Usefulness of Collagen Carboxy-Terminal Propeptide and Telopeptide to Predict Disturbances of Long-Term Mortality in Patients ≥60 Years With Heart Failure and Reduced Ejection Fraction.

Disturbances of collagen metabolism may alter the myocardial collagen network and contribute to cardiac remodeling and prognosis in heart failure (HF). Collagen type I synthesis and degradation can be assessed indirectly by the circulating biomarkers carboxy-terminal propeptide (PICP) and carboxy-terminal telopeptide (CITP), respectively. We examined the associations between PICP and CITP and long-term mortality in patients with HF. The Optimizing Congestive Heart Failure Outpatient Clinic (OPTIMAL) project studied patients aged ≥60 years with New York Heart Association class II to IV and HF with reduced ejection fraction (EF) hospitalized with acute HF during 1996 to 1999. On entry, mean age was 75 years, blood pressure 134/80 mm Hg, EF 34%, brain natriuretic peptide 312 pg/ml; 55% had atrial fibrillation. Dates of mortality were collected from administrative databases and medical records up until 2008. Follow-up was 9 to 13 years in all 132 patients, and mean survival was 5.5 ± 4.0 years. Baseline PICP tended to be higher, CITP was higher, and the PICP:CITP ratio was lower in the 102 deceased, compared with the 30 patients alive. Multivariable Cox regression analyses including 2 established risk factor models performed for all-cause (n = 101) and cardiovascular mortality (n = 61) show PICP and CITP to be independent predictors for all-cause and cardiovascular mortality. In conclusion, disturbances of collagen type I metabolism have independent prognostic implications for long-term all-cause and cardiovascular mortality in patients with HF with reduced EF. The results suggest excessive degradation to be the predominant disturbance associated with untoward prognosis and adds information on possible target mechanisms for future therapy.

How to best assess quality of drug treatment in patients with heart failure.

BACKGROUND: The proportion of patients with heart failure (HF) treated with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) is frequently used as quality indicator. This study aimed to compare agreement between different methods of calculating this quality indicator. In addition, characteristics for patients and care providers associated with a high proportion treated with ACEI or ARB were analyzed. METHODS: This Swedish cross-sectional register-based study was conducted in the Stockholm region (2.1 million inhabitants). The proportion of patients with HF treated with ACEI or ARB was calculated by different methods applied on an administrative database on healthcare consumption, diagnoses, and dispensed drugs and by self-reported data from all primary care centers in the region. RESULTS: A total of 32,677 patients recorded with a HF diagnosis 2008-2012 and alive July-December 2012 were identified. The proportion treated with ACEI or ARB varied depending on observation period and care provider included (range register 52-74 %). There was a large variation between different primary care centers (range register 36-88 %, range self-reported 8-100 %) and a poor agreement between methods (Bland-Altman; rhoc range 0.07-0.23). Predictors for high proportion treated were low age, high socioeconomic status, cardiovascular comorbidity, and diagnosis recorded both in primary care and in hospitals. CONCLUSIONS: There is poor agreement between different methods to evaluate adherence to guidelines for drug treatment in HF. Differences between practices concerning patient age, socioeconomic status, comorbidity, and care given by different providers should be taken into account in quality assessment.

Determinants of Utility Based on the EuroQol Five-Dimensional Questionnaire in Patients with Chronic Heart Failure and Their Change Over Time: Results from the Swedish Heart Failure Registry.

BACKGROUND: There is limited information on drivers of utilities in patients with chronic heart failure (CHF). OBJECTIVES: To analyze determinants of utility in CHF and drivers of change over 1 year in a large sample from clinical practice. METHODS: We included 5334 patients from the Swedish Heart Failure Registry with EuroQol five-dimensional questionnaire information available following inpatient or outpatient care during 2008 to 2010; 3495 had 1-year follow-up data. Utilities based on Swedish and UK value sets were derived. We applied ordinary least squares (OLS) and two-part models for utility at inclusion and OLS regression for change over 1 year, all with robust standard errors. We assessed the predictive accuracy of both models using cross-validation. RESULTS: Patients' mean age was 73 years, 65% were men, 19% had a left ventricular ejection fraction of 50% or more, 23% had 40% to 49%, 27% had 30% to 39%, and 31% had less than 30%. For both models and value sets, utility at inclusion was affected by sex, age, New York Heart Association class, ejection fraction, hemoglobin, blood pressure, lung disease, diabetes, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, nitrates, antiplatelets, and diuretics. The OLS model performed slightly better than did the two-part model on a population level and for capturing utility ranges. Change in utility over 1 year was influenced by age, sex, and (measured at inclusion) disease duration, New York Heart Association class, blood pressure, ischemic heart disease, lung disease, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and antiplatelets. CONCLUSIONS: Utilities in CHF and their change over time are influenced by diverse demographic and clinical factors. Our findings can be used to target clinical interventions and for economic evaluations of new therapies.

