Simulated case management of home telemonitoring to assess the impact of different alert algorithms on work-load and clinical decisions.

BACKGROUND: Home telemonitoring (HTM) of chronic heart failure (HF) promises to improve care by timely indications when a patient's condition is worsening. Simple rules of sudden weight change have been demonstrated to generate many alerts with poor sensitivity. Trend alert algorithms and bio-impedance (a more sensitive marker of fluid change), should produce fewer false alerts and reduce workload. However, comparisons between such approaches on the decisions made and the time spent reviewing alerts has not been studied. METHODS: Using HTM data from an observational trial of 91 HF patients, a simulated telemonitoring station was created and used to present virtual caseloads to clinicians experienced with HF HTM systems. Clinicians were randomised to either a simple (i.e. an increase of 2 kg in the past 3 days) or advanced alert method (either a moving average weight algorithm or bio-impedance cumulative sum algorithm). RESULTS: In total 16 clinicians reviewed the caseloads, 8 randomised to a simple alert method and 8 to the advanced alert methods. Total time to review the caseloads was lower in the advanced arms than the simple arm (80 ± 42 vs. 149 ± 82 min) but agreements on actions between clinicians were low (Fleiss kappa 0.33 and 0.31) and despite having high sensitivity many alerts in the bio-impedance arm were not considered to need further action. CONCLUSION: Advanced alerting algorithms with higher specificity are likely to reduce the time spent by clinicians and increase the percentage of time spent on changes rated as most meaningful. Work is needed to present bio-impedance alerts in a manner which is intuitive for clinicians.

Long-term changes of renal function in relation to ace inhibitor/angiotensin receptor blocker dosing in patients with heart failure and chronic kidney disease.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have become cornerstones of therapy for chronic heart failure (CHF). Guidelines advise high target doses for ACEIs/ARBs, but fear of worsening renal function may limit dose titration in patients with concomitant chronic kidney disease (CKD). METHODS: In this retrospective observational study, we identified 722 consecutive patients with systolic CHF, stable CKD stage III/IV (estimated glomerular filtration rate [eGFR] 15-60 mL min(-1) 1.73 m(-2)) and chronic ACEI/ARB treatment from the outpatient heart failure clinics at the Universities of Hull, UK, and Heidelberg, Germany. Change of renal function, worsening CHF, and hyperkalemia at 12-month follow-up were analyzed as a function of both baseline ACEI/ARB dose and dose change from baseline. RESULTS: ΔeGFR was not related to baseline dose of ACEI/ARB (P = .58), or to relative (P = .18) or absolute change of ACEI/ARB dose (P = .21) during follow-up. Expressing change of renal function as a categorical variable (improved/stable/decreased) as well as subgroup analyses with respect to age, sex, New York Heart Association functional class, left ventricular ejection fraction, diabetes, concomitant aldosterone antagonists, CKD stage, hypertension, ACEI vs ARB, and congestion status yielded similar results. There was no association of dose/dose change with incidence of either worsening CHF or hyperkalemia. CONCLUSIONS: In patients with systolic CHF and stable CKD stage III/IV, neither continuation of high doses of ACEI/ARB nor up-titration was related to adverse changes in longer-term renal function. Conversely, down-titration was not associated with improvement in eGFR. Use of high doses of ACEI/ARB and their up-titration in patients with CHF and CKD III/IV may be appropriate provided that the patient is adequately monitored.

The in vitro stability of novel cardiovascular and sepsis biomarkers at ambient temperature.

