Norwegian Heart Failure Registry Research Articles

Quality of life in patients with heart failure and implantable cardioverter defibrillator. Results from 42 heart failure clinics in norway

Abstract Background Patients with heart failure (HF) have an increased risk of sudden cardiac death, and treatment with an implantable cardioverter defibrillator (ICD) has become standard treatment for selected patient groups. HF is associated with impaired QoL, but there is no consensus regarding the implication of having an ICD. Knowledge regarding QoL in patients with HF and ICD attending follow-up in outpatient HF-clinics is sparse. Purpose The aim of this study was to determine QoL in patients with HF and ICD. Further, to compare QoL in patients with HF with and without ICD, using data from the first and follow-up visits in outpatient HF clinics. Methods Longitudinal data from the National Norwegian Heart Failure Registry (NNHFR), including 9 274 patients, of which 1 206 with an ICD, were studied. QoL was assessed using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Data was collected at the first and follow-up visits in outpatient HF clinics approximately six months after optimal treatment was achieved. Results Patients with an ICD were younger, more often men, and had higher frequency of coronary artery disease (all p<0.001). At the first visit, there was no significant difference in QoL between patients with and without ICD, with both groups reporting moderate QoL. Both groups had a significant improvement in QoL from the first visit to the follow-up visit (p<0.001). However, patients with ICD reported significantly less improvement in QoL (p<0.001) at follow-up. This disparity was evident regarding both the physical (p<0.001) and the emotional (p<0.001) dimension. Conclusion QoL in patients with HF and ICD improves after follow-up in outpatient HF clinics, although not to the same extent as in patients without ICD. Thus, tailored interventions in outpatient HF clinics may be necessary to improve outcomes in this subgroup of patients with both HF and ICD.

6 min walk test is a strong independent predictor of death in outpatients with heart failure.

AimsThe aim of this study was to examine the prognostic value of the 6 min walk test (6MWT) in a large cohort of outpatients with heart failure.Methods and resultsA total of 5519 outpatients with heart failure from the National Norwegian Heart Failure Registry (NNHFR), which is part of the Norwegian Cardiovascular Disease Registry, were included in this analysis. The NNHFR recommended the use of the 6MWT for prognostic assessment of all patients included in the registry. Patients were categorized according to the 6MWT: Category 1 walked the longest and Category 3 the shortest. During a median (25th–75th percentiles) follow‐up of 24 (14–36), 12.9% of the patients died. Patients in Category 3 had the overall worst outcome than had patients in Categories 1 and 2. 6MWT used as a continuous variable was a highly significant independent predictor for mortality in a multivariate Cox regression model adjusted for 16 other variables with a hazard ratio of 0.979 [(95% confidence interval 0.972–0.986), P < 0.001]. The four most important predictors for mortality were active cancer in the last 5 years, age, 6MWT, and natriuretic peptides (all P < 0.001).Conclusions6MWT is a strong independent predictor of mortality in outpatients with HF. The findings support the use of the 6MWT in the prognostic assessment of patients with HF irrespective of HF aetiology.

β-Blocker Doses and Heart Rate in Patients with Heart Failure: Results from the National Norwegian Heart Failure Registry

