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Peter van der Meer,
Douwe Postmus,
Piotr Ponikowski, John G Cleland,
Christopher M O'Connor,
Gad Cotter,
Marco Metra,
Beth A Davison,
Michael M Givertz,
George A Mansoor,
John R Teerlink,
Barry M Massie,
Hans L Hillege,
Adriaan A Voors
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ABSTRACT: OBJECTIVE: Study the clinical correlates and prognostic role of anemia and changes in hemoglobin in patients hospitalized for acute decompensated heart failure (AHF). BACKGROUND: Anemia is related to a poor outcome in patients with heart failure. In addition, an increase in hemoglobin during hospitalization might be a sign of effective decongestion and therefore related to improved outcome. METHODS: This is a post hoc analysis of the PROTECT study in 1969 patients with AHF and mild to moderate impaired renal function. Hemoglobin levels were measured daily for the first 4 days and at day 7. The endpoint was 180 day all cause mortality. RESULTS: Anemia at baseline was observed in 50.3% of the patients. During follow up 359 patients (18.2%) died. Hemoglobin increased in 69.1% and was associated with a better renal function at baseline and more weight loss, but was associated with a deterioration of renal function (p=0.01), whereas total dose diuretics was lower in patients with hemoconcentration (p<0.01). Interaction analysis showed that greater weight loss and better baseline renal function were associated with a more rapid increase in hemoglobin concentration (p<0.01 for both). The absolute change in hemoglobin (g/dL) independently predicted outcome (HR:0.66,[0.51-0.86],p=0.002), whereas baseline hemoglobin levels did not. CONCLUSIONS: Patients with AHF and preserved renal function are decongested better, as shown by an increase in hemoglobin. A rapid increase in hemoglobin during the first week is independently associated with a favorable outcome, despite a slight decrease in renal function.
Journal of the American College of Cardiology 03/2013; · 14.16 Impact Factor
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ABSTRACT: BACKGROUND: Whether sex differences in ICD benefit exist remains unanswered. We evaluated sex differences in mode of death among a large cohort of ambulatory heart failure patients who meet criteria for a primary prevention ICD. METHODS AND RESULTS: Patients from 5 trials or registries were included if they met ACC/AHA/HRS guideline criteria for implantation of a primary prevention ICD. We investigated the potential sex-differences in total deaths and total deaths by mode of death. The relationship between the estimated total mortality and mode of death by percentage of total mortality was also analyzed by gender. The Seattle Heart Failure Model was used to estimate total mortality in this analysis. A total of 8,337 patients (1,685 (20%) women) met inclusion criteria. One year mortality was 10.8±0.3%. In women, the age-adjusted all-cause mortality was 24% lower (HR=0.76, CI = 0.68-0.85; p<0.0001), the risk of sudden death was 31% lower (HR=0.69, CI = 0.58-0.83; p<0.0001), but no significant difference in pump failure death was observed. Throughout a range of total mortality risk, women had a 20% lower all cause mortality (HR=0.80, CI=0.71-0.89; p<0.001) and 29% fewer deaths that were sudden (HR=0.71, CI=0.59-0.86; p<0.001) compared to men. CONCLUSIONS: Women with heart failure have a lower mortality than men and fewer of those deaths are sudden throughout a spectrum of all cause mortality risk. This data provides a plausible reason for and thus supports the possibility that sex differences in ICD benefit may exist.
Circulation 10/2012; · 14.74 Impact Factor
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Christopher M O'Connor,
Robert J Mentz,
Gad Cotter,
Marco Metra, John G Cleland,
Beth A Davison,
Michael M Givertz,
George A Mansoor,
Piotr Ponikowski,
John R Teerlink,
Adriaan A Voors,
Mona Fiuzat,
Daniel Wojdyla,
Karen Chiswell,
Barry M Massie
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ABSTRACT: In patients with acute heart failure (AHF), early worsening heart failure (WHF) predicts a significant proportion of post-discharge readmissions and mortality. We aimed to identify the predictors of 7-day heart failure events or death in patients hospitalized with AHF.
A predictive model and risk score for the short-term primary composite endpoint of 7-day death, HF rehospitalization, or WHF was created using variables collected within 24 h of admission from patients with complete data (n = 2015) enrolled in the PROTECT trial of AHF patients. The 7-day composite was experienced by 294 patients (14.6%), with a mortality rate of 1.8% (n = 37), HF rehospitalization rate of 0.5% (n = 9), and WHF rate of 13.1% (n = 264). In multivariable analyses, the strongest predictor of short-term morbidity and mortality was higher blood urea nitrogen (BUN) concentration. Additional independent predictors of a worse outcome were lower serum albumin, cholesterol, and systolic blood pressure, as well as higher heart rate and respiratory rate. Model coefficients were converted to an additive risk score for predicting the 7-day composite endpoint with a total point range of 0-100. The risk score allowed discrimination of a wide spectrum of risk (4.8% risk with score ≤35, to 28.7% risk with score >55).