BACKGROUND: The in vitro stability of a biomarker can determine whether it should be used in clinical practice where long delays between sampling and assay are common. We measured the in vitro stability of five novel biomarkers that are being evaluated for their diagnostic and/or prognostic utility in patients with heart failure: mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adreno-medullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), C-terminal pro-arginine vasopressin (copeptin) and ultrasensitive procalcitonin (PCT). METHODS: Peripheral venous blood samples were obtained from 19 patients with chronic heart failure into four EDTA tubes. The first tubes were centrifuged immediately at 4°C with the other tubes stored at 20°C for 4, 24 or 72 hours (h) before centrifuging. Supernatant plasma was frozen and stored at -80°C until assay. The levels of analyte in samples processed with and without delay were compared using correlation analysis, paired t-tests and Bland-Altman plots. RESULTS: Copeptin and PCT were stable up to 72 h at 20°C in whole blood and MR-proANP and MR-proADM up to 24 h. However, CT-proET-1 showed some signs of degradation after only 4 h with 94% of analyte recovered after 24 h, dropping to 80% after 72 h. CONCLUSIONS: MR-proANP, MR-proADM, copeptin and PCT are stable biomarkers and therefore suitable for introduction into routine clinical practice in a primary or secondary care setting where delays in sample preparation and assay are likely. Ideally, samples for measurement of CT-proET-1 should be centrifuged soon after venepuncture but the analyte is stable enough for most routine clinical purposes.

Glycaemic control and insulin therapy are significant confounders of the obesity paradox in patients with heart failure and diabetes mellitus.

BACKGROUND: A high body mass index (BMI) confers a paradoxical survival benefit in patients with heart failure (HF) or diabetes mellitus (DM). There is, however, controversy whether an obesity paradox is also present in patients with HF and concomitant DM. In addition, the influence of glycaemic control and diabetes treatment on the presence or absence of the obesity paradox in patients with HF and DM is unknown. METHODS: We identified 2936 patients with HF with reduced ejection fraction (HFrEF) in the HF registries of the universities of Heidelberg, Germany, and Hull, UK (general sample). Of these, 598 (20%) were treated for concomitant DM (DM subgroup). The relationship between BMI and all-cause mortality was analysed in both the general sample and the DM subgroup. Patients with concomitant DM were stratified according to HbA1c levels or type of diabetes treatment and analyses were repeated. RESULTS: We found an inverse BMI-mortality relationship in both the general sample and the DM subgroup. However, the obesity paradox was less pronounced in patients with diabetes treated with insulin and it disappeared in those with poor glycaemic control as defined by HbA1c levels > 7.5%. CONCLUSION: In patients with HFrEF, a higher BMI is associated with better survival irrespective of concomitant DM. However, insulin treatment and poor glycaemic control make the relationship much weaker.

Prevalence of, associations with, and prognostic value of tricuspid annular plane systolic excursion (TAPSE) among out-patients referred for the evaluation of heart failure.

BACKGROUND: Prevalence, predictors, and prognostic value of right ventricular (RV) function measured by the tricuspid annular plane systolic excursion (TAPSE) in patients with chronic heart failure (CHF) symptoms with a broad range of left ventricular ejection fraction (LVEF) are unknown. METHODS AND RESULTS: Of 1,547 patients, mean (±SD) age was 71 ± 11 years, 48% were women, median (interquartile range [IQR]) TAPSE was 18.5 (14.0-22.7) mm, mean LVEF was 47 ± 16%, 47% had LVEF ≤45% and 67% were diagnosed with CHF, defined as systolic (S-HF) if LVEF was ≤45% and as heart failure with preserved ejection fraction (HFPEF) if LVEF was >45% and treated with a loop diuretic. During a median (IQR) follow-up of 63 (41-75) months, mortality was 34%. In multivariable analysis, increasing age, N-terminal pro-B-type natriuretic peptide (NT-proBNP), New York Heart Association functional class, right atrial volume index, and transtricuspid pressure gradient; lower TAPSE, diastolic blood pressure, and hemoglobin; and atrial fibrillation (AF) or COPD were associated with an adverse prognosis. Receiver operating characteristic curve analysis identified a TAPSE of 15.9 mm as the best prognostic threshold (P = .0001); 47% of S-HF and 20% of HFPEF had a TAPSE of <15.9 mm. The main associations with a TAPSE <15.9 mm were higher NT-proBNP, presence of atrial fibrillation and presence of LV systolic dysfunction. CONCLUSIONS: In patients with CHF, low values for TAPSE are common, especially in those with reduced LVEF. TAPSE, unlike LVEF, was an independent predictor of outcome.

