Gillian A. Whalley

Left Ventricular Remodeling With Carvedilol in Patients With Congestive Heart Failure Due to Ischemic Heart Disease

Objectives. The aim of this study, a substudy of the Australia–New Zealand trial of carvedilol in patients with heart failure due to ischemic heart disease, was to determine the effects of this treatment on left ventricular size and function with the use of quantitative two-dimensional (2D) echocardiography. Background. Beta-adrenergic blocking drugs have been shown to improve left ventricular ejection fraction in patients with heart failure due to either ischemic heart disease or idiopathic dilated cardiomyopathy. However, the effects of such treatment on left ventricular size remain uncertain. Methods. One hundred twenty-three patients from 10 centers in New Zealand and Australia participated in the 2D echocardiographic substudy. Echocardiography was performed before randomization and was repeated after 6 and 12 months of treatment. Left ventricular end-diastolic and end-systolic volumes were measured from apical four- and two-chamber views with the use of a modified Simpson’s rule method. Results. After 12 months, heart rate was 8 beats/min lower in the carvedilol than in the placebo group, whereas left ventricular end-diastolic and end-systolic volumes were increased in the placebo group but reduced in the carvedilol group. At 12 months, left ventricular end-diastolic volume index was 14 ml/m2less in the carvedilol than in the placebo group (p = 0.0015); left ventricular end-systolic volume index was 15.3 ml/m2less (p = 0.0001), and left ventricular ejection fraction was 5.8% greater (p = 0.0015). Conclusions. In patients with heart failure due to ischemic heart disease, carvedilol therapy for 12 months reduced left ventricular volumes, increased left ventricular ejection fraction and prevented progressive left ventricular dilation. These changes demonstrate a beneficial effect of carvedilol on left ventricular remodeling in heart failure. The observed changes may explain in part the improved clinical outcomes produced by treatment with carvedilol. (J Am Coll Cardiol 1997;29:1060–6) © 1997 by the American College of Cardiology

Predicting survival in heart failure: a risk score based on 39 372 patients from 30 studies

AIMS Using a large international database from multiple cohort studies, the aim is to create a generalizable easily used risk score for mortality in patients with heart failure (HF). METHODS AND RESULTS The MAGGIC meta-analysis includes individual data on 39 372 patients with HF, both reduced and preserved left-ventricular ejection fraction (EF), from 30 cohort studies, six of which were clinical trials. 40.2% of patients died during a median follow-up of 2.5 years. Using multivariable piecewise Poisson regression methods with stepwise variable selection, a final model included 13 highly significant independent predictors of mortality in the following order of predictive strength: age, lower EF, NYHA class, serum creatinine, diabetes, not prescribed beta-blocker, lower systolic BP, lower body mass, time since diagnosis, current smoker, chronic obstructive pulmonary disease, male gender, and not prescribed ACE-inhibitor or angiotensin-receptor blockers. In preserved EF, age was more predictive and systolic BP was less predictive of mortality than in reduced EF. Conversion into an easy-to-use integer risk score identified a very marked gradient in risk, with 3-year mortality rates of 10 and 70% in the bottom quintile and top decile of risk, respectively. CONCLUSION In patients with HF of both reduced and preserved EF, the influences of readily available predictors of mortality can be quantified in an integer score accessible by an easy-to-use website www.heartfailurerisk.org. The score has the potential for widespread implementation in a clinical setting.

Effects of carvedilol on left ventricular remodeling after acute myocardial infarction: the CAPRICORN Echo Substudy.

