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.

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.

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.

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.

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.

What impact do anxiety, depression, perceived control and technology capability have on whether patients with chronic heart failure take-up or continue to use home tele-monitoring services? Study design of ADaPT-HF.

BACKGROUND: Home tele-monitoring (HTM) is used to monitor the clinical signs and symptoms of patients with chronic heart failure (CHF) in order to reduce unplanned hospital admissions. However, not all patients who are referred will agree to use HTM, and some patients choose to withdraw early from its use. AIMS: ADaPT-HF will investigate whether depression, anxiety, low perceived control, reduced technology capability, level of education, age or the severity or complexity of a patient's illness can predict refusal of, or early withdrawal from, HTM in patients with CHF. METHODS: The study will recruit 288 patients who have been recently admitted to hospital with heart failure who have been referred for HTM. At the time of referral, patients will complete depression (nine-item Patient Health Questionnaire), anxiety (seven-item Generalised Anxiety Disorder questionnaire), perceived control (eight-item revised Controlled Attitudes Scale) and technology capability (ten-item Technology Readiness Index 2.0) screening questionnaires. In addition, data on demographics, diagnosis, clinical examination, socio-economic status, history of comorbidities, medication, biochemistry and haematology will be recorded. The primary outcome will be a composite of refusal of or early withdrawal from HTM. The principle analysis will be made using logistic regression. CONCLUSION: By establishing which factors influence a patient's decision to refuse or withdraw early from HTM, it may be possible to redesign HTM referral processes. It may be that patients with CHF who also have depression, anxiety, low control and poor technology skills should not be referred until they receive appropriate support or that they should be managed differently when they do receive HTM. The results of ADAPT-HF may provide a way of making more efficient and cost-effective use of HTM services.

Statins attenuate but do not eliminate the reverse epidemiology of total serum cholesterol in patients with non-ischemic chronic heart failure.

BACKGROUND: In patients with chronic heart failure (CHF) increasing levels of total serum cholesterol are associated with improved survival - while statin usage is not. The impact of statin treatment on the "reverse epidemiology" of cholesterol is unclear. METHODS: 2992 consecutive patients with non-ischemic CHF due to left ventricular systolic dysfunction from the Norwegian CHF Registry and the CHF Registries of the Universities of Hull, UK, and Heidelberg, Germany, were studied. 1736 patients were individually double-matched on both cholesterol levels and the individual propensity scores for statin treatment. All-cause mortality was analyzed as a function of baseline cholesterol and statin use in both the general and the matched sample. RESULTS: 1209 patients (40.4%) received a statin. During a follow-up of 13,740 patient-years, 360 statin users (29.8%) and 573 (32.1%) statin non-users died. When grouped according to total cholesterol levels as low (≤3.6mmol/L), moderate (3.7-4.9mmol/L), high (4.8-6.2mmol/L), and very high (>6.2mmol/L), we found improved survival with very high as compared with low cholesterol levels. This association was present in statin users and non-users in both the general and matched sample (p<0.05 for each group comparison). The negative association of total cholesterol and mortality persisted when cholesterol was treated as a continuous variable (HR 0.83, 95%CI 0.77-0.90, p<0.001 for matched patients), but it was less pronounced in statin users than in non-users (F-test p<0.001). CONCLUSIONS: Statins attenuate but do not eliminate the reverse epidemiological association between increasing total serum cholesterol and improved survival in patients with non-ischemic CHF.

Regional circulatory distribution of novel cardiac bio-markers and their relationships with haemodynamic measurements.

