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1.
Heart Fail Rev ; 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31364027

RESUMO

This study aims to assess the comparative benefit and risk profile of treatment with mineralocorticoid receptor antagonists (MRAs) with regard to all-cause mortality (primary endpoint), cardiovascular mortality, or heart failure (HF)-related hospitalization (secondary endpoints) and the safety endpoints hyperkalemia, acute renal failure, and gynecomastia in patients with chronic HF. We conducted a systematic review and network meta-analysis following PRISMA-P and PRISMA-NMA guidelines. From 16 different sources, 14 randomized controlled trials totaling 12,213 patients testing an active treatment of either spironolactone, eplerenone, or canrenone/potassium-canreonate in adults with symptomatic HF due to systolic dysfunction reporting any of the above endpoints were retained. Efficacy in comparison to placebo/standard medical care with respect to all-cause mortality was confirmed for spironolactone and eplerenone while no conclusion could be drawn for canrenone (HR 0.69 (0.62; 0.77), 0.82 (0.75; 0.91), and 0.50 (0.17; 1.45), respectively). Indirect comparisons hint a potential (non-significant) preference of spironolactone over eplerenone (HR 0.84 (0.68; 1.03)). The overall risk of bias was low to intermediate. Results for secondary endpoints as well as sensitivity analyses essentially mirrored these findings. The beta-blocker adjusted meta-analysis for the primary endpoint showed the same tendency as the unadjusted one (HR 0.39 (0.07; 2.03)). Results need to be interpreted with caution, though, as the resultant mix of patient- and study-level covariates produced unstable statistical modeling. We found no significant and systematic superiority of either MRA regarding efficacy toward all endpoints considered in both direct and indirect comparisons.

2.
ESC Heart Fail ; 6(4): 640-648, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31259484

RESUMO

AIMS: Co-morbid atrial fibrillation (AF) increases both mortality and N-terminal pro brain natriuretic peptide (NT-proBNP) concentrations in patients with chronic heart failure (CHF). It is unclear whether AF worsens prognosis independently from NT-proBNP concentrations. If AF was an independent risk factor, NT-proBNP levels for outcome prediction would need to be adjusted in patients with AF. We aimed to analyse the influence of AF on the prognostic value of NT-proBNP in patients with CHF. METHODS AND RESULTS: A total of 2541 consecutive CHF patients with sinus rhythm (SR) or AF were identified in the outpatients' CHF registry of the University of Heidelberg, Germany. Of these, 250 patients with SR were individually matched to 250 patients with AF with respect to NT-proBNP, New York Heart Association functional class, sex, age, and aetiology of CHF. In the general sample, both AF and NT-proBNP were associated with all-cause mortality [hazard ratio (HR) = 1.96, 95% confidence interval (CI) 1.61-2.39, P < 0.001; and HR = 1.03 per 1000 ng/L increase, 95% CI 1.02 to 1.04, P < 0.001, respectively]. After matching, NT-proBNP retained its prognostic power (HR = 1.13 per 1000 ng/L increase, 95% CI 1.10 to 1.16, P < 0.001), but AF did not (HR = 0.91, 95% CI 0.66 to 1.25, P = 0.56). Despite similar prognosis, matched patients with SR were in more advanced CHF than were AF patients as indicated by a lower left ventricular ejection fraction (30 ± 13% vs. 34 ± 14%, P < 0.001). CONCLUSIONS: The prognostic value of NT-proBNP in CHF is not influenced by concomitant AF. AF, in return, might be a surrogate of a worse cardiac condition rather than an independent risk factor.

3.
Heart Fail Rev ; 24(4): 461-472, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30874955

RESUMO

The majority of patients with chronic heart failure (HF) receive long-term treatment with loop diuretics. The comparative effectiveness of different loop diuretics is unknown. We searched PubMed, clinicaltrials.gov , the Cochrane Central Register of Controlled Trials and the European Union Clinical Trials Register for randomised clinical trials exploring the efficacy of the loop diuretics azosemide, bumetanide, furosemide or torasemide in patients with HF. Comparators included placebo, standard medical care or any other active treatment. The primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular mortality, HF-related hospitalisation and any combined endpoint thereof. Hypokalaemia and acute renal failure were defined as additional safety endpoints. Evidence was synthesised using network meta-analysis (NMA). Thirty-four trials reporting on 2647 patients were included. The overall quality of evidence was rated as moderate. NMA demonstrated no significant differences between loop diuretics with respect to all-cause mortality, cardiovascular mortality or hypokalaemia. In contrast, torasemide ranked best in terms of HF hospitalisation, and there was a trend towards benefits with torasemide with regard to occurrence of acute renal failure. Sensitivity analyses excluding trials with a follow-up < 6 months, trials with a cross-over design and those including < 25 patients confirmed the main results. We found no significant superiority of either loop diuretic with respect to mortality and safety endpoints. However, clinicians may prefer torasemide, as it was associated with fewer HF-related hospitalisations.

