Clinical evaluation of unselected cardiac arrest survivors in a tertiary center over a 1-year period (the LAZARUZ study).

OBJECTIVES: When the cause of an aborted cardiac arrest is unclear the initiation of therapy, counseling and family screening is challenging. METHODS: We included 43 unselected, prospectively identified cardiac arrest survivors with or without a diagnosis. Family history for cardiac disease and supplemental electrocardiograms were evaluated for additional diagnostic information. RESULTS: 43 cardiac arrest survivors were included, 34 (79%) were male and the average age was 48years (range 23-64, SD 13.0). The most common etiologies identified in cardiac arrest survivors were ischemic heart disease (33%), cardiomyopathies (14%), miscellaneous (e.g. drug induced arrhythmias, coronary spasms) (12%) and channelopathies (5%). Family history of cardiac disease - even inheritable conditions - was not indicative of etiology in cardiac arrest survivors. Supplemental ECGs were abnormal in 10 of 43 patients; in the majority of these patients (7) no conclusive diagnosis was reached. CONCLUSIONS: In this study 16/43 (37%) of unselected, prospectively included cardiac arrest survivors remained without a diagnosis despite exhaustive investigations. We may extract additional diagnostic information from simple maneuvers during the recording of the electrocardiogram. We suggest that these ECG derived clues be investigated in future studies including genetic test results and data from relatives.

Efficacy and safety of the angiotensin II receptor blocker losartan for hypertrophic cardiomyopathy: the INHERIT randomised, double-blind, placebo-controlled trial.

BACKGROUND: No medical treatment has been reliably shown to halt or reverse disease progression in hypertrophic cardiomyopathy, but the results of several pilot studies have suggested beneficial effects of angiotensin II receptor blockers on left ventricular hypertrophy and fibrosis, which are predictive of an adverse outcome. We aimed to assess the effect of the angiotensin II receptor blocker losartan on left ventricular hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy. METHODS: In this single-centre, randomised, double-blind, placebo-controlled trial, adult patients (aged 18 years and older) with obstructive or non-obstructive hypertrophic cardiomyopathy were randomly assigned via computer-based system to losartan (100 mg per day) or placebo for 12 months. Patients and investigators were masked to assigned treatment. The primary endpoint was change in left ventricular mass as assessed by cardiac magnetic resonance imaging (CMR) or CT. Efficacy analyses were done in the modified intention-to-treat population (all patients with data available at the 12-month follow-up). The trial is registered with ClinicalTrials.gov, number NCT01447654. FINDINGS: Between Dec 1, 2011, and May 1, 2013, 318 patients were screened. 133 patients (mean age 52 years [SD 13], 35% women) consented and were randomly assigned to placebo (n=69) or losartan (n=64). 124 (93%) patients completed the study and were included in the modified intention-to-treat analysis for the primary endpoint. After 12 months we noted no significant difference in the change in left ventricular mass between the placebo group and the losartan group (mean difference 1 g/m(2), 95% CI -3 to 6; p=0·60). A decrease in systolic blood pressure in the losartan group (from mean 127 mm Hg [SD 12] to 121 mm Hg [14]; p=0·0001) confirmed drug compliance; blood pressure did not decrease in the placebo group. Two (2%) patients, both in the placebo group, died from sudden cardiac death during follow-up. In the losartan group, one (1%) patient had angioedema, one (1%) had deterioration of renal function, and one (1%) had hyperkalaemia. Treatment was well tolerated by patients with left ventricular outflow obstruction at baseline. INTERPRETATION: Our findings challenge the generally held view that angiotensin II receptor blockers reduce cardiac hypertrophy. Treatment with losartan was safe, suggesting that it can be used for other indications in patients with hypertrophic cardiomyopathy, irrespective of obstructive physiology. Additional studies are needed to assess the effect of angiotensin II receptor blockers in preclinical hypertrophic cardiomyopathy-eg, in genotype-positive but phenotype-negative individuals.

Effects of computer-assisted oral anticoagulant therapy.