Background: Use of β-blockers and titration to the highest tolerated dose are highly recommended by the European Society of Cardiology (ESC) guidelines for treatment of chronic heart failure (HF) with a reduced ejection fraction (HFrEF), but little attention has been paid to the achieved heart rate (HR) during this treatment. Objectives: The aim of the present study was to examine the achieved HR in relation to the use of β-blockers in these patients. Methods: All of the patients (n = 2,689) in the National Norwegian Heart Failure Registry as part of the Norwegian Cardiovascular Disease Registry with a sinus rhythm and left ventricular ejection fraction (LVEF) <40% at stable follow-up visiting specialised hospital outpatient HF clinics in Norway were included. The β-blocker doses were calculated as a percent of the target dose according to ESC HF guidelines. Differences between baseline variables according to the achieved HR were analysed by the Student’s t test for continuous variables and Pearson’s χ² test for categorical variables. Linear regression was used to determine the predictors of HR ≥70 beats/min (bpm) in the multivariate analysis. Results: One third of the patients had a resting HR ≥70 bpm. Of the patients with an HR ≥70 bpm, 72.3% used less than the target dose of β-blocker; they were younger and had a higher NYHA class, more diabetes mellitus and chronic obstructive pulmonary disease (COPD), and higher N-terminal pro-B type natriuretic peptide (NT-proBNP) levels and estimated glomerular filtration rates compared to the patients with an HR <70 bpm. The 1-year mortality was 3.1, 3.7, 5.8, and 9.1% among the patients with an HR <70, 70–79, 80–89, and >89 bpm, respectively. Only 2 patients used ivabradine. Conclusions: In patients with HFrEF and sinus rhythm, an HR ≥70 bpm was associated with worse clinical variables and outcomes. A high proportion of the patients who had an HR ≥70 bpm was not treated with or/did not tolerate the target dose of a β-blocker, although the β-blocker dose was higher than in patients with an HR <70 bpm. This may suggest that increased efforts should be made to further increase the β-blocker dose, and treatment with ivabradine could be considered among patients with an HR ≥70 bpm.

Gender differences in association between uric acid and all-cause mortality in patients with chronic heart failure

BackgroundElevated serum uric acid (SUA) is associated with poor prognosis in patients with cardiovascular disease, yet it is still not decided whether the role of SUA is causal or only reflects an underlying disease. The purpose of the study was to investigate if SUA was an independent predictor of 5-year all-cause mortality in a propensity score matched cohort of chronic heart failure (HF) outpatients. Furthermore, to assess whether gender or renal function modified the effect of SUA.MethodsPatients (n = 4684) from the Norwegian Heart Failure Registry with baseline SUA were included in the study. Individuals in the highest gender-specific SUA quartile were propensity score matched 1:1 with patients in the lowest three SUA quartiles. The propensity score matching procedure created 928 pairs of patients (73.4% males, mean age 71.4 ± 11.5 years) with comparable baseline characteristics. Kaplan Meier and Cox regression analyses were used to investigate the independent effect of SUA on all-cause mortality.ResultsSUA in the highest quartile was an independent predictor of all-cause mortality in HF outpatients (hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.03–1.37, p-value 0.021). Gender was found to interact the relationship between SUA and all-cause mortality (p-value for interaction 0.007). High SUA was an independent predictor of all-cause mortality in women (HR 1.65, 95% CI 1.24–2.20, p-value 0.001), but not in men (HR 1.06, 95% CI 0.89–1.25, p-value 0.527). Renal function did not influence the relationship between SUA and all-cause mortality (p-value for interaction 0.539).ConclusionsHigh SUA was independently associated with inferior 5-year survival in Norwegian HF outpatients. The finding was modified by gender and high SUA was only an independent predictor of 5-year all-cause mortality in women, not in men.

Spironolactone Treatment and Effect on Survival in Chronic Heart Failure Patients with Reduced Renal Function: A Propensity-Matched Study

Background/Aims: Spironolactone may be hazardous in heart failure (HF) patients with renal dysfunction due to risk of hyperkalemia and worsened renal function. We aimed to evaluate the effect of spironolactone on all-cause mortality in HF outpatients with renal dysfunction in a propensity-score-matched study. Methods: A total of 2,077 patients from the Norwegian Heart Failure Registry with renal dysfunction (eGFR <60 mL/min/1.73 m²) not treated with spironolactone at the first visit at the HF clinic were eligible for the study. Patients started on spironolactone at the outpatient HF clinics (n = 206) were propensity-score-matched 1:1 with patients not started on spironolactone, based on 16 measured baseline characteristics. Kaplan-Meier and Cox regression analyses were used to investigate the independent effect of spironolactone on 2-year all-cause mortality. Results: Propensity score matching identified 170 pairs of patients, one group receiving spironolactone and the other not. The two groups were well matched (mean age 76.7 ± 8.1 years, 66.4% males, and eGFR 46.2 ± 10.2 mL/min/1.73 m²). Treatment with spironolactone was associated with increased potassium (delta potassium 0.31 ± 0.55 vs. 0.05 ± 0.41 mmol/L, p < 0.001) and decreased eGFR (delta eGFR -4.12 ± 12.2 vs. -0.98 ± 7.88 mL/min/1.73 m², p = 0.006) compared to the non-spironolactone group. After 2 years, 84% of patients were alive in the spironolactone group and 73% of patients in the non-spironolactone group (HR 0.59, 95% CI 0.37-0.92, p = 0.020). Conclusion: In HF outpatients with renal dysfunction, treatment with spironolactone was associated with improved 2-year survival compared to well-matched patients not treated with spironolactone. Favorable survival was observed despite worsened renal function and increased potassium in the spironolactone group.