A management programme for suspected heart failure in primary care in cooperation with specialists in cardiology.

BACKGROUND: The diagnosis of new onset congestive heart failure (CHF) is often difficult as symptoms and signs are non-specific. Proper diagnostic investigations and treatments are underused in primary care. OBJECTIVE: To describe a management programme for patients with suspected CHF in primary care in cooperation with specialists in cardiology. METHODS: Prospective study of 102 consecutive primary care patients with suspected new onset CHF referred to an easily accessible hospital-based cardiology outpatient clinic management programme. Following clinical examination, ECG, echocardiography, blood chemistry including NT-proBNP, and assessment of NYHA class and quality of life (EQ5D), patients with a confirmed diagnosis of CHF were prescribed medication with advice on titration and target doses. Trained CHF nurses gave Information on CHF and provided follow up. RESULTS: Half (47%) of the referred patients had the diagnosis of CHF confirmed. Low NT-proBNP values (< 300 ng/l) provided a negative predictive value of 73%. Respiratory tract diseases were common differential diagnoses. At one year of follow-up, medication in the CHF group was 86% ACE-inhibitors/angiotensin receptor blockers, 61% ß-blocking agents, and 81% diuretics (P < 0.001 for the increase in ACE-inhibitors/angiotensin receptor blockers from baseline). NYHA class improved from baseline (median 2, range: 1-3) to one year (P < 0.05), whereas NT-proBNP (1491-1261 ng/l), and quality of life (EQ5D; 67-67) were unchanged. CONCLUSION: A management programme to optimize quality of care for patients with suspected new onset CHF in primary care, with referral to a hospital-based specialist team, can be applied successfully.

Health-related quality of life and long-term morbidity and mortality in patients hospitalised with systolic heart failure.

BACKGROUND: Health-related quality of life has been shown to impact prognosis in chronic heart failure, however with limited long-term follow-up. We analysed data spanning 8-12 years to assess the impact of health-related quality of life using the Nottingham Health Profile on first hospitalisation and mortality, for cardiovascular and all causes. METHODS: We included 208 patients aged ≥60 years with New York Heart Association class II-IV and left ventricular systolic dysfunction hospitalised in Stockholm during 1996-99. Data on hospital admissions, discharge diagnoses and date and cause of death were collected from administrative databases and medical records until 2007. Cox proportional hazard models were employed to analyse the time to event for mortality and hospitalisations. RESULTS: Mean age was 76 years, 58% were male and mean ejection fraction was 34%. Median survival was 4.6 years (range 6 days-11.9 years); 148 patients died. All-cause and cardiovascular mortality were determined by physical mobility (by Nottingham Health Profile), age, gender, diuretic dose and haemoglobin level. Glomerular filtration rate was significant for all-cause mortality, while atrioventricular plane displacement was predictive of cardiovascular mortality. Median time to first all-cause and cardiovascular hospitalisation was 5.7 and 11.2 months, respectively. Time to first all-cause hospitalisation was determined by physical mobility, emotional reactions, age, gender and haemoglobin level, while only physical mobility and diuretic dose predicted time to first cardiovascular hospitalisation. CONCLUSIONS: In conclusion, in patients with systolic chronic heart failure, physical mobility as part of health-related quality of life is an independent prognostic marker for cardiovascular and all-cause readmissions and mortality over 12 years.

Biomarkers of collagen type I metabolism are related to B-type natriuretic peptide, left ventricular size, and diastolic function in heart failure.