BACKGROUND: Computer-assistance and self-monitoring lower the cost and may improve the quality of anticoagulation therapy. The main purpose of this clinical investigation was to use computer-assisted oral anticoagulant therapy to improve the time to reach and the time spent within the therapeutic target range compared to traditional oral anticoagulant therapy by physicians. METHODS: 54 patients were randomized equally into 3 groups. Patients in two groups used CoaguChek® systems to measure international normalized ratio (INR) values and had dosages of anticoagulation treatment calculated in a computer system by an algorithm specific to each group. The third group received traditional anticoagulation treatment by physicians. The obtained INR values were compared regarding the time to reach, and the time spent within, the therapeutic target range, corresponding to INR values from 2 to 3. RESULTS: Patients randomized to computer-assisted anticoagulation and the CoaguChek® system reached the therapeutic target range after 8 days compared to 14 days by prescriptions from physicians (p = 0.04). Time spent in the therapeutic target range did not differ between groups. The median INR value measured throughout the study from all patients by CoaguChek® at 2.5 (2.42-2.62) was lower than measured by a hospital-based Clinical and Biochemical Laboratory at 2.6 (2.45-2.76), (p = 0.02). CONCLUSIONS: The therapeutic target range was reached faster by the use of computer-assisted anticoagulation treatment than prescribed by physicians, and the total time spent within the therapeutic target range was similar. Thus computer-assisted oral anticoagulant therapy may reduce the cost of anticoagulation therapy without lowering the quality. INR values measured by CoaguChek® were reliable compared to measurements by a clinical and biochemical laboratory.

Paroxysmal atrial fibrillation is uncommon in outpatients with chronic heart failure.

OBJECTIVES: The objective was to evaluate the prevalence of paroxysmal atrial fibrillation (PAF) in patients with heart failure (HF) due to systolic dysfunction. DESIGN: We included 79 patients (age 68 years, LVEF 30%) with HF and sinus-rhythm (SR) referred to a HF outpatient clinic. A 48 hours Holter ECG and a follow-up ECG were performed. RESULTS. One patient had one episode of PAF. Thirty-two (41%) patients had episodes of irregular atrial runs (AR). The numbers of QRS complexes during AR were 7.2+/-2.9 (mean+/-SD). Patients with AR were older than patients with SR, p =0.02 and more often of female sex, p =0.04. Multivariate logistic regression analysis showed that age and female sex were independently correlated with AR with adjusted OR of 1.1 (per year, 95% CI 1.02-1.14, p =0.01) and 4.0 (1.05-15.07, p =0.04), respectively. The presence of AR did not predict development of new-onset AF. CONCLUSION: Outpatients with HF due to systolic dysfunction did not present with PAF during 48 hours Holter, but had several episodes of AR. The clinical and prognostic importance of AR deserves further investigation.

Influence of atrial fibrillation on plasma von willebrand factor, soluble E-selectin, and N-terminal pro B-type natriuretic peptide levels in systolic heart failure.

BACKGROUND: Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. It is unknown whether AF influences the degree of endothelial dysfunction in patients with systolic HF. METHODS: We measured levels of plasma von Willebrand factor (vWF) and E-selectin (as indexes of endothelial damage/dysfunction and endothelial activation, respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis. RESULTS: One hundred ninety patients (73% men; mean age, 69.0 +/- 10.1 years [+/- SD]) with systolic HF were studied, who were compared to 117 healthy control subjects: 52 subjects (27%) were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and New York Heart Association class were similar. There were significant differences in NT-proBNP (p < 0.0001) and plasma vWF (p = 0.003) between patients and control subjects. On Tukey post hoc analysis, AF-HF patients had significantly increased NT-proBNP (p < 0.001) and vWF (p = 0.0183) but not E-selectin (p = 0.071) levels when compared to SR-HF patients. On multivariate analysis, the presence of AF was related to plasma vWF levels (p = 0.018). Plasma vWF was also significantly correlated with NT-proBNP levels (Spearman r = 0.139; p = 0.017). CONCLUSIONS: There is evidence of greater endothelial damage/dysfunction in AF-HF patients when compared to SR-HF patients. The clinical significance of this is unclear but may have prognostic value.

Prognostic usefulness of anemia and N-terminal pro-brain natriuretic peptide in outpatients with systolic heart failure.

