Urban Alehagen

Heart failure registry: a valuable tool for improving the management of patients with heart failure

Guidelines on how to diagnose and treat patients with heart failure (HF) are published regularly. However, many patients do not fulfil the diagnostic criteria and are not treated with recommended drugs. The Swedish Heart Failure Registry (S‐HFR) is an instrument which may help to optimize the handling of HF patients.

The Effect of Coenzyme Q10 on Morbidity and Mortality in Chronic Heart Failure: Results From Q-SYMBIO: A Randomized Double-Blind Trial

OBJECTIVES This randomized controlled multicenter trial evaluated coenzyme Q10 (CoQ10) as adjunctive treatment in chronic heart failure (HF). BACKGROUND CoQ10 is an essential cofactor for energy production and is also a powerful antioxidant. A low level of myocardial CoQ10 is related to the severity of HF. Previous randomized controlled trials of CoQ10 in HF were underpowered to address major clinical endpoints. METHODS Patients with moderate to severe HF were randomly assigned in a 2-year prospective trial to either CoQ10 100 mg 3 times daily or placebo, in addition to standard therapy. The primary short-term endpoints at 16 weeks were changes in New York Heart Association (NYHA) functional classification, 6-min walk test, and levels of N-terminal pro-B type natriuretic peptide. The primary long-term endpoint at 2 years was composite major adverse cardiovascular events as determined by a time to first event analysis. RESULTS A total of 420 patients were enrolled. There were no significant changes in short-term endpoints. The primary long-term endpoint was reached by 15% of the patients in the CoQ10 group versus 26% in the placebo group (hazard ratio: 0.50; 95% confidence interval: 0.32 to 0.80; p = 0.003) by intention-to-treat analysis. The following secondary endpoints were significantly lower in the CoQ10 group compared with the placebo group: cardiovascular mortality (9% vs. 16%, p = 0.026), all-cause mortality (10% vs. 18%, p = 0.018), and incidence of hospital stays for HF (p = 0.033). In addition, a significant improvement of NYHA class was found in the CoQ10 group after 2 years (p = 0.028). CONCLUSIONS Long-term CoQ10 treatment of patients with chronic HF is safe, improves symptoms, and reduces major adverse cardiovascular events. (Coenzyme Q10 as adjunctive treatment of chronic heart failure: a randomised, double-blind, multicentre trial with focus on SYMptoms, BIomarker status [Brain-Natriuretic Peptide (BNP)], and long-term Outcome [hospitalisations/mortality]; ISRCTN94506234).

Association of Copeptin and N-Terminal proBNP Concentrations With Risk of Cardiovascular Death in Older Patients With Symptoms of Heart Failure

CONTEXT Measurement of plasma concentrations of the biomarker copeptin may help identify patients with heart failure at high and low risk of mortality, although the value of copeptin measurement in elderly patients is not fully known. OBJECTIVE To evaluate the association between plasma concentrations of copeptin, a surrogate marker of vasopressin, combined with concentrations of the N-terminal fragment of the precursor to B-type natriuretic peptide (NT-proBNP), and mortality in a cohort of elderly patients with symptoms of heart failure. DESIGN, SETTING, AND PARTICIPANTS Primary health care population in Sweden enrolling 470 elderly patients with heart failure symptoms between January and December 1996. Clinical examination, echocardiography, and measurement of peptide concentrations were performed, with follow-up through December 2009. MAIN OUTCOME MEASURES All-cause mortality and cardiovascular mortality. RESULTS After a median follow-up of 13 years, there were 226 deaths from all causes, including 146 deaths from cardiovascular causes. Increased concentration of copeptin was associated with increased risk of all-cause mortality (fourth quartile vs first quartile: 69.5% vs 38.5%, respectively; hazard ratio [HR], 2.04 [95% confidence interval {CI}, 1.38-3.02]) and cardiovascular mortality (fourth quartile vs first quartile: 46.6% vs 26.5%; HR, 1.94 [95% CI, 1.20-3.13]). The combination of elevated NT-proBNP concentrations and elevated copeptin concentrations also was associated with increased risk of all-cause mortality (copeptin fourth quartile: HR, 1.63 [95% CI, 1.08-2.47]; P = .01; NT-proBNP fourth quartile: HR, 3.17 [95% CI, 2.02-4.98]; P < .001). Using the 2 biomarkers simultaneously in the evaluation of cardiovascular mortality, there was a significant association for copeptin in the presence of NT-proBNP (log likelihood trend test, P = .048) and a significant association for NT-proBNP (fourth quartile: HR, 4.68 [95% CI 2.63-8.34]; P < .001). CONCLUSION Among elderly patients with symptoms of heart failure, elevated concentrations of copeptin and the combination of elevated concentrations of copeptin and NT-proBNP were associated with increased risk of all-cause mortality.

