Andrew Davie

Randomised controlled trial of specialist nurse intervention in heart failure

Abstract Objectives: To determine whether specialist nurse intervention improves outcome in patients with chronic heart failure. Design: Randomised controlled trial. Setting: Acute medical admissions unit in a teaching hospital. Participants: 165 patients admitted with heart failure due to left ventricular systolic dysfunction. The intervention started before discharge and continued thereafter with home visits for up to 1 year. Main outcome measures: Time to first event analysis of death from all causes or readmission to hospital with worsening heart failure. Results: 31 patients (37%) in the intervention group died or were readmitted with heart failure compared with 45 (53%) in the usual care group (hazard ratio=0.61, 95% confidence interval 0.33 to 0.96).Compared with usual care, patients in the intervention group had fewer readmissions for any reason (86 v 114, P=0.018), fewer admissions for heart failure (19 v 45, P<0.001) and spent fewer days in hospital for heart failure (mean 3.43 v 7.46 days, P=0.0051). Conclusions: Specially trained nurses can improve the outcome of patients admitted to hospital with heart failure. What is already known on this topic Studies have suggested that nurse intervention may reduce readmission in patients with heart failure What this study adds Home based intervention from nurses reduces readmissions for worsening heart failure Regular contact to review treatment and patient education are likely to contribute to this effect

Do patients with suspected heart failure and preserved left ventricular systolic function suffer from “diastolic heart failure” or from misdiagnosis? A prospective descriptive study

Abstract Objectives: To characterise the clinical features of patients with suspected heart failure but preserved left ventricular systolic function to determine if they have other potential causes for their symptoms rather than being diagnosed with “diastolic heart failure.” Design: Prospective descriptive study. Setting: Outpatient based direct access echocardiography service. Participants: 159 consecutive patients with suspected heart failure referred by general practitioners. Main outcome measures: Symptoms (including shortness of breath, ankle oedema, and paroxysmal nocturnal dyspnoea) and history of coronary heart disease and chronic pulmonary disease. Transthoracic echocardiography, body mass index, pulmonary function tests, and electrocardiography. Results: 109 of 159 participants had suspected heart failure in the absence of left ventricular systolic dysfunction, valvular heart disease, or atrial fibrillation. Of these 109, 40 were either obese or very obese, 54 had a reduction in forced expiratory volume in 1 second to ≤70%, and 97 had a peak expiratory flow rate ≤70% of normal. Thirty one patients had a history of angina, 12 had had a myocardial infarction, and seven had undergone a coronary artery bypass graft. Only seven patients lacked a recognised explanation for their symptoms. Conclusions: For most patients with a diagnosis of heart failure but preserved left ventricular systolic function there is an alternative explanation for their symptoms—for example, obesity, lung disease, and myocardial ischaemia—and the diagnosis of diastolic heart failure is rarely needed. These alternative diagnoses should be rigorously sought and managed accordingly.

Failure of women's hearts.

Recently, differences in the management of men and women with ischemic heart disease have been highlighted.1 Although at least as great, sex differences in heart failure have received little attention. In this article, we review the evidence that men and women with heart failure may differ with respect to epidemiology, etiology, diagnosis, prognosis, and treatment. To date, most studies of the prevalence and incidence of heart failure have identified cases on clinical grounds and, in some instances, with the aid of an ECG and chest radiograph. Thus, the precise type of heart failure (eg, left ventricular systolic dysfunction, or valvular disease) is unclear in most reports. This is important in view of the evidence that left ventricular systolic dysfunction is less common in women than in men with suspected heart failure (see the “Diagnosis” section below). ### Prevalence With these caveats in mind, the major epidemiological surveys of heart failure (see the Figure⇓)2 3 4 5 show that the overall prevalence rate of heart failure is similar in men and women. This balance, however, reflects a much lower female prevalence <70 to 75 years of age and a higher prevalence in older women than in older men. Overall, within the population, there appear to be more women than men with heart failure.6 7 8 Although age-adjusted rates for both sexes have decreased from 1988–1995, rates for women have fallen less than those for men.8B Figure 1. Sex differences in prevalence of heart failure and left ventricular systolic dysfunction in major epidemiological studies. *Based on clinical criteria; **based on echocardiography. ### Incidence Although the absolute incidence rate is lower than the prevalence rate, the effect of age on sex incidence is similar.3 Risk factors for heart failure appear to differ markedly between the sexes. ### Hypertension The risk of heart failure imparted …

The index of microcirculatory resistance measured acutely predicts the extent and severity of myocardial infarction in patients with ST-segment elevation myocardial infarction.

