Aleem Khand

Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial

BACKGROUND Bivalirudin, with selective use of glycoprotein (GP) IIb/IIIa inhibitor agents, is an accepted standard of care in primary percutaneous coronary intervention (PPCI). We aimed to compare antithrombotic therapy with bivalirudin or unfractionated heparin during this procedure. METHODS In our open-label, randomised controlled trial, we enrolled consecutive adults scheduled for angiography in the context of a PPCI presentation at Liverpool Heart and Chest Hospital (Liverpool, UK) with a strategy of delayed consent. Before angiography, we randomly allocated patients (1:1; stratified by age [<75 years vs ≥75 years] and presence of cardiogenic shock [yes vs no]) to heparin (70 U/kg) or bivalirudin (bolus 0·75 mg/kg; infusion 1·75 mg/kg per h). Patients were followed up for 28 days. The primary efficacy outcome was a composite of all-cause mortality, cerebrovascular accident, reinfarction, or unplanned target lesion revascularisation. The primary safety outcome was incidence of major bleeding (type 3-5 as per Bleeding Academic Research Consortium definitions). This study is registered with ClinicalTrials.gov, number NCT01519518. FINDINGS Between Feb 7, 2012, and Nov 20, 2013, 1829 of 1917 patients undergoing emergency angiography at our centre (representing 97% of trial-naive presentations) were randomly allocated treatment, with 1812 included in the final analyses. 751 (83%) of 905 patients in the bivalirudin group and 740 (82%) of 907 patients in the heparin group had a percutaneous coronary intervention. The rate of GP IIb/IIIa inhibitor use was much the same between groups (122 patients [13%] in the bivalirudin group and 140 patients [15%] in the heparin group). The primary efficacy outcome occurred in 79 (8·7%) of 905 patients in the bivalirudin group and 52 (5·7%) of 907 patients in the heparin group (absolute risk difference 3·0%; relative risk [RR] 1·52, 95% CI 1·09-2·13, p=0·01). The primary safety outcome occurred in 32 (3·5%) of 905 patients in the bivalirudin group and 28 (3·1%) of 907 patients in the heparin group (0·4%; 1·15, 0·70-1·89, p=0·59). INTERPRETATION Compared with bivalirudin, heparin reduces the incidence of major adverse ischaemic events in the setting of PPCI, with no increase in bleeding complications. Systematic use of heparin rather than bivalirudin would reduce drug costs substantially. FUNDING Liverpool Heart and Chest Hospital, UK National Institute of Health Research, The Medicines Company, AstraZeneca, The Bentley Drivers Club (UK).

Is the prognosis of heart failure improving

Heart failure is common and effective therapy exists but as yet there is little evidence that the overall prognosis is improving in clinical practice. We sought to determine if mortality, re‐admission with heart failure and re‐admission for any cause, had changed between cohorts of first‐time admissions for heart failure identified in 1984, 1988 and 1992 using linked hospital discharge and mortality data from Scotland (population approximately 5 million).

Diastolic heart failure: neglected or misdiagnosed?

Recent epidemiological studies suggest that 30% to 50% of patients with heart failure (HF) have preserved left ventricular (LV) systolic function. These patients, often presumed to have diastolic heart failure (DHF), appear to have lower short-term but similar long-term mortality when compared to patients with HF and LV systolic dysfunction. Rates of recurrent hospitalization and costs of care appear similar in the two groups of patients. Therefore, DHF may contribute significantly to the burden of disease caused by HF. Exertional breathlessness, the principal symptom of HF, has many causes, including obesity, pulmonary disease and myocardial ischemia. A diagnosis of DHF by exclusion, based on symptoms in the absence of important LV systolic dysfunction or major valve disease, is unsatisfactory. Unfortunately, as yet, no reliable definition with which to make a positive diagnosis of DHF has been agreed on, frequently rendering this diagnosis uncertain. Echocardiography has several limitations, whereas hemodynamic confirmation of DHF by cardiac catheterization is potentially complex and not practically feasible for many patients. Treatment of DHF remains empirical and unsatisfactory because of the lack of large-scale randomized controlled trials in this area. Currently, three large outcome studies on DHF are in progress along with other smaller trials. These should start to provide some of the answers we need to diagnose and effectively treat DHF.