N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and anemia are predictors of outcome in systolic heart failure. It is currently unclear how these 2 markers interact in particular with regard to the prognostic information carried by each risk marker. We therefore tested the hypothesis that anemia (World Health Organization criteria, hemoglobin levels <7.5 mmol/L for women and <8.0 mmol/L for men) and NT-pro-BNP are associated and evaluated how a possible association affects the prognostic value of each risk marker. Clinical data from 345 patients with systolic heart failure were obtained prospectively at the baseline visit to our heart failure clinic (inclusion criterion left ventricular ejection fraction <0.45, no exclusion criteria). Follow-up was 30 months (median), and 70 events (mortality) occurred. Prevalence of anemia was 27%. In a multivariate logistic regression model, anemia (p = 0.041) was closely associated with NT-pro-BNP levels above the median (1,381 pg/ml) after adjustment for traditional confounders (left ventricular ejection fraction, age, body mass index, atrial fibrillation, chronic kidney disease). In an adjusted Cox proportional hazard model, the 2 parameters were associated with mortality after adjustment for traditional confounders (hazard ratio for anemia 1.73, 95% confidence interval 1.06 to 2.83, p = 0.029; hazard ratio for NT-pro-BNP >1,381 pg/ml 2.68, 95% confidence interval 1.58 to 4.66, p <0.001). Patients with anemia and high NT-pro-BNP levels had a fivefold increased risk for mortality (hazard ratio 4.77, 95% confidence interval 2.47 to 9.18, p <0.001). In conclusion, anemia is closely associated with NT-pro-BNP in patients with systolic heart failure, and anemia and NT-pro-BNP carry independent prognostic information. Patients with anemia and high levels of NT-pro-BNP have a markedly increased mortality risk.

Effects of body mass index and age on N-terminal pro brain natriuretic peptide are associated with glomerular filtration rate in chronic heart failure patients.

BACKGROUND: Obesity is a state characterized by glomerular hyperfiltration and age-related decreases in glomerular filtration rate (GFR). Body mass index (BMI), age, and GFR are associated with plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) in chronic heart failure (CHF) patients. We hypothesized that the effects of BMI and age on plasma concentrations of NT-proBNP are associated with GFR. METHODS: We obtained clinical data and laboratory test results from 345 CHF patients at the baseline visit in our heart failure clinic and examined the hypothesis using multiple linear regression models. RESULTS: Age (P = 0.0184), BMI (P = 0.0098), hemoglobin (P = 0.0043), heart rhythm (P <0.0001), and left ventricular ejection fraction (P <0.0001) were associated with log(NT-proBNP). After adjustment for GFR estimated by the Cockcroft and Gault equation, the parameter estimates for BMI (P = 0.3807) and age (P = 0.7238) changed markedly and became insignificant. In another model, after adjustment for GFR estimated by the 4-component Modification of Diet in Renal Disease formula (eGFR(MDRD)), the parameter estimates for age (P = 0.0674) changed markedly and became insignificant, but BMI (P = 0.0067) remained significant and unchanged. The eGFR(MDRD) is adjusted for body surface area, which may explain the difference. CONCLUSIONS: In CHF patients, the effect of age on NT-proBNP is associated with estimates for GFR derived from serum creatinine, and the significance of the effects of BMI on NT-proBNP depends on the method by which GFR is estimated.

The relationship between N-terminal pro-brain natriuretic peptide and risk for hospitalization and mortality is curvilinear in patients with chronic heart failure.

BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) carries prognostic information in patients with chronic heart failure and predicts risk for mortality and cardiovascular events. It is unknown whether NT-proBNP predicts risk for hospitalization for any cause. Furthermore, a clinically useful algorithm for risk stratification based on NT-proBNP as a continuous variable has not yet been described. We therefore evaluated NT-proBNP as a risk marker for mortality and hospitalization and developed a simple algorithm for risk stratification based on NT-proBNP as a continuous variable. METHODS: Data from 345 patients with chronic heart failure were collected prospectively in our heart failure clinic, and the patients were followed for 28 months (median). Seventy patients died, and 201 patients were hospitalized. Cox proportional hazard models for mortality and hospitalization were constructed with NT-proBNP as a dichotomous (median 1381 pg/mL) and a continuous variable (log2 NT-proBNP). RESULTS: Patients with supramedian levels of NT-proBNP had a 2.40-fold (95% CI 1.40-4.10) increased risk for mortality and 1.71-fold (95% CI 1.24-2.36) increased risk for hospitalization. The effect of doubling NT-proBNP on adjusted hazard ratios was 1.56 (95% CI 1.32-1.85) for mortality and 1.19 (95% CI 1.09-1.31) for hospitalization. We observed a curvilinear relationship between NT-proBNP and risk for mortality and hospitalization in the whole range of NT-proBNP. CONCLUSIONS: N-terminal pro-brain natriuretic peptide predicts risk for hospitalization and mortality. A simple algorithm indicates that every time NT-proBNP is doubled, estimated hazard ratio for death increases by a factor of 1.56 (56%) and by a factor of 1.19 (19%) for hospitalization. Finally, the relationship between NT-proBNP and risk is curvilinear if NT-proBNP is considered as a continuous variable.