Influence of body mass on risk prediction during cardiopulmonary exercise testing in patients with chronic heart failure.

INTRODUCTION: Peak oxygen uptake (VO2) during a maximal exercise test is used to stratify patients with chronic heart failure (CHF) and is usually corrected for body mass. OBJECTIVE: To explore the influence of body mass on risk prediction during treadmill cardiopulmonary exercise testing (CPET) in patients with CHF. METHODS: A total of 411 patients with suspected CHF (mean [± SD] age 64±12 years; 81% male; mean left ventricular ejection fraction 39±6%) underwent symptom-limited, maximal CPET on a treadmill. Patients were categorized as normal weight, overweight or obese based on body mass index. RESULTS: One hundred fifteen patients died during a median follow-up period of 8.7±2.3 years in survivors. In the univariable analysis, peak VO2 adjusted for body mass (χ(2)=41.4) and unadjusted (χ(2)=40.2) were similar for predicting all-cause mortality. Peak VO2 adjusted for body mass showed marginally higher χ(2) values in normal weight, overweight and obese categories than unadjusted values. Anaerobic threshold had similar prognostic power regardless of whether it was corrected for body mass (χ(2)=22.4 and χ(2)=24.4), with no difference between the two in any of the subgroups separately. In all patients, unadjusted ventilation (VE)/carbon dioxide production (VCO2) slope (χ(2)=40.6) was a stronger predictor of all-cause mortality than body mass adjusted values (χ(2)=32.8), and unadjusted values remained stronger in normal weight, overweight and obese subgroups. CONCLUSION: Correcting peak VO2 for body mass slightly improves risk prediction, especially in obese patients with CHF. The adjustment of other CPET-derived variables including anaerobic threshold and VE/VCO2 slope for body mass appears to provide less prognostic value.

Determinants and prognostic value of pulmonary arterial pressure in patients with chronic heart failure.

AIMS: The epidemiology of pulmonary arterial hypertension (PAH) in patients with heart failure (HF) is poorly described. Our aim was to investigate the determinants and prognostic significance of PAH in a large representative outpatient population with HF. METHODS AND RESULTS: Routine measurement of right ventricular tricuspid pressure gradient (RVTG) was attempted among unselected, consecutive referrals to an HF clinic. The diagnosis of HF was based on symptoms, signs, echocardiography, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Of 2100 patients referred, 1380 were diagnosed as HF, of whom 1026 had left ventricular systolic dysfunction (LVSD) and 354 did not. Right ventricular tricuspid pressure gradient could be measured in 270 (26%) patients with and 143 (40%) without LVSD. The highest RVTG quartile [RVTG > 35 mmHg equivalent to an estimated PA systolic pressure (PASP) > 45 mmHg] constituted 7% of all those with HF and was associated with higher LV filling pressures, LV end-diastolic volume, LVSD, and more severe mitral regurgitation (MR). During a median (inter-quartile range) follow-up of 66 (56-74) months, mortality was 40.3%. Mortality was similar in the lowest quartile of RVTG and in those in whom RVTG could not be measured and rose with increasing RVTG quartile (log-rank: 26.9; P < 0.0001). The highest RVTG quartile, age, blood pressure, and log NT-proBNP independently predicted mortality. Right ventricular tricuspid pressure gradient >35 mmHg had a 96% specificity to discriminate between those with and without HF in patients without LVSD. CONCLUSION: Using a definition of PASP > 45 mmHg, 7% of the patients with HF have PAH, which is associated with worse LV function, MR, and prognosis. Whether PAH is a target for therapy in this population remains to be elucidated.

Statistical methods in epidemiology. IX. Survival (failure-time) models.

