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.

Influence of case definition on incidence and outcome of acute coronary syndromes.

OBJECTIVE: Acute coronary syndromes (ACS) are common, but their incidence and outcome might depend greatly on how data are collected. We compared case ascertainment rates for ACS and myocardial infarction (MI) in a single institution using several different strategies. METHODS: The Hull and East Yorkshire Hospitals serve a population of ∼560 000. Patients admitted with ACS to cardiology or general medical wards were identified prospectively by trained nurses during 2005. Patients with a death or discharge code of MI were also identified by the hospital information department and, independently, from Myocardial Infarction National Audit Project (MINAP) records. The hospital laboratory identified all patients with an elevated serum troponin-T (TnT) by contemporary criteria (>0.03 µg/L in 2005). RESULTS: The prospective survey identified 1731 admissions (1439 patients) with ACS, including 764 admissions (704 patients) with MIs. The hospital information department reported only 552 admissions (544 patients) with MI and only 206 admissions (203 patients) were reported to the MINAP. Using all 3 strategies, 934 admissions (873 patients) for MI were identified, for which TnT was >1 µg/L in 443, 0.04-1.0 µg/L in 435, ≤0.03 µg/L in 19 and not recorded in 37. A further 823 patients had TnT >0.03 µg/L, but did not have ACS ascertained by any survey method. Of the 873 patients with MI, 146 (16.7%) died during admission and 218 (25.0%) by 1 year, but ranging from 9% for patients enrolled in the MINAP to 27% for those identified by the hospital information department. CONCLUSIONS: MINAP and hospital statistics grossly underestimated the incidence of MI managed by our hospital. The 1-year mortality was highly dependent on the method of ascertainment.

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.

Development and course of heart failure after a myocardial infarction in younger and older people.

BACKGROUND: Acute myocardial infarction (AMI) is a common cause of heart failure (HF), which can develop soon after AMI and may persist or resolve or develop late. HF after an MI is a major source of mortality. The cumulative incidence, prevalence and resolution of HF after MI in different age groups are poorly described. This study describes the natural history of HF after AMI according to age. METHODS: Patients with AMI during 1998 were identified from hospital records. HF was defined as treatment of symptoms and signs of HF with loop diuretics and was considered to have resolved if loop diuretic therapy could be stopped without recurrence of symptoms. Patients were categorised into those aged < 65 years, 65-75 years, and > 75 years. RESULTS: Of 896 patients, 311, 297 and 288 were aged < 65, 65-75 and >75 years and of whom 24%, 57% and 82% had died respectively by December 2005. Of these deaths, 24 (8%), 68 (23%) and 107 (37%) occurred during the index admission, many associated with acute HF. A further 37 (12%), 63 (21%) and 82 (29%) developed HF that persisted until discharge, of whom 15, 44 and 62 subsequently died. After discharge, 53 (24%), 55 (40%) and 37 (47%) patients developed HF for the first time, of whom 26%, 62% and 76% subsequently died. Death was preceded by the development of HF in 35 (70%), 93 (91%) and 107 (85%) in aged < 65 years, 65-75 years and >75 years, respectively. CONCLUSIONS: The risk of developing HF and of dying after an MI increases progressively with age. Regardless of age, most deaths after a MI are preceded by the development of HF.

Old and newer biomarkers in heart failure: from pathophysiology to clinical significance.

Heart failure is a complex disease in which a careful clinical examination and the measurement of cardiac function may not always be sufficient for making a correct diagnosis. Measuring plasma levels of natriuretic peptides may assist in this process, also offering a good tool for accurate risk stratification. Other alternative biomarkers may give insight into the different pathways of heart failure genesis and pathophysiology, and may help to identify those patients with overt heart failure and a more adverse outcome, or distinguish between those at risk of developing heart failure. Despite a high number of potentially useful biomarkers, only a few will likely be introduced routinely into clinical practice. However, a multi-marker approach might increase the diagnostic accuracy and it might identify different phenotypes of heart failure patients who might benefit from individualized therapy in the future.

IVC diameter in patients with chronic heart failure: relationships and prognostic significance.

