[Show abstract][Hide abstract] ABSTRACT: AimsThe 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 resultsPatients 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.
No preview · Article · Nov 2014 · European Journal of Heart Failure
[Show abstract][Hide abstract] ABSTRACT: Purpose: Most European countries have implemented Heart Failure (HF) clinic programs to educate the patients in self-care and optimize doses and adherence of neurohormonal blockade. The optimal duration of the HF clinic program is, however, unknown. This study was, therefore, designed to evaluate the effect of extended follow up in an outpatient HF clinic on long-term adherence to guideline based therapy.
Methods: Multicenter (18 HF clinic's) randomized clinical trial. After education in self-care and optimization in guideline therapy in HF clinic systolic HF patients (N=921) were randomized to either extended follow up the HF clinic (N=461) or discharge to the primary care (N=460) and the patients were followed for a median of 2.5 years (range: 3 months-4.5 years). The effect of the HF clinic intervention on treatment adherence (time to 90 days break in treatment) estimated by drug dispensing from pharmacies with either an Angiotensin Converting Enzyme-Inhibitor/Angiotensin II Receptor Blocker (ACE-I/ARB), a Beta-Blocker (BB) or an Aldosterone Receptor Antagonist (ARA) was then evaluated in Cox Proportional Hazard Models. Subgroup analyses were performed to identify high-risk patients with particular benefit.
Results: At randomization the two groups of patients were matched on baseline characteristics. Median Age was 69 years, 25% were females, LVEF was 30%, 90% were in NYHA class II-III and NT-proBNP was 801 pg/ml, 89% were treated with an ACE-I/ARB, 85% with a BB and 32% with an ARA. The HF clinic intervention did not reduce time to a 90 days break in treatment with either an ACE-I/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 ARA (HR: 1.30, 95% CI: 0.85-2.00, P=0.238). No interaction between adherence, the HF clinic intervention or any high-risk subgroup was observed (NT-proBNP > 1000 pg/ml, eGFR < 60 ml/min/1.73 m2, NYHA class III, high doses of diuretics, elderly, low educational level, low income or living alone) (P> 0.05 for all). At follow up end adherence was 90% for ACE-I/ARB's, 88% for BB's and 75% for ARA's and did not differ between treatment arms (LogRank > 0.05 for all).
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. However, novel strategies to improve long term adherence for aldosterone receptor antagonists are needed.
Preview · Article · Aug 2013 · European Heart Journal
[Show abstract][Hide abstract] ABSTRACT: AimsTo investigate whether left ventricular (LV) systolic shortening velocity (s′), diastolic lengthening velocity (e′), and non-invasively estimated LV filling pressure (E/e′) during low-dose dobutamine echocardiography (LDDE) reflect invasive measures of cardiac output and pulmonary capillary wedge pressure (PCWP) in stable patients with chronic systolic heart failure.Methods and resultsFourteen patients with heart failure (aged 65 ± 8 years, LVEF 36 ± 8%) underwent simultaneous tissue Doppler echocardiography and invasive measurements of cardiac output and PCWP by right heart catheterization at rest and during dobutamine infusion at rates of 10 and 20 μg/kg/min. Cardiac output increased from rest to peak dobutamine (4.9 ± 1.2 to 6.6 ± 2.0 L/min, P < 0.001) and correlated with the peak systolic tissue velocity (s′) at rest (R = 0.61, P = 0.02) and during dobutamine stimulation (R = 0.79, P < 0.001). Increases in early diastolic mitral inflow (E, 74.9 ± 29.0-90.8 ± 29.5 cm/s) and LV lengthening (e′, 6.5 ± 2.4-8.2 ± 2.8 cm/s) velocities were observed during LDDE leaving the E/e′ ratio unchanged. Although a mean PCWP was also unchanged from rest to peak dobutamine (16.6 ± 8.3-14.2 ± 9.2, P = 0.25), E/e′ and PCWP only correlated at rest (R = 0.64, P = 0.014).Conclusion
The LV systolic shortening velocity is closely associated with cardiac output during LDDE in CHF patients. Dobutamine stimulation increases early diastolic mitral inflow and lengthening velocities, but the E/e′ ratio does not reflect the PCWP during LDDE, which warrants some caution in converting changes in E/e′ into changes in LV filling pressure. The sample size is, however, small and the observation need to be confirmed in a larger population.