Using the PROTECT 7-day risk model and score, the main determinants of an adverse outcome for AHF patients included impaired metabolic status, neurohormonal activation, and reduced cardiac performance, gauged by BUN, serum albumin and cholesterol levels, systolic blood pressure, heart rate, and respiratory rate.
European Journal of Heart Failure 04/2012; 14(6):605-12. · 4.90 Impact Factor
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Matthew E Harinstein,
James D Flaherty,
Gregg C Fonarow,
Mandeep R Mehra,
Roberto M Lang,
Raymond J Kim, John G Cleland,
Bradley P Knight,
Peter S Pang,
Robert O Bonow,
Mihai Gheorghiade
Heart (British Cardiac Society) 10/2011; 97(19):1607-18. · 4.22 Impact Factor
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Inder S Anand,
Thomas S Rector, John G Cleland,
Michael Kuskowski,
Robert S McKelvie,
Hans Persson,
John J McMurray,
Michael R Zile,
Michel Komajda,
Barry M Massie,
Peter E Carson
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ABSTRACT: Plasma concentrations of natriuretic peptides (NPs) are associated with morbidity and mortality in patients with systolic heart failure (HF). However, the role of NP as a prognostic marker in patients with HF and preserved ejection fraction (HFpEF) has not been studied in a large cohort of well-characterized patients. Moreover, it is unclear whether treatments have a differential effect on morbidity and mortality across the spectrum of NP levels.
N-terminal pro-brain natriuretic peptide (NT-proBNP) was measured at baseline in 3480 patients in the I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction Trial). In a multivariable Cox regression model, NT-proBNP above the median of 339 pg/mL was independently associated with an increased risk of the primary end point of all-cause mortality and prespecified cardiovascular hospitalizations (adjusted hazard ratio [HR], 1.79; 95% CI, 1.56 to 2.10; P<0.001); all-cause mortality (adjusted HR, 2.04; 95% CI, 1.68 to 2.47; P<0.001); and a composite of HF events, including death due to worsening HF or sudden death or hospitalization due to worsening HF (adjusted HR, 1.77; 95% CI, 1.43 to 2.20; P<0.001). There were significant interactions between the effect of irbesartan and median split of baseline NT-proBNP for the primary outcome (P=0.005), all-cause mortality (P=0.05), and the HF composite outcome (P<0.001). Use of irbesartan was associated with improved outcomes in patients with NT-proBNP below, but not above, the median. After adjusting for 20 baseline covariates, irbesartan still had a beneficial effect on the primary outcome (HR, 0.74; 95% CI, 0.60 to 90; P=0.003), all-cause mortality (HR, 0.75; 95% CI, 0.56 to 0.99; P=0.046), and HF composite outcome (HR, 0.57; 95% CI, 0.41 to 0.80; P=0.001) in patients with NT-proBNP below the median.
The unexpected benefit of irbesartan in lower-risk patients with HFpEF in this post hoc analysis may indicate effects on early, but not later, high-risk stages of the disease. These findings question the strategy of using elevated plasma concentrations of NP as a patient selection criterion in HFpEF trials. More studies are needed to support or contest this practice. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00095238.
Circulation Heart Failure 06/2011; 4(5):569-77. · 6.29 Impact Factor
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Stephan von Haehling,
Mitja Lainscak,
Wolfram Doehner,
Piotr Ponikowski,
Giuseppe Rosano,
Jens Jordan,
Piotr Rozentryt,
Mathias Rauchhaus,
Rostislav Karpov,
Vsevolod Tkachuk,
Yelena Parfyonova,
Andrey Y Zaritskey,
Eugeniy V Shlyakhto, John G Cleland,
Stefan D Anker
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ABSTRACT: BACKGROUND: Chronic heart failure (CHF) is increasing in prevalence. Patients with CHF usually have co-morbid conditions, but these have been subjected to little research and consequently there is a paucity of guidance on how to manage them. Obesity and diabetes mellitus are common antecedents of CHF and often complicate management and influence outcome. Cachexia is an ominous and often missed sign in patients with CHF. METHODS: This manuscript describes the rationale and the design of Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF), a prospective, multicentre, multinational, longitudinal, pathophysiological evaluation study, which is being conducted in 11 centres across six countries in the European Union and in Russia. We aim to recruit >1,600 patients with CHF due to various common aetiologies, irrespective of left ventricular ejection fraction, and with or without co-morbidities at study entry. In addition, >300 patients with type 2 diabetes mellitus without CHF and >150 healthy subjects will serve as control groups. Participants will be systematically investigated at annual intervals for up to 48 months. Additional investigations focusing on cellular and subcellular mechanisms, adipose and skeletal muscle tissue, and in endothelial progenitor cells will be performed in selected subgroups. CONCLUSIONS: SICA-HF will provide insights into common co-morbidities in CHF with a specific emphasis on diabetes mellitus and body mass. This will provide a more thorough pathophysiological understanding of the complexity of CHF that will help develop therapies tailored to manage specific co-morbidities.
