The benefit of an implantable cardioverter-defibrillator (ICD) in patients with symptomatic systolic heart failure caused by coronary artery disease has been well documented. However, the evidence ...for a benefit of prophylactic ICDs in patients with systolic heart failure that is not due to coronary artery disease has been based primarily on subgroup analyses. The management of heart failure has improved since the landmark ICD trials, and many patients now receive cardiac resynchronization therapy (CRT).
In a randomized, controlled trial, 556 patients with symptomatic systolic heart failure (left ventricular ejection fraction, ≤35%) not caused by coronary artery disease were assigned to receive an ICD, and 560 patients were assigned to receive usual clinical care (control group). In both groups, 58% of the patients received CRT. The primary outcome of the trial was death from any cause. The secondary outcomes were sudden cardiac death and cardiovascular death.
After a median follow-up period of 67.6 months, the primary outcome had occurred in 120 patients (21.6%) in the ICD group and in 131 patients (23.4%) in the control group (hazard ratio, 0.87; 95% confidence interval CI, 0.68 to 1.12; P=0.28). Sudden cardiac death occurred in 24 patients (4.3%) in the ICD group and in 46 patients (8.2%) in the control group (hazard ratio, 0.50; 95% CI, 0.31 to 0.82; P=0.005). Device infection occurred in 27 patients (4.9%) in the ICD group and in 20 patients (3.6%) in the control group (P=0.29).
In this trial, prophylactic ICD implantation in patients with symptomatic systolic heart failure not caused by coronary artery disease was not associated with a significantly lower long-term rate of death from any cause than was usual clinical care. (Funded by Medtronic and others; DANISH ClinicalTrials.gov number, NCT00542945 .).
Background. There are concerns about highly active antiretroviral therapy (HAART) causing a progressive increase in the risk of ischemic heart disease. We examined this issue in a nationwide cohort ...study of patients with human immunodeficiency virus (HIV) infection and a population-based control group. Methods. We determined the rate of first hospitalization for ischemic heart disease in all Danish patients with HIV infection (3953 patients) from 1 January 1995 through 31 December 2004 and compared this rate with that for 373,856 subjects in a population-based control group. Data on first hospitalization for ischemic heart disease and comorbidity were obtained from the Danish National Hospital Registry for all study participants. We used Cox's regression to compute the hospitalization rate ratio as an estimate of relative risk, adjusting for comorbidity. Results. Although the difference was not statistically significant, patients with HIV infection who had not initiated HAART were slightly more likely to be hospitalized for the first time with ischemic heart disease than were control subjects (adjusted relative risk, 1.39; 95% confidence interval, 0.81–2.33). After HAART initiation, the risk increase became substantially higher (adjusted relative risk, 2.12; 95% confidence interval, 1.62–2.76), but the relative risk did not further increase in the initial 8 years of HAART. Conclusions. Compared with the general population, HIV-infected patients receiving HAART have an increased risk of ischemic heart disease, but the relative risk is stable up to 8 years after treatment initiation.
Aims
With improvement in survival of chronic heart failure (HF), the clinical importance of co‐morbidity is increasing. The aim of this study was to assess the incidence and risk of cancer and ...all‐cause mortality in a large Danish HF cohort.
Methods and results
A total of 9307 outpatients with verified HF without a prior diagnosis of cancer (27% female, mean age 68 years, 89% with LVEF <45%) were included in the study. A diagnosis of any cancer and all‐cause mortality was obtained from Danish national registries. Outcome was compared with the general Danish population. Overall and type‐specific risk of cancer was analysed in an adjusted Poisson and Cox regression analysis. The 975 diagnoses of cancer in the HF cohort and 330 843 in the background population corresponded to incidence rates per 10 000 patient‐years of 188.9 95% confidence interval (CI) 177.2–200.6 and 63.0 (95% CI 63.0–63.4), respectively. When stratified by age, incidence rates were increased in all age groups in the HF cohort. Risk of any type of cancer was increased, with an incidence rate ratio of 1.24 (95% CI 1.15–1.33, c < 0.0001). Type‐specific analysis demonstrated an increased hazard ratio for all major types of cancer except for prostate cancer. All‐cause mortality was higher in HF patients with cancer compared with cancer patients from the background population.
Conclusions
Patients with HF have an increased risk of cancer, which persists after the first year after the diagnosis of HF, and their prognosis is worse compared with that of cancer patients without HF.
The level of the inactive N-terminal fragment of pro-brain (B-type) natriuretic peptide (BNP) is a strong predictor of mortality among patients with acute coronary syndromes and may be a strong ...prognostic marker in patients with chronic coronary heart disease as well. We assessed the relationship between N-terminal pro-BNP (NT-pro-BNP) levels and long-term mortality from all causes in a large cohort of patients with stable coronary heart disease.
NT-pro-BNP was measured in baseline serum samples from 1034 patients referred for angiography because of symptoms or signs of coronary heart disease. The rate of death from all causes was determined after a median follow-up of nine years.