Prevalence and Incidence of Arrhythmias and Sudden Death in Heart Failure

Patients with heart failure are prone to a variety of arrhythmias, symptomatic and asymptomatic, that are prognostically significant and have an important bearing on the management of these patients. However there are some inherent problems in assessing the frequency of these arrhythmias within a large patient population, due to a lack of uniformity in defining heart failure and the transient nature of these rhythms. Patients with heart failure commonly die suddenly. The causes of these deaths are difficult to ascertain accurately and are often presumed arrhythmic. With the advent of effective interventions to prevent sudden death, accurately defining the causal relationship between the arrhythmias and sudden death has assumed great importance to appropriately target therapy. Several attempts have been made to predict such deaths on the basis of non-invasive and invasive diagnostic investigations with variable success. In this article we review the incidence and prevalence of atrial and ventricular arrhythmias and sudden deaths in epidemiological studies, surveys and randomised control trials of patients with heart failure. We discuss the prognostic significance of these arrhythmias, the inherent problems in their diagnosis and whether their presence predicts the risk of sudden deaths and the mode of such deaths in the heart failure population. The role of various investigations in risk stratification of sudden death has also been discussed

Do discharge codes underestimate hospitalisation due to heart failure? Validation study of hospital discharge coding for heart failure

Discharge codes are frequently used to describe hospital activity related to heart failure (HF).

Clinical trials update: highlights of the scientific sessions of the American Heart Association year 2000: Val HeFT, COPERNICUS, MERIT, CIBIS-II, BEST, AMIOVIRT, V-MAC, BREATHE, HEAT, MIRACL, FLORIDA, VIVA and the first human cardiac skeletal muscle myoblast transfer for heart failure.

This article continues a series of reports summarising recent research developments pertinent to the topic of heart failure. This is a summary of presentations made at scientific sessions of the American Heart Association in November 2000. Clinical studies of particular interest to people caring for patients with heart failure include Val‐HeFT, AMIOVIRT and V‐MAC. New data from β‐blockers trials are reviewed, highlights from some important developments in post‐infarction care, including MIRACL and FLORIDA, discussed and results of some early studies of gene therapy reported.

Prevention of and Medical Therapy for Atrial Arrhythmias in Heart Failure

A large proportion of heart failure patients suffer from atrial arrhythmias, prime amongst them being atrial fibrillation (AF). Ventricular dysfunction and the syndrome of heart failure can also be a concomitant pathology in up to 50% of patients with AF. However this association is more than just due to shared risk factors, research from animal and human studies suggest a causal relationship between AF and heart failure. There are numerous reports of tachycardia-induced heart failure where uncontrolled ventricular rate in AF results in heart failure, which is reversible with cardioversion to sinus rhythm or ventricular rate control. However the relationship extends beyond tachycardia-induced cardiomyopathy. Optimal treatment of AF may delay progressive ventricular dysfunction and the onset of heart failure whilst improved management of heart failure can prevent AF or improve ventricular rate control. Prevention and treatment of atrial arrhythmias, and in particular atrial fibrillation, is therefore an important aspect of the management of patients with heart failure.This review describes the incidence and possible predictors of AF and other atrial arrhythmias in patients with heart failure and discusses the feasibility of primary prevention. The evidence for the management of atrial fibrillation in heart failure is systematically reviewed and the strategies of rate versus rhythm control discussed in light of the prevailing evidence.

The collateral circulation of the heart in coronary total arterial occlusions in man: systematic review of assessment and pathophysiology.

