Left atrial function measured by cardiac magnetic resonance imaging in patients with heart failure: clinical associations and prognostic value.

BACKGROUND: Left atrial (LA) volume is an important marker of cardiac dysfunction and cardiovascular outcome in heart failure (HF), but LA function is rarely measured. METHODS: Left atrial emptying function (LAEF), its clinical associations and prognostic value was studied in outpatients referred with suspected HF who were in sinus rhythm and had cardiac magnetic resonance imaging (CMRI). Heart failure was defined as relevant symptoms and signs with either a left ventricular ejection fraction (LVEF) <50% or amino-terminal pro-B-type natriuretic peptide (NTproBNP) >400 pg/mL (or >125 pg/mL if taking loop diuretics). RESULTS: Of 982 patients, 664 fulfilled the HF criteria and were in sinus rhythm. The median (interquartile range, IQR) LAEF was 42 (31-51)% and 55 (48-61)% in patients with and without HF (P < 0.001). Patients with HF in the lowest quartile of LAEF (23%; IQR: 17-28%) had lower LV and right ventricular (RV) EF, and greater LV and RV mass and higher plasma NTproBNP than those in the highest quartile of LAEF (56%; IQR: 53-61%). Log[LAEF] and log[NTproBNP] were inversely correlated (r = -0.410, P < 0.001). During a median follow-up of 883 (IQR: 469-1626) days, 394 (59%) patients with HF died or were admitted with HF and 101 (15%) developed atrial fibrillation (AF). In a multivariable Cox model, increasing LAEF, but not LVEF, was independently associated with survival (HR for 10% change: 0.81 (95%CI: 0.73-0.90), P = <0.001). Increasing age and decreasing LAEF predicted incident AF. CONCLUSIONS: In patients with HF, LAEF predicts adverse outcome independently of other measures of cardiac dysfunction.

Atherosclerotic disease of the abdominal aorta and its branches: prognostic implications in patients with heart failure.

Aortic atherosclerosis reduces compliance in the systemic circulation and increases peripheral resistance, afterload and left ventricular wall stress. In patients with heart failure, these changes can impair left ventricular systolic function and energy efficiency, which could reduce exercise capacity. Though the interaction and the impact of aortic atherosclerosis on left ventricular function have been investigated, its prognostic implications in patients with heart failure are unclear. We used cardiac magnetic resonance imaging and gadolinium-enhanced abdominal aortography to investigate the prevalence and prognostic impact of atherosclerotic disease of the abdominal aorta and its side branches in 355 patients with heart failure. Sclerotic abdominal aortic disease was defined as a luminal narrowing >50% of the aorta and its side branches or the presence of abdominal aortic aneurysm. Patients with disease of the aorta and its branches were older (P < 0.0001), had overall longer stay in hospital (P = 0.006) and had more admissions (P = 0.001) and worse prognosis (hazard ratio: 1.97, 95% confidence interval: 1.29-3.00, P = 0.002) than those without. In a multivariable model, increasing age and pulse pressure, diabetes mellitus and increasing left ventricular end-diastolic volume were associated with a worse prognosis, but sclerotic abdominal aortic disease was not independently related to outcome (hazard ratio: 1.06; 95% confidence interval: 0.64-1.74; P = 0.823). These data demonstrate that atherosclerosis of the abdominal aorta and its side branches is common and associated with increased morbidity in patients with chronic heart failure. How such disease should be managed remains uncertain, but its recognition and characterisation are the first steps in finding out.

Prevalence of scarred and dysfunctional myocardium in patients with heart failure of ischaemic origin: a cardiovascular magnetic resonance study.