Prevalent Diabetes Mellitus: Mortality and Management in Norwegian Heart Failure Outpatients

Objectives: Heart failure (HF) patients with diabetes mellitus experience poor prognosis. We assessed the independent predictive effect of prevalent diabetes mellitus on all-cause mortality in HF outpatients. Furthermore, we investigated if optimized HF medication differed in diabetic versus nondiabetic patients. Methods: From 6,289 patients included in the Norwegian HF registry during 2000-2012, 724 diabetic HF outpatients were propensity-score-matched with nondiabetic HF outpatients (1:1), based on 21 measured baseline variables. Baseline characteristics, measured comorbidities and medication were balanced in the matched sample. Results: Diabetes was not an independent predictor of all-cause mortality in the propensity-matched analyses (hazard ratio 1.041; 95% confidence interval 0.875-1.240). No interactions were found between the prognostic impact of diabetes and the strata renal function, systolic function or etiology of chronic HF. Diabetic HF outpatients were independently prescribed higher doses of β-blockers and loop diuretics (both p < 0.001) and were more prone to receive statins (p = 0.003) than nondiabetics. Conclusions: Prevalent diabetes mellitus was not an independent predictor of all-cause mortality in HF outpatients. Explanations other than tight glycemic control should be assessed to improve the prognosis of diabetic HF outpatients. The more intensive, optimized HF medication for diabetic HF outpatients may, to a certain degree, explain our results.

Carvedilol Compared With Metoprolol Succinate in the Treatment and Prognosis of Patients With Stable Chronic Heart Failure: Carvedilol or Metoprolol Evaluation Study.

β-Blockers exert a prognostic benefit in the treatment of chronic heart failure. Their pharmacological properties vary. The only substantial comparative trial to date-the Carvedilol or Metoprolol European Trial-has compared carvedilol with short-acting metoprolol tartrate at different dose equivalents. We therefore addressed the relative efficacy of equal doses of carvedilol and metoprolol succinate on survival in multicenter hospital outpatients with chronic heart failure. Four thousand sixteen patients with stable systolic chronic heart failure who were using either carvedilol or metoprolol succinate were identified in the Norwegian Heart Failure Registry and The Heart Failure Registry of the University of Heidelberg, Germany. Patients were individually matched on both the dose equivalents and the respective propensity scores for β-blocker treatment. During a follow-up for 17 672 patient-years, it was found that 304 (27.2%) patients died in the carvedilol group and 1066 (36.8%) in the metoprolol group. In a univariable analysis of the general sample, metoprolol therapy was associated with higher mortality compared with carvedilol therapy (hazard ratio, 1.49; 95% confidence interval, 1.31-1.69; P<0.001). This difference was not seen after multivariable adjustment (hazard ratio, 0.93; 95% confidence interval, 0.57-1.50; P=0.75) and adjustment for propensity score and dose equivalents (hazard ratio, 1.06; 95% confidence interval, 0.94-1.20; P=0.36) or in the propensity and dose equivalent-matched sample (hazard ratio, 1.00; 95% confidence interval, 0.82-1.23; P=0.99). These results were essentially unchanged for all prespecified subgroups. In outpatients with chronic heart failure, no conclusive association between all-cause mortality and treatment with carvedilol or metoprolol succinate was observed after either multivariable adjustment or multilevel propensity score matching.

ESC guidelines adherence is associated with improved survival in patients from the Norwegian Heart Failure Registry.