BACKGROUND: Regional sampling may identify sites of production or removal of novel biomarkers in the circulation; their relationship to haemodynamic measurements may clarify their association with the pathophysiology of heart failure. METHODS: Samples were obtained from up to eight circulatory sites from 22 patients with left ventricular dysfunction undergoing elective cardiac catheterisation. The plasma concentrations (PC) of six biomarkers [mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1), mid-regional pro-adreno-medullin (MR-proADM), high sensitivity pro-calcitonin (hsPCT), copeptin and galectin-3 (Gal-3)] were measured. RESULTS: Plasma concentrations of MR-proANP were highest in the pulmonary artery (PA) and left ventricle, suggesting myocardial production. Lower concentrations of copeptin, CT-proET-1, MR-proADM and hsPCT were found in the supra-renal inferior vena cava (SRIVC) sample suggesting renal extraction. Plasma concentrations of Galectin-3 varied little by sampling site. Plasma concentrations of MR-proANP (R=0.69, P=0.002), MR-proADM (R=0.51, P=0.03), CT-proET-1 (R=0.60, P=0.009) and Copeptin (R=0.47, P<0.05) measured from PA samples correlated with PA systolic pressure. There was no relation between any measured marker and cardiac index. CONCLUSIONS: Regional sampling shows variation in the plasma concentration of various novel peptides that provides clues to sites of net production and removal. Plasma concentrations of several biomarkers were positively correlated with pulmonary artery pressure.

Early Indication of Decompensated Heart Failure in Patients on Home-Telemonitoring: A Comparison of Prediction Algorithms Based on Daily Weight and Noninvasive Transthoracic Bio-impedance.

BACKGROUND: Heart Failure (HF) is a common reason for hospitalization. Admissions might be prevented by early detection of and intervention for decompensation. Conventionally, changes in weight, a possible measure of fluid accumulation, have been used to detect deterioration. Transthoracic impedance may be a more sensitive and accurate measure of fluid accumulation. OBJECTIVE: In this study, we review previously proposed predictive algorithms using body weight and noninvasive transthoracic bio-impedance (NITTI) to predict HF decompensations. METHODS: We monitored 91 patients with chronic HF for an average of 10 months using a weight scale and a wearable bio-impedance vest. Three algorithms were tested using either simple rule-of-thumb differences (RoT), moving averages (MACD), or cumulative sums (CUSUM). RESULTS: Algorithms using NITTI in the 2 weeks preceding decompensation predicted events (P<.001); however, using weight alone did not. Cross-validation showed that NITTI improved sensitivity of all algorithms tested and that trend algorithms provided the best performance for either measurement (Weight-MACD: 33%, NITTI-CUSUM: 60%) in contrast to the simpler rules-of-thumb (Weight-RoT: 20%, NITTI-RoT: 33%) as proposed in HF guidelines. CONCLUSIONS: NITTI measurements decrease before decompensations, and combined with trend algorithms, improve the detection of HF decompensation over current guideline rules; however, many alerts are not associated with clinically overt decompensation.

Is the diagnostic coding position of acute heart failure related to mortality? A report from the Euro Heart Failure Survey-1.

AIMS: Most studies on acute heart failure (HF) exploring the relationship between admissions to hospital for HF and subsequent outcomes have focused only on HF coded as the primary diagnosis, but many other patients have admissions complicated by HF requiring attention. Failure to quantify the total hospital burden of HF underestimates its health economic impact, leading to underprovision of resources for its care. METHODS AND RESULTS: The First Euro Heart Failure Survey (EHFS-1) screened consecutive deaths and discharges, regardless of cause, from medical wards in 115 hospitals from 24 European countries during 2000-2001, to identify patients with known or suspected HF. Information on presenting symptoms and signs were gathered. Of 10 701 patients enrolled, HF was reported as the primary reason for admission in 4234 (40%), a secondary reason for admission if it complicated or prolonged stay in 1772 (17%), and in 4695 (43%) patients it was uncertain whether HF was actively contributing to the admission. Mortality on the index admission was 301 (7%), 290 (16%), and 189 (4%), respectively, with hazard ratios of 1.73 (P < 0.001) and 3.26 (P < 0.001) compared with the 'uncertain' group. In the 12 weeks following discharge, 287 (7%) patients with a primary, 117 (8%) with a secondary, and 238 (5%) with an incidental or uncertain diagnosis of HF died. CONCLUSION: Patients admitted to hospital with HF as a secondary rather than a primary diagnosis have a high mortality. More attention should be focused on patients with a secondary diagnosis of HF in terms of both care and research.