Brain natriuretic peptide-guided treatment does not improve morbidity and mortality in extensively treated patients with chronic heart failure: responders to treatment have a significantly better outcome

To determine whether brain natriuretic peptide (BNP)‐guided heart failure (HF) treatment improves morbidity and/or mortality when compared with conventional treatment.

Elevated circulating levels of thioredoxin and stress in chronic heart failure.

Chronic heart failure (CHF) is a complex syndrome, in which reactive oxygen species and inflammatory cytokines are important stressors that contribute to the pathogenesis.

Prevalence, correlates, and prognostic significance of QRS prolongation in heart failure with reduced and preserved ejection fraction

AIMS The independent clinical correlates and prognostic impact of QRS prolongation in heart failure (HF) with reduced and preserved ejection fraction (EF) are poorly understood. The rationale for cardiac resynchronization therapy (CRT) in preserved EF is unknown. The aim was to determine the prevalence of, correlates with, and prognostic impact of QRS prolongation in HF with reduced and preserved EF. METHODS AND RESULTS We studied 25,171 patients (age 74.6 ± 12.0 years, 39.9% women) in the Swedish Heart Failure Registry. We assessed QRS width and 40 other clinically relevant variables. Correlates with QRS width were assessed with multivariable logistic regression, and the association between QRS width and all-cause mortality with multivariable Cox regression. Pre-specified subgroup analyses by EF were performed. Thirty-one per cent had QRS ≥120 ms. Strong predictors of QRS ≥120 ms were higher age, male gender, dilated cardiomyopathy, longer duration of HF, and lower EF. One-year survival was 77% in QRS ≥120 vs. 82% in QRS <120 ms, and 5-year survival was 42 vs. 51%, respectively (P < 0.001). The adjusted hazard ratio for all-cause mortality was 1.11 (95% confidence interval 1.04-1.18, P = 0.001) for QRS ≥120 vs. <120 ms. There was no interaction between QRS width and EF. CONCLUSION QRS prolongation is associated with other markers of severity in HF but is also an independent risk factor for all-cause mortality. The risk associated with QRS prolongation may be similar regardless of EF. This provides a rationale for trials of CRT in HF with preserved EF.

Sleep disordered breathing in an elderly community-living population: Relationship to cardiac function, insomnia symptoms and daytime sleepiness

OBJECTIVE To describe the prevalence of sleep disordered breathing (SDB) and its relationship to systolic function, different insomnia symptoms as well as excessive daytime sleepiness (EDS) in elderly community-living people. This has not been investigated previously. METHOD Three hundred thirty-one subjects (71-87 years) healthy enough to be independently living in their own homes underwent echocardiographic examinations and sleep respiratory recordings. Questionnaires were used to evaluate insomnia symptoms and EDS. RESULTS Mild SDB (AHI 5-15) was found in 32%. Moderate SDB (AHI 15-30) occurred in 16%, and 7% had severe SDB (AHI>30). Median AHI was significantly higher (p<0.001) in those with mildly impaired systolic function (AHI 11.7) and moderately impaired systolic function (AHI 10.9) compared to those with normal systolic function (AHI 5.0). Impaired systolic function was associated with central sleep apnea (CSA) but not with obstructive sleep apnea. Concerning insomnia symptoms and EDS, only difficulties in initiating sleep correlated significantly (p<0.05) with AHI. CONCLUSION SDB is common among the elderly. CSA may be related to impaired systolic function/heart failure. However, detection of SDB in this population may be problematic since insomnia symptoms and EDS correlated poorly with SDB.

