidemiological enigma of heart failure with preserved systolic function

BACKGROUND: Current epidemiological evidence suggests that the prevalence of preserved systolic function in patients with heart failure varies widely from 13 to 74%. This inconsistency suggests a lack of consensus as to what this condition really is and how it has been characterised for epidemiological studies. AIMS: In this review, we summarise and discuss the current understanding of the epidemiology of heart failure with preserved systolic function and the challenges that this raises. METHODS: Studies were identified from Medline and Embase Literature Database searches using the subject headings heart failure, diastolic heart failure, epidemiology, incidence, prevalence, diagnosis, prognosis and mortality. RESULTS: Sixty-one studies of congestive heart failure with preserved systolic function were reviewed. There is great diversity in the criteria used to determine whether heart failure is present, the patient population, the setting of the study and methods of evaluating left ventricular function. This makes epidemiological studies of prevalence, morbidity and mortality impossible to compare. CONCLUSIONS: The diagnosis of this syndrome might be better defined in terms of symptoms, elevated neuro hormones and impaired cardiac workload. This would allow accurate identification of cases so that further research could be conducted to measure outcome and assess therapeutic benefit.     

Clinical characteristics and long-term outcomes of patients with heart failure and preserved systolic function

Although the syndrome of heart failure with preserved systolic function may occur in up to 40% of all heart failure patients, the clinical, angiographic characteristics, and long-term outcomes of these patients are poorly understood. We prospectively evaluated 2,498 consecutive patients with New York Heart Association class II to IV symptoms and ejection fractions of >40%, who underwent cardiac catheterization between January 1984 and December 1996 at Duke University Medical Center. The median age for the entire cohort was 63 years; 25% of the population was >71 years old. In addition, 55% of the patients were women, 65% had ischemic heart disease, 28% had a history of diabetes, and 62% had a history of hypertension. The median ejection fraction was 58%. One third of the patients had multivessel disease by coronary angiography. The overall 5-year mortality of the total population was 28%. The independent predictors of mortality (p <0.05) using a multivariable Cox proportional hazard model were age, class IV symptoms, ejection fraction, coronary artery disease index, diabetes, peripheral vascular disease, and minority ethnic group. Heart failure with preserved systolic function is characterized by unique clinical and angiographic characteristics associated with a 5-year mortality rate of 28%. Furthermore, several clinical and angiographic characteristics are predictive of long-term survival.