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ABSTRACT: 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.
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.
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.
European Heart Journal 09/2010; 31(18):2280-90. · 10.48 Impact Factor
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ABSTRACT: This article provides information and a commentary on key trials relevant to the pathophysiology, prevention and treatment of heart failure (HF) presented at the annual meeting of the Heart Failure Association of the European Society of Cardiology held in Berlin. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. Tonapofylline failed to show efficacy and was associated with an approximately 1% increased risk of seizures in patients with acute decompensated heart failure (ADHF) and renal dysfunction in TRIDENT. Results from BENEFICIAL do not support the use of alagebrium, an advanced glycation end-product breaker, in clinically stable patients with relatively mild HF symptoms. CUPID showed encouraging preliminary results for augmentation of SERCA2a enzyme activity by gene transfection in patients with severe HF. The RFA-HF study did not provide convincing evidence for the use of radiofrequency ablation for atrial fibrillation but was underpowered. A wearable, multi-sensor patch showed potential for detecting impending HF decompensation in MUSIC. A comparison of low-intensity oral diuretic therapy in patients hospitalized with ADHF suggested that torasemide was superior to furosemide in DUEL. The use of point-of-care B-type natriuretic peptide and echocardiography failed to improve the rate of correct HF diagnosis in primary care. Phrenic nerve stimulation improved symptoms of sleep apnoea in a small study of patients with HF and central sleep apnoea. The use of a novel implantable pulmonary artery pressure monitoring system to guide patient management improved outcomes in the CHAMPION study. A study to evaluate a combined coronary artery bypass grafting (CABG) and epicardial cardiac resynchronization therapy implantation procedure reduced mortality compared with CABG alone.
European Journal of Heart Failure 08/2010; 12(8):883-8. · 4.90 Impact Factor
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Circulation Heart Failure 07/2010; 3(4):e24; author reply e25. · 6.29 Impact Factor
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ABSTRACT: This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure presented at the annual meeting of the American College of Cardiology held in March 2010. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. Results from DOSE suggest that giving diuretics using a high-dose, bolus strategy may be better than using lower doses or a continuous infusion for patients with acute decompensated heart failure. In the ASPIRE study, addition of aliskiren to standard therapy failed to attenuate left ventricular remodelling in post-MI patients and was associated with more adverse events. In CONNECT, remote monitoring reduced the time from CRT-D- or ICD-detected events to clinical decision and this was associated with fewer clinic visits and shorter hospitalizations. An analysis from STICH testing the effects of surgical ventricular reconstruction showed no benefit in the sub-group of patients who achieved a greater reduction in LV volume. STOP-AF and CABANA did not provide convincing evidence of the effectiveness or safety of catheter ablation for the treatment of AF. RACE II suggests that lenient heart rate control might be as effective as strict rate control in patients with permanent atrial fibrillation. In EVEREST II, a catheter-based mitral valve repair procedure using the MitraClip system had similar efficacy to traditional surgery but with fewer short-term adverse effects. Valsartan reduced progression to diabetes in patients with impaired glucose tolerance but had no effect on cardiovascular events in NAVIGATOR. In ACCORD, strict blood pressure control failed to reduce the risk of overall cardiovascular events in high-risk diabetic patients.
European Journal of Heart Failure 06/2010; 12(6):623-9. · 4.90 Impact Factor
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JACC. Cardiovascular imaging 05/2010; 3(5):541-9. · 14.29 Impact Factor
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G Michael Felker,
Peter S Pang,
Kirkwood F Adams, John G F Cleland,
Gad Cotter,
Kenneth Dickstein,
Gerasimos S Filippatos,
Gregg C Fonarow,
Barry H Greenberg,
Adrian F Hernandez, [......],
John O'Connell,
Christopher M O'Connor,
Ileana L Pina,
Piotr Ponikowski,
Hani N Sabbah,
John R Teerlink,
James E Udelson,
Clyde W Yancy,
Faiez Zannad,
Mihai Gheorghiade
Circulation Heart Failure 03/2010; 3(2):314-25. · 6.29 Impact Factor
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ABSTRACT: This article presents findings and a commentary on late-breaking trials presented during the meeting of the Heart Failure Society of America in September 2009. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. The FAST trial showed somewhat better performance of intrathoracic impedance for prediction of deterioration in patients with heart failure (HF) when compared with daily weighing. The IMPROVE-HF study reported the benefits of education on the management of patients with systolic HF. Galectin-3 appeared a useful method for improving risk stratification of patients with chronic HF in a substudy of the COACH trial. A nuclear substudy of the HF-ACTION trial failed to demonstrate that resting myocardial perfusion imaging, a measure of myocardial scar and viability, was clinically useful. A small randomized controlled trial (DAD-HF) suggested that the use of low-dose dopamine in patients with acutely decompensated HF was associated with less deterioration in renal function and less hypokalaemia. The MARVEL-1 trial raises further concerns about the safety of myoblast transplantation in ischaemic HF.