BACKGROUND: Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) can provide unique data on the transmural extent of scar/viability. We assessed the prevalence of dysfunctional myocardium, including partial thickness scar, which could contribute to left ventricular contractile dysfunction in patients with heart failure and ischaemic heart disease who denied angina symptoms. METHODS: We invited patients with ischaemic heart disease and a left ventricular ejection fraction < 50% by echocardiography to have LGE CMR. Myocardial contractility and transmural extent of scar were assessed using a 17-segment model. RESULTS: The median age of the 193 patients enrolled was 70 (interquartile range: 63-76) years and 167 (87%) were men. Of 3281 myocardial segments assessed, 1759 (54%) were dysfunctional, of which 581 (33%) showed no scar, 623 (35%) had scar affecting ≤50% of wall thickness and 555 (32%) had scar affecting > 50% of wall thickness. Of 1522 segments with normal contractile function, only 98 (6%) had evidence of scar on CMR. Overall, 182 (94%) patients had ≥1 and 107 (55%) patients had ≥5 segments with contractile dysfunction that had no scar or ≤50% transmural scar suggesting viability. CONCLUSIONS: In this cohort of patients with left ventricular systolic dysfunction and ischaemic heart disease, about half of all segments had contractile dysfunction but only one third of these had > 50% of the wall thickness affected by scar, suggesting that most dysfunctional segments could improve in response to an appropriate intervention.

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.

Effects of applying a standardised management algorithm for moderate to severe renal dysfunction in patients with chronic stable heart failure.

BACKGROUND: No specific guidelines exist on how to manage renal dysfunction (RD) in patients with chronic heart failure (CHF). AIMS: To identify the proportion of patients with moderate to severe RD and CHF who showed an improvement in their renal function in response to a systematic management algorithm. METHODS: Stable patients with CHF and RD (defined by a serum creatinine (SCr) of >130 micromol/l (>1.5 mg/dl)) were enrolled into a systematic management algorithm. The following changes were implemented: switching aspirin to clopidogrel, halving the dose of both diuretics and angiotensin converting enzyme (ACE) inhibitors and switching between bisoprolol and carvedilol. RESULTS: Two thirds of patients in whom diuretics were reduced, and one fifth of patients in whom ACE inhibitors were reduced, improved their SCr by >25.5 micromol/l (0.3 mg/dl). All these changes were more marked in the presence of bilateral renal artery stenosis. Compared to a reference group, in whom no changes were implemented, the treatment group showed an improvement in their mean SCr by 35 micromol/l (0.4 mg/dl), p<0.001. CONCLUSION: Manipulation of pharmacological therapy for patients with CHF and RD results in a substantial recovery of renal function in a minority of patients.

Clinical trials update from the European Society of Cardiology meeting 2005: CARE-HF extension study, ESSENTIAL, CIBIS-III, S-ICD, ISSUE-2, STRIDE-2, SOFA, IMAGINE, PREAMI, SIRIUS-II and ACTIVE.

This article provides information and a commentary on trials presented at the European Society of Cardiology meeting held in September 2005, relevant to the pathophysiology, prevention and treatment of heart failure. All reports should be considered as preliminary data, as analyses may change in the final publication. In the CARE-HF extension study, the benefits of cardiac resynchronisation therapy (CRT) observed in the original study were maintained over an increased follow-up period. A study of oral enoximone (25-50 mg t.i.d.) in advanced heart failure (ESSENTIAL) showed limited benefit compared to placebo. The CIBIS-III study showed that heart failure therapy could be safely initiated with bisoprolol followed by the addition of enalapril. A subcutaneous ICD system (S-ICD) showed potential as an alternative to a transvenous ICD. In the ISSUE-2 study, an implantable loop recorder was used to guide therapy in patients with recurrent syncope. The selective endothelin antagonist sitaxsentan improved 6-MWT and functional class in patients with pulmonary arterial hypertension in the STRIDE-2 study. In SOFA, fish oil had no beneficial effect on the incidence of life-threatening arrhythmias in patients with an ICD. In IMAGINE, quinapril showed no benefit when administered to patients following CABG. Perindopril reduced cardiac remodelling in post-MI patients with normal LV function in PREAMI. SIRIUS-II showed encouraging results for the use of intravenous ularitide in symptomatic decompensated chronic heart failure. The ACTIVE W study of warfarin versus aspirin plus clopidogrel in atrial fibrillation has been stopped due to superiority of warfarin.

The relationship of QRS morphology with cardiac structure and function in patients with heart failure.