To assess the adherence to heart failure (HF) guidelines for angiotensin-converting enzyme-I (ACE-I), angiotensin II receptor blockers (ARB), and β-blockers and the possible association of ACE-I or ARB, β-blockers, and statins with survival in the large contemporary Norwegian Heart Failure Registry. The study included 5761 outpatients who were diagnosed with HF of any aetiology (mean left ventricular ejection fraction 32% ± 11%) from January 2000 to January 2010 and followed up until death or February 2010. Adherence to treatment according to the guidelines was high. Cox regression analysis to identify risk factors for all-cause mortality, after adjustment for many factors, showed that ACE-I ≥ 50% of target dose, use of beta-blockers, and statins were significantly related to improved survival (P = 0.003, P < 0.001, and P < 0.001, respectively). Propensity scoring showed the same benefit for these variables. Both multivariable and propensity scoring analyses showed survival benefits with β-blockers, statins, and adequate doses of ACE-I in this contemporary HF cohort. This study stresses the importance of guidelines adherence, even in the context of high levels of adherence to guidelines. Moreover, respecting the recommended target doses of ACE-I appears to have a crucial role in survival improvement and, in the multivariate Cox regression analysis, ARB treatment was not significantly associated with a lower all-cause mortality.

Association between spironolactone added to beta-blockers and ACE inhibition and survival in heart failure patients with reduced ejection fraction: a propensity score-matched cohort study

Heart failure (CHF) guidelines recommend mineralocorticoid receptor antagonists for all symptomatic patients treated with a combination of ACE inhibitors/angiotensin receptor blockers (ARBs) and beta-blockers. As opposed to both eplerenone trials, patients in RALES (spironolactone) received almost no beta-blockers. Since pharmacological properties differ between eplerenone and spironolactone, the prognostic benefit of spironolactone added to this baseline combination therapy needs clarification. We included 4,832 CHF patients with chronic systolic dysfunction from the Norwegian Heart Failure Registry and the heart failure outpatients' clinic of the University of Heidelberg. Propensity scores for spironolactone receipt were calculated for each patient and used for matching to patients without spironolactone. During a total follow-up of 17,869 patient-years, 881 patients (27.0 %) died in the non-spironolactone group and 445 (28.4 %) in the spironolactone group. Spironolactone was not associated with improved survival, neither in the complete sample (HR 0.82; 95 % CI 0.64-1.07; HR 1.03; 95 % CI 0.88-1.20; multivariate and propensity score adjusted respectively), nor in the propensity-matched cohort (HR 0.98; 95 % CI 0.82-1.18). In CHF outpatients we were unable to observe an association between the use of spironolactone and improved survival when administered in addition to a combination of ACE/ARB and beta-blockers.

Prognostic utility of B-type natriuretic peptides in patients with heart failure and renal dysfunction

BackgroundRenal dysfunction is considered a confounding variable in the interpretation of B-type natriuretic peptides (BNPs) and their amino-terminal fragments (NT-ProBNP) in patients with heart failure (HF). Our aim was to investigate the prognostic utility of BNPs and NT-proBNP in HF outpatients with renal dysfunction, and compare the prognostic significance of the corresponding BNP/NT-ProBNP levels in patients with and without renal dysfunction.MethodsA total of 2076 patients from 13 HF clinics in the Norwegian Heart Failure Registry were investigated. The BNP/NT-ProBNP levels were categorized centre-wise into four groups using the quartile limits found in patients with preserved renal function. Patients with renal dysfunction, i.e. glomerular filtration rate (GFR) ≤60 mL/min/1.73 m2, were then assigned to BNP groups 1–4 centre-wise according to their level of natriuretic peptides.ResultsRenal dysfunction was present in 37.5% of the patients, of whom the majority (59.1%) had levels of natriuretic peptide in the highest BNP group. Patients with renal dysfunction and BNP levels in the lower three BNP groups had similar 2-year survival as patients without renal dysfunction and comparable BNP levels [crude hazard ratio (HR) 1.25, 95% CI 0.82–1.89, P = 0.302, multiple adjusted HR 0.85, 95% CI 0.54–1.33, P = 0.457]. Beyond 2 years of follow-up, renal dysfunction predicted all-cause mortality irrespective of the level of natriuretic peptides at the start of follow-up.ConclusionIn HF outpatients, the BNP/NT-ProBNP level predicted 2-year mortality irrespective of renal function and provided important prognostic information on patients with renal dysfunction.