European Journal of Heart Failure 02/2010; 12(2):193-6. · 4.90 Impact Factor
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ABSTRACT: Chronic breathlessness is a major symptom for patients with compensated chronic heart failure (CHF) and its impact is different to the breathlessness resulting from pulmonary oedema. This systematic review aims to establish which tools have been used for research into the subjective severity of breathlessness in patients with compensated CHF and to discuss recommendations for the future.
Medline (1950-2008), Embase (1980-2008), Cinahl (1982-2008), and Cochrane databases were searched for clinical studies in patients with compensated CHF including a subjective measure of breathlessness severity as an outcome measure. A total of 322 studies were found of which 41 were retrieved and 26 studies met the review criteria. Few studies had severity of breathlessness as a primary endpoint. Nineteen used a uni-dimensional tool including visual analogue, Borg or Likert scales, either alone, or as a subscale of a quality of life measure. Five used the CHF questionnaire. Two papers used the Baseline Dyspnoea Index-Transitional Dyspnoea Index (BDI-TDI).
Despite breathlessness being an important and limiting problem for patients with CHF, we found no consensus on which tool should be used for breathlessness severity, little methodological research to develop such a tool, and a lack of focus on breathlessness as a symptom. A consistent approach to studying breathlessness in patients with CHF is needed in order to make headway in managing this key patient priority.
European Journal of Heart Failure 02/2010; 12(2):137-47. · 4.90 Impact Factor
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ABSTRACT: This article provides information and a commentary on trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the annual meeting of the American Heart Association held in Orlando, Florida in 2009. Unpublished reports should be considered as preliminary, as analyses may change in the final publication. Patients with heart failure randomized to high-dose losartan treatment (150 mg) in the HEAAL study had a reduced risk of death or heart failure hospitalization compared with patients in the low-dose (50 mg) group. In FAIR-HF, patients with heart failure and concomitant iron deficiency but without severe anaemia who received iron supplementation therapy demonstrated an improvement in symptoms at 24 weeks compared with placebo. The J-CHF study was too small and was stopped too early to provide definitive evidence about the optimal dose of carvedilol for Japanese patients with heart failure. Results from the HeartMate II study suggest that continuous-flow left ventricular assist devices may offer benefits over pulsatile-flow devices for long-term support in patients with advanced heart failure. In the PACE study, atrial synchronized right ventricular pacing induced adverse effects on left ventricular function compared with atrial synchronized biventricular pacing in patients with standard pacing indications and a normal ejection fraction.
European Journal of Heart Failure 02/2010; 12(2):197-201. · 4.90 Impact Factor
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Nature Reviews Cardiology 02/2010; 7(2):69-70. · 8.83 Impact Factor
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BMJ (Clinical research ed.). 01/2010; 341:c3856.
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BMJ British medical journal 01/2010; 341:c4991. · 13.66 Impact Factor
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Journal of the American College of Cardiology 12/2009; 55(1):79-81; author reply 81. · 14.16 Impact Factor
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Mark E Patterson,
William C Grant,
Seth W Glickman,
Barry M Massie,
Susan E Ammon,
Paul W Armstrong, John G F Cleland,
Joseph F Collins,
Koon K Teo,
Kevin A Schulman,
Shelby D Reed
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ABSTRACT: The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial revealed no significant differences among 1587 symptomatic heart failure patients randomized to warfarin, clopidogrel, or aspirin in time to all-cause death, nonfatal myocardial infarction, or nonfatal stroke. We compared within-trial medical resource use and costs between treatments.
We assigned country-specific costs to medical resources incurred during follow-up. Annualized rates of hospitalizations, inpatient and outpatient procedures, and emergency department visits did not differ significantly between groups. Annualized total costs averaged $5901 (95% confidence interval [CI], $4776-$7520) for the aspirin group, $5646 (95% CI, $4903-$6584) for the clopidogrel group, and $5830 (95% CI, $4838-$7400) for the warfarin group.
Consistent with clinical findings, our analyses did not identify significant cost differences between treatments.
Journal of cardiac failure 12/2009; 15(10):819-27. · 3.25 Impact Factor
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ABSTRACT: Red cell distribution width (RDW) is prognostic in patients with heart failure (HF), but it has not been compared with N-terminal brain natriuretic peptide (NT-proBNP). We sought to make this comparison.