INTRODUCTION: The relationship of QRS morphology with cardiac structure and function in patients with heart failure is uncertain. METHODS: Patients with a clinical diagnosis of heart failure and objective evidence of cardiac dysfunction [either a left ventricular ejection fraction (LVEF) <50 % or an amino-terminal pro-brain natriuretic peptide (NT-proBNP) ≥400 pg/ml] who had been investigated by cardiac magnetic resonance imaging (CMRI) were identified. QRS duration ≥120 ms was grouped morphologically as left (LBBB), right bundle branch block (RBBB) or indeterminate. RESULTS: Of 877 patients, 320 (36 %) had QRS ≥ 120 ms. Compared to patients with LBBB, those with RBBB had a lower median [inter-quartile range (IQR)] right ventricular (RV) ejection fraction [RBBB: 46 (37-57); LBBB: 52 (42-61) %; p = 0.014], greater median (IQR) RV mass [RBBB: 53 (42-73); LBBB: 45 (36-56) g; p < 0.001], higher median (IQR) plasma NT-proBNP [RBBB: 2013 (659-3573); LBBB: 1159 (589-2207) pg/ml, p = 0.026], more signs of peripheral congestion and higher prevalence of atrial fibrillation but had similar LVEF. During a median follow-up of 1302 days (IQR: 742-2237), 311 patients died. Compared with patients who had QRS < 120 ms, those with RBBB [HR 1.98, 95 % CI (1.37-2.86); p < 0.001] had a higher mortality. Age and NT-proBNP were the strongest independent predictors of mortality; neither QRS nor CMRI variables improved prediction. CONCLUSIONS: In patients with heart failure and QRS ≥ 120 ms, RBBB is associated with more severe RV dysfunction and congestion and a worse prognosis. However, neither QRS morphology nor CMRI data provide independent prognostic information in a multivariable analysis including NT-proBNP.

Clinical trials update from the European Society of Cardiology: CHARM, BASEL, EUROPA and ESTEEM.

This article contains a series of reports on recent research developments in the field of heart failure. Reports of key presentations made at the European Society of Cardiology meeting, held in Vienna, Austria, between 30 August and 3 September 2003 are reported. In the CHARM study, candesartan reduced cardiovascular deaths and hospital admissions for heart failure, both in patients who were already taking an ACE-inhibitor and in those who were ACE intolerant. However, results in patients with preserved left ventricular function were less conclusive. The BASEL study supports the use of B-type natriuretic peptide testing to confirm the diagnosis of heart failure in patients presenting with acute dyspnoea. In EUROPA, the largest ever study of secondary prevention of coronary artery disease, long-term treatment with perindopril reduced the incidence of cardiovascular death, myocardial infarction (MI) and cardiac arrest. The ESTEEM study showed that the oral thrombin inhibitor ximelagatran plus aspirin was more effective than aspirin alone in the prophylaxis of major cardiovascular events following MI.

Predictive power of late gadolinium enhancement for myocardial recovery in chronic ischaemic heart failure: a HEART sub-study.

BACKGROUND: The amount of myocardial scar measured by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging predicts regional recovery in wall motion following revascularization. Previous studies have been conducted in patients with a relatively recent myocardial insult and relatively preserved left ventricular (LV) function. In this sub-study of a clinical trial, the predictive value of LGE, and other CMR-derived data, for myocardial recovery in patients with chronic severe ischaemic cardiomyopathy was assessed. METHODS: Twenty-two patients with severe LV impairment of ischaemic origin were enrolled as a sub-study of a trial that randomly assigned patients to revascularization or not in addition to guideline-indicated pharmacological therapy. Patients underwent a CMR study at baseline and 6 months. Scans were qualitatively and quantitatively assessed for wall motion, rest/stress myocardial perfusion, and LGE. RESULTS: The median duration of heart failure was 13 (inter-quartile range 5-21) months. Patients had severe LV dilatation [end-diastolic volume (EDV) 280 ± 77 mL] and reduction in LV ejection fraction (LVEF) (29 ± 10%). The percentage scar burden by LGE was 17 ± 9%. Patient characteristics of those undergoing revascularization (n = 7) or not (n = 14) were similar. Myocardial perfusion reserve index (MPRI) improved following revascularization (MPRI 1.17 vs. 1.57, P < 0.0001) but not following medical therapy (1.39 vs. 1.32, P = 0.54). However, LVEF improved in patients whether or not they had revascularization. In the revascularization group, 14% of dysfunctional segments with LGE <25% and 22% of dysfunctional segments with LGE <50% had improved contractile function. However, the transmural extent of LGE did not predict contractile recovery following revascularization or pharmacological therapy (P = 0.19, P = 0.42). LVEDV improved overall (280 ± 77 to 269 ± 83 mL, P = 0.05); improvement was associated with heart failure duration (P = 0.04). CONCLUSIONS: In patients with chronic severe LV impairment of ischaemic origin, duration of heart failure is a better predictor of recovery than transmural extent of LGE, following medical therapy or successful revascularization. This suggests that the extent of myocardial remodelling is more important for LV recovery than the presence and extent of prior infarction alone and that LGE should not be the sole determinant of treatment method in severe LV systolic dysfunction of ischaemic origin.