AIMS: Myocardial collagen metabolism can be assessed indirectly by circulating biomarkers. We aimed to examine associations between myocardial collagen type I synthesis and degradation, and echocardiographic, clinical, and B-type natriuretic peptide (BNP) findings in heart failure. METHODS: We studied 57 women and 75 men 60 years or older with systolic heart failure (New York Heart Association II-IV and an ejection fraction ≤ 45%). Mean age was 75 years, blood pressure 134/80  mmHg, ejection fraction 34%, and median BNP 210  ng/l. Analyses of the carboxy-terminal propeptide of procollagen type I (PICP, biomarker of collagen type I synthesis) and the serum carboxy-terminal telopeptide of collagen type I (CITP, biomarker of collagen type I degradation) were measured. Extensive echocardiographic examinations were performed, including variables of dyssynchrony. RESULTS: Increased collagen synthesis (PICP) was independently related to increased BNP levels (r = 0.24, P = 0.018). Furthermore, independent associations were found between PICP and left ventricular size, isovolumic relaxation time, and relative wall thickness. Increased collagen degradation (CITP) was independently related to increased BNP levels (r = 0.35, P < 0.001). Also, univariable, but not multivariable, associations were found between CITP and E/E' septal and QRS duration. CONCLUSION: Biomarkers of collagen type I synthesis and degradation are independently related to BNP and to indices of left ventricular size and diastolic function in systolic heart failure. It is proposed that BNP may contribute to alterations in collagen type I metabolism in systolic heart failure.

Atrial fibrillation and biomarkers of myocardial fibrosis in heart failure.

OBJECTIVES: Alterations of collagen metabolism present in heart failure promote the fibrotic substrate for the development of atrial fibrillation (AF). Myocardial collagen I synthesis and degradation can be assessed indirectly by circulating biomarkers such as the carboxy terminal propeptide (PICP) and carboxy-terminal telopeptide (CITP), respectively. DESIGN: We examined myocardial collagen type-I metabolism in 143 patients with systolic heart failure (New York Heart Association Class 2-4) in relation to coexisting AF. RESULTS: Mean age was 75 years, blood pressure 134/80 mm Hg, ejection fraction 34%, serum PICP 81 µg/L and CITP 8.3 µg/L, and median plasma brain natriuretic peptide 215 pg/L; 77 were in AF. PICP and CITP were related to left atrial diameter (r = 0.22, P = 0.013, and r = 0.26, P = 0.003) and CITP to pulmonary capillary wedge pressure and C-reactive protein (r = 0.19, P = 0.044, and r = 0.29, P = 0.003). A logistic regression suggested that PICP (odds ratio per 1 µg/L change 1.01, P = 0.012) and left ventricular end-diastolic volume (odds ratio per 1 mL change 0.98, P < 0.001) were independently associated with coexisting AF. CONCLUSION: Collagen type-I metabolism is associated to left atrial size. Heart failure patients with coexisting AF exhibit more altered collagen type-I metabolism than patients in sinus rhythm. This might represent more severe atrial and ventricular fibrosis.

The epidemiology of heart failure, based on data for 2.1 million inhabitants in Sweden.

AIMS: The epidemiology of congestive heart failure (CHF) is likely to have changed due to changes in demography, risk factors, diagnostic procedures, and medical care. Prevailing information is in part old, incomplete, and to some extent contradictory. We determined the current prevalence, incidence, mortality, and 5-year survival rate of CHF, and possible temporal changes in Sweden. METHODS AND RESULTS: This was a cross-sectional study on individual patient data from an administrative health data register in the Stockholm region, Sweden, comprising 2.1 million inhabitants. This contained all recorded diagnoses on all consultations in primary and secondary care (defined as specialist outpatient care), and on all hospitalizations. Prevalence, incidence, and mortality were estimated for the entire Swedish population, adjusted for demographic composition in 2010. The study population consisted of 88 038 patients (51% women). The prevalence was 2.2% (both women and men), the incidence was 3.8/1000 person-years (both women and men), and mortality was 3.2/1000 person-years in women and 3.0/1000 person-years in men (P < 0.001); the 5-year survival rate was 48%. Mortality (age adjusted; hazard ratio and 95% confidence intervals) was higher in men, 1.29, 1.24-1.34; P < 0.001. Prevalence remained essentially unchanged from 2006 to 2010, while incidence decreased by 24% (P < 0.001) and mortality by 19% (both women and men; P < 0.001). CONCLUSIONS: The estimated prevalence of CHF in Sweden is 2.2%, incidence 3.8/1000 person-years, and mortality 3.1/1000 person-years. There has been a decrease in incidence and mortality from 2006 to 2010 in both women and men, with no major change in prevalence over time.

Long term health care consumption and cost expenditure in systolic heart failure.