Patients referred to a specialist HF clinic between 2001 and 2008 were assessed comprehensively including medical history, echocardiogram, and blood tests. Cox-regression was used to assess the multivariable relationship between RDW, NT-proBNP, and all-cause mortality. A total of 1087 patients were recruited; median (IQR) follow-up was 52 months (29-66); age 72 years (64-78); 74% male; 70% ischaemic heart disease; 20% diabetic; 85% NYHA >or= 2, and 63% with at least moderate LV impairment (EF < 35% equivalent). In a multivariable model, both RDW and NT-proBNP were independently prognostic (RDW: chi(2) = 21.8 vs. 49.1 both P < 0.001). In a model using quartiles of each variable, the relative risk for each was similar for the second and third quartiles compared with the first. A larger increase in risk for NT-proBNP is seen in the fourth quartile.
Red cell distribution width is a readily available test in the HF-population with similar independent prognostic power to NT-proBNP across the first to third quartiles. Prognostic models in HF should include RDW and further investigation is necessary to determine the pathological mechanism of the relationship.
European Journal of Heart Failure 12/2009; 11(12):1155-62. · 4.90 Impact Factor
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ABSTRACT: This article provides information and a commentary on trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the annual meeting of the European Society of Cardiology held in Barcelona in 2009. The AAA study does not support the routine use of aspirin for the prevention of vascular events in patients with asymptomatic atherosclerosis. RELY suggests that dabigatran may be more effective than warfarin for the prevention of stroke in patients with atrial fibrillation. Rolofylline was not superior to placebo in improving outcomes in patients with acute heart failure enrolled in the PROTECT study, but dyspnoea was improved. Data from ACTIVE-I suggest that irbesartan does not provide additional therapeutic benefit in patients with atrial fibrillation who are well controlled on current therapy. The European cardiac resynchronization therapy (CRT) survey provides interesting epidemiological data on current CRT device usage. The German pre-SCD II registry identified a low prevalence of patients with a reduced ejection fraction following myocardial infarction. Implantation of CRT-D rather than an implantable cardioverter defibrillator in patients with mild heart failure and QRS >/=130 ms reduced the risk of hospitalization for heart failure in MADIT-CRT; mortality was similarly low with each device.
European Journal of Heart Failure 12/2009; 11(12):1214-9. · 4.90 Impact Factor
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John G F Cleland,
John J V McMurray,
John Kjekshus,
Jan H Cornel,
Peter Dunselman,
Cândida Fonseca,
Ake Hjalmarson,
Jerzy Korewicki,
Magnus Lindberg,
Naresh Ranjith,
Dirk J van Veldhuisen,
Finn Waagstein,
Hans Wedel,
John Wikstrand
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ABSTRACT: We investigated whether plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of cardiac dysfunction and prognosis measured in CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure), could be used to identify the severity of heart failure at which statins become ineffective.
Statins reduce cardiovascular morbidity and mortality in many patients with ischemic heart disease but not, overall, those with heart failure. There must be a transition point at which treatment with a statin becomes futile.
In CORONA, patients with heart failure, reduced left ventricular ejection fraction, and ischemic heart disease were randomly assigned to 10 mg/day rosuvastatin or placebo. The primary composite outcome was cardiovascular death, nonfatal myocardial infarction, or stroke.
Of 5,011 patients enrolled, NT-proBNP was measured in 3,664 (73%). The midtertile included values between 103 pmol/l (868 pg/ml) and 277 pmol/l (2,348 pg/ml). Log NT-proBNP was the strongest predictor (per log unit) of every outcome assessed but was strongest for death from worsening heart failure (hazard ratio [HR]: 1.99; 95% confidence interval [CI]: 1.71 to 2.30), was weaker for sudden death (HR: 1.69; 95% CI: 1.52 to 1.88), and was weakest for atherothrombotic events (HR: 1.24; 95% CI: 1.10 to 1.40). Patients in the lowest tertile of NT-proBNP had the best prognosis and, if assigned to rosuvastatin rather than placebo, had a greater reduction in the primary end point (HR: 0.65; 95% CI: 0.47 to 0.88) than patients in the other tertiles (heterogeneity test, p = 0.0192). This reflected fewer atherothrombotic events and sudden deaths with rosuvastatin.
Patients with heart failure due to ischemic heart disease who have NT-proBNP values <103 pmol/l (868 pg/ml) may benefit from rosuvastatin.