Baseline Anemia Is Not a Predictor of All-Cause Mortality in Outpatients With Advanced Heart Failure or Severe Renal Dysfunction: Results From the Norwegian Heart Failure Registry

The aim of this study was to evaluate the prognostic impact of anemia in outpatients with chronic heart failure attending specialized heart failure clinics and specifically to investigate its prognostic utility in patients with severe renal dysfunction or advanced heart failure. Anemia is an independent prognostic marker in patients with heart failure. The effect of anemia on mortality decreases with increasing creatinine levels. Multivariate Cox regression analyses were used to investigate the prognostic effect of anemia in 4,144 patients with heart failure from 21 outpatient heart failure clinics in Norway. Severe renal failure was defined as estimated glomerular filtration rate ≤45 ml/min/1.73 m2 and advanced heart failure as New York Heart Association functional classes IIIb and IV. Baseline anemia was present in 24% and was a strong predictor of all-cause mortality (adjusted hazard ratio [HR]: 1.30, 95% CI: 1.09 to 1.56, p = 0.004). Baseline anemia did not predict mortality in the 752 patients with severe renal dysfunction (adjusted HR: 1.08, 95 % CI: 0.77 to 1.51, p = 0.662) and the 528 patients with advanced heart failure (adjusted HR: 0.87, 95% CI: 0.56 to 1.34, p = 0.542). In the 1,743 patients who attended subsequent visits, sustained anemia independently predicted worse prognosis (adjusted HR: 1.47, 95% CI: 1.10 to 1.94, p = 0.008), whereas transient and new-onset anemia did not. According to our study, baseline anemia was not an independent predictor of all-cause mortality in outpatients with heart failure and accompanied severe renal dysfunction or advanced heart disease. Sustained anemia after optimizing heart failure treatment might imply worse prognosis independently of renal function and New York Heart Association functional class.

No Impact of Atrial Fibrillation on Mortality Risk in Optimally Treated Heart Failure Patients

Several studies have shown that atrial fibrillation (AF) is associated with increased risk of death in heart failure (HF) patients. However, it is not clear whether this increased risk is independent of other risk factors. We hypothesized that AF would be an independent risk factor for death in a large cohort of HF patients. Patients referred to Norwegian HF outpatient clinics were enrolled between October 2000 and February 2008. Patients with heart rhythm other than AF or sinus rhythm were excluded. Mortality data were obtained from the National Statistics Bureau, Statistics Norway with the last update February 2008. There were 4048 patients included in the analysis, with a median follow-up of 28 months. Adherence to guidelines regarding medical treatment was high. In univariate analysis, AF patients (n = 1391) had a higher risk of death than patients in sinus rhythm (n = 2657) (hazard ratio [HR] 1.181; 95% confidence interval (CI), 1.044-1.336; P = 0.008). However, after adjusting for confounding factors (age, New York Heart Association class, coronary artery disease as the main cause of HF, use of any loop diuretic, hemoglobin level, and serum creatinine), AF was no longer associated with increased risk of death (HR 1.037; 95% CI, 0.901-1.193; P = 0.619). In this cohort of heart failure patients receiving optimal medical treatment at specialized HF clinics, AF was not associated with increased risk of death after adjusting for confounding factors.

Characteristics, Implementation of Evidence-Based Management and Outcome in Patients with Chronic Heart Failure Results from the Norwegian Heart Failure Registry

Hospitalization rates, morbidity and mortality are undesirably high in heart failure (HF) patients. An organized system of HF specialist outpatient care has been recommended, but the best way to implement such programmes is not clearly established. To evaluate HF patient characteristics, management and outcome in outpatient HF clinics. Data from HF patients at 24 hospital outpatient clinics were entered in a common database allowing each centre to monitor its own practice against the rest. A total of 3632 patients were included. At the last registered visit, ACE inhibitors or angiotensin receptor blockers were prescribed for 87%; beta blockers, 83%; spironolactone, 33% and loop diuretics 87% of the patients. The number of hospital admissions and days stayed in hospital for cardiovascular reasons were significantly reduced (p<0.001). Mortality was high, 11.5 and 22% after one and two years, respectively. The use of evidence-based medication increased over time in HF clinics with the ability of the individual clinics to compare their treatment to other sites. Thus, establishment of specialized HF clinics managed in a registry network might improve the quality of care.