At follow-up, 288 patients had died. The median NT-pro-BNP level was significantly lower among patients who survived than among those who died (120 pg per milliliter interquartile range, 50 to 318 vs. 386 pg per milliliter interquartile range, 146 to 897, P<0.001). Patients with NT-pro-BNP levels in the highest quartile were older, had a lower left ventricular ejection fraction (LVEF) and a lower creatinine clearance rate, and were more likely to have a history of myocardial infarction, clinically significant coronary artery disease, and diabetes than patients with NT-pro-BNP levels in the lowest quartile. In a multivariable Cox regression model, the hazard ratio for death from any cause for the patients with NT-pro-BNP levels in the fourth quartile as compared with those in the first quartile was 2.4 (95 percent confidence interval, 1.5 to 4.0; P<0.001); the NT-pro-BNP level added prognostic information beyond that provided by conventional risk factors, including the patient's age; sex; family history with respect to ischemic heart disease; the presence or absence of a history of myocardial infarction, angina, hypertension, diabetes, or chronic heart failure; creatinine clearance rate; body-mass index; smoking status; plasma lipid levels; LVEF; and the presence or absence of clinically significant coronary artery disease on angiography.
NT-pro-BNP is a marker of long-term mortality in patients with stable coronary disease and provides prognostic information above and beyond that provided by conventional cardiovascular risk factors and the degree of left ventricular systolic dysfunction.
Outpatient follow-up in specialized heart failure clinics (HFCs) is recommended by current guidelines and implemented in most European countries, but the optimal duration of HFC programmes has not ...been established. Nor is it known whether all or only high-risk patients, e.g. identified by NT-proBNP, might benefit from an extended HFC follow-up.
In a multi-centre setting, we randomly assigned 921 clinically stable systolic heart failure (HF) outpatients on optimal medical therapy to undergo either an extended follow-up in the HFC (n = 461) or referral back to their general practitioner (GP) (n = 460). The primary composite endpoint was death or a cardiovascular admission. Secondary endpoints included mortality, an HF admission, quality of life, number of days admitted, and number of admissions. The median age of the patients was 69 years; 23% were females; the median left ventricular ejection fraction was 0.30; and the median NT-proBNP was 801 pg/mL; 89% were in NYHA class I-II. The median follow-up was 2.5 years. Time-to-event did not differ between groups (HFC vs. GP) (HR: 1.17, 95% CI: 0.95-1.45, P = 0.149). The two groups did not differ with respect to any of the secondary endpoints at the follow-up (P> 0.05 for all). In high-risk patients identified by NT-proBNP ≥1000 pg/mL, no benefit from HFC follow-up was found (P = 0.721).
Irrespective of the level of NT-proBNP stable HF patients on optimal medical therapy do not benefit from long-term follow-up in a specialized HFC in a publicly funded universal access healthcare system. Heart failure patients on optimal medical therapy with mild or moderate symptoms are safely managed by their personal GP.
www.Centerwatch.com: 173491 (NorthStar).
A Randomized, Placebo-Controlled Trial Assessing the Effects of Rosiglitazone on Echocardiographic Function and Cardiac Status in Type 2 Diabetic Patients With New York Heart Association Functional ...Class I or II Heart Failure Henry J. Dargie, Per R. Hildebrandt, Günter A. J. Riegger, John J. V. McMurray, Stephen O. McMorn, Jeremy N. Roberts, Andrew Zambanini, John P. H. Wilding Thiazolidinedione-associated fluid retention may contribute to symptoms of congestive heart failure in patients with type 2 diabetes. We compared the effect of rosiglitazone with placebo on cardiac function in type 2 diabetes patients with New York Heart Association functional class I to II congestive heart failure. Rosiglitazone treatment did not adversely affect left ventricular ejection fraction compared with placebo (mean difference 1.49%, p = 0.1), but it was associated with a significant improvement in glycemic control (mean difference hemoglobin A1c –0.65%, p < 0.0001). There was a higher incidence of fluid-related events with rosiglitazone, but the majority did not lead to withdrawal from the study.
Whether continued follow-up in specialized heart failure (HF) clinics after optimization of guideline-directed therapy improves long-term outcomes in patients with HF with reduced ejection fraction ...(HFrEF) is unknown.
921 medically optimized HFrEF patients enrolled in the NorthStar study were randomly assigned to follow up in a specialized HF clinic or primary care and followed for 10 years using Danish nationwide registries. The primary outcome was a composite of HF hospitalization or cardiovascular death. We further assessed the 5-year adherence to prescribed neurohormonal blockade in 5-year survivors. At enrollment, the median age was 69 years, 24,7% were females, and the median NT-proBNP was 1139 pg/ml. During a median follow-up time of 4.1 (Q1-Q3 1.5-10.0) years, the primary outcome occurred in 321 patients (69.8%) randomized to follow-up in specialized HF clinics and 325 patients (70.5%) randomized to follow-up in primary care. The rate of the primary outcome, its individual components, and all-cause death did not differ between groups (primary outcome, hazard ratio 0.96 95% CI, 0.82-1.12; cardiovascular death, 1.00 0.81-1.24; HF hospitalization, 0.97 0.82-1.14; all-cause death, 1.00 0.83-1.20). In 5-year survivors (N = 660), the 5-year adherence did not differ between groups for angiotensin-converting enzyme inhibitors (p = 0.78), beta-blockers (p = 0.74), or mineralocorticoid receptor antagonists (p = 0.47).