Effect of atrial fibrillation on plasma NT-proBNP in chronic heart failure.

BACKGROUND: Brain natriuretic peptides are elevated in patients with systolic heart failure (HF) as well as in patients with atrial fibrillation (AF) and normal left ventricular ejection fraction (LVEF) and are strong predictors of death in HF patients. The aim of our study was to examine the levels of N-terminal pro brain natriuretic peptide (NT-proBNP) in patients with HF and AF versus HF and sinus rhythm (SR) and if NT-proBNP has prognostic influence in patients with AF. METHODS: We included 245 patients (72% men, 70 years) with HF referred to a HF clinic. NT-proBNP was measured at referral (baseline). RESULTS: At baseline, 26% had AF and at follow-up 35% of the surviving patients. Patients with AF were older than patients with SR (p=0.009), but LVEF and NYHA distribution were similar. Median NT-proBNP levels were higher: 2528 vs. 899 pg/ml (p<0.001). NT-proBNP was significantly correlated with AF at baseline (p<0.001), age (p=0.001), P-creatinine (p<0.001) and reduced LVEF (p=0.002). NT-proBNP was an independent predictor of death in patients with AF, adjusted HR 4.0 (95% CI 1.6-10.2) (p=0.003). CONCLUSION: NT-proBNP levels are higher in HF patients with AF than in HF patients with SR and has prognostic value despite the presence of AF.

Prevalence and prognostic significance of atrial fibrillation in outpatients with heart failure due to left ventricular systolic dysfunction.

INTRODUCTION: Atrial fibrillation (AF) is common in patients with heart failure (HF) due to left ventricular systolic dysfunction (LVSD), with conflicting prognostic data. The aim of our study was to assess the prevalence and incidence of AF in patients with HF and to determine the prognostic impact of baseline AF and the development of new onset AF. METHODS AND RESULTS: We included 1019 outpatients with HF due to LVSD; follow-up time ranged from 3 to 64 months. At baseline 26.4% of patients had AF. Of the 284 patients with a follow-up ECG and baseline SR, 18.7% developed new onset AF. Patients with AF were older (p<0.001), more often male (p=0.04), and more likely to have a history of stroke (p=0.03), but were less likely to have IHD (p<0.001). Baseline rhythm was independent of LVEF and NYHA-class. Baseline AF was associated with increased all-cause mortality (HR 1.38; CI 1.07-1.78, p=0.01) and all-cause mortality/hospitalisation (HR 1.43; CI 1.22-1.68, p<0.001). When adjusted for baseline covariates, baseline AF was independently associated with an increased risk of experiencing the combined endpoint (HR 1.29; CI 1.05-1.58; p=0.02), but did not predict all-cause mortality. By multivariable analyses, new-onset AF was associated with increased risk of all-cause mortality/hospitalisation (HR 1.45; CI 1.05-2.00; p=0.02). CONCLUSION: In outpatients with HF due to LVSD, AF is a common co-morbidity, which adversely affects morbidity and mortality outcomes.

Incidence and outcome of atrial fibrillation in stable symptomatic coronary disease.

OBJECTIVES: Evaluate the prevalence, incidence and impact on prognosis of existing and new onset atrial fibrillation (AF) in patients with stable, symptomatic coronary artery disease. DESIGN: Data from the 7 665 participants included in the ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) trial was used. RESULTS: Over a mean follow-up of 4.9 years, the incidence of recurrent AF in patients with AF at baseline (4.1%) was 13.5/100 patient-years and 1.64/100 patient-years for patients without baseline AF. Patients with AF at baseline had increased mortality and new overt heart failure. New onset AF was associated with increased morbidity and mortality and in particular soon after onset. [adjusted 30-day relative risk for mortality 23, 95% CI 14-36; for debilitating stroke 37, 95% CI 18-77; and for heart failure 54, 95% CI 32-93]. The incidence of AF was not affected by treatment with nifedipine GITS. CONCLUSION: The presence of AF in patients with stable symptomatic CAD is an independent risk factor and in particular in the first 30 days for subsequent mortality and morbidity.

[Predictive factors of maintenance of sinus rhythm after direct current (DC) cardioversion of atrial fibrillation/atrial flutter]. / Praediktive faktorer for opretholdelse af sinusrytme efter direct current (DC)-konvertering af atrieflimren/atrieflagren.