Preview · Article · Nov 2012 · European Heart Journal Cardiovascular Imaging
[Show abstract][Hide abstract] ABSTRACT: AimsTo investigate the associations between glucose metabolism, left ventricular (LV) contractile reserve, and exercise capacity in patients with chronic systolic heart failure (HF).Methods and resultsFrom an outpatient HF clinic, 161 patients with systolic HF were included (mean age 70 ± 10 years, 69 male, 59 had ischaemic heart disease, mean LV ejection fraction (LVEF) 37 ± 9). Thirty-four (21) patients had known diabetes mellitus (DM). Oral glucose tolerance testing (OGTT) classified patients without a prior DM diagnosis as normal glucose tolerance (NGT), impaired glucose tolerance or new DM. All patients completed low-dose dobutamine echocardiography (LDDE) and 154 patients a 6-min walking distance test (6MWD). Compared with patients with NGT, patients with known DM had lower resting LVEF (33.4 vs. 39.1, P < 0.05) and higher E/e′ (13.9 vs. 11.4, P < 0.05). During LDDE, an increase in LVEF could be observed in all glycemic groups (mean 8.2 absolute increase), but the contractile reserve was lower in patients with known DM (-5.4, P 0.001) and new DM (-3.5, P 0.035) compared to patients with NGT. 6MWD was lower in known DM (349 m) and new DM (379 m) compared with NGT (467 m) (P < 0.001). Differences in clinical variables, resting echocardiographic parameters or contractile reserve, did not explain the exercise intolerance related to diabetes.Conclusion
Diabetes, known or newly detected by OGTT, is independently associated with reduced LV contractile reserve and exercise intolerance in outpatients with systolic HF. These findings may offer one explanation for the excess mortality related to diabetes in HF.
Full-text · Article · Aug 2012 · European Heart Journal Cardiovascular Imaging
[Show abstract][Hide abstract] ABSTRACT: Our aim was to assess the prognostic impact of a high-sensitivity cardiac troponin T (hs-cTnT) assay in an outpatient population with chronic systolic left ventricular heart failure (HF). Four hundred sixteen patients with chronic HF and left ventricular ejection fraction ≤ 45% were enrolled in a prospective cohort study. In addition to hs-cTnT, plasma amino-terminal pro-B-type natriuretic peptide was measured at baseline. Mean age was 71 years, 29% were women, 62% had coronary artery disease (CAD), mean left ventricular ejection fraction was 31%, and 57% had abnormal level of hs-cTnT. During 4.4 years of follow-up, 211 (51%) patients died. In multivariate Cox regression models, hs-cTnT was categorized as quartiles or dichotomized by the 99th percentile of a healthy population. Adjusted hazard ratios for all-cause mortality for quartiles 2 to 4, with quartile 1 as reference, were 1.4 (95% confidence interval 0.9 to 2.4, p = 0.16) for quartile 2, 1.7 (0.9 to 2.5, p = 0.12) for quartile 3, and 2.6 (1.6 to 4.4, p <0.001) for quartile 4 and 1.7 (1.2 to 2.5, p = 0.003) for abnormal versus normal level of hs-cTnT. In patients without CAD, quartile 4 of hs-cTnT was associated with an adjusted hazard ratio of 6.8. In conclusion, hs-cTnT is increased in most outpatients with chronic systolic HF and carries prognostic information beyond clinical parameters and amino-terminal pro-B-type natriuretic peptide. Increased hs-cTnT indicated a particularly deleterious prognosis in patients without CAD.
No preview · Article · May 2012 · The American journal of cardiology
[Show abstract][Hide abstract] ABSTRACT: No consensus exists whether subclinical thyroid disease should be treated or just observed. Untreated overt thyroid disease is associated with increased risk of cardiovascular disease, and this study was conducted to assess the risk of cardiovascular events in subclinical thyroid disease. The population-based prospective study was conducted in Denmark. A total of 609 subjects from general practice aged 50 years or above with normal left ventricular function were examined. During a median of 5 years of follow-up, major cardiovascular events were documented. In subjects with abnormal TSH at baseline, information about potential thyroid treatment during follow-up was obtained from case reports and mailings. At baseline, 549 (90.7%) were euthyroid (TSH 0.40-4.00 mU/l), 31 (5.1%) were subclinical hypothyroid (TSH>4.00 mU/l), and 25 (4.1%) were subclinical hyperthyroid (TSH<0.40 mU/l). 1 overt hyperthyroid and 3 overt hypothyroid participants were excluded from the analyses. At baseline, the levels of NT-proBNP were inversely associated with the levels of TSH; the lower the levels of TSH, the higher the NT-proBNP concentration. During follow-up, 88 participants died, 81 had a major cardiovascular event, and 28 had a stroke. The incidence of stroke was increased among subjects with subclinical hyperthyroidism, HR 3.39 (95% CI 1.15-10.00, p=0.027) after adjusting for sex, age, and atrial fibrillation. Subclinical hypothyroidism was not related with any of the outcome measurements. Subclinical hyperthyroidism seems to be a risk factor of developing major cardiovascular events, especially stroke in older adults from the general population with normal left ventricular function.