PURPOSE: This article introduces readers to survival (failure-time) models, with a focus on Kaplan-Meier curves, Cox regression and sample size estimation. METHODS: An example is used to show readers how to calculate a Kaplan-Meier curve from first principles. RESULTS: What makes survival data unique is censoring. Readers should understand censoring before undertaking an analysis of survival data. CONCLUSION: The Cox model continues to set the standard for survival models, and will continue well into the future.

The prognostic value of repeated measurement of N-terminal pro-B-type natriuretic peptide in patients with chronic heart failure due to left ventricular systolic dysfunction.

AIMS: Decreased N-terminal pro-B-type natriuretic peptide (NT-proBNP) during treatment of chronic heart failure (CHF) is associated with improved prognosis. However, there is lack of data from community-based HF programmes. We hypothesized that plasma levels of NT-proBNP, measured after optimization of pharmacotherapy in patients with CHF, may provide independent prognostic information when compared with baseline values and conventional prognostic markers. METHODS AND RESULTS: N-terminal pro-B-type natriuretic peptide was measured in 354 patients with CHF and left ventricular ejection fraction <45%, who had recently been enrolled in a community-based HF programme. Patients underwent a 6 min walk test and clinical, echocardiographic and laboratory examinations. Pharmacotherapy was optimized; 318 patients survived until the second examination and measurement of NT-proBNP, which was performed between the 4th and 6th month of follow-up. During a median follow-up of 38.8 months, 125 patients died. Follow-up log NT-proBNP was a better predictor of death than either baseline log NT-proBNP or change in NT-proBNP (chi(2): 46.5 vs. 30.4 and 12.5, all P < 0.001). N-terminal pro-B-type natriuretic peptide was consistently the strongest independent prognostic marker at predicting death or unplanned cardiovascular hospitalizations after baseline or follow-up assessment. CONCLUSION: The measurement of NT-proBNP after optimization of pharmacotherapy provides stronger prognostic information than either the baseline value, the change in NT-proBNP, or other conventional methods of assessment.

Predicting hospitalization due to worsening heart failure using daily weight measurement: analysis of the Trans-European Network-Home-Care Management System (TEN-HMS) study.

AIMS: We sought to test the utility of weight gain algorithms to predict episodes of worsening heart failure (WHF) using home-telemonitoring data collected as part of the TEN-HMS study. METHODS AND RESULTS: Simple rule-of-thumb (RoT) algorithms (i.e. 3 lbs in 1 day and 5 lbs in 3 days) and a moving average convergence divergence (MACD) algorithm were compared. WHF was defined as hospitalization for WHF or worsening of breathlessness or leg oedema. Of 168 patients, 45 were hospitalized with WHF and 76 were hospitalized for other reasons. On average, weight gain occurred in the 14 days prior to WHF hospitalizations but not in the 14 days prior to non-WHF hospitalizations [1.9 +/- 4.7 lbs (0.9 +/- 2.1 kg) vs. -0.4 +/- 2.5 lbs (-0.2 +/- 1.1 kg), P < 0.0001]. The true alerts rate was higher for the RoT algorithms compared with the MACD (58 and 65% vs. 20%). However, the RoT algorithms had much higher false alert rates (54 and 58% vs. 9%) rendering them of little practical use for predicting WHF events. CONCLUSION: A MACD algorithm is more specific but less sensitive than RoT when trying to predict episodes of WHF based on daily weight measurements. However, many episodes of WHF do not appear to be associated with weight gain and therefore telemonitoring of weight alone may not have great value for heart failure management.

Epidemiology and long-term outcome in outpatients with chronic heart failure in Northwestern Europe.