OBJECTIVES: The aim of this study was to assess the relation between inferior vena cava (IVC) diameter, clinical variables, and outcome in patients with chronic heart failure (HF). BACKGROUND: The IVC distends as right atrial pressure rises. Therefore it might represent an index of HF severity independent of left ventricular ejection fraction (LVEF). The relation between IVC diameter and other clinical variables and its prognostic significance in patients with HF has not been explored. METHODS: Outpatients attending a community HF service between 2008 and 2010 were enrolled. Heart failure was defined as the presence of relevant symptoms and signs and objective evidence of cardiac dysfunction: either LVEF <45% or the combination of both left atrial dilation (≥4 cm) and raised amino-terminal pro-brain natriuretic peptide (NT-proBNP) ≥400 pg/ml. Patients were followed for a median of 567 (interquartile range: 413 to 736) days. The primary composite endpoint was cardiovascular death and HF hospitalization. RESULTS: Among the 693 patients enrolled, median age was 73 years, 33% were women, and 568 had HF. Patients with HF in the highest tertile of IVC diameter were older; had lower body mass index; were more likely to have atrial fibrillation and to be treated with diuretics; and had larger left atrial volumes, higher pulmonary pressures, and less negative values for global longitudinal strain. The LVEF and systolic blood pressure were similar across tertiles of IVC diameter. The IVC diameter and log [NT-proBNP] were correlated (r = 0.55, p < 0.001). During follow-up, 158 patients reached a primary endpoint. In a multivariable Cox regression model, including NT-proBNP, only increasing IVC diameter, urea, and the trans-tricuspid systolic gradient independently predicted a poor outcome. Neither global longitudinal strain nor LVEF were adverse predictors. CONCLUSIONS: In patients with chronic HF with or without a reduced LVEF, increasing IVC diameter identifies patients with an adverse outcome.

Personalizing biomarker strategies in heart failure with galectin-3.

Heart failure is a leading cause of death and disability. Galectin-3 expression is associated with myocardial fibrosis; recombinant galectin-3 can induce myocardial fibrosis in experimental animals. However, the fact that endogenous galectin-3 is causative of myocardial fibrosis is yet to be firmly established. Nevertheless, the important discovery that N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), a naturally occurring anti-inflammatory and antifibrotic peptide, inhibits galectin-3 expression, which prevents cardiac remodeling and dysfunction, provides impetus for translational research into anti-galectin therapy. The lack of a close relationship between galectin-3 and brain natriuretic peptide creates the possibility of a complimentary role. Thus, whilst brain natriuretic peptide is a useful biomarker for diagnosing heart failure, galectin-3 appears to be a culprit biomarker that mediates the development of heart failure, raising the possibility that specific anti-galectin therapy may halt the development of heart failure. Furthermore, data are beginning to emerge supporting the hypothesis that galectin-3 is crucial in the angiotensin-aldosterone pathway leading to salt and water retention, a key mechanism which can result in the development of heart failure. Thus, one might expect patients with heart failure and raised levels of galectin-3 to benefit from aldosterone antagonist therapy. Numerous clinical trials have already established the role of galectin-3 in predicting response to heart failure management, in particular how high levels of galectin-3 predicts mortality. A recent post hoc analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) suggested that patients with relatively low galectin-3 levels (<19 ng/ml) are most likely to benefit from statin therapy. This generated an important hypothesis that deserves further study.

An atrial mass: the value of echocardiographic three-dimensional reconstruction.

An 88-year-old lady was referred to our Heart Failure Clinic with a history of 'occasional' breathlessness. Electrocardiography showed sinus rhythm and no other major abnormalities and N-terminal pro-B-type natriuretic peptide (NT-proBNP) was normal. Transthoracic echocardiography showed a non-dilated left ventricle with good systolic function. A bright and well-circumscribed, echogenic mass appeared inside a mildly dilated left atrium, visible in both parasternal and apical views. A three-dimensional echocardiographic reconstruction showed no mass within the left atrium; however, an extracardiac mass impinging its posterior wall was seen. Suspicion of an intrathoracic tumour was raised and cardiac magnetic resonance showed a hiatus hernia immediately adjacent to the left atrium. Care must be taken when evaluating masses in or close to the heart.

Clinical trials update from the Heart Failure Society of America Meeting 2009: FAST, IMPROVE-HF, COACH galectin-3 substudy, HF-ACTION nuclear substudy, DAD-HF, and MARVEL-1.

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.