OBJECTIVES This study investigated the relationship between the index of microcirculatory resistance (IMR) with myocardial injury and microvascular obstruction (MVO) assessed by contrast-enhanced cardiac magnetic resonance (ceCMR) imaging in a broad range of ST-segment elevation myocardial infarction (STEMI) patients undergoing emergency percutaneous coronary intervention (PCI). BACKGROUND Contrast-enhanced cardiac magnetic resonance imaging is the gold standard for assessment of microvascular obstruction (MVO), left ventricular (LV) ejection fraction, and infarct volumes in ST-segment elevation myocardial infarction (STEMI). However, ceCMR is not available acutely. The index of microcirculatory resistance is a simple invasive measure of microvascular function available at the time of emergency PCI. We investigated the relationship between IMR with myocardial injury and MVO assessed by ceCMR in STEMI patients undergoing emergency PCI. METHODS Fifty-seven patients with STEMI were included and 53 (93%) and 47 (82%) patients had complete ceCMR scans 2 days and 3 months following MI, respectively. Microvascular obstruction was defined as a dark core of hypoenhancement within the area of hyperenhanced infarct tissue 10 to 15 min following intravenous gadolinium (0.1 mmol/kg). RESULTS The median IMR (interquartile range [IQR]) was 35 (24 to 63) U. Twenty-seven patients (46%) had MVO. We found that IMR (median [IQR]) was higher in patients with MVO (38 [29 to 55] U) than in patients without MVO (27 [18 to 36] U); p = 0.003). The index of microcirculatory resistance was a negative multivariable predictor of LV ejection fraction, (p < or = 0.001) and infarct volume (p = 0.01) on the ceCMR scan 2 days after MI, and IMR was a multivariable predictor of LV ejection fraction (p = 0.028) and infarct volume (p = 0.048) at 3 months. CONCLUSIONS The index of microcirculatory resistance measured acutely was higher in patients with MVO on ceCMR, and IMR independently predicted LV function and infarct volume. This easily measured physiological parameter provides important prognostic information at the time of emergency PCI.

Cohort study of plasma natriuretic peptides for identifying left ventricular systolic dysfunction in primary care

Abstract Objectives : To determine whether blood natriuretic peptide concentrations are helpful in identifying or excluding left ventricular systolic dysfunction in stable survivors of acute myocardial infarction. Design : Comparison of blood natriuretic peptide concentrations with echocardiographic assessment of left ventricular systolic function in a general practice population. Setting : Practices in Western District of Glasgow audit group. Subjects : 134 long term survivors of myocardial infarction recalled for echocardiography as part of a primary care secondary prevention audit. Main outcome measures : Area under the receiver operating curve for brain natriuretic peptide and N-terminal atrial natriuretic peptide. Results : Brain natriuretic peptide was of some diagnostic utility in identifying the minority of subjects with severe left ventricular dysfunction (area under curve=0.73) but was unable to discriminate between patients with moderately severe dysfunction and those with preserved left ventricular function (area under curve for moderate or severe dysfunction=0.54). The corresponding values forN-terminal atrial natriuretic peptide for severe and moderate or severe dysfunction were 0.55 and 0.56 respectively. Conclusions : Blood natriuretic peptide concentrations are not useful in identifying important left ventricular systolic dysfunction in stable survivors of myocardial infarction.

Assessment of Atrioventricular Junction Ablation and VVIR Pacemaker Versus Pharmacological Treatment in Patients With Heart Failure and Chronic Atrial Fibrillation

Background—Uncontrolled studies have suggested that atrioventricular junction ablation and pacemaker implantation have beneficial effects on quality of life in patients with chronic atrial fibrillation (AF). Methods and Results—We performed a multicenter, controlled, randomized, 12-month evaluation of the clinical effects of atrioventricular junction ablation and VVIR pacemaker (Abl+Pm) versus pharmacological (drug) treatment in 66 patients with chronic (lasting >6 months) AF who had clinically manifest heart failure and heart rate >90 bpm on 3 standard ECGs recorded at rest during stable clinical conditions on different days. Before completion of the study, withdrawals occurred in 8 patients of the drug group and in 4 patients of the Abl+Pm group. At the end of the 12 months, the 28 Abl+Pm patients who completed the study showed lower scores in palpitations (−78%; P=0.000) and effort dyspnea (−22%; P=0.05) than the 26 of the drug group. Lower scores, although not significant, were also observed for exerc...

Effect of Angiotensin-(1-7) and Bradykinin in Patients With Heart Failure Treated With an ACE Inhibitor

Angiotensin-(1-7) is a product of angiotensin processing that has been proposed to have vasodepressor effects, both on its own and in combination with bradykinin, which may be pathophysiologically and therapeutically important. Despite this, there has been very little examination of its effects in humans and none in heart failure patients or in other patients treated with ACE inhibitors. We therefore sought to determine the effects of angiotensin-(1-7) in patients with heart failure treated with an ACE inhibitor, as well as any interaction with the effects of bradykinin. A locally active dose of angiotensin-(1-7), alone and in combination with bradykinin, was infused into the nondominant brachial artery while forearm blood flow was measured by venous occlusion plethysmography in 8 patients with heart failure treated with ACE inhibitors. Although bradykinin on its own caused profound vasodilation, there was no effect of angiotensin-(1 to 7) on its own or any effect of angiotensin-(1-7) on the response to bradykinin. We conclude that angiotensin-(1-7) is biologically inactive in the forearm circulation of patients with heart failure treated with an ACE inhibitor. The contrast between these findings and previously reported preclinical findings calls into question the relevance of angiotensin-(1-7) to the hemodynamic effects of ACE inhibitors.

