Katrina Poppe

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.

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.

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.

The obesity paradox in heart failure patients with preserved versus reduced ejection fraction: a meta-analysis of individual patient data

Background:In heart failure (HF), obesity, defined as body mass index (BMI) ⩾30 kg m−2, is paradoxically associated with higher survival rates compared with normal-weight patients (the ‘obesity paradox’). We sought to determine if the obesity paradox differed by HF subtype (reduced ejection fraction (HF-REF) versus preserved ejection fraction (HF-PEF)).Patients and Methods:A sub-analysis of the MAGGIC meta-analysis of patient-level data from 14 HF studies was performed. Subjects were divided into five BMI groups: <22.5, 22.5–24.9 (referent), 25–29.9, 30–34.9 and ⩾35 kg m−2. Cox proportional hazards models adjusted for age, sex, aetiology (ischaemic or non-ischaemic), hypertension, diabetes and baseline blood pressure, stratified by study, were used to examine the independent association between BMI and 3-year total mortality. Analyses were conducted for the overall group and within HF-REF and HF-PEF groups.Results:BMI data were available for 23 967 subjects (mean age, 66.8 years; 32% women; 46% NYHA Class II; 50% Class III) and 5609 (23%) died by 3 years. Obese patients were younger, more likely to receive cardiovascular (CV) drug treatment, and had higher comorbidity burdens. Compared with BMI levels between 22.5 and 24.9 kg m−2, the adjusted relative hazards for 3-year mortality in subjects with HF-REF were: hazard ratios (HR)=1.31 (95% confidence interval=1.15–1.50) for BMI <22.5, 0.85 (0.76–0.96) for BMI 25.0–29.9, 0.64 (0.55–0.74) for BMI 30.0–34.9 and 0.95 (0.78–1.15) for BMI ⩾35. Corresponding adjusted HRs for those with HF-PEF were: 1.12 (95% confidence interval=0.80–1.57) for BMI <22.5, 0.74 (0.56–0.97) for BMI 25.0–29.9, 0.64 (0.46–0.88) for BMI 30.0–34.9 and 0.71 (0.49–1.05) for BMI ⩾35.Conclusions:In patients with chronic HF, the obesity paradox was present in both those with reduced and preserved ventricular systolic function. Mortality in both HF subtypes was U-shaped, with a nadir at 30.0–34.9 kg m−2.

Relationship of serum sodium concentration to mortality in a wide spectrum of heart failure patients with preserved and with reduced ejection fraction: an individual patient data meta-analysis

Hyponatraemia has been associated with reduced survival in patients with heart failure and reduced ejection fraction (HF‐REF). The relationship between serum sodium and outcome is unclear in heart failure with preserved (≥50%) ejection fraction (HF‐PEF). Therefore, we used a large individual patient data meta‐analysis to study the risk of death associated with hyponatraemia in HF‐REF and in HF‐PEF.

Renal Dysfunction in Patients With Heart Failure With Preserved Versus Reduced Ejection Fraction