Journal of cachexia, sarcopenia and muscle. 12/2010; 1(2):187-194.
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Mihai Gheorghiade,
Ferenc Follath,
Piotr Ponikowski,
Jeffrey H Barsuk,
John E A Blair, John G Cleland,
Kenneth Dickstein,
Mark H Drazner,
Gregg C Fonarow,
Tiny Jaarsma, [......],
Markku Nieminen,
Peter S Pang,
Petar Seferovic,
Lynne W Stevenson,
Dirk J van Veldhuisen,
Faiez Zannad,
Stefan D Anker,
Andrew Rhodes,
John J V McMurray,
Gerasimos Filippatos
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ABSTRACT: Patients with acute heart failure (AHF) require urgent in-hospital treatment for relief of symptoms. The main reason for hospitalization is congestion, rather than low cardiac output. Although congestion is associated with a poor prognosis, many patients are discharged with persistent signs and symptoms of congestion and/or a high left ventricular filling pressure. Available data suggest that a pre-discharge clinical assessment of congestion is often not performed, and even when it is performed, it is not done systematically because no method to assess congestion prior to discharge has been validated. Grading congestion would be helpful for initiating and following response to therapy. We have reviewed a variety of strategies to assess congestion which should be considered in the care of patients admitted with HF. We propose a combination of available measurements of congestion. Key elements in the measurement of congestion include bedside assessment, laboratory analysis, and dynamic manoeuvres. These strategies expand by suggesting a routine assessment of congestion and a pre-discharge scoring system. A point system is used to quantify the degree of congestion. This score offers a new instrument to direct both current and investigational therapies designed to optimize volume status during and after hospitalization. In conclusion, this document reviews the available methods of evaluating congestion, provides suggestions on how to properly perform these measurements, and proposes a method to quantify the amount of congestion present.
European Journal of Heart Failure 03/2010; 12(5):423-33. · 4.90 Impact Factor
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Marco Metra, John G Cleland,
Beth Davison Weatherley,
Howard C Dittrich,
Michael M Givertz,
Barry M Massie,
Christopher M O'Connor,
Piotr Ponikowski,
John R Teerlink,
Adriaan A Voors,
Gad Cotter
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ABSTRACT: Dyspnoea is the most common symptom leading to hospitalization for acute heart failure (AHF). Its early and persistent relief is an important goal of therapy, but little is known about its course, determinants, and prognostic significance.
In a post hoc analysis, we studied changes in dyspnoea and in-hospital course in 303 subjects with AHF enrolled in the PROTECT pilot trial. Changes in dyspnoea were assessed by patient self-report using a seven-point Likert scale daily to discharge and at Days 7 and 14. We defined dyspnoea relief as a moderate to marked improvement of dyspnoea at both 24 and 48 h, and treatment success as dyspnoea relief without worsening HF or renal function or death during the first 7 days. Dyspnoea relief occurred in 54% of the patients, while treatment success was achieved in 44% of the patients. By Day 14, only 75% of patients reported a moderate or marked improvement in dyspnoea. Both dyspnoea relief and treatment success were associated with greater improvement in signs of congestion, shorter hospitalization duration, and a lower 60-day mortality rate. Treatment success, but not dyspnoea relief, was also associated with a lower incidence of 60-day death or re-hospitalization for HF or renal failure.
Half of patients admitted for AHF do not have substantial improvement in dyspnoea at 24 h and 25% do not have substantial improvement at 7 and 14 days from admission. Dyspnoea relief and treatment success are associated with shorter length of stay and lower 60-day mortality. These analyses should be confirmed in larger studies.
