Michael R. MacDonald

Treatment of Type 2 Diabetes and Outcomes in Patients With Heart Failure: A Nested Case–Control Study From the U.K. General Practice Research Database

OBJECTIVE Diabetes and heart failure commonly coexist, and prior studies have suggested better outcomes with metformin than other antidiabetic agents. We designed this study to determine whether this association reflects a beneficial effect of metformin or a harmful effect of other agents. RESEARCH DESIGN AND METHODS We performed a case-control study nested within the U.K. General Practice Research Database cohort in which diagnoses were assigned by each patients primary care physician. Case subjects were patients 35 years or older, newly diagnosed with both heart failure and diabetes after January 1988, and who died prior to October 2007. Control subjects were matched to case subjects based on age, sex, clinic site, calendar year, and duration of follow-up. Analyses were adjusted for comorbidities, A1C, renal function, and BMI. RESULTS The duration of concurrent diabetes and heart failure was 2.8 years (SD 2.6) in our 1,633 case subjects and 1,633 control subjects (mean age 78 years, 53% male). Compared with patients who were not exposed to antidiabetic drugs, the current use of metformin monotherapy (adjusted odds ratio 0.65 [0.48–0.87]) or metformin with or without other agents (0.72 [0.59–0.90]) was associated with lower mortality; however, use of other antidiabetic drugs or insulin was not associated with all-cause mortality. Conversely, the use of ACE inhibitors/angiotensin receptor blockers (0.55 [0.45–0.68]) and β-blockers (0.76 [0.61–0.95]) were associated with reduced mortality. CONCLUSIONS Our results confirm the benefits of trial-proven anti-failure therapies in patients with diabetes and support the use of metformin-based strategies to lower glucose.

Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure - An analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme

AIMS To determine whether the risk of adverse cardiovascular (CV) outcomes associated with diabetes differs in patients with low and preserved ejection fraction (EF) heart failure (HF). METHODS AND RESULTS We analysed outcomes in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) programme which randomized 7599 patients with symptomatic HF and a broad range of EF. The prevalence of diabetes was 28.3% in patients with preserved EF (>40%) and 28.5% in those with low EF (<or=40%). Diabetes was associated with a greater relative risk of CV death or HF hospitalization in patients with preserved EF [hazard ratio (HR) 2.0 (1.70-2.36)] than in patients with low EF [HR 1.60 (1.44-1.77); interaction test P = 0.0009]. For all-cause mortality, the risk conferred by diabetes was similar in both low and preserved EF groups. The effect of candesartan in reducing CV morbidity and mortality outcomes was not modified by having diabetes at baseline (P = 0.09 test for interaction). CONCLUSION Diabetes was an independent predictor of CV morbidity and mortality in patients with HF, regardless of EF. The relative risk of CV death or HF hospitalization conferred by diabetes was significantly greater in patients with preserved when compared with those with low EF HF.

Diabetes, left ventricular systolic dysfunction and chronic heart failure

Chronic heart failure (HF) and diabetes mellitus (DM) commonly coexist. Each condition increases the likelihood of developing the other, and when they occur together in the same patient the risk of morbidity and mortality increases markedly. We discuss the epidemiological overlap and consider the complex patho-physiological pathways linking the two diseases. The treatment of each condition is made more problematic by the presence of the other. We review the evidence-based treatment strategies and discuss the common problems faced by physicians when treating patients with both conditions. This article forms a comprehensive overview of a fascinating intersection between two common diseases.

Radiofrequency ablation for persistent atrial fibrillation in patients with advanced heart failure and severe left ventricular systolic dysfunction: a randomised controlled trial

Objective To determine whether or not radiofrequency ablation (RFA) for persistent atrial fibrillation in patients with advanced heart failure leads to improvements in cardiac function. Setting Patients were recruited from heart failure outpatient clinics in Scotland. Design and intervention Patients with advanced heart failure and severe left ventricular dysfunction were randomised to RFA (rhythm control) or continued medical treatment (rate control). Patients were followed up for a minimum of 6 months. Main outcome measure Change in left ventricular ejection fraction (LVEF) measured by cardiovascular MRI. Results 22 patients were randomised to RFA and 19 to medical treatment. In the RFA group, 50% of patients were in sinus rhythm at the end of the study (compared with none in the medical treatment group). The increase in cardiovascular magnetic resonance (CMR) LVEF in the RFA group was 4.5±11.1% compared with 2.8±6.7% in the medical treatment group (p=0.6). The RFA group had a greater increase in radionuclide LVEF (a prespecified secondary end point) than patients in the medical treatment group (+8.2±12.0% vs +1.4±5.9%; p=0.032). RFA did not improve N-terminal pro-B-type natriuretic peptide, 6 min walk distance or quality of life. The rate of serious complications related to RFA was 15%. Conclusions RFA resulted in long-term restoration of sinus rhythm in only 50% of patients. RFA did not improve CMR LVEF compared with a strategy of rate control. RFA did improve radionuclide LVEF but did not improve other secondary outcomes and was associated with a significant rate of serious complications. Clinical trials registration number NCT00292162.