OBJECTIVE: To describe the epidemiology, long-term outcomes and temporal trends in mortality in ambulatory patients with chronic heart failure (HF) with reduced (HFrEF), mid-range (HFmrEF) or preserved ejection fraction (HFpEF) from three European countries. METHODS: We identified 10 312 patients from the Norwegian HF Registry and the HF registries of the universities of Heidelberg, Germany, and Hull, UK. Patients were classified according to baseline left ventricular ejection fraction (LVEF) and time of enrolment (period 1: 1995-2005 vs period 2: 2006-2015). Predictors of mortality were analysed by use of univariable and multivariable Cox regression analyses. RESULTS: Among 10 312 patients with stable HF, 7080 (68.7%), 2086 (20.2%) and 1146 (11.1%) were classified as having HFrEF, HFmrEF or HFpEF, respectively. A total of 4617 (44.8%) patients were included in period 1, and 5695 (55.2%) patients were included in period 2. Baseline characteristics significantly differed with respect to type of HF and time of enrolment. During a median follow-up of 66 (33-105) months, 5297 patients (51.4%) died. In multivariable analyses, survival was independent of LVEF category (p>0.05), while mortality was lower in period 2 as compared with period 1 (HR 0.81, 95% CI 0.72 to 0.91, p<0.001). Significant predictors of all-cause mortality regardless of HF category were increasing age, New York Heart Association functional class, N-terminal pro-brain natriuretic peptide and use of loop diuretics. CONCLUSION: Ambulatory patients with HF stratified by LVEF represent different phenotypes. However, after adjusting for a wide range of covariates, long-term survival is independent of LVEF category. Outcome significantly improved during the last two decades irrespective from type of HF.

Comparative effectiveness of loop diuretics on mortality in the treatment of patients with chronic heart failure - A multicenter propensity score matched analysis.

BACKGROUND: Loop diuretics are given to the majority of patients with chronic heart failure (HF). Whether the different pharmacological properties of the three guideline-recommended loop diuretics result in differential effects on survival is unknown. METHODS: 6293 patients with chronic HF using either bumetanide, furosemide or torasemide were identified in three European HF registries. Patients were individually matched on both the respective propensity scores for receipt of the individual drug and dose-equivalents thereof. RESULTS: During a follow-up of 35,038 patient-years, 652 (53.7%), 2179 (51.9%), and 268 (30.4%) patients died amongst those prescribed bumetanide, furosemide, and torasemide, respectively. In univariable analyses of the general sample, bumetanide and furosemide were both associated with higher mortality as compared with torasemide treatment (HR 1.50, 95% CI 1.31-1.73, p < 0.001, and HR 1.34, CI 1.18-1.52, p < 0.001, respectively). Mortality was higher in bumetanide users when compared to furosemide users (HR 1.11, 95% CI 1.02-1.20, p = 0.01). However, there was no significant association between loop diuretic choice and all-cause mortality in any of the matched samples (bumetanide vs. furosemide, HR 1.03, 95% CI 0.93-1.14, p = 0.53; bumetanide vs. torasemide, HR 0.98, 95% CI 0.78-1.24, p = 0.89; furosemide vs. torasemide, HR 1.02, 95% CI 0.84-1.24, p = 0.82). The results were confirmed in subgroup analyses with respect to age, sex, left ventricular ejection fraction, NYHA functional class, cause of HF, rhythm, and systolic blood pressure. CONCLUSIONS: In patients with HF, mortality is not affected by the choice of individual loop diuretics.

A comparison of patient and physician-rated New York Heart Association class in a community-based heart failure clinic.

OBJECTIVE: The New York Heart Association (NYHA) classification is recommended for grading symptoms of chronic heart failure and is a powerful prognostic marker. Patient-rated NYHA (Pa-NYHA) and physician-rated NYHA (Dr-NYHA) class have never been compared directly, and it is unknown whether they carry similar prognostic significance. METHODS AND RESULTS: NYHA class was rated independently by a physician and patient in 1752 patients referred with suspected heart failure. Pa-NYHA and Dr-NYHA varied by 1 class in 37.1% cases and by 2 classes in 12.8% cases. Mean Dr-NYHA and Pa-NYHA were higher in women than men (1.98 vs 1.89, P = .016; 2.17 vs 2.02, P = .002) despite less cardiac disease. Dr-NYHA correlated more with 6-minute walk test distance and severity of left ventricular systolic dysfunction than Pa-NYHA (Spearman's rho: -0.53 vs -0.44 and 0.32 vs 0.16). Dr-NYHA better predicted mortality when compared with Pa-NYHA (log-rank: chi(2) = 105 vs 46, both P < .001). CONCLUSION: Patients rate NYHA differently from physicians, and women rate NYHA differently from men. Dr-NYHA relates more strongly to survival and severity of left ventricular systolic dysfunction, suggesting that for physicians the NYHA classification may have become a "heart failure severity score" and not as was intended, purely a measure of a patient's symptoms and functional status.

