Declining risk of sudden death in heart failure

No abstract available

Population prevalence, incidence, and predictors of atrial fibrillation in the Renfrew/Paisley study

<b>OBJECTIVES</b> Though atrial fibrillation (AF) is an important cause of cardiovascular morbidity, there are few large epidemiological studies of its prevalence, incidence, and risk factors. The epidemiological features of AF are described in one of the largest population cohorts ever studied. <b>METHODS</b> The prevalence and incidence of AF were studied in the Renfrew/Paisley population cohort of 15 406 men and women aged 45-64 years living in the west of Scotland. This cohort was initially screened between 1972 and 1976 and again between 1977 and 1979. Incident hospitalisations with AF in the 20 year period following initial screening were also studied. <b>RESULTS</b> The population prevalence of AF in this cohort was 6.5 cases/1000 examinations. Prevalence was higher in men and older subjects. In those who were rescreened, the four year incidence of AF was 0.54 cases/1000 person years. Radiological cardiomegaly was the most powerful predictor of new AF (adjusted odds ratio 14.0). During 20 year follow up, 3.5% of this cohort was discharged from hospital with a diagnosis of AF; the rate of incident hospitalisation for AF was 1.9 cases/1000 person years. Radiological cardiomegaly (adjusted odds ratio 1.46) and systolic blood pressure (adjusted odds ratio 2.1 for ≥ 169 mm Hg) were independent predictors of this outcome. <b>CONCLUSIONS</b> Data from one of the largest epidemiological studies ever undertaken confirm that AF has a large population prevalence and incidence, even in middle aged people. More important, it was shown that the long term incidence of hospitalisation related to AF is high and that two simple clinical measurements are highly predictive of incident AF. These findings have important implications for the prevention of AF

Dementia-related adverse events in PARADIGM-HF and other trials in heart failure with reduced ejection fraction.

Aims: Inhibition of neprilysin, an enzyme degrading natriuretic and other vasoactive peptides, is beneficial in heart failure with reduced ejection fraction (HFrEF), as shown in PARADIGM-HF which compared the angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan with enalapril. As neprilysin is also one of many enzymes clearing amyloid-β peptides from the brain, there is a theoretical concern about the long-term effects of sacubitril/valsartan on cognition. Therefore, we have examined dementia-related adverse effects (AEs) in PARADIGM-HF and placed these findings in the context of other recently conducted HFrEF trials. Methods and results: In PARADIGM-HF, patients with symptomatic HFrEF were randomized to sacubitril/valsartan 97/103 mg b.i.d. or enalapril 10 mg b.i.d. in a 1:1 ratio. We systematically searched AE reports, coded using the Medical Dictionary for Regulatory Activities (MedDRA), using Standardized MedDRA Queries (SMQs) with ‘broad’ and ‘narrow’ preferred terms related to dementia. In PARADIGM-HF, 8399 patients aged 18–96 years were randomized and followed for a median of 2.25 years (up to 4.3 years). The narrow SMQ search identified 27 dementia-related AEs: 15 (0.36%) on enalapril and 12 (0.29%) on sacubitril/valsartan [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.33–1.59]. The broad search identified 97 (2.30%) and 104 (2.48%) AEs (HR 1.01, 95% CI 0.75–1.37), respectively. The rates of dementia-related AEs in both treatment groups in PARADIGM-HF were similar to those in three other recent trials in HFrEF. Conclusion: We found no evidence that sacubitril/valsartan, compared with enalapril, increased dementia-related AEs, although longer follow-up may be necessary to detect such a signal and more sensitive tools are needed to detect lesser degrees of cognitive impairment. Further studies to address this question are warranted

A qualitative study of the contribution of pharmacists to heart failure management in Scotland