THE PHARMACOECONOMICS OF ACE INHIBITORS IN CHRONIC HEART FAILURE

SummaryBecause heart failure is common and disabling, patients with this condition utilise healthcare resources to a considerable extent. In particular, patients with heart failure frequently require hospital admission, and inpatient care is often protracted. Patients with the most advanced stages of heart failure make the greatest demands on the healthcare system. Expenditure related to the consumption of healthcare resources accounts for the 1 to 2% of total healthcare spending related to heart failure. Between two-thirds and three-quarters of this is due to the costs of hospital care.ACE inhibitors reduce progression of heart failure and also reduce the need for hospitalisation by approximately 30%. In so doing, these drugs substantially or totally offset their cost and the cost of extended life. Five independent economic analyses collectively show ACE inhibitors, at worst, to be very cost effective (in comparison to other cardiovascular therapies), cost neutral or to lead to overall cost savings when used to treat heart failure.

Pathophysiology of LV Remodeling in Survivors of STEMI: Inflammation, Remote Myocardium, and Prognosis

Objectives The aim of this study was to investigate the clinical significance of native T1 values in remote myocardium in survivors of acute ST-segment elevation myocardial infarction (STEMI). Background The pathophysiology and prognostic significance of remote myocardium in the natural history of STEMI is uncertain. Cardiac magnetic resonance (CMR) reveals myocardial function and pathology. Native T1 (relaxation time in ms) is a fundamental magnetic resonance tissue property determined by water content and cellularity. Results A total of 300 STEMI patients (mean age 59 years; 74% male) gave informed consent. A total of 288 STEMI patients had evaluable native T1 CMR, and 267 patients (91%) had follow-up CMR at 6 months. Health outcome information was obtained for all of the participants (median follow-up 845 days). Infarct size was 18 ± 13% of left ventricular (LV) mass. Two days post-STEMI, native T1 was lower in remote myocardium than in the infarct zone (961 ± 25 ms vs. 1,097 ± 52 ms; p < 0.01). In multivariable regression, incomplete ST-segment resolution was associated with myocardial remote zone native T1 (regression coefficient 9.42; 95% confidence interval [CI]: 2.37 to 16.47; p = 0.009), as were the log of the admission C-reactive protein concentration (3.01; 95% CI: 0.016 to 5.85; p = 0.038) and the peak monocyte count (10.20; 95% CI: 0.74 to 19.67; p = 0.035). Remote T1 at baseline was associated with log N-terminal pro–B-type natriuretic peptide at 6 months (0.01; 95% CI: 0.00 to 0.02; p = 0.002; n = 151) and the change in LV end-diastolic volume from baseline to 6 months (0.13; 95% CI: 0.01 to 0.24; p = 0.035). Remote zone native T1 was independently associated with post-discharge major adverse cardiac events (n = 20 events; hazard ratio: 1.016; 95% CI: 1.000 to 1.032; p = 0.048) and all-cause death or heart failure hospitalization (n = 30 events during admission and post-discharge; hazard ratio: 1.014; 95% CI: 1.000 to 1.028; p = 0.049). Conclusions Reperfusion injury and inflammation early post-MI was associated with remote zone T1, which in turn was independently associated with LV remodeling and adverse cardiac events post-STEMI. (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction [BHF MR-MI]; NCT02072850)

Role of Bradykinin in the Vasodilator Effects of Losartan and Enalapril in Patients With Heart Failure

BACKGROUND ACE inhibitors have been shown to potentiate the effects of exogenous bradykinin by inhibition of its breakdown. Despite this, there is little evidence that inhibition of endogenous bradykinin breakdown actually contributes to the effects of ACE inhibitors, or indeed, other inhibitors of the renin-angiotensin system, such as angiotensin II type I receptor (AT(1)) antagonists, and no evidence at all that it does so in patients with heart failure. METHODS AND RESULTS Twelve patients with heart failure (11 male, 1 female, ages 59 to 81 years) were randomized to double-blind crossover treatment with enalapril 10 mg BID followed by losartan 25 mg BID, or the reverse, each for 5 weeks. At the end of each treatment period, forearm blood flow was measured by venous occlusion plethysmography during an intrabrachial infusion of bradykinin before and after an intrabrachial infusion of Hoe-140 (a potent, selective, and long-acting bradykinin antagonist). Bradykinin caused profound vasodilatation after enalapril (peak, 357+/-67%) and less after losartan (peak, 230+/-46%). Despite this, Hoe-140 had no discernible effects after enalapril or losartan. Similarly, this was despite the finding that Hoe-140 significantly reduced vasodilatation to bradykinin after enalapril (peak, 192+/-35%) and losartan (peak, 66+/-13%). CONCLUSIONS Inhibition of endogenous bradykinin breakdown does not appear to contribute to the effects of ACE inhibition or AT(1) antagonism in the forearm of patients with heart failure at rest, despite the very obvious effects of ACE inhibition compared with AT(1) antagonism on exogenous bradykinin.