Journal of the American College of Cardiology 11/2009; 54(20):1850-9. · 14.16 Impact Factor
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ABSTRACT: The prognosis of patients included in clinical trials is often better than might be anticipated from epidemiological data. Patients volunteering to take part in a study might be unrepresentative of the potential treatment population or the trial itself may confer benefit by offering closer supervision.
A total of 2332 consecutive patients (average +/- SD age 70.1 +/- 10.8; 26% female) who presented to a community heart failure clinic were diagnosed as having heart failure due to left ventricular systolic dysfunction. All patients were asked whether they would be prepared to take part in clinical research projects at their initial visit. During a median follow-up in survivors of 55.7 months (interquartile range 30.4-74.3), 792 (34%) patients died. Agreeing to take part in clinical trials strongly predicted a good outcome (approximately halving the risk of death). In multivariate modelling, willingness to take part [hazard ratio (95% confidence intervals) 0.33 (0.26-0.40)] was a predictor of good outcome independent of age, severity of left ventricular dysfunction, renal function, sodium levels, drug use, and comorbidities. In a subset in whom N-terminal pro-B type natriuretic peptide (NT-proBNP) was available (n = 1256), agreeing to take part in trials remained an independent predictor of survival with log [NT-proBNP].
Those patients with chronic heart failure who express a willingness to take part in a clinical trial, appear to have a better prognosis than those who do not.
European Journal of Heart Failure 11/2009; 11(11):1078-83. · 4.90 Impact Factor
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Alexandre Mebazaa,
Peter S Pang,
Miguel Tavares,
Sean P Collins,
Alan B Storrow,
Said Laribi,
Stephanie Andre,
Daniel Mark Courtney,
Jennifer Hasa,
Jindrich Spinar,
Josep Masip,
William Frank Peacock,
Karen Sliwa,
Etienne Gayat,
Gerasimos Filippatos, John G F Cleland,
Mihai Gheorghiade
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ABSTRACT: The vast majority of acute heart failure (AHF) trials to date have targeted dyspnoea. However, they enrolled patients relatively late and did not standardize their methods of dyspnoea measurement. URGENT Dyspnoea was designed to determine changes in dyspnoea in response to initial, standard therapy in patients presenting with AHF using a standardized approach.
URGENT Dyspnoea was an international, multi-centre, observational cohort study of AHF patients managed conventionally and enrolled within 1 h of first hospital medical evaluation. Patient-assessed dyspnoea was recorded in the sitting position at baseline and at 6 hours by Likert and visual analog scales. Less symptomatic patients were placed supine to determine whether this provoked worsening dyspnoea (orthopnoea). Of the 524 patients with AHF, the mean age was 68 years, 43% were women, and 83% received intravenous diuretics. On a 5-point Likert scale, dyspnoea improvement was reported by 76% of patients after 6 h of standard therapy. Supine positioning (orthopnoea test) led to worse dyspnoea in 47% of patients compared to sitting upright.
When sitting upright, dyspnoea in the sitting position improves rapidly and substantially in patients with AHF after administration of conventional therapy, mainly intra-venous diuretics. However, many patients remain orthopnoeic. Improving the methodology of clinical trials in AHF by standardizing the conditions under which dyspnoea is assessed could enhance their ability to identify effective treatments. Relief of orthopnoea is clinically valuable and may represent a useful goal for clinical trials.
European Heart Journal 11/2009; 31(7):832-41. · 10.48 Impact Factor
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ABSTRACT: BACKGROUND: The genesis of symptoms in patients with heart failure (HF) and normal ejection fraction (HFNEF) is unclear. Most investigations of HFNEF have focused on cardiac function at rest although most of these patients are breathless only on exercise. Stress-induced impairment in systolic or diastolic function could result in these symptoms. Method and Result- Forty-one patients with HFNEF and 29 controls underwent dobutamine stress echocardiography with color tissue Doppler imaging. Wall motion score index and regional myocardial systolic velocity (Sm) were measured at and peak stress. Systolic (Sa), early diastolic (Ea), and late diastolic (Aa) mitral annular velocities were averaged over the 6 periannular sites. Mitral annular long-axis velocity was lower in the HFNEF than controls at rest. Global, regional, and long-axis systolic function did not worsen with stress in the HFNEF group. The Ea decreased and the E/Ea increased with stress in the HFNEF but not in controls. The 6-minute walk distance was shorter and negatively correlated to the E/EA ratio at rest and stress in the HFNEF group. CONCLUSIONS: Impaired diastolic reserve results in stress-induced increase in the left ventricular end-diastolic pressure in patients with HFNEF giving rise to exercise intolerance.
Circulation Heart Failure 10/2009; 3(1):35-43. · 6.29 Impact Factor