INTRODUCTION: Our aim was to determine the immediate and long-term outcome of direct current (DC) electrical cardioversion in patients with atrial fibrillation or flutter, and to determine factors predicting clinical outcome. MATERIALS AND METHODS: A retrospective one-year follow-up study of 220 patients with atrial fibrillation or flutter undergoing electrical cardioversion between September 1998 and April 2001 was done. RESULTS: Electrical cardioversion was successful in 82% of the patients. Multivariate analysis revealed that female gender was associated with successful cardioversion (p=0.008). Only 29% remained in sinus rhythm after the one-year follow-up. Maintenance of sinus rhythm was associated with anti-arrhythmic drug treatment (p=0.042). Relapse of atrial fibrillation was associated with reduced left ventricular ejection fraction (p=0.002). Complications occurred in 7.7% of the electrical cardioversions; of these, 1.2% were thromboembolic events. DISCUSSION: Less than one third of the patients remained in sinus rhythm after the one-year follow-up despite the use of anti-arrhythmic drugs. Electrical cardioversion is not without risk. Thorough consideration of choice of treatment in patients with atrial fibrillation or flutter is therefore important. According to Danish and international guidelines, electrical cardioversion should be considered primarily when symptoms of AF are unacceptable despite optimal frequency regulation or in patients with AF detected for the first time.

Diagnostic and prognostic performance of N-terminal ProBNP in primary care patients with suspected heart failure.

BACKGROUND: The value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in terms of diagnosis and prognosis in congestive heart failure (CHF) and left ventricular systolic dysfunction (LVSD) has been demonstrated previously in various populations, but data on primary care patients are sparse. The aim of this study was to evaluate the diagnostic and prognostic performance of NT-proBNP in primary care patients with suspected CHF. METHODS AND RESULTS: Three hundred sixty-seven consecutive patients (mean age, 68.8 years; range, 39.0-84.0 years) who had been referred by their general practitioner for echocardiographic evaluation because of suspected CHF. In all patients, NT-proBNP was measured at baseline and left ventricular ejection fraction (LVEF) was estimated with echocardiography. LVSD (LVEF < or =0.40) was found in 9% of the patients. NT-proBNP was significantly higher in patients with LVSD (P < .0001). With predefined cut off values for NT-proBNP (125 pg/mL), the sensitivity, specificity, positive predictive value, and negative predictive value for the detection of LVSD were 0.97, 0.46, 0.15 and 0.99, respectively. Area under the receiver operating characteristic curve was 0.87. The application of an age-differentiated cut-off value for NT-proBNP (125 pg/mL for <75 years old and 450 pg/mL for > or =75 years old) did not increase diagnostic performance. Patients were followed for a median of 778 days; 8% of the patients died during the follow-up period. The mortality rate was higher in patients with NT-proBNP of >125 pg/mL than in patients with normal values (P < .002, log rank), and the difference persisted after controlling for age, gender, and LVEF (hazard ratio per unit increase in log NT-proBNP, 2.2; range, 1.2-4.1; P = .015). CONCLUSION: In primary care patients who were referred for echocardiography because of suspected CHF, NT-proBNP values <125 pg/mL effectively rule out LVSD. Furthermore low NT-proBNP values are associated with a lower risk of death, independently of age, gender, and LVEF.

Prevalence and characteristics of diabetic patients in a chronic heart failure population.

BACKGROUND: Previously, estimates of the prevalence of diabetes mellitus (DM) in patients with chronic heart failure (CHF) have solely been based on history in retrospective studies. The aim of this study was to investigate the prevalence of DM and glucose abnormalities in patients with CHF in accordance with the modern diagnostic criteria of DM. A second aim was to characterize patients with DM with respect to severity of CHF. METHODS AND RESULTS: A prospective study including patients with systolic CHF admitted to a heart failure clinic. Fasting blood glucose (FBG) levels were measured on two occasions, for classification of DM. Severity of CHF was assessed by NYHA class, echocardiography, 6 min walk test and plasma NT-proBNP levels. A total of 195 consecutive patients were included in the study, of these 188 were eligible for classification of DM. A total of 21% had DM by history, 11% of the patients without known DM had FBG> or =6.1 mmol/l, and a diagnosis of DM was confirmed in half of these patients. There were no differences in severity of heart failure between patients with DM by definition and non-DM patients; however, high body mass index was related to worse CHF symptoms. CONCLUSION: Twenty six percent of the patients had DM by definition, 20% of these were undiagnosed at the time of admission. One single measurement of FBG is not sufficient to establish a diagnosis of DM. Diabetes was not related to CHF symptoms or to a degree of left ventricular dysfunction.