No preview · Article · Aug 2011 · Hormone and Metabolic Research
[Show abstract][Hide abstract] ABSTRACT: We evaluated the applicability and prognostic importance of oral glucose tolerance testing (OGTT) among outpatients with systolic heart failure (SHF).
Consecutive patients with SHF and left ventricular ejection fraction (LVEF) ≤ 45% referred to a heart failure clinic (n= 413) were included in this study. An OGTT was conducted in patients without a history of diabetes. Information on NYHA class, aetiology of SHF, LVEF, treatment, and biochemical parameters were collected at baseline. The survival status was obtained after a median follow-up time of 591 days. Of the 413 patients, 82 (20%) had known diabetes. Of the remaining 331 patients, 227 (69%) agreed to undergo an OGTT. Among the tested subjects, 136 (60%) were classified as having normal glucose tolerance (NGT), 51 (23%) impaired glucose tolerance (IGT), and 40 (18%) newly diagnosed diabetes. Assuming a similar prevalence of unrecognized diabetes among the patients who refused OGTT, the prevalence of diabetes in the total population was 34%. If only fasting blood glucose had been used, 16 of the 40 newly diagnosed diabetic patients would have been undiagnosed. During follow-up, 24 (29%) patients with known diabetes, 6 (15%) of the newly diagnosed diabetic patients, 9 (18%) of those with IGT, and 13 (9%) patients with NGT died. Patients with diabetes had higher mortality rate compared with non-diabetic patients [multivariate hazard ratio 1.89 (1.02-3.59); P = 0.047].
It is feasible to perform diabetes screening using OGTT in outpatients with SHF. A substantial proportion of patients tested were found to have unrecognized diabetes. The presence of diabetes was associated with a higher mortality rate.
No preview · Article · Mar 2011 · European Journal of Heart Failure
[Show abstract][Hide abstract] ABSTRACT: Randomized clinical trials have shown that newly discharged and symptomatic patients with chronic heart failure (CHF) benefit from follow-up in a specialized heart failure clinic (HFC). Clinical stable and educated patients are usually discharged from the HFC when on optimal therapy. It is unknown if risk stratification using natriuretic peptides could identify patients who would benefit from longer-term follow-up. Furthermore, data on the use of natriuretic peptides for monitoring of stable patients with CHF are sparse.
The aims of this study are to test the hypothesis that clinical stable, educated, and medical optimized patients with CHF with N-terminal pro-brain natriuretic peptide (NT-proBNP) levels > or = 1,000 pg/mL benefit from long-term follow-up in an HFC and to assess the efficacy of NT-proBNP monitoring.
A total of 1,250 clinically stable, medically optimized, and educated patients with CHF will be enrolled from 18 HFCs in Denmark. The patients will be randomized to treatment in general practice, to a standard follow-up program in the HFC, or to NT-proBNP monitoring in the HFC. The patients will be followed for 30 months (median).
Data will be collected from 2006 to 2009. At present (March 2008), 720 patients are randomized. Results expect to be presented in the second half of 2010.
This article outlines the design of the NorthStar study. If our hypotheses are confirmed, the results will help cardiologists and nurses in HFCs to identify patients who may benefit from long-term follow-up. Our results may also indicate whether patients with CHF will benefit from adding serial NT-proBNP measurements to usual clinical monitoring.
Full-text · Article · Oct 2008 · American heart journal
[Show abstract][Hide abstract] ABSTRACT: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study showed that losartan-based treatment reduced risk of the composite endpoint of cardiovascular death, stroke and myocardial infarction compared with atenolol-based treatment in patients with hypertension and left ventricular hypertrophy with similar office blood pressure (BP) reduction. Our aim was to investigate the effect of losartan- and atenolol-based treatment on 24-h ambulatory BP and heart rate (HR) in LIFE.
In 110 patients, 24-h ambulatory BP and heart rate were recorded at baseline and 1 year after randomization.