Improved quality of life in Norwegian heart failure patients after follow‐up in outpatient heart failure clinics: results from the Norwegian heart failure registry

To evaluate the quality of life in heart failure (HF) outpatients attending multidisciplinary disease management programmes at HF clinics in Norwegian hospitals. Data from HF patients at 24 hospital outpatient clinics were entered in a common database; The Norwegian Heart Failure Registry. Quality of life assessment was done using Minnesota Living with Heart Failure Questionnaire (MLHF). The quality of life assessment was optional at each hospital and was done both at initial evaluation and after 6 months of stable follow-up. A total of 3632 patients were included in the registry and 1778 patients had at least one assessment of quality of life. The mean MLHF score improved significantly from 2.1 at the initial evaluation to 1.4 six months after leaving the clinic (P < 0.001). There was a significant difference in MLHF score between hospitals and baseline MLHF score was significantly associated with NYHA functional class, hospitalizations 6 months before entering the registry, and brain natriuretic peptide; and inversely related to age and systolic blood pressure. Minnesota Living with Heart Failure score was an independent predictor of mortality in this population. Quality of life assessed with MLHF improved after follow-up at outpatient HF clinics. Minnesota Living with Heart Failure score was significantly related to functional status, laboratory and demographic variables, and was an important predictor of prognosis.

COPD Predicts Mortality in HF: The Norwegian Heart Failure Registry

BackgroundChronic obstructive pulmonary disease (COPD) and chronic heart failure (HF) are common clinical conditions that share tobacco as a risk factor. Our aim was to evaluate the prognostic impact of COPD on HF patients. Methods and ResultsThe Norwegian Heart Failure Registry was used. The study included 4132 HF patients (COPD, n = 699) from 22 hospitals (mean follow-up, 13.3 months). COPD patients were older, more often smokers and diabetics, less often on β-blockers and had a higher heart rate. They were more often in New York Heart Association (NYHA) Class III or IV (COPD, 63%; no COPD, 51%), although left ventricular ejection fraction (LVEF) distribution was similar. COPD independently predicted death (adjusted hazard ratio [HR], 1.188; 95% CI: 1.015 to 1.391; P = 0.03) along with age, creatinine, NYHA Class III/IV (HR, 1.464; 95% CI: 1.286 to 1.667) and diabetes. β-blockers at baseline were associated with improved survival in patients with LVEF ≤40% independently of COPD. ConclusionCOPD is associated with a poorer survival in HF patients. COPD patients are overrated in terms of NYHA class in comparison with patients with similar LVEF. Nonetheless, NYHA class remains the strongest predictor of death in these patients.

Gender differences among Norwegian patients with heart failure

Recent studies have suggested differences in outcome and treatment between men and women with heart failure. The aim of this study was to see if there were gender differences in the treatment and outcome in real life heart failure patients. Norwegian Heart Failure Registry was used. Three-thousand-six-hundred-and-thirty-two patients (men, n = 2545 (70%), women, n = 1087 (30%)) were included in the study from January 2000 to February 2006. Patients were followed up until death or December 31 2006. The cohort was split into patients with an ejection fraction (EF) less and above 50% and genders were then compared. In the group with EF ≥ 50% the only difference between basic characteristics was that men had a lower heart rate. In the group with an EF<50% women were older, had a higher heart rate, had less often atrial fibrillation, were less often smokers and had a more severe NYHA-classification compared to men. More men used statins and warfarin and coronary heart disease (CHD) was more common as the underlying cause of heart failure among men compared to women. In a Kaplan-Meier analysis there was no significant difference between men and women concerning survival. There are differences in basic characteristics, medical history and treatment between men and women in the Norwegian Heart Failure Registry. The survival rates were equal between men and women in this group of real life patients with heart failure.