BACKGROUND: The prevalence, health care consumption, and mortality increase in elderly patients with heart failure. This study aimed to analyse long term cost expenditure and predictors of health care consumption in these patients. METHODS: We included 208 patients aged 60 years or older and hospitalised with heart failure (NYHA class II-IV and left ventricular systolic dysfunction); 58% were men, mean age 76 years, and mean ejection fraction 0.34. Data on all hospital admissions, discharge diagnoses, lengths of stay, and outpatient visits were collected from the National Board of Health and Welfare. We obtained data of all health care consumption for each individual. RESULTS: After 8-12 years of prospective follow up 72% were dead (median survival 4.6 years). Main drivers of health care expenditure were non-cardiac (40%) and cardiac (29%) hospitalizations, and visits to primary care centres (16%), and hospital outpatient clinics (15%). On average, health care expenditures were € 36,447 per patient during follow up. The average yearly cost per patient was about 5,700€, in contrast to the estimated consumption of primary and hospital care in the general population: € 1,956 in 65-74 year olds and € 2,701 in 75-84 year olds. Poor quality of life (Nottingham Health Profile) was the strongest independent predictor of total health care consumption and costs (p<0.001; by multivariate analyses). CONCLUSION: Health care costs in chronic systolic heart failure are at least two-fold higher than in the general population. Quality of life is a strong independent predictor of health care consumption.

Ten-year follow-up after autologous stem cell transplantation of a patient with immunoglobulin light-chain (AL) amyloidosis with deposits in the heart, liver and gastrointestinal tract.

The prognosis in amyloid light chain (AL)-amyloidosis and multiorgan involvement is poor, with a high-treatment-related mortality after high-dose melphalan and autologous stem cell transplantation (HDM/SCT). Some patients, however, might benefit from the therapy. We report a case of cardiac AL-amyloidosis with multiorgan involvement where the progressive cardiomyopathy was halted after successful treatment with HDM/SCT in 2001. The patient is in an excellent cardiac condition with a good quality of life, receiving treatment with angiotensinogen receptor blockers and a flexible diuretics regimen at follow-up after 10 years.

Quality of life in chronic disease: a comparison between patients with heart failure and patients with aphasia after stroke.

OBJECTIVES: This study aimed to describe the impact of heart failure and of stroke with aphasia on quality of life (QoL) and to compare the different domains of QoL in these groups. BACKGROUND: The prevalence of chronic conditions has increased during the last decades, and chronic diseases such as stroke and heart failure may have a great impact on QoL. DESIGN: Comparative study of patients from two randomised controlled studies. METHOD: Seventy-nine patients with heart failure and 70 patients with aphasia after stroke were evaluated concerning the severity of their disease and by QoL, as measured with the Nottingham Health Profile, in the acute phase and after six months. RESULTS: The severity of the disease improved between baseline and six month for both groups. Correlations between New York Heart Association (NYHA) class and all QoL domains were seen in patients with heart failure after six months. The degree of aphasia correlated to mobility, social, emotional and total score after six month. QoL in patients with heart failure was more affected in the domains of sleep and energy in the acute phase and in the energy domain at six months. CONCLUSION: Although low energy is more frequent among patients with heart failure, both groups report poor QoL. Improvement in severity of the disease is not necessarily accompanied by improvement in QoL. RELEVANCE TO CLINICAL PRACTICE: Nottingham Health Profile can easily be used as a screening instrument, aiming to identify patients at risk for adverse effects on QoL. A better understanding of the subjective QoL of patients with chronic disease is fundamental for health care professionals to be able to identify and support vulnerable patients.

Congestive heart failure with and without atrial fibrillation - different patient populations?

OBJECTIVES: Heart failure (HF) and atrial fibrillation (AF) are common comorbid conditions in hospitalised patients. AF may occur when left ventricular (LV) systolic function deteriorates. The aim was to compare HF patients with AF to patients in sinus rhythm (SR). DESIGN: Echocardiography and a cardiopulmonary exercise test were performed in 67 patients with HF. Peak VO(2) was determined, as were LV-mass, enddiastolic, endsystolic volume indices (EDVI, ESVI), and ejection fraction (EF). RESULTS: EF tended to be higher in AF compared to SR patients (39+/-10 vs. 31+/-10%), LV volume indices were smaller (ESVI:35+/-19 vs. 59+/-25 ml/m(2), p<0.0001, EDVI:56+/-24 vs. 83+/-29 ml/m(2), p<0.001). LV hypertrophy was prevalent (59% vs. 63%) and concentric hypertrophy tended to be more common with AF (50% vs. 21%). Peak VO(2) was similarly reduced in AF and SR (11.4+/-3.2 vs. 12.1+/-4.3 ml/kg*min). CONCLUSIONS: HF patients with AF compared to SR tend to have smaller LV volumes, less compromised systolic function and more frequent LV concentric hypertrophy. Our study supports the concept that AF in HF indicates a different patient population rather than an effect of progressive LV systolic dysfunction.