The prevalence and incidence of left bundle branch block in ambulant patients with chronic heart failure.

BACKGROUND: Approximately one third of patients with chronic heart failure have left bundle branch block (LBBB) on their 12-lead ECG. METHODS AND RESULTS: 1418 consecutive patients (average (SD) age 70.5 (10.4) years; 74% male) first seen in a community heart failure clinic between December 2001 and June 2006 had a 12 lead electrocardiogram (ECG). 485 (34%) had a QRS duration >or=120 ms. Patients with a broad QRS were older (72.2 v 69.3 years), had worse left ventricular systolic function, were on a higher daily dose of diuretic and were more likely to be on amiodarone (14.4 v 7.1%). 12 lead ECG was available for 734 patients (52%) at 1 year follow up. The QRS interval increased from 115.1 ms at baseline to 117.6 (P<0.0001). There were 52 incident cases of LBBB, an incidence of 10.9%. The only predictors of incident LBBB were QRS duration at baseline and amiodarone use at baseline. The proportion of patients with LBBB increased from 34.0% at baseline to 36.7%, 37.7% and 42.3% at 1, 2 and 3 years follow up, respectively. Baseline LBBB was associated with a worse outcome (HR 1.25 (95% CI 1.01-1.55). New LBBB was an independent adverse prognostic feature (HR 2.09 (95% CI 1.17-3.73); P=0.013). CONCLUSIONS: The crude incidence of LBBB is 10.9% in the first year of follow up in an unselected population of ambulatory outpatients with chronic stable heart failure. Ongoing care of patients with chronic heart failure should include a regular 12 lead electrocardiogram.

Prevalence, predictors, and prognostic implications of PR interval prolongation in patients with heart failure.

AIMS: To determine the prevalence, incidence, predictors, and prognostic implications of PR interval prolongation in patients referred with suspected heart failure. METHODS AND RESULTS: Consecutive patients referred with suspected heart failure were prospectively enrolled. After excluding patients with implantable cardiac devices and atrial fibrillation, 1420 patients with heart failure and reduced ejection fraction (HeFREF) [age: median 71 (interquartile range IQR 63-78) years; men: 71%; NT-ProBNP: 1319 (583-3378) ng/L], 1094 with heart failure and normal ejection fraction (HeFNEF) [age: 76 (70-82) years; men: 47%; NT-ProBNP: 547 (321-1171) ng/L], and 1150 without heart failure [age: 68 (60-75) years; men: 51%; NT-ProBNP: 86 (46-140) ng/L] were included. The prevalence of first-degree heart block [heart rate corrected PR interval (PRc) > 200 ms] was higher in patients with heart failure (21% HeFREF, 20% HeFNEF, 9% without heart failure). In patients with HeFREF or HeFNEF, longer baseline PRc was associated with greater age, male sex, and longer QRS duration, and, in those with HeFREF, treatment with amiodarone or digoxin. Patients with heart failure in the longest PRc quartile had worse survival compared to shorter PRc quartiles, but PRc was not independently associated with survival in multivariable analysis. For patients without heart failure, shorter baseline PRc was independently associated with worse survival. CONCLUSION: PRc prolongation is common in patients with HeFREF or HeFNEF and associated with worse survival, although not an independent predictor of outcome. The results of clinical trials investigating the therapeutic potential of shortening the PR interval by pacing are awaited.

