Prevalence, correlates, effects and detection of left ventricular systolic dysfunction in an urban population

The prevalence of chronic heart failure (CHF) in most epidemiological studies has been determined by using clinical criteria.In this thesis, in contrast, left ventricular systolic function was assessed objectively by echocardiography in a cross -sectional survey of 2000 men and women aged 25 -74, randomly sampled from a geographical area. Left ventricular ejection fraction (LVEF) was measured using the Biplane Simpson's Rule Method. Its aims were to document the prevalence of both symptomatic and asymptomatic left ventricular systolic dysfunction; ascertain the correlates of left ventricular systolic dysfunction; assess its effects on effort capacity; determine the usefulness of the natriuretic peptides in detecting systolic dysfunction; and to explore the possibility of a genetic component to left ventricular systolic dysfunction by examining the relationship between left ventricular systolic dysfunction and the angiotensinconverting enzyme insertion /deletion polymorphism (ACE I /D).In the 1640 subjects who attended (83%), the mean left ventricular ejection fraction was 47.3%. The prevalence of `definite' left ventricular systolic dysfunction (a LVEF ≤30%) was 2.9%: it was 0.7% in men aged 35-44 years and 6.4% in men >65 years being also higher in men (4%) than women (2%). One point five percent (1.5%) had symptomatic left ventricular systolic dysfunction and 1.4% asymptomatic left ventricular systolic dysfunction.In those with left ventricular systolic dysfunction, 83% had evidence of ischaemic heart disease (IHD), in contrast to 21% of those without left ventricular systolic dysfunction (p<0.001). Hypertension was more common in those with an abnormal ejection fraction (60% compared to 22%), p <0.001) but hypertension unaccompanied by IHD was not significantly more common in those with left ventricular systolic dysfunction.Left systolic ventricular dysfunction was associated with a significant reduction in exercise duration. In subjects in whom this was asymptomatic there was a trend towards decreased effort capacity.Plasma concentrations of the natriuretic peptides were significantly higher in those with left ventricular systolic dysfunction (the median concentration (interquartile range) of N-ANP was 2.8 [1.8,4.6] ng /ml and BNP; 24 [18,33]pg/ml) than in those without (N-ANP; 1.3[0.9,1.8] ng/ml and BNP; 7.7pg/mI[3.4,13], p <0.001). The area under the Receiver Operator Characteristic Curves (SD) was greater using BNP; 0.88 (0.03) for all, 0.841 (0.03) in those with IHD, 0.86(0.03) for subjects ≥55 years and 0.84 (0.04) for those ≥55 years with IHD. The same areas under the curve for N-ANP were 0.75(0.05), 0.71(0.05), 0.72 (0.05) and 0.70 (0.06), respectively. A BNP concentration of ≥17.9pg /ml gave a sensitivity of 77% (specificity 87 %) for detecting left ventricular systolic dysfunction in all subjects, improving to 92% (specificity 72 %) when the analysis was restricted to individuals ≥ 55 with IHD.The DD genotype of the ACE I/D polymorphism was significantly more common in subjects with electrocardiographic evidence of myocardial infarction (MI) or major ischaemia. (Using II as a reference, the odds ratios normal versus major ischaemia or MI were: DD 1.53, ID 1.18:p =0.03 for 10 trend). In older patients (≥51 yr.) with an ECG MI or major abnormality, LVEF was higher in those with the DD genotype (LVEF%: DD 44.6, ID 42.9, II 40;p <0.02). LVEF was also greater in older patients with a systolic blood pressure (SBP) > than the median value (LVEF%: DD 47.5, ID 45.8, Il 44.6; p= 0.012).This work has shown that left ventricular systolic dysfunction is at least as twice as common than previous studies based on clinical criteria of CHF would suggest; about half is asymptomatic. Only 18% of subjects with definite left ventricular systolic dysfunction were taking an ACE inhibitor. Its main risk factors are IHD and hypertension in the presence of IHD; screening such high risk groups for left ventricular systolic dysfunction is worthy of consideration. Using a test such as BNP and targetting its use to individuals at high risk would lead to the identification of many more patients with left ventricular systolic dysfunction and, therefore, to the uptake of effective treatment. It would also lead to a more cost effective use of further investigation.This thesis also provides a mechanistic insight into the development of left ventricular systolic dysfunction by suggesting that while the DD genotype confers a higher risk of MI, it is associated with better preservation of LV function post MI, possibly by enabling more adequate compensatory hypertrophy. The ACE gene I/D polymorphism may, therefore, have a bidirectional importance in determining both the risk of MI and post MI LV systolic dysfunction

Chronic heart failure: epidemiology, investigation and management

Heart failure (HF) is a clinical syndrome characterized by dyspnoea, fatigue and fluid retention accompanied by objective evidence of cardiac dysfunction. The syndrome affects around 2% of the adult population, men more commonly than women (&lt;80 years old), with the incidence and prevalence rising steeply with age. HF causes substantial morbidity and reduced life expectancy, and coronary artery disease accounts for two-thirds of cases in developed countries. Investigation is important to ascertain the diagnosis, identify the aetiology (which may be reversible) and give some indication of prognosis. The diagnosis of HF confers a significantly increased risk of hospital admission and death. Treatment has been revolutionized by large randomized controlled clinical trials studying the effects of antagonists of the renin–angiotensin–aldosterone, neutral endopeptidase and sympathetic nervous systems, and the effects of device therapy. Cardiac transplantation remains an option for patients who are severely symptomatic (and at high risk) despite optimal use of such therapy

In-hospital worsening heart failure: a clinically relevant endpoint?