Background—The CAPRICORN trial has shown that carvedilol improved outcome in patients with left ventricular dysfunction after acute myocardial infarction treated with ACE inhibitors. The aim of this substudy was to determine the effects of carvedilol on left ventricular remodeling in this patient group. Methods and Results—Patients entering the CAPRICORN trial from 13 centers in New Zealand, Australia, and Spain were recruited for this echocardiographic substudy. In 127 patients, quantitative 2D echocardiography was performed according to a standard protocol before randomization and repeated after 1, 3, and 6 months of treatment with carvedilol or placebo. Left ventricular volumes, ejection fraction (Simpson’s method), and wall motion score index were determined in a blinded analysis at the Core Echo Laboratory. At 6 months, left ventricular end systolic volume was 9.2 mL less in the carvedilol group than in the placebo group (P =0.023), and left ventricular ejection fraction was 3.9% higher (P =0.015). Left ventricular end diastolic volume and wall motion score index were not statistically different between the 2 groups at 6 months. Conclusions—In patients with left ventricular dysfunction after acute myocardial infarction treated with ACE inhibitors, carvedilol had a beneficial effect on ventricular remodeling, which may, in part, mediate the substantial clinical beneficial effects of carvedilol in this patient population.

Uptake of self-management strategies in a heart failure management programme

Multidisciplinary heart failure programs including patient education and self‐management strategies such as daily recording of body weight and use of a patient diary decrease hospital readmissions and improve quality of life. However, the degree of uptake of individual components of these programs and their contribution to patient benefit are uncertain.

Independent prognostic importance of a restrictive left ventricular filling pattern after myocardial infarction an individual patient meta-analysis: Meta-analysis research group in echocardiography acute myocardial infarction

Background— Restrictive mitral filling pattern (RFP), the most severe form of diastolic dysfunction, is a predictor of outcome after acute myocardial infarction (AMI). Low power has precluded a definite conclusion on the independent importance of RFP, especially when overall systolic function is preserved. We undertook an individual patient meta-analysis to determine whether RFP is predictive of mortality independently of LV ejection fraction (LVEF), end-systolic volume index, and Killip class in patients after AMI. Methods and Results— Twelve prospective studies (3396 patients) assessing the relationship between prognosis and Doppler echocardiographic LV filling pattern in patients after AMI were included. Individual patient data from each study were extracted and collated into a single database for analysis. RFP was associated with higher all-cause mortality (hazard ratio, 2.67; 95% CI, 2.23 to 3.20; P<0.001) and remained an independent predictor in multivariate analysis with age, gender, and LVEF. The overall prevalence of RFP was 20% but was highest (36%) in the quartile of patients with lowest LVEF (<39%) and lowest (9%) in patients with the highest LVEF (>53%; P<0.0001). RFP remained significant within each quartile of LVEF, and no interaction was found for RFP and LVEF (P=0.42). RFP also predicted mortality in patients with above- and below-median end-systolic volume index (1575 patients) and in different Killip classes (1746 patients). Importantly, when diabetes, current medication, and prior AMI were included in the model, RFP remained an independent predictor of outcome. Conclusions— Restrictive filling is an important independent predictor of mortality after AMI regardless of LVEF, end-systolic volume index, and Killip class.

Determinants of Left Ventricular Hypertrophy and Systolic Dysfunction in Chronic Renal Failure

To evaluate determinants of left ventricular hypertrophy (LVH) and left ventricular (LV) systolic dysfunction in chronic renal failure (CRF), M-mode and two-dimensional echocardiography were performed in 38 undialyzed patients with CRF (serum creatinine > or = 3.4 mg/dL), 54 patients receiving continuous ambulatory peritoneal dialysis, 30 patients receiving hemodialysis, and 59 healthy age- and sex-matched volunteers. Left ventricular (LV) wall thickness and LV dimensions were greatest in dialysis patients, intermediate in CRF patients, and least in control subjects. LV mass index calculated from M-mode measurements was 78.7 g/m2 +/- 14.8 g/m2 in controls, 120.5 g/m2 +/- 28.7 g/m2 in CRF patients, and 136 +/- 45.0 g/m2 in dialysis patients (P < 0.0001). LV fractional shortening and LV velocity of circumferential shortening were lower in dialysis patients than in CRF patients and controls (fractional shortening 36.5% +/- 5.6% in controls, 36.2% +/- 7.2% in CRF patients, and 29.8% +/- 8.9% in dialysis patients; P < 0.0001). Echocardiography was normal in only 24 dialysis patients (29%) and 14 CRF patients (37%) (P = NS). Thirty-nine dialysis patients (46%) and 10 CRF patients (26%) had LVH (P = NS). Thirty dialysis patients (36%) and five CRF patients (13%) had LV systolic dysfunction (P < 0.05). LV hypertrophy with LV systolic dysfunction was present in 15 dialysis patients but no CRF patients (P < 0.05). There were no significant differences between hemodialysis patients and continuous ambulatory peritoneal dialysis patients in M-mode echocardiographic measurements or the frequency of LVH and LV systolic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