Comparative effectiveness of enalapril, lisinopril, and ramipril in the treatment of patients with chronic heart failure: a propensity score-matched cohort study.

Aims: Angiotensin-converting enzyme inhibitors (ACEIs) are recommended as first-line therapy in patients with heart failure with reduced ejection fraction (HFrEF). The comparative effectiveness of different ACEIs is not known. Methods and results: A total of 4723 outpatients with stable HFrEF prescribed enalapril, lisinopril, or ramipril were identified from three registries in Norway, England, and Germany. In three separate matching procedures, patients were individually matched with respect to both dose equivalents and their respective propensity scores for ACEI treatment. During a follow-up of 21 939 patient-years, 360 (49.5%), 337 (52.4%), and 1119 (33.4%) patients died among those prescribed enalapril, lisinopril, and ramipril, respectively. In univariable analysis of the general sample, enalapril and lisinopril were both associated with higher mortality when compared with ramipril treatment [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.30-1.65, P < 0.001 and HR 1.38, 95% CI 1.22-1.56, P < 0.001, respectively). Patients prescribed enalapril or lisinopril had similar mortality (HR 1.06, 95% CI 0.92-1.24, P = 0.41). However, there was no significant association between ACEI choice and all-cause mortality in any of the matched samples (HR 1.07, 95% CI 0.91-1.25, P = 0.40; HR 1.12, 95% CI 0.96-1.32, P = 0.16; and HR 1.10, 95% CI 0.93-1.31, P = 0.25 for enalapril vs. ramipril, lisinopril vs. ramipril, and enalapril vs. lisinopril, respectively). Results were confirmed in subgroup analyses with respect to age, sex, left ventricular ejection fraction, New York Class Association functional class, cause of HFrEF, rhythm, and systolic blood pressure. Conclusion: Our results suggest that enalapril, lisinopril, and ramipril are equally effective in the treatment of patients with HFrEF when given at equivalent doses.

Epidemiology, associated factors, and prognostic outcomes of renal artery stenosis in chronic heart failure assessed by magnetic resonance angiography.

Our aim was to determine the prevalence, morbidity, and mortality associated with the presence of significant renal artery stenosis (RAS) in patients with chronic heart failure (HF), and to explore the use of angiotensin-converting enzyme (ACE) inhibitors and diuretics in this population during a 3-year follow-up period. We identified 97 patients with significant renal dysfunction (RD, defined as a calculated glomerular filtration rate of <60 ml/min) and 38 patients without RD, with ejection fractions of <40%. A stenosis of >50% using magnetic resonance angiography of the renal arteries was used to define significant RAS. Seventy-three (54%) patients had significant RAS of >or=1 artery. Mean follow-up time was 37.3 (+/- 7.9) months. Compared with patients with no significant RAS, these patients were on higher doses of diuretics, lower doses of ACE inhibitors, had prolonged hospital admissions, were admitted with exacerbation of HF, and had a higher mortality (p = 0.007 for mortality). In conclusion, RAS is common in patients with chronic HF, especially among patients with RD and is a predictor of a poor clinical outcome. Interventional trials on renal revascularization are underway that contain subsets of patients with HF that may provide evidence on how best to manage RAS in this setting.

Nonpharmacologic measures and drug compliance in patients with heart failure: data from the EuroHeart Failure Survey.