Sex differences in systolic heart failure in the elderly: the prognostic importance of left ventricular mass in women.

HYPOTHESIS: We investigated the hypothesis that there are prognostic differences in the importance of left ventricular (LV) mass and function between male and female patients hospitalized with heart failure. METHODS: Patients > or =60 years old hospitalized with New York Heart Association class II-IV heart failure and LV systolic dysfunction were prospectively followed for > or =18 months. At study start, a physical examination and echocardiography were performed, and blood chemistry samples were obtained. RESULTS: Of 158 patients, 66 (42%) women were included and were followed for a mean of 3.1 years. The women were older (77 +/- 7 vs. 74 +/- 7 years, p < 0.01) and had lower mortality (24% vs. 43%, p < 0.05) than the men. No gender differences in etiology or medication were found. LV mass index (LVMI 132 +/- 42 vs. 156 +/- 21 g/m(2), p < 0.01) was lower in women. Mortality in women was related to lower LV ejection fraction, larger LV volumes, and higher LVMI (all p < 0.05). In multivariate analysis, LVMI was the strongest independent mortality predictor in women (adjusted hazard ratio [HR] LMVI >125 g/m(2) 7.4 [1.5-35.5], p = 0.01), whereas this association was not found in men. CONCLUSIONS: In patients hospitalized with systolic heart failure, women had lower mortality than men. In women, an increased LVMI was a stronger predictor of mortality than traditional measures of LV size and function. LVMI should be considered for assessment of prognosis in women with heart failure.

Post-systolic motion in patients with heart failure--a marker of left ventricular dyssynchrony?

AIMS: The pathophysiology of post- systolic motion (PSM) is not yet fully resolved. Our aim was to study PSM in patients with heart failure (HF) and its relation to left ventricular (LV) function, brain natriuretic peptide (BNP) and to mortality. METHOD AND RESULTS: Forty seven HF patients, mean-age 75+/-8 years with LV ejection fraction (EF) 31+/-11% were studied prospectively and compared with 10 age-matched healthy controls. Doppler Tissue Imaging data were obtained in the basal 4-chamber segments of the septal wall and PSM were measured as the ratio between velocity time integral (vti) of the positive post-systolic and systolic motion. Mean septal wall PSM was increased 0.52+/-0.41 vs controls 0.05+/-0.07 (p<0.001) and abnormal PSM (>0.18) was detected in 79% of all HF patients (92% if QRS >130 ms). Septal wall PSM correlated with QRS-duration, LV volume indices, myocardial isovolumic relaxation time (IVRT(m)) and inversely with heart rate and diastolic blood pressure, but not with BNP levels or LVEF. Only IVRT(m) correlated independently with the PSM (R(2)=0.55, p<0.001). Seventeen patients died during a mean follow-up time of 30+/-18 months. The PSM value was similar in non-survivors and survivors, 0.53+/-0.45 vs 0.52+/-0.45 (ns). CONCLUSIONS: PSM is a common phenomenon in patients with HF especially in patients with wide QRS and long IVRT(m) suggesting that PSM is a manifestation of LV intra-ventricular dyssynchrony. In this study PSM did not predict mortality.

A nurse-based management program in heart failure patients affects females and persons with cognitive dysfunction most.

It is important that congestive heart failure (CHF) patients know how to monitor and manage disease-associated signs and symptoms. CHF patients were randomised to follow-up at a nurse-based outpatient clinic (intervention group (IG); n = 103), or to follow-up in primary healthcare (control group (CG); n = 105). Patient knowledge of CHF and self-care were assessed by a questionnaire and cognitive function by a Mini Mental State Examination (MMSE) at baseline and at six months. Men knew more about CHF as compared to females at baseline (p < 0.01). However, females in the IG increased their knowledge of self-care between baseline and six months as compared to CG females (p < 0.05). Patients with cognitive dysfunction (MMSE < 24) presented lower scores on knowledge as compared to those with a MMSE of >24 at baseline (p < 0.01). These differences disappeared after the intervention. Thus, females seemed to gain more than men from a nurse-based management program and patients with in-hospital signs of cognitive dysfunction should be encouraged to participate.