HFrEF patients on optimal medical therapy did not benefit from continued follow-up in a specialized HF clinic after initial optimization. Development and implementation of new monitoring strategies are needed.
Aims
The optimal duration of a public heart failure (HF) clinic programme is unknown. This substudy of the NT‐proBNP stratified follow‐up in outpatient heart failure clinics (NorthStar) trial was ...designed to evaluate the effect of extended follow‐up in an outpatient HF clinic on long‐term adherence to guideline‐based therapy.
Methods and results
Patients with HF with reduced EF on optimal medical therapy (n = 921) were randomized to either extended follow‐up in the HF clinic (n = 461) or discharge to primary care (n = 460) and followed for a median of 4.1 years (range: 13 months to 6.1 years). The effect of the HF clinic intervention on treatment adherence (time to at least a 90 day break in treatment) was estimated by drug dispensing from pharmacies of an ACE inhibitor/ARB, beta‐blocker (BB), or mineralocorticoid receptor antagonist (MRA). Median age was 69 years, 25% were females, LVEF was 30%, and 90% were in NYHA class II–III. The HF clinic intervention did not reduce time to a 90 day break in treatment with either an ACE inhibitor/ARB hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.34–1.97, P = 0.650, a BB (HR 1.09, 95% CI 0.53–2.66, P = 0.820), or an MRA (HR 1.30, 95% CI 0.85–2.00, P = 0.238).
Conclusions
Extended follow‐up in an outpatient HF clinic did not improve long‐term adherence to guideline‐based therapy, and adherence did not deteriorate when follow‐up was shifted from the HF clinic to primary care.
The natriuretic peptides, especially the B-type peptide (BNP) and its inactive split-product N-terminal proBNP (Nt-proBNP) are increasingly used in screening for heart failure, primarily with reduced ...systolic function, in patients with symptoms suggestive of heart failure, as well in the stable (General Practitioner) setting as in the acute setting. Supporting this use is a very strong prognostic value of the natriuretic peptides. This has been shown in as well heart failure as acute coronary syndromes, but also in the general population and in high-risk groups as patients with diabetes, hypertension and coronary artery disease. This has of course raised interest for the use of the natriuretic peptides as a risk marker and for screening for heart failure with reduced systolic function in these populations. In symptomatic persons and in high risk populations, the natriuretic peptides have demonstrated a high sensitivity for ruling out the disease, if the right decision limits are choosen. Thus the number of normal echocardiographies can be reduced. More recently, the use in screening asymptomatic persons for left ventricular systolic dysfunction has gained more interest. In the unselected population, screening would probably not be cost-effective. In populations with a higher pre-test probability for heart failure, as patients with diabetes, hypertension and stable coronary artery disease, screening would presumably be more cost-effective, but evidence for the use in this setting is still lacking.
Treatment with beta-blockers is currently recommended after myocardial infarction (MI). The evidence relies on trials conducted decades ago before implementation of revascularization and contemporary ...medical therapy or in trials enrolling patients with heart failure or reduced left ventricular ejection fraction (LVEF ≤ 40%). Accordingly, the impact of beta-blockers on mortality and morbidity following acute MI in patients without reduced LVEF or heart failure is unclear.
The Danish trial of beta-blocker treatment after myocardial infarction without reduced ejection fraction (DANBLOCK) is a prospective, randomized, controlled, open-label, non-blinded endpoint clinical trial designed to evaluate the efficacy of beta-blocker treatment in post-MI patients in the absence of reduced LVEF or heart failure. We will randomize 3570 patients will be randomized within 14 days of index MI to beta-blocker or control for a minimum of 2 years. The primary endpoint is a composite of all-cause mortality, recurrent MI, acute decompensated heart failure, unstable angina pectoris, or stroke. The primary composite endpoint will be assessed through locally reported and adjudicated endpoints supplemented by linkage to the Danish national registers. A number of secondary endpoints will be investigated including patient reported outcomes and cardiovascular mortality. Data from similar ongoing trials in Norway and Sweden will be pooled to perform an individual patient data meta-analysis.
DANBLOCK is a randomized clinical trial investigating the effect of long-term beta-blocker therapy after myocardial infarction in patients without heart failure and reduced LVEF. Results from the trial will add important scientific evidence to inform future clinical guidelines.
Clinicaltrials.gov, NCT03778554. Registered on 19 December 2018. European Clinical Trials Database, 2018-002699-42, registered on 28 September 2018.
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