Primary care burden and treatment of patients with heart failure and chronic obstructive pulmonary disease in Scotland

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) frequently coexist and present major challenges to healthcare providers. The epidemiology, consultation rate, and treatment of patients with HF and COPD in primary care are ill‐defined.

Intensive glycemic control has no impact on the risk of heart failure in type 2 diabetic patients: Evidence from a 37,229 patient meta-analysis

BACKGROUND More intensive glycemic control reduces the risk of microvascular disease in patients with diabetes mellitus but has not been proven to reduce the risk of macrovascular events such as myocardial infarction and stroke. Poorer glycemic control, as indicated by glycated hemoglobin level concentration, is associated with an increased risk of heart failure (HF), but it is not known whether improved glycemic control reduces this risk. We conducted a meta-analysis of randomized controlled trials comparing strategies of more versus less intensive glucose-lowering that reported HF events. METHODS Two investigators independently searched PubMed, the Cochrane CENTRAL register of controlled trials, metaRegister, pre-MEDLINE, and CINAHL from January 1970 to October 2010 for prospective controlled randomized trials comparing a more intensive glucose-lowering regimen to a standard regimen. The outcome of interest was HF-related events (both fatal and nonfatal). Odds ratios (ORs) were calculated from published data from relevant trials and pooled with a random-effects meta-analysis. RESULTS A total of 37,229 patients from 8 randomized trials were included in the analysis. Follow-up ranged from 2.3 to 10.1 years, and the overall number of HF-related events was 1469 (55% in the intensive treatment arm). The mean difference in glycated hemoglobin level between patients given standard treatment and those allocated to a more intensive regimen was 0.9%. Overall, the risk of HF-related events did not differ significantly between intensive glycemic control and standard treatment (OR 1.20, 95% CI 0.96-1.48), but the effect estimate was highly heterogeneous (I(2) = 69%). At subgroup analysis, intensive glycemic control achieved with high thiazolidinediones use significantly increased HF risk (OR 1.33, 95% CI 1.02-1.72). CONCLUSIONS More intensive glycemic control in patients with type 2 diabetes mellitus did not reduce the occurrence of HF events. Furthermore, intensive glycemic control with thiazolidinediones increased the risk of HF. These findings question a direct mechanistic link between hyperglycemia and HF.

Bisoprolol in patients with heart failure and moderate to severe chronic obstructive pulmonary disease: a randomized controlled trial

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) frequently coexist. No study has prospectively examined the effects of beta‐blockade in those with both conditions.

Clinical characteristics and outcomes of young and very young adults with heart failure: The CHARM programme (Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity).

OBJECTIVES This study sought to determine the characteristics and outcomes of young adults with heart failure (HF). BACKGROUND Few studies have focused on young and very young adults with HF. METHODS Patients were categorized into 5 age groups: 20 to 39, 40 to 49, 50 to 59, 60 to 69, and ≥70 years. RESULTS The youngest patients with HF were more likely to be obese (youngest vs. oldest: body mass index ≥35 kg/m(2): 23% vs. 6%), of black ethnicity (18% vs. 2%), and have idiopathic-dilated cardiomyopathy (62% vs. 9%) (all p < 0.0001). They were less likely to adhere to medication (nonadherence in youngest vs. oldest: 24% vs. 7%, p = 0.001), salt intake, and other dietary measures (21% vs. 9%, p = 0.002). The youngest patients were less likely to have clinical and radiological signs of HF during hospitalization. Quality of life was worse, but all-cause mortality was lowest in the youngest age group (3-year mortality rates across the respective age categories: 12%, 13%, 13%, 19%, and 31%, respectively). Compared with the referent age group of 60 to 69 years, both all-cause and cardiovascular mortality were lower in the youngest group even after multivariable adjustment (hazard ratio: 0.60, 95% confidence interval: 0.36 to 1.00; p = 0.049, and hazard ratio: 0.71, 95% confidence interval: 0.42 to 1.18, p = 0.186, respectively). Three-year HF hospitalization rates were 24%, 15%, 15%, 22%, and 28% in ages 20 to 39, 40 to 49, 50 to 59, 60 to 69, and ≥70 years, respectively (p < 0.0001). CONCLUSIONS Beyond divergent etiology and comorbidities, younger patients exhibited striking differences in presentation and outcomes compared with older counterparts. Clinical and radiological signs of HF were less common, yet quality of life was more significantly impaired. Fatal and nonfatal outcomes were discordant, with better survival despite higher hospitalization rates.