Study objectives: (1) To identify the medication management needs of chronic heart failure (CHF) patients and their caregivers; (2) To examine the perceived support for medication management available to these people from health professionals; (3) To identify the actual and potential perceived contribution of pharmacists to medication management. Setting: A mixed urban/ rural region in the west of Scotland. Design: Semi-structured qualitative research interviews. Participants: A total of 50 people with CHF (NYHA Class II and III) due to left ventricular systolic dysfunction (33 males; mean age 67 years, 17 females; mean age 68 years) and 30 nominated caregivers recruited from the outpatient departments of two hospitals in the West of Scotland. Sampling was purposive to include patients from a range of CHF severity, ages and sexes. Main results: Managing medications was a responsibility shared by both the patients with CHF and caregivers. Treatment regimens were reported to be difficult to comply with. Health professionals were seen to provide little support for medication management. Pharmacists were viewed as being a good and accessible source of practical assistance who were also knowledgeable about the individual’s heart health history. Participants reported valuing advice from pharmacists about the side effects of medications and for their assistance in reducing the complex logistics of medication management and in having medications delivered. Conclusions: Patients with CHF and caregivers voiced a willingness to try to manage their medication regimen accurately but had a limited capacity to do so. Pharmacists were viewed as providing valuable support to patients with CHF and their caregivers, in terms of medication management. The extended role of pharmacists in medication management of CHF should be encouraged

Non-ischaemic cardiomyopathy, sudden death and implantable defibrillators: a review and meta-analysis

Objective: The recent Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) trial suggested that implantable cardioverter defibrillators (ICDs) do not reduce overall mortality in patients with non-ischaemic cardiomyopathy (NICM), despite reducing sudden cardiac death. We performed an updated meta-analysis to examine the impact of ICD therapy on mortality in NICM patients. Methods: A systematic search for studies that examined the effect of ICDs on outcomes in NICM was performed. Our analysis compared patients randomised to an ICD with those randomised to no ICD, and examined the endpoint of overall mortality. Results: Six primary prevention trials and two secondary prevention trials were identified that met the pre-specified search criteria. Using a fixed-effects model, analysis of primary prevention trials revealed a reduction in overall mortality with ICD therapy (RR 0.76, 95% CI 0.65 to 0.91). Conclusions: Although our updated meta-analysis demonstrates a survival benefit of ICD therapy, the effect is substantively weakened by the inclusion of the DANISH trial—which is both the largest and most recent of the analysed trials—indicating that the residual pooled benefit of ICDs may reflect the risk of sudden death in older trials which included patients treated sub-optimally by contemporary standards. As such, these data must be interpreted cautiously. The results of the DANISH trial emphasise that there is no ‘one size fits all’ indication for primary prevention ICDs in NICM patients, and clinicians must consider age and comorbidity on an individual basis when determining whether a defibrillator is appropriate

Relation between socioeconomic deprivation and death from a first myocardial infarction in Scotland: population based analysis

No abstract available

Short-term and long-term outcomes in 133 429 emergency patients admitted with angina or myocardial infarction in Scotland, 1990-2000: population-based cohort study

Objective: To analyse short- and long-term outcomes and prognostic factors in a large population-based cohort of unselected patients with a first emergency admission for suspected acute coronary syndrome between 1990 and 2000 in Scotland. Methods: All first emergency admissions for acute myocardial infarction (AMI) and all first emergency admissions for angina (the proxy for unstable angina) between 1990 and 2000 in Scotland (population 5.1 million) were identified. Survival to five years was examined by Cox multivariate modelling to examine the independent prognostic effects of diagnosis, age, sex, year of admission, socioeconomic deprivation and co-morbidity. Results: In Scotland between 1990 and 2000, 133 429 individual patients had a first emergency admission for suspected acute coronary syndrome: 96 026 with AMI and 37 403 with angina. After exclusion of deaths within 30 days, crude five-year case fatality was similarly poor for patients with angina and those with AMI (23.9% v 21.6% in men and 23.5% v 26.0% in women). The longer-term risk of a subsequent fatal or non-fatal event in the five years after first hospital admission was high: 54% in men after AMI (53% in women) and 56% after angina (49% in women). Event rates increased threefold with increasing age and 20–60% with different co-morbidities, but were 11–34% lower in women. Conclusions: Longer-term case fatality was similarly high in patients with angina and in survivors of AMI, about 5% a year. Furthermore, half the patients experienced a fatal or non-fatal event within five years. These data may strengthen the case for aggressive secondary prevention in all patients presenting with acute coronary syndrome

Association is not causation: treatment effects cannot be estimated from observational data in heart failure