Ambulatory BP was comparably reduced throughout the 24-h period after 1 year of losartan- vs atenolol-based antihypertensive treatment. Office and ambulatory BP were comparably reduced in the follow-up period. Early morning surge in BP was similar between groups. Non-dipping status was more frequent in the losartan group (p = 0.01). From baseline to Year 1 the 24-h HR profile for the losartan group was unchanged, but, as expected, there was a significant decrease in daytime HR in the atenolol group, which was not as large during early night-time.
There were no differences in 24-h BP burden and HR that could explain the difference in outcome in favor of losartan vs atenolol in the LIFE study.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the effects of losartan- vs atenolol-based antihypertensive treatment on circulating collagen markers beyond the initial blood pressure (BP) reduction.
In 204 patients with hypertension and left ventricular (LV) hypertrophy we measured serum concentration of carboxy-terminal telopeptide of type I procollagen (ICTP), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), amino-terminal propeptide of type I procollagen (PINP) and LV mass by echocardiography at baseline and annually during 4 years of losartan- or atenolol-based antihypertensive treatment; 185 patients completed the study.
Beyond the first year of treatment systolic and diastolic BP, LV mass index (LVMI) as well as collagen markers did not change significantly and were equal in the two treatment groups. Changes in PICP during first year of treatment were related to subsequent changes in LV mass index after 2 and 3 years of treatment (r=0.28 and r=0.29, both p<0.05) in patients randomized to losartan, but not atenolol.
Long-term losartan- vs atenolol-based antihypertensive treatment did not influence collagen markers differently, making a BP-independent effect of losartan on collagen markers unlikely. However, initial reduction in circulating PICP may predict later regression of LV hypertrophy during losartan-based antihypertensive treatment.
[Show abstract][Hide abstract] ABSTRACT: Type 2 diabetic patients with hypertension have an increased left ventricular (LV) mass and impaired cardiac function compared to hypertensive patients without diabetes. However, it is unknown if the impaired cardiac function can be explained solely by LV hypertrophy, or is independently related to diabetes. The aim of the present study was to compare LV function between diabetic and non-diabetic hypertensive patients with electrocardiographic LV hypertrophy.
In 937 patients participating in the LIFE echocardiographic substudy, all echocardiograms were centrally evaluated by a core reading centre measuring LV mass, systolic and diastolic LV function. Known diabetes was present in 105 patients.
Left ventricular mass was similar in diabetic and non-diabetic patients. Endocardial systolic LV function, estimated by LV ejection fraction, was reduced and indices of midwall systolic LV function were impaired in the diabetic patients. Diastolic LV filling pattern was impaired and arterial stiffness, measured by pulse pressure/stroke index, was increased in diabetic patients.
Systolic and diastolic LV function in hypertensive patients with electrocardiographic LV hypertrophy and diabetes are impaired independent of LV mass, most likely reflecting the adverse effects of diabetes per se.
Full-text · Article · Sep 2005 · Diabetic Medicine
[Show abstract][Hide abstract] ABSTRACT: Secretion of natriuretic peptides is related to cardiac wall stress and influenced by the renin-angiotensin system. Therefore, we investigated the influence of blood pressure (BP) reduction with losartan versus atenolol on N-terminal pro-atrial natriuretic peptide (Nt-proANP) and N-terminal pro-brain natriuretic peptide (Nt-proBNP).
In 183 patients with hypertension and electrocardiographic left ventricular (LV) hypertrophy, enrolled in the LIFE Study, we measured BP and serum Nt-proANP and Nt-proBNP by immunoassay after 2 weeks of placebo treatment and after 1, 2, 4, 6, 12, 24, 36 and 48 months of randomized treatment with losartan- or atenolol-based antihypertensive regimens.
There was no significant difference in BP at any time point between the two treatment groups. In patients treated with losartan, median Nt-proANP decreased gradually throughout the study, reaching significance after 6 months of treatment (1125-1060 pmol/l, P < 0.001), and Nt-proBNP decreased within the first month (24.7-18.7 pmol/l, P < 0.01) and stayed reduced throughout the study. During losartan-based antihypertensive treatment, Nt-proANP and Nt-proBNP as a percentage of baseline values were correlated to reductions in systolic BP (r = 0.11, P < 0.01 and r = 0.10, P = 0.01) and diastolic BP (r = 0.17, P < 0.001 and r = 0.07, P = 0.09). In atenolol-treated patients, Nt-proANP (1100-1640 pmol/l, P < 0.001) and Nt-proBNP (20.0-37.7 pmol/l, P < 0.001) increased during the first month, and remained elevated throughout the study. During atenolol-based antihypertensive treatment, changes in Nt-proANP (r = -0.16, P < 0.001) and Nt-proBNP (r = -0.07, P = 0.08) were negatively related to change in heart rate.