The prognostic significance of heart failure with preserved left ventricular ejection fraction: a literature-based meta-analysis.

Heart failure (HF) with normal or preserved left ventricular (LV) ejection fraction (HFPEF) has been reported to be associated with similar outcome as HF with reduced EF (HFREF) in registry‐based and epidemiological analyses, but many of these studies excluded patients who did not have EF measurements. Conversely, prior prospective studies have reported better outcome for patients with HFPEF. We performed a meta‐analysis of prospective observational studies comparing all‐cause mortality in patients with HFREF and HFPEF.

Pseudonormal mitral filling pattern predicts hospital re-admission in patients with congestive heart failure.

OBJECTIVES We sought to investigate whether pseudonormal (PN) filling was associated with death or hospital admission in patients with congestive heart failure (CHF). BACKGROUND The high mortality rate associated with CHF is related to many clinical and echocardiographic variables. In particular, a short mitral deceleration time and restrictive diastolic filling predict death and/or hospital admission. We hypothesized that differentiating patients with nonrestrictive filling might identify an intermediate PN group that may be associated with intermediate risk. METHODS A total of 115 patients admitted to the hospital for exacerbation of CHF symptoms underwent pre-discharge Doppler echocardiography to determine mitral inflow (before and after preload reduction) and pulmonary venous return. Patients were followed up for one year, and all-cause mortality and re-admission data were analyzed. RESULTS The classification of filling patterns was: abnormal relaxation (AR) in 46 (40%) patients, pseudonormal (PN) filling in 42 (36.5%) patients and restrictive filling pattern (RFP) in 27 (23.4%) patients. When comparing the RFP group with the AR group, all-cause mortality was higher (38.4% vs. 17.4%, p = 0.033), hospital admission was higher (70.3% vs. 54.3%, p = 0.073), death/hospital admission was higher (77.8% vs. 56.5%, p = 0.02), CHF hospital admission was higher (40.7% vs. 15.2%, p = 0.01) and death/CHF hospital admission was higher (62.9% vs. 26.1%, p = 0.0005). Mortality in the PN group was not significantly different from that in the two other groups, but re-admissions were higher than the AR group (76.2% vs. 54.3%, p = 0.006), as was death/re-admission (78.6% vs. 56.5%, p = 0.004) and death/CHF re-admission (47.6% vs. 26.1%, p = 0.03). Re-admissions in the PN and RFP groups were comparable. CONCLUSIONS In a general hospital population of older patients with CHF, PN filling was associated with hospital admission rates similar to those seen with restrictive filling. The combined end point of death/CHF hospital admission was similar for restrictive filling and AR. Measurement of these variables is easy to add to routine clinical echocardiography and may provide important prognostic information in a wide range of patients with CHF.

Independent relationship of left atrial size and mortality in patients with heart failure: an individual patient meta-analysis of longitudinal data (MeRGE Heart Failure)

Left atrial (LA) size is considered a marker of poor prognosis in heart failure (HF) patients. Prior studies have recruited relatively few subjects limiting their power to adequately analyse the interaction between LA size, left ventricular (LV) systolic and diastolic function, and prognosis.

Independence of restrictive filling pattern and LV ejection fraction with mortality in heart failure: an individual patient meta-analysis.

The Doppler echocardiographic restrictive mitral filling pattern (RFP) is an important prognostic indicator in patients with heart failure (HF), but the interaction between RFP, left ventricular ejection fraction (LVEF) and filling pattern remains uncertain.