Outcome measures used for the clinical evaluation of patients with acute heart failure differ between studies and may neither adequately address the characteristic presenting symptoms and signs nor reflect the pathophysiological processes involved. In‐hospital worsening of heart failure (WHF) is associated with poor outcomes and thus a potential endpoint conveying clinically meaningful prognostic information.Current definitions of WHF are based on the combination of worsening symptoms and signs and the intensification of treatment during admission. Definitions vary across studies and do not fully account for baseline therapy or circumstances in which there is failure to respond to treatment. Further, there are limited data to inform healthcare professionals as to which patients are most at risk of developing in‐hospital WHF.In this opinion piece, we review the definitions for WHF used in recent and ongoing clinical trials and propose a novel definition, which captures failure to respond to treatment as well as clinical worsening (deterioration of symptoms and signs) of the patient's condition. Such a definition, applied consistently across studies, would help clarify the characteristics of patients likely to develop in‐hospital WHF, allow comparative assessments of the effectiveness of interventions, and help guide appropriate patient management in order to improve outcomes

Referral for specialist follow-up and its association with post-discharge mortality among patients with systolic heart failure (from the National Heart Failure Audit for England and Wales)

For patients admitted with worsening heart failure, early follow-up after discharge is recommended. Whether outcomes can be improved when follow-up is done by cardiologists is uncertain. We aimed to determine the association between cardiology follow-up and risk of death for patients with heart failure discharged from hospital. Using data from the National Heart Failure Audit (England &amp; Wales), we investigated the effect of referral to cardiology follow-up on 30-day and one-year mortality in 68 772 patients with heart failure and a reduced left ventricular ejection fraction (HFREF) discharged from 185 hospitals between 2007 to 2013. The primary analyses used instrumental variable analysis complemented by hierarchical logistic and propensity matched models. At the hospital level, rates of referral to cardiologists varied from 6% to 96%. The median odds ratio (OR) for referral to cardiologist was 2.3 (95% confidence interval [CI] 2.1, 2.5), suggesting that, on average, the odds of a patient being referred for cardiologist follow-up after discharge differed approximately 2.3 times from one randomly selected hospital to another one. Based on the proportion of patients (per region) referred for cardiology follow-up, referral for cardiology follow-up was associated with lower 30-day (OR 0.70; CI 0.55, 0.89) and one-year mortality (OR 0.81; CI 0.68, 0.95) compared with no plans for cardiology follow-up (i.e., standard follow-up done by family doctors). Results from hierarchical logistic models and propensity matched models were consistent (30-day mortality OR 0.66; CI 0.61, 0.72 and 0.66; CI 0.58, 0.76 for hierarchical and propensity matched models, respectively). For patients with HFREF admitted to hospital with worsening symptoms, referral to cardiology services for follow-up after discharge is strongly associated with reduced mortality, both early and late

Does rhythm matter in acute heart failure? An insight from the British Society for Heart Failure National Audit

Peer reviewedPublisher PD

Hearts and Minds:Real-Life Cardiotoxicity with Clozapine in Psychosis

Schizophrenia has a 1% prevalence in the population; 30% of these patients are treatment refractory. Clozapine is the only drug licensed to treat treatment refractory psychosis, but concerns about potential adverse effects result in only a proportion of eligible patients being treated. Although a well-documented neutropenia risk is mitigated by routine blood testing, cardiac toxicity is a commonly cited reason to discontinue clozapine treatment. However, there is little data on the real-life cardiac outcomes in those receiving clozapine treatment. Retrospective review of electrocardiogram, echocardiogram, and clinical outcomes in 39 inpatients with treatment-refractory schizophrenia, treated with clozapine and other antipsychotic medication, referred for cardiology opinion. Commonest reasons for referral were development of left ventricular (LV) impairment or sinus tachycardia with normal LV function. Patients were reviewed by a range of cardiologists, receiving varied interventions.Median LV ejection fraction in the clozapine group was normal (52%). Serial echocardiograms demonstrated that clozapine-treated patients with LV impairment had no change in LV ejection fraction over a 4-month follow-up. Left ventricular ejection fraction did not differ between patients treated with clozapine and other antipsychotics. However, over an 11-year follow-up period, 48% of patients had discontinued clozapine treatment. This naturalistic study demonstrates that clozapine is not associated with significant cardiac mortality or morbidity. There is a real need for multidisciplinary working between specialist cardiologists and psychiatrists caring for these complex patients to facilitate optimal long-term physical and mental health outcomes

ST2 in patients with severe aortic stenosis and heart failure

Background: ST2 is a circulating biomarker that is well established for predicting outcome in heart failure (HF). This is the first study to look at ST2 concentrations in optimally treated patients with stable but significant left ventricular systolic dysfunction (LVSD) compared to patients with severe aortic stenosis (AS).Methods: Two cohorts were retrospectively studied: 94 patients undergoing transcatheter aortic valveimplantation for severe AS (63 with normal ejection fraction [EF] and 31 with reduced EF), and 50 patients with severe LVSD from non-valvular causes. ST2 pre-procedural samples were taken, and repeated again at 3 and 6 months. Patients were followed-up for 2 years. Data was analyzed using SPSS software.Results: Baseline concentrations of soluble ST2 did not differ significantly between the HF group and AS group with normal EF (EF ≥ 50%). However, in the AS group with a low EF (EF &lt; 50%) ST2 concentrationswere significantly higher that the HF group (p = 0.009). New York Heart Association class IV HF, baseline N-terminal pro-B-type natriuretic peptide and gender were all independent predictors of soluble ST2 (sST2) baseline concentrations.Conclusions: Raised ST2 concentrations in the context of severe AS may be a marker for subclinical or clinical left ventricular dysfunction. More research is required to assess its use for assessment of prognosis and response to treatment