Utility of the Amino-Terminal Fragment of Pro-Brain Natriuretic Peptide in Plasma for the Evaluation of Cardiac Dysfunction in Elderly Patients in Primary Health Care

BACKGROUND The aims of this study were to measure the N-terminal fragment of pro-brain natriuretic peptide (proBNP) in plasma in medical conditions commonly found in primary care and to evaluate the utility of these measurements in identifying impaired cardiac function in elderly patients with symptoms associated with heart failure. METHODS We studied 415 patients (221 men and 194 women; mean age, 72 years) who had contacted a primary healthcare center for dyspnea, fatigue, and/or peripheral edema. One cardiologist evaluated the patients in terms of history, physical examination, functional capacity, electrocardiography, and suspicion of heart failure. Plasma N-terminal proBNP was measured by an in-house RIA. An ejection fraction < or =40% by Doppler echocardiography was regarded as reduced cardiac function. Abnormal diastolic function was defined as an abnormal mitral inflow defined as reduced ratio of peak early diastolic filling velocity to peak filling velocity at atrial contraction (E/A ratio), or as abnormal pulmonary venous flow pattern. RESULTS Patients with impaired functional capacity, impaired systolic function, and/or impaired renal function had significantly increased N-terminal proBNP concentrations. By multiple regression analysis, N-terminal proBNP concentrations were also influenced by ischemic heart disease, cardiac enlargement, and certain medications but not by increased creatinine. No gender differences were observed. Patients with isolated diastolic dysfunction attributable to relaxation abnormalities had lower concentrations than those with normal cardiac function, whereas those with pseudonormal E/A ratios or restrictive filling patterns had higher concentrations. CONCLUSIONS Plasma N-terminal proBNP concentrations increase as a result of impaired systolic function, age, impaired renal function, cardiac ischemia and enlargement, and certain medications. Values are high in diastolic dysfunction with pseudonormal patterns, but not in patients with relaxation abnormalities. An increase in plasma N-terminal proBNP might be an earlier sign of abnormal cardiac function than abnormalities identified by currently used echocardiographic measurements.

Cystatin C and NT‐proBNP, a powerful combination of biomarkers for predicting cardiovascular mortality in elderly patients with heart failure: results from a 10‐year study in primary care

Heart failure (HF) is common among the elderly patients. It is essential to identify those at high risk in order to optimize the use of resources. We aimed to evaluate whether a combination of two biomarkers might give better prognostic information about the risk of cardiovascular (CV) mortality in patients with symptoms associated with HF, compared with only one biomarker.

Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation : a 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens

BACKGROUND Selenium and coenzyme Q10 are essential for the cell. Low cardiac contents of selenium and coenzyme Q10 have been shown in patients with cardiomyopathy, but inconsistent results are published on the effect of supplementation of the two components separately. A vital relationship exists between the two substances to obtain optimal function of the cell. However, reports on combined supplements are lacking. METHODS A 5-year prospective randomized double-blind placebo-controlled trial among Swedish citizens aged 70 to 88 was performed in 443 participants given combined supplementation of selenium and coenzyme Q10 or a placebo. Clinical examinations, echocardiography and biomarker measurements were performed. Participants were monitored every 6th month throughout the intervention. The cardiac biomarker N-terminal proBNP (NT-proBNP) and echocardiographic changes were monitored and mortalities were registered. End-points of mortality were evaluated by Kaplan-Meier plots and Cox proportional hazard ratios were adjusted for potential confounding factors. Intention-to-treat and per-protocol analyses were applied. RESULTS During a follow up time of 5.2 years a significant reduction of cardiovascular mortality was found in the active treatment group vs. the placebo group (5.9% vs. 12.6%; P=0.015). NT-proBNP levels were significantly lower in the active group compared with the placebo group (mean values: 214 ng/L vs. 302 ng/L at 48 months; P=0.014). In echocardiography a significant better cardiac function score was found in the active supplementation compared to the placebo group (P=0.03). CONCLUSION Long-term supplementation of selenium/coenzyme Q10 reduces cardiovascular mortality. The positive effects could also be seen in NT-proBNP levels and on echocardiography.