Renal artery stenosis: an innocent bystander or an independent predictor of worse outcome in patients with chronic heart failure? A magnetic resonance imaging study.

AIMS: To investigate the prognostic impact of atherosclerotic renovascular disease in patients with chronic heart failure. METHODS AND RESULTS: Patients with heart failure due to left ventricular systolic dysfunction underwent cardiac magnetic resonance imaging and contrast-enhanced magnetic resonance angiography. Renal artery stenosis (RAS) was defined as a luminal narrowing >50%. Of the 366 patients investigated, 112 (31%) had RAS, of whom 41 had bilateral RAS. Patients with RAS were older (P < 0.001), had higher blood pressure (P < 0.001), and worse renal function (P = 0.001). In addition, these patients had more admissions and more prolonged hospital stays because of vascular events (0.09 ± 0.26 vs. 0.02 ± 0.16 admissions/per patient/year; P < 0.001; and 1.26 ± 5.79 vs. 0.31 ± 2.54 days/per patient/year; P < 0.001, respectively) and worse prognosis (hazard ratio 1.60, 95% confidence interval 1.10-2.34, P = 0.015). However, in multivariable analysis, a history of diabetes mellitus, decreasing haemoglobin, and increasing left ventricular end-systolic volume index, but not age and RAS, were independently related to outcome. CONCLUSIONS: RAS is a common finding in patients suffering from heart failure. Although it is associated with an increased vascular morbidity, it is not an independent predictor of mortality.

Relationship between right ventricular volumes measured by cardiac magnetic resonance imaging and prognosis in patients with chronic heart failure.

AIMS: The aim of this study was to investigate the prognostic impact of right ventricular (RV) size in patients with chronic heart failure. METHODS AND RESULTS: Normal volunteers (n = 80) and patients (n = 380) with left ventricular (LV) ejection fraction <45% on echocardiography and on optimal treatment for heart failure underwent cardiac magnetic resonance imaging with measurement of LV and RV volumes, mass and ejection fraction. The mean and the standard deviation (SD) of the RV end-systolic volume index in normal subjects were used to define the normal range as: mean RV end-systolic volume index +2 SD. Patients with dilated RV (>2 SD beyond the mean) (25%) had more frequent evidence of fluid overload in clinical examination and greater LV dimensions (P < 0.0001). During follow-up (median 45, interquartile range: 28-66 months), 37% of patients with and 24% without RV dilation died (log-rank test = 8.4; P = 0.004). In a multivariable Cox regression model, including 13 other clinical variables, RV (HR: 1.08/10 mL/m(2), 95% CI: 1.00-1.18, P = 0.044), but not LV, end-systolic volume index predicted a worse outcome. CONCLUSION: Twenty-five per cent of patients with heart failure due to LV systolic dysfunction have a dilated right ventricle. Greater RV dimensions predict mortality in patients with chronic heart failure. Treatments aimed at preserving or enhancing RV structure and function, possibly by unloading the RV by reducing pulmonary vascular resistance or left atrial pressure, should be investigated.