BACKGROUND Anatomical and functional assessment of the collateral circulation of the heart in total arterial occlusions is challenging, and this is particularly true of the microcirculation. The pathophysiology of the collateral circulation has historically been and remains of considerable research focus but with diverging and sometimes conflicting results. Our purpose was to conduct a systematic review on the assessment and pathophysiology of the collateral circulation of the heart in total coronary arterial occlusions. METHODS We extracted data from Pubmed, Ovid, EMBASE, and Cochrane database from 1966 to December 2012. Two investigators independently reviewed the identified articles for eligibility and extracted the data. RESULTS Seventy-seven studies met inclusion criterion. An invasive assessment of the collateral circulation with pressure and/or Doppler wires is the gold standard in the assessment of collateral physiology and anatomy, although this can only be undertaken after successful passage of the sensor in the true lumen of the occluded vessel. A collateral circulation can provide resting metabolic requirements for the heart but invariably cannot meet demands on stress irrespective of the degree of collateralization as assessed by coronary angiography. In the case of myocardium subtending a totally occluded epicardial artery coronary collateral grading systems or physiological assessment of collateral flow is only moderately sensitive and poorly specific at predicting viability. Regression of collaterals seems more profound in totally occluded arteries versus nonoccluded lesions postrevascularization. CONCLUSIONS Key controversies in the assessment and pathophysiology of the collateral circulation of the heart in total coronary arterial occlusions are systematically evaluated.

The effect of carvedilol on B-type natriuretic peptide and cardiac function in patients with heart failure and persistent atrial fibrillation.

Objectives: We sought to determine the relationship between changes in natriuretic peptides and symptoms as a consequence of introducing beta-blocker therapy, in patients with chronic heart failure (CHF) and persistent atrial fibrillation (AF). Methods: In a randomised, double-blind, placebo-controlled study involving 47 patients with CHF and persistent AF (mean age 68 years and 62% men), we analysed the individual change (Δ) in B-type natriuretic peptide (BNP) level to the introduction of carvedilol (titrated to a target dose of 25 mg twice daily, group A) or placebo (group B) in addition to background treatment with digoxin. Symptoms score, 6-min walk distance, New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), heart rate (24-hour ECG) and BNP were measured at baseline and at 4 months. Results: LVEF (Δ median +5 vs. +0.4, p = 0.048), symptoms score (Δ median -4 vs. 0, p = 0.04), NYHA class (Δ median -33% vs. +3% in NYHA class 3-4, p = 0.046) and heart rate [Δ median 24-hour ventricular rate (VR) -19 vs. -2, p < 0.0001] improved with combination therapy of digoxin and carvedilol compared to digoxin alone, but BNP (Δ median +28 vs. -6 , p = 0.11) trended in the opposite direction. There was no relationship between the degree of symptomatic improvement or VR control and BNP response. Conclusion: After the introduction of carvedilol, clinical outcome appears unrelated to BNP changes in patients with CHF and AF. Changes in BNP cannot be used as a marker of clinical response in terms of symptoms or cardiac function in this setting.

The Prognostic Value of Heart Type Fatty Acid Binding Protein in Patients with Suspected Acute Coronary Syndrome: A Systematic Review.

Background: Heart type fatty acid protein (HFABP) is a cytosolic protein released early after acute coronary syndrome (ACS) even in the absence of myocardial necrosis. Objectives: The purpose of this systematic review was to determine whether HFABP levels in patients with suspected, or confirmed ACS, improve risk stratification when added to established means of risk assessment. Methods: We searched Medline, Pubmed and Embase databases from inception to July 2015 to identify prospective studies with suspected or confirmed ACS, who had HFABP measured during the index admission with at least 1 month follow up data. A prognostic event was defined as all-cause mortality or acute myocardial infarction (AMI). Results: 7 trials providing data on 6935 patients fulfilled inclusion criteria. There were considerable differences between studies and this was manifest in variation in prognostic impact of elevated HFABP(Odds ratio range 1.2-15.2 for death). All studies demonstrated that HFABP provide unadjusted prognostic information and in only one study this was negated after adjusting for covariates. A combination of both negative troponin and normal HFABP conferred a very low event rate. No study evaluated the incremental value of HFABP beyond that of standard risk scores. Only one study used a high sensitive troponin assay. Conclusion: There was marked heterogeneity in prognostic impact of HFABP in ACS between studies reflecting differences in sampling times and population risk. Prospective studies of suspected ACS with early sampling of HFABP in the era of high sensitivity troponin are necessary to determine the clinical value of HFABP. HFABP should not currently be used clinically as a prognostic marker in patients with suspected ACS.