European Journal of Heart Failure 03/2010; 12(5):499-507. · 4.90 Impact Factor
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ABSTRACT: The European cardiac resynchronization therapy (CRT) survey is a joint initiative taken by the Heart Failure Association and the European Heart Rhythm Association of the European Society of Cardiology. The primary aim of this survey is to describe current European practice associated with CRT implantations.
A total of 140 centres from 13 European countries contributed data from consecutive patients successfully implanted with a CRT device with or without an ICD between November 2008 and June 2009. The total number of patients enrolled was 2438. The median age of the patients was 70 years (IQR 62-76) and 31% were > or =75 years. It was found that 78% were in NYHA functional class III or IV and 22% in I or II. The mean ejection fraction was 27% +/- 8 and the mean QRS duration 157 ms +/- 32. The QRS duration was <120 ms in 9%. Atrial fibrillation was reported in 23%. It was found that 26% of patients had a previously implanted permanent pacemaker or ICD; 76% of procedures were performed by an electrophysiologist; 82% had an elective admission for implantation and the median duration of hospitalization was 3 days (IQR 2-7); and 73% received a CRT-D device which was more often implanted in men, younger patients, and with ischaemic aetiology. The mean QRS duration was reduced to 133 ms +/- 27 (P < 0.0001) at discharge. Peri-procedural complication rates were comparable to the rates reported in randomized trials.
This CRT survey provides important information describing current European practice with regard to patient demographics, selection criteria, procedural routines, and status at discharge. These data should be useful for benchmarking individual patient management and national practice against wider experience.
European Heart Journal 08/2009; 30(20):2450-60. · 10.48 Impact Factor
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ABSTRACT: Many chronic heart failure (CHF) patients take beta-blockers. When such patients are hospitalized for decompensation, it remains unclear how ongoing beta-blocker treatment will affect outcomes of acute inotrope therapy. We aimed to assess outcomes of SURVIVE patients who were on beta-blocker therapy before receiving a single intravenous infusion of levosimendan or dobutamine.
Cox proportional hazard regression revealed all-cause mortality benefits of levosimendan treatment over dobutamine when the SURVIVE population was stratified according to baseline presence/absence of CHF history and use/non-use of beta-blocker treatment at baseline. All-cause mortality was lower in the CHF/levosimendan group than in the CHF/dobutamine group, showing treatment differences by hazard ratio (HR) at days 5 (3.4 vs. 5.8%; HR, 0.58, CI 0.33-1.01, P = 0.05) and 14 (7.0 vs. 10.3%; HR, 0.67, CI 0.45-0.99, P = 0.045). For patients who used beta-blockers (n = 669), mortality was significantly lower for levosimendan than dobutamine at day 5 (1.5 vs. 5.1% deaths; HR, 0.29; CI 0.11-0.78, P = 0.01).
Levosimendan may be better than dobutamine for treating patients with a history of CHF or those on beta-blocker therapy when they are hospitalized with acute decompensations. These findings are preliminary but important for planning future studies.
European Journal of Heart Failure 02/2009; 11(3):304-11. · 4.90 Impact Factor
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Willem J Remme, John G Cleland,
Leif Erhardt,
Phillip Spark,
Christian Torp-Pedersen,
Marco Metra,
Michel Komajda,
Christine Moullet,
Mary Ann Lukas,
Philip Poole-Wilson,
Andrea Di Lenarda,
Karl Swedberg
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ABSTRACT: In the COMET study, carvedilol improved survival compared to metoprolol tartrate in 3029 patients with NYHA II-IV heart failure and EF <35%, followed for an average of 58 months.
To evaluate whether the effect on overall mortality was specific for a particular mode of death. This may help to identify the mechanism of the observed difference.
Of the 1112 total deaths, 972 were adjudicated as cardiovascular, including 480 sudden, 365 circulatory failure (CF) and 51 stroke deaths. For each mode of death, the effect of pre-specified baseline variables was assessed, including sex, age, NYHA class, aetiology, heart rate, systolic blood pressure, EF, atrial fibrillation, previous myocardial infarction or hypertension, renal function, concomitant medication, and study treatment allocation.
In multivariate Cox regression analyses, compared to metoprolol, carvedilol reduced cardiovascular (RR 0.80, CI 0.7-0.91, p=0.0009), sudden (RR 0.77, CI 0.64-0.93, p=0.0073) and stroke deaths (RR 0.37, CI 0.19-0.71, p=0.0027) with a non-significant trend for CF death (RR 0.83, CI 0.66-1.04, p=0.07). Treatment benefit with carvedilol did not differ between modes of death, except for a greater reduction in stroke death with carvedilol (competing risk analysis, p=0.0071 vs CF death). There were no interactions between treatment allocation and baseline characteristics.