Aims: Treatment ‘effects’ are often inferred from non-randomized and observational studies. These studies have inherent biases and limitations, which may make therapeutic inferences based on their results unreliable. We compared the conflicting findings of these studies to those of prospective randomized controlled trials (RCTs) in relation to pharmacological treatments for heart failure (HF). Methods and results: We searched Medline and Embase to identify studies of the association between non-randomized drug therapy and all-cause mortality in patients with HF until 31 December 2017. The treatments of interest were: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, mineralocorticoid receptor antagonists (MRAs), statins, and digoxin. We compared the findings of these observational studies with those of relevant RCTs. We identified 92 publications, reporting 94 non-randomized studies, describing 158 estimates of the ‘effect’ of the six treatments of interest on all-cause mortality, i.e. some studies examined more than one treatment and/or HF phenotype. These six treatments had been tested in 25 RCTs. For example, two pivotal RCTs showed that MRAs reduced mortality in patients with HF with reduced ejection fraction. However, only one of 12 non-randomized studies found that MRAs were of benefit, with 10 finding a neutral effect, and one a harmful effect. Conclusion: This comprehensive comparison of studies of non-randomized data with the findings of RCTs in HF shows that it is not possible to make reliable therapeutic inferences from observational associations. While trials undoubtedly leave gaps in evidence and enrol selected participants, they clearly remain the best guide to the treatment of patients

How small is too small? A systematic review of center volume and outcome after cardiac transplantation

Background—The aim of this study was to assess the relationship between the volume of cardiac transplantation procedures performed in a center and the outcome after cardiac transplantation. Methods and Results—PubMed, Embase, and the Cochrane library were searched for articles on the volume–outcome relationship in cardiac transplantation. Ten studies were identified, and all adopted a different approach to data analysis and varied in adjustment for baseline characteristics. The number of patients in each study ranged from 798 to 14401, and observed 1-year mortality ranged from 12.6% to 34%. There was no association between the continuous variables of center volume and observed mortality. There was a weak association between the continuous variables of center volume and adjusted mortality up to 1 year and a stronger association at 5 years. When centers were grouped in volume categories, low-volume centers had the highest adjusted mortality, intermediate-volume centers had lower adjusted mortality, and high-volume centers had the lowest adjusted mortality but were not significantly better than intermediate-volume centers. Category limits were arbitrary and varied between studies. Conclusions—There is a relationship between center volume and mortality in heart transplantation. The existence of a minimum acceptable center volume or threshold is unproven. However, a level of 10 to 12 heart transplants per year corresponds to the upper limit of low-volume categories that may have relatively higher mortality. It is not known whether outcomes for patients treated in low-volume transplant centers would be improved by reorganizing centers to ensure volumes in excess of 10 to 12 heart transplants per year

National survey of the prevalence, incidence, primary care burden, and treatment of heart failure in Scotland

Objective: To examine the epidemiology, primary care burden, and treatment of heart failure in Scotland, UK. Design: Cross sectional data from primary care practices participating in the Scottish continuous morbidity recording scheme between 1 April 1999 and 31 March 2000. Setting: 53 primary care practices (307 741 patients). Subjects: 2186 adult patients with heart failure. Results: The prevalence of heart failure in Scotland was 7.1 in 1000, increasing with age to 90.1 in 1000 among patients 85 years. The incidence of heart failure was 2.0 in 1000, increasing with age to 22.4 in 1000 among patients 85 years. For older patients, consultation rates for heart failure equalled or exceeded those for angina and hypertension. Respiratory tract infection was the most common co-morbidity leading to consultation. Among men, 23% were prescribed a ß blocker, 11% spironolactone, and 46% an angiotensin converting enzyme inhibitor. The corresponding figures for women were 20% (p = 0.29 versus men), 7% (p = 0.02), and 34% (p < 0.001). Among patients < 75 years 26% were prescribed a β blocker, 11% spironolactone, and 50% an angiotensin converting enzyme inhibitor. The corresponding figures for patients 75 years were 19% (p = 0.04 versus patients < 75), 7% (p = 0.04), and 33% (p < 0.001). Conclusions: Heart failure is a common condition, especially with advancing age. In the elderly, the community burden of heart failure is at least as great as that of angina or hypertension. The high rate of concomitant respiratory tract infection emphasises the need for strategies to immunise patients with heart failure against influenza and pneumococcal infection. Drugs proven to improve survival in heart failure are used less frequently for elderly patients and women