Background— Prior studies in heart failure (HF) have used the Modification of Diet in Renal Disease (MDRD) equation to calculate estimated glomerular filtration rate (eGFR). The Chronic Kidney Disease-Epidemiology Collaboration Group (CKD-EPI) equation provides a more-accurate eGFR than the MDRD when compared against the radionuclide gold standard. The prevalence and prognostic import of renal dysfunction in HF if the CKD-EPI equation is used rather than the MDRD is uncertain. Methods and Results— We used individual patient data from 25 prospective studies to stratify patients with HF by eGFR using the CKD-EPI and the MDRD equations and examined survival across eGFR strata. In 20 754 patients (15 962 with HF with reduced ejection fraction [HF-REF] and 4792 with HF with preserved ejection fraction [HF-PEF]; mean age, 68 years; deaths per 1000 patient-years, 151; 95% CI, 146–155), 10 589 (51%) and 11 422 (55%) had an eGFR <60 mL/min using the MDRD and CKD-EPI equations, respectively. Use of the CKD-EPI equation resulted in 3760 (18%) patients being reclassified into different eGFR risk strata; 3089 (82%) were placed in a lower eGFR category and exhibited higher all-cause mortality rates (net reclassification improvement with CKD-EPI, 3.7%; 95% CI, 1.5%–5.9%). Reduced eGFR was a stronger predictor of all-cause mortality in HF-REF than in HF-PEF. Conclusions— Use of the CKD-EPI rather than the MDRD equation to calculate eGFR leads to higher estimates of renal dysfunction in HF and a more-accurate categorization of mortality risk. Renal function is more closely related to outcomes in HF-REF than in HF-PEF.Background —Prior studies in heart failure have used the Modification of Diet in Renal Disease (MDRD) equation to estimate Glomerular Filtration Rate (eGFR). The Chronic Kidney Disease-Epidemiology Collaboration Group equation (CKD-EPI) more accurately estimates GFR than the MDRD when compared against the radionuclide gold standard. The prevalence and prognostic import of renal dysfunction in HF if the CKD-EPI equation is used rather than the MDRD is uncertain. Methods and Results —We used individual patient data from 25 prospective studies to stratify heart failure patients by eGFR using the CKD-EPI and the MDRD equations and examined survival across eGFR strata. In 20 754 patients (15 962 with reduced ejection fraction [HF-REF] and 4792 with preserved ejection fraction [HF-PEF], mean age 68 years, 151 [95%CI 146-155] deaths per 1000 patient-years), 10 589 (51%) had eGFR < 60 ml/min using the MDRD equation and 11 422 (55%) using the CKD-EPI equation. Using the CKD-EPI equation resulted in 3760 (18%) patients being re-classified into different eGFR risk strata; 3089 (82%) were placed in a lower eGFR category and exhibited higher all-cause mortality rates (net reclassification improvement with CKD-EPI 3.7%, 95% CI 1.5% to 5.9%). Reduced eGFR was a stronger predictor of all-cause mortality in HF-REF than HF-PEF. Conclusions —Use of the CKD-EPI equation rather than the MDRD to calculate eGFR leads to higher estimates of renal dysfunction in heart failure and more accurate categorization of mortality risk. Renal function is more closely related to outcomes in HF-REF than in HF-PEF.Background— Prior studies in heart failure (HF) have used the Modification of Diet in Renal Disease (MDRD) equation to calculate estimated glomerular filtration rate (eGFR). The Chronic Kidney Disease-Epidemiology Collaboration Group (CKD-EPI) equation provides a more-accurate eGFR than the MDRD when compared against the radionuclide gold standard. The prevalence and prognostic import of renal dysfunction in HF if the CKD-EPI equation is used rather than the MDRD is uncertain. Methods and Results— We used individual patient data from 25 prospective studies to stratify patients with HF by eGFR using the CKD-EPI and the MDRD equations and examined survival across eGFR strata. In 20 754 patients (15 962 with HF with reduced ejection fraction [HF-REF] and 4792 with HF with preserved ejection fraction [HF-PEF]; mean age, 68 years; deaths per 1000 patient-years, 151; 95% CI, 146–155), 10 589 (51%) and 11 422 (55%) had an eGFR <60 mL/min using the MDRD and CKD-EPI equations, respectively. Use of the CKD-EPI equation resulted in 3760 (18%) patients being reclassified into different eGFR risk strata; 3089 (82%) were placed in a lower eGFR category and exhibited higher all-cause mortality rates (net reclassification improvement with CKD-EPI, 3.7%; 95% CI, 1.5%–5.9%). Reduced eGFR was a stronger predictor of all-cause mortality in HF-REF than in HF-PEF. Conclusions— Use of the CKD-EPI rather than the MDRD equation to calculate eGFR leads to higher estimates of renal dysfunction in HF and a more-accurate categorization of mortality risk. Renal function is more closely related to outcomes in HF-REF than in HF-PEF.