Is heart rate important for patients with heart failure in atrial fibrillation?

OBJECTIVES: This study sought to investigate the relationship between resting ventricular rate and mortality in patients with chronic heart failure (CHF) and reduced left ventricular ejection fraction (LVEF) who were in sinus rhythm (SR) or atrial fibrillation (AF). BACKGROUND: Slower heart rates are associated with better survival in patients with CHF in SR, but it is not clear whether this is true for those in AF. METHODS: We assessed 2,039 outpatients with CHF and LVEF ≤50% undergoing baseline assessment, of whom 24% (n = 488) were in AF; and 841 outpatients reassessed after attempted treatment optimization at 1 year, of whom 22% (n = 184) were in AF. Cox proportional hazards models were used to assess the relationships between heart rate and survival in patients with CHF and AF or sinus rhythm. We analyzed heart rate and rhythm data recorded at the baseline review and after 1-year follow-up. Proportional hazards assumptions were checked by Schoenfeld and Martingale residuals. RESULTS: The median survival for those in AF was 6.1 years (interquartile range [IQR]: 5.3 to 6.9 years) and 7.3 years (IQR: 6.5 to 8.1 years) for those in SR. In univariable analysis, patients with AF had a worse survival (hazard ratio [HR]: 1.26, 95% confidence interval [CI]: 1.08 to 1.47; p = 0.003) but after covariate adjustment, survival rates were similar. After adjusting Cox regression models, there was no association between heart rate (per 10 beats/min increments) and survival in patients with AF before (HR: 0.94, 95% CI: 0.88 to 1.00, p = 0.07) or after (HR: 1.00, 95% CI: 0.99 to 1.00, p = 0.84) therapy optimization. For patients in SR, higher heart rates were associated with worse survival, both before (HR: 1.10, 95% CI: 1.05 to 1.15, p <0.0001) and after (HR: 1.13, 95% CI: 1.03 to 1.24, p = 0.008) therapy optimization. CONCLUSIONS: In patients with CHF and a reduced LVEF, slower resting ventricular rate is associated with better survival for patients in SR but not for those with AF.

Development of a composite model derived from cardiopulmonary exercise tests to predict mortality risk in patients with mild-to-moderate heart failure.

OBJECTIVE: Cardiopulmonary exercise testing (CPET) is used to predict outcome in patients with mild-to-moderate heart failure (HF). Single CPET-derived variables are often used, but we wanted to see if a composite score achieved better predictive power. METHODS: Retrospective analysis of patient records at the department of cardiology, Castle Hill Hospital, Kingston-upon-Hull. 387 patients (median (25th-75th percentile)) (age 65 (56-72) years; 79% men; LVEF 34 (31-37) %) were included. Patients underwent a symptom-limited, maximal CPET on a treadmill. During a median follow-up of 8.6±2.1 years in survivors, 107 patients died. Survival models were built and validated using a hybrid approach between the bootstrap and Cox regression. Nine CPET-derived variables were included. Z-score defined each variable's predictive strength. Model coefficients were converted to a risk score. RESULTS: Four CPET-related variables were independent predictors of all-cause mortality in the survival model: the presence of exertional oscillatory ventilation (EOV), increasing slope of the relation between ventilation and carbon dioxide production (VE/VCO2 slope), decreasing oxygen uptake efficiency slope (OUES), and an increase in the lowest ventilatory equivalent for carbon dioxide (VEqCO2 nadir). Individual predictors of mortality ranged from 0.60 to 0.71 using Harrell's C-statistic, but the optimal combination of EOV+VE/VCO2 slope+OUES+VEqCO2 nadir reached 0.75. The Hull CPET risk score had a significantly higher area under the curve (0.78) when compared to the HF Survival Score (AUC=0.70; p<0.001). CONCLUSIONS: A composite risk score using variables from CPET out-performs the traditional single variable approach in predicting outcome in patients with mild-to-moderate HF.