Nt-proANP and Nt-proBNP were reduced in parallel with BP in losartan-treated patients whereas they increased in parallel with decreased heart rate in atenolol-treated patients.
No preview · Article · Jun 2005 · Journal of Hypertension
[Show abstract][Hide abstract] ABSTRACT: Purpose: To investigate the relation between neurohormones and brachial artery compliance (BAC) and distensibility (BAD) and vascular
collagen degredation (ICTP) in hypertensive patients with a high prevalence of left ventricular hypertrophy (LVH).
No preview · Article · May 2005 · American Journal of Hypertension
[Show abstract][Hide abstract] ABSTRACT: Cardiac fibrosis and high levels of circulating collagen markers has been associated with left ventricular (LV) hypertrophy. However, the relationship to vascular hypertrophy and blood pressure (BP) load is unclear. In 204 patients with essential hypertension and electrocardiographic LV hypertrophy, we measured sitting BP, serum collagen type I carboxy-terminal telopeptide (ICTP) reflecting degradation, procollagen type I carboxy-terminal propeptide (PICP) reflecting synthesis and LV mass by echocardiography after 2 weeks of placebo treatment and after 1 year of antihypertensive treatment with a losartan- or an atenolol-based regimen. Furthermore, we measured intima-media thickness of the common carotid arteries (IMT), minimal forearm vascular resistance (MFVR) by plethysmography and ambulatory 24-h BP in around half of the patients. At baseline, PICP/ICTP was positively related to IMT (r=0.24, P<0.05), MFVR(men) (r=0.35, P<0.01), 24-h systolic BP (r=0.24, P<0.05) and 24-h diastolic BP (r=0.22, P<0.05), but not to LV mass. After 1 year of treatment with reduction in systolic BP (175+/-15 vs 151+/-17 mmHg, P<0.001) and diastolic BP (99+/-8 vs 88+/-9 mmHg, P<0.001), ICTP was unchanged (3.7+/-1.4 vs 3.8+/-1.4 microg/l, NS) while PICP (121+/-39 vs 102+/-29 microg/l, P<0.001) decreased. The reduction in PICP/ICTP was related to the reduction in sitting diastolic BP (r=0.31, P<0.01) and regression of IMT (r=0.37, P<0.05) in patients receiving atenolol and to reduction in heart rate in patients receiving losartan (r=0.30, P<0.01). In conclusion, collagen markers reflecting net synthesis of type I collagen were positively related to vascular hypertrophy and BP load, suggesting that collagen synthesis in the vascular wall is increased in relation to high haemodynamic load in a reversible manner.
Full-text · Article · Apr 2005 · Journal of Human Hypertension
[Show abstract][Hide abstract] ABSTRACT: N-terminal pro-brain natriuretic peptide (Nt-proBNP) and N-terminal pro-atrial natriuretic peptide (Nt-proANP) are strong cardiovascular risk markers in patients with chronic heart failure, as well as in the general population. We investigated whether high Nt-proBNP or Nt-proANP could also predict the composite endpoint (CEP) of cardiovascular death, non-fatal stroke or non-fatal myocardial infarction in patients with hypertension and left ventricular (LV) hypertrophy.
After 2 weeks of placebo treatment, clinical, laboratory and echocardiographic variables were assessed in 183 hypertensive participants in the LIFE echo substudy with electrocardiographic LV hypertrophy. Nt-proBNP and Nt-proANP were measured by immunoassay at baseline. The patients were followed for 60 +/- 5 months.
Using Cox regression analysis, the 25 CEP were predicted by ln(Nt-proBNP) (hazard ratio 1.61 per 2.73-fold increase, P < 0.01) as well as ln(Nt-proANP) (hazard ratio 2.93, P < 0.05). Nt-proBNP above the median value of 21.8 pmol/ml was associated with higher incidence of CEP (19.6 versus 7.7%, P < 0.05). Nt-proBNP above the median value was associated with higher incidence of CEP in the 123 patients without history of diabetes or cardiovascular disease (14.8 versus 4.3%, P < 0.05), but the association was insignificant in the 60 patients with a history of diabetes or cardiovascular disease (26.3 versus 18.2%, NS). Nt-proANP showed the same tendency.
Nt-proBNP, more than Nt-proANP, strongly predicts cardiovascular events in patients with hypertension and LV hypertrophy, especially in patients without diabetes or clinically overt cardiovascular disease.
Full-text · Article · Aug 2004 · Journal of Hypertension