Screening for left ventricular hypertrophy in patients with type 2 diabetes mellitus in the community

BackgroundLeft ventricular hypertrophy (LVH) is a strong predictor of cardiovascular disease and is common among patients with type 2 diabetes. However, no systematic screening for LVH is currently recommended for patients with type 2 diabetes. The purpose of this study was to determine whether NT-proBNP was superior to 12-lead electrocardiography (ECG) for detection of LVH in patients with type 2 diabetes.MethodsProspective cross-sectional study comparing diagnostic accuracy of ECG and NT-proBNP for the detection of LVH among patients with type 2 diabetes. Inclusion criteria included having been diagnosed for > 5 years and/or on treatment for type 2 diabetes; patients with Stage 3/4 chronic kidney disease and known cardiovascular disease were excluded. ECG LVH was defined as either the Sokolow-Lyon or Cornell voltage criteria. NT-proBNP level was measured using the Roche Diagnostics Elecsys assay. Left ventricular mass was assessed from echocardiography. Receiver operating characteristic curve analysis was carried out and area under the curve (AUC) was calculated.Results294 patients with type 2 diabetes were recruited, mean age 58 (SD 11) years, BP 134/81 ± 18/11 mmHg, HbA1c 7.3 ± 1.5%. LVH was present in 164 patients (56%). In a logistic regression model age, gender, BMI and a history of hypertension were important determinants of LVH (p < 0.05). Only 5 patients with LVH were detected by either ECG voltage criteria. The AUC for NT-proBNP in detecting LVH was 0.68.ConclusionsLVH was highly prevalent in asymptomatic patients with type 2 diabetes. ECG was an inadequate test to identify LVH and while NT-proBNP was superior to ECG it remained unsuitable for detecting LVH. Thus, there remains a need for a screening tool to detect LVH in primary care patients with type 2 diabetes to enhance risk stratification and management.

Atrial fibrillation and the risk of death in patients with heart failure: a literature-based meta-analysis.

Background: Heart failure (HF) and atrial fibrillation (AF) are common, associated with significant morbidity and mortality, and frequently coexist. It is uncertain from published data if the presence of AF in patients with HF is associated with an incremental adverse outcome. The aim of this study was to combine the results of all studies investigating prognosis for patients with HF and AF compared with those in sinus rhythm (SR) to asses the mortality risk associated with this arrhythmia.

Structural and Functional Cardiac Abnormalities in Adolescent Girls with Poorly Controlled Type 2 Diabetes

OBJECTIVE Type 2 diabetes is associated with left ventricular hypertrophy (LVH) and diastolic dysfunction, which may eventually lead to clinical heart failure. We sought to determine the cardiovascular effects of adolescent-onset type 2 diabetes. RESEARCH DESIGN AND METHODS We recruited diabetic girls (8 with type 2 and 11 with type 1 diabetes) from a hospital diabetes service and nondiabetic control subjects (9 lean and 11 overweight) from the schools of the diabetic subjects. Echocardiography and measurements were performed by a single observer, blinded to subject group allocation, and included M-mode left ventricular dimensions, two-dimensional left ventricular mass, Doppler diastolic flows, estimation of left ventricular filling pressure, and systolic longitudinal motion. Left ventricular mass was indexed to height and fat-free body mass. ANOVA was used to compare the groups. RESULTS The groups were similar in age and height, but significant differences in body composition were observed. Subjects with type 2 diabetes had larger left ventricular dimensions and left ventricular mass, which persisted when indexed to height. Diastolic filling was impaired in both diabetic groups, and systolic longitudinal function was lower in the type 2 diabetic group. Half of the group with type 2 diabetes met the published criteria for LVH and left ventricular dilatation; 25% had evidence of elevated left ventricular filling pressure in association with structural abnormalities. CONCLUSIONS This study has demonstrated preclinical abnormalities of cardiac structure and function in adolescent girls with type 2 diabetes, despite the short duration of diabetes and highlights the potential high cardiovascular risk occurring in adolescent type 2 diabetes.