Advice on lifestyle, diet, vaccination, and therapy are part of the standard management of heart failure (HF). However, there is little information on whether patients with HF recall receiving such recommendations and, if so, whether they report following them. We obtained information on the recall of and adherence to nonpharmacologic advice from patients enrolled in the EuroHeart Failure Survey. This article focuses on 2,331 patients who had a clinical diagnosis of HF during the index admission and attended an interview 12 weeks after discharge. Their mean age was 67 +/- 12 years and 38% were women. Patients recalled receiving 4.1 +/- 2.7 items of advice with higher rates in Central Europe and the Mediterranean region. Recall of dietary advice (cholesterol or fat intake, 63%; dietary salt, 60%) was higher than for some other interventions (influenza vaccination, 36%; avoidance of nonsteroidal anti-inflammatory drugs, 17%). Among those who recalled the advice, a substantial proportion indicated that they did not follow advice completely (cholesterol and fat intake, 61%; dietary salt, 63%; influenza vaccination, 75%; avoidance of nonsteroidal anti-inflammatory drugs, 80%), although few patients indicated they ignored the advice completely. Patients who recalled >4 items versus < or =4 items of advice were younger and more often received angiotensin-converting enzyme inhibitors (71% vs 62%), beta-blockers (51% vs 38%), and spironolactone (25% vs 21%). In conclusion, after hospitalization for HF, many patients do not recall nonpharmacologic advice. In addition, a substantial proportion of those who recall the advice follow it incompletely. Younger age and prescription of appropriate pharmacologic treatment are associated with higher rates of recall and implementation.

Screening for left ventricular systolic dysfunction in high-risk patients in primary-care: a cost-benefit analysis.

BACKGROUND: Appropriate screening strategies are needed to cost effectively identify patients with undiagnosed and untreated left ventricular systolic dysfunction (LVSD). AIM: To investigate the cost-benefit of screening high-risk patients in primary-care for LVSD (EF<40%) using various screening strategies. METHODS: Patients considered at high-risk of developing LVSD were recruited from three primary-care practices. Patients with known LVSD were excluded. Echocardiography, electrocardiography and blood tests were performed blinded to an NT-proBNP result. Logistic regression (LR) and receiver-operating characteristic analysis were used to assess the univariate and multivariable utility of NT-proBNP, QRS duration, symptoms and evidence of myocardial infarction (MI) to detect LVSD. RESULTS: 427 patients were assessed. 7.5% had undiagnosed LVSD. NT-proBNP, QRS, symptoms and MI were independent predictors of LVSD (p<0.014) and the resultant LR-model had an area-under-the-curve of 0.89 (0.84-0.94) and specificity of 54% (51-79%) at a sensitivity of 100%. The LR-model avoided 24.1% (18.1- 48.3%) of the cost and 50.1% (44.1-74.3%) of the echocardiograms compared to screening using echocardiography alone. CONCLUSIONS: Screening high-risk groups in primary-care increases the pick-up rate for undiagnosed LVSD and using an LR-model combining NT-proBNP, QRS, symptoms and evidence of MI has significant cost benefits.

Prevalence of ECG abnormalities in an international survey of patients with suspected or confirmed heart failure at death or discharge.

BACKGROUND: Most patients suspected of having heart failure (HF) will get a 12-lead electrocardiogram (ECG) but its utility for excluding HF or assisting in its management has rarely been investigated. METHODS: The EuroHeart Failure survey identified 11,327 patients hospitalised with a suspected diagnosis of HF from 115 hospitals in 24 countries. ECGs were obtained from 9315 patients, of whom 5934 had cardiac imaging tests. The utility of the ECG was assessed for excluding or diagnosing major structural heart disease (MSHD) or major left ventricular systolic dysfunction (MLVSD) and for therapeutic decision making. FINDINGS: MSHD was present in 70% and MLVSD in 54% of patients overall but in only 21% and 5%, respectively, if the ECG was entirely normal. However, <2% of patients had a normal ECG. No single ECG characteristic identified a probability <25% of MSHD or <20% of MLVSD. Patients with QRS width >or=120 ms or anterior pathological Q-waves had a probability >80% of MSHD and >70% of MLVSD. Diagnostic models suggested that electrocardiographic criteria alone were not accurate for the diagnosis or exclusion of important heart disease in this population. However, 2468 patients (42%) had an electrocardiographic finding that should be used to guide the choice of therapy. CONCLUSIONS: A normal ECG is rare in patients with suspected HF but has limited diagnostic value in this setting. The ECG has an important role in guiding therapy.