Clinical characteristics and outcomes of young and very young adults with heart failure: the CHARM programme

OBJECTIVES This study sought to determine the characteristics and outcomes of young adults with heart failure (HF). BACKGROUND Few studies have focused on young and very young adults with HF. METHODS Patients were categorized into 5 age groups: 20 to 39, 40 to 49, 50 to 59, 60 to 69, and ≥70 years. RESULTS The youngest patients with HF were more likely to be obese (youngest vs. oldest: body mass index ≥35 kg/m(2): 23% vs. 6%), of black ethnicity (18% vs. 2%), and have idiopathic-dilated cardiomyopathy (62% vs. 9%) (all p < 0.0001). They were less likely to adhere to medication (nonadherence in youngest vs. oldest: 24% vs. 7%, p = 0.001), salt intake, and other dietary measures (21% vs. 9%, p = 0.002). The youngest patients were less likely to have clinical and radiological signs of HF during hospitalization. Quality of life was worse, but all-cause mortality was lowest in the youngest age group (3-year mortality rates across the respective age categories: 12%, 13%, 13%, 19%, and 31%, respectively). Compared with the referent age group of 60 to 69 years, both all-cause and cardiovascular mortality were lower in the youngest group even after multivariable adjustment (hazard ratio: 0.60, 95% confidence interval: 0.36 to 1.00; p = 0.049, and hazard ratio: 0.71, 95% confidence interval: 0.42 to 1.18, p = 0.186, respectively). Three-year HF hospitalization rates were 24%, 15%, 15%, 22%, and 28% in ages 20 to 39, 40 to 49, 50 to 59, 60 to 69, and ≥70 years, respectively (p < 0.0001). CONCLUSIONS Beyond divergent etiology and comorbidities, younger patients exhibited striking differences in presentation and outcomes compared with older counterparts. Clinical and radiological signs of HF were less common, yet quality of life was more significantly impaired. Fatal and nonfatal outcomes were discordant, with better survival despite higher hospitalization rates.

Discordant Short- and Long-Term Outcomes Associated With Diabetes in Patients With Heart Failure: Importance of Age and Sex A Population Study of 5.1 Million People in Scotland

Background—Diabetes and heart failure frequently coexist. Our aim was to assess the association between diabetes and short- and long-term outcomes in all patients admitted to the hospital for the first time with heart failure in Scotland between 1986 and 2003. Methods and Results—A total of 116 556 patients were studied, of whom 13% (n=15 161) had a diagnosis of diabetes. At 30 days, diabetes was associated with a lower case fatality. By 1 year, the association between diabetes and better outcome was reversed, and diabetes was a significant independent predictor of higher case fatality. The longer term risk of death associated with diabetes was greatest in younger patients. In patients aged 65 years or younger, the hazard ratio for mortality at 5 years associated with diabetes was 1.41 (95% CI, 1.31 to 1.52) for men and 1.64 (1.50 to 1.79) for women. The risk associated with diabetes was less in patients aged 75 years or older: a hazard ratio in men 1.16 (1.10 to 1.22) and in women 1.15 (1.10 to 1.20). In the younger age group the risk associated with diabetes was significantly greater in women than in men (P=0.005 for diabetes-sex interaction). Diabetes was also a significant independent predictor of heart failure readmission, and again the risk was greatest in younger women. Conclusions—Although diabetes was associated with a lower case fatality at 30 days, by 1 year it was a significant independent predictor of higher case fatality. The risk associated with diabetes was greatest in young patients, and in young patients the risk was greatest in women.