Mortality reduction with carvedilol compared to metoprolol appears relatively non-specific and could be consistent with a superior effect of carvedilol on cardiac function, arrhythmias or, in view of the greater reduction in stroke deaths, on vascular events.
European Journal of Heart Failure 11/2007; 9(11):1128-35. · 4.90 Impact Factor
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ABSTRACT: To study the role of sex, age and concomitant diseases for prescription of cardiovascular drugs among patients with heart failure cared for in the community.
In 15 European countries, a survey was conducted during 1999 and 2000 among 1363 primary care physicians who included 8256 patients with symptoms of heart failure. Predictors of drug prescription were assessed with multivariate logistic regression. Overall prescription rates for ACE-inhibitors/angiotensin receptor blockers (ACE-I/ARB), beta-blockers, digitalis, diuretics and oral anticoagulants were 69%, 30%, 41%, 75% and 18%. Women had no reduced likelihood to receive ACE-I/ARB and beta-blockers (odds ratio [OR]=0.96 [95% CI 0.87-1.06] and 1.02 [0.92-1.13], respectively), but prescription of oral anticoagulants was decreased (OR=0.74, 95% CI 0.65-0.84). Compared to patients <65 years of age, ACE-I/ARB prescription did not materially decline up to 75-85 years (R=0.91, 95% CI 0.81-1.04), whereas beta-blocker prescription was already significantly decreased in this age category (OR=0.49, 95% CI 0.43-0.56). There was no general under-prescription of evidence-based cardiovascular drugs in patients with concomitant diseases.
Among heart failure patients cared for in the community advanced age strongly predicts decreased prescription of beta-blockers. Female sex and comorbidity is not associated with a consistent underutilization of evidence-based cardiovascular drugs.
European Journal of Heart Failure 08/2004; 6(5):663-8. · 4.90 Impact Factor
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Barry M Massie,
William F Krol,
Susan E Ammon,
Paul W Armstrong, John G Cleland,
Joseph F Collins,
Michael Ezekowitz,
Syed M Jafri,
Christopher M O'Connor,
Milton Packer,
Kevin A Schulman,
Koon Teo,
Stuart Warren
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ABSTRACT: BACKGROUND: The role of anticoagulation in patients with chronic heart failure has long been an area of interest and controversy. Traditionally the goal of anticoagulation has been to prevent embolic events, but recent trials also demonstrated that oral anticoagulation also prevents vascular events in patients with prior myocardial infarction, who constitute the majority of heart failure patients. Although antiplatelet agents also reduce postinfarction vascular events, few data are available in heart failure patients, and some evidence suggests that aspirin may also have the potential to worsen heart failure morbidity and mortality, possibly by interfering with the effects of angiotensin-converting enzyme inhibitors. Methods and results The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial was undertaken to determine the optimal antithrombotic agent for heart failure patients. WATCH was a prospective-randomized trial in which symptomatic heart failure patients in sinus rhythm with ejection fractions < or =35% taking angiotensin-converting enzyme inhibitors (unless not tolerated) and diuretics were randomized to open-label warfarin (target International Normalized Ratio 2.5-3.0) or double-blind antiplatelet therapy with aspirin 162 mg or clopidogrel 75 mg. Two primary comparisons were specified: anticoagulation with warfarin versus antiplatelet therapy with aspirin and antiplatelet therapy with clopidogrel versus antiplatelet therapy with aspirin. The primary outcome is the composite of death from all causes, nonfatal myocardial infarction, and nonfatal stroke analyzed as time to first event using the intent-to-treat approach. The secondary endpoint was the broader composite of death from all causes, nonfatal myocardial infarction, non-fatal stroke, and hospitalizations for worsening heart failure, unstable angina pectoris, and systemic or pulmonary artery embolic events. Additional prespecified analyses include heart failure events, coronary events, and resource utilization. CONCLUSIONS: Although the trial was designed to enter 4500 patients, it was terminated 18 months prematurely in June 2003 by the VA Cooperative Study Program because of poor enrollment with a resulting reduction of its power to achieve its original objective. This manuscript describes the study rationale, protocol design, and the baseline characteristics of the 1587 patients who were entered into the study. The WATCH trial will help define the optimal approach to antithrombotic therapy in the contemporary management of patients with chronic heart failure resulting from left ventricular systolic dysfunction.
Journal of Cardiac Failure 05/2004; 10(2):101-12. · 3.66 Impact Factor