4.
Clin Biochem ; 67: 7-11, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30872042

RESUMO

OBJECTIVE: To evaluate the long term biological variation of high-sensitivity cardiac troponin T (hs-cTnT) in stable outpatients with cardiovascular disease (CVD). METHODS: After applying 8 exclusion criteria to 965 patients, hs-cTnT was measured at index visit and at a 12-month interval in 169 stable outpatients presenting for routine follow-up visits for any CVD. Stability was defined as absence of any endpoint within the follow-up period. Reference change values (RCVs) and minimal important differences (MIDs) were determined to assess biological variation of hs-cTnT. RESULTS: MID and RCV for the 12 months interval in patients were 3.8 ng/L or 44.2%, respectively. MID and transformed MID values were lower than the corresponding RCV with a value of 5.1 ng/L for the transformed RCV and 28.1% for the transformed MID. Similar patterns were shown in different subgroups as sex, age, and renal function. We observed a baseline hs-cTnT value dependent change of MID and RCV with increasing values for MID and decreasing values for RCV which converge to stable values between a baseline hs-cTNT value of 11 to 25 ng/L. CONCLUSIONS: Biological variation of hs-cTnT over 12 months in stable outpatients depends on the concentration at index visit, and is consistent among important prespecified subgroups. MID shows a low biovariability over 12 months. Clinical Trials Identifier:NCT01954303.


Assuntos
Doenças Cardiovasculares/sangue , Pacientes Ambulatoriais , Troponina T/sangue , Idoso , Idoso de 80 Anos ou mais , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Fatores de Tempo
5.
Int J Cardiol ; 289: 83-90, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-30827731

RESUMO

BACKGROUND: Loop diuretics are given to the majority of patients with chronic heart failure (HF). Whether the different pharmacological properties of the three guideline-recommended loop diuretics result in differential effects on survival is unknown. METHODS: 6293 patients with chronic HF using either bumetanide, furosemide or torasemide were identified in three European HF registries. Patients were individually matched on both the respective propensity scores for receipt of the individual drug and dose-equivalents thereof. RESULTS: During a follow-up of 35,038 patient-years, 652 (53.7%), 2179 (51.9%), and 268 (30.4%) patients died amongst those prescribed bumetanide, furosemide, and torasemide, respectively. In univariable analyses of the general sample, bumetanide and furosemide were both associated with higher mortality as compared with torasemide treatment (HR 1.50, 95% CI 1.31-1.73, p < 0.001, and HR 1.34, CI 1.18-1.52, p < 0.001, respectively). Mortality was higher in bumetanide users when compared to furosemide users (HR 1.11, 95% CI 1.02-1.20, p = 0.01). However, there was no significant association between loop diuretic choice and all-cause mortality in any of the matched samples (bumetanide vs. furosemide, HR 1.03, 95% CI 0.93-1.14, p = 0.53; bumetanide vs. torasemide, HR 0.98, 95% CI 0.78-1.24, p = 0.89; furosemide vs. torasemide, HR 1.02, 95% CI 0.84-1.24, p = 0.82). The results were confirmed in subgroup analyses with respect to age, sex, left ventricular ejection fraction, NYHA functional class, cause of HF, rhythm, and systolic blood pressure. CONCLUSIONS: In patients with HF, mortality is not affected by the choice of individual loop diuretics.

6.
Heart ; 105(16): 1252-1259, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30792238

RESUMO

OBJECTIVE: To describe the epidemiology, long-term outcomes and temporal trends in mortality in ambulatory patients with chronic heart failure (HF) with reduced (HFrEF), mid-range (HFmrEF) or preserved ejection fraction (HFpEF) from three European countries. METHODS: We identified 10 312 patients from the Norwegian HF Registry and the HF registries of the universities of Heidelberg, Germany, and Hull, UK. Patients were classified according to baseline left ventricular ejection fraction (LVEF) and time of enrolment (period 1: 1995-2005 vs period 2: 2006-2015). Predictors of mortality were analysed by use of univariable and multivariable Cox regression analyses. RESULTS: Among 10 312 patients with stable HF, 7080 (68.7%), 2086 (20.2%) and 1146 (11.1%) were classified as having HFrEF, HFmrEF or HFpEF, respectively. A total of 4617 (44.8%) patients were included in period 1, and 5695 (55.2%) patients were included in period 2. Baseline characteristics significantly differed with respect to type of HF and time of enrolment. During a median follow-up of 66 (33-105) months, 5297 patients (51.4%) died. In multivariable analyses, survival was independent of LVEF category (p>0.05), while mortality was lower in period 2 as compared with period 1 (HR 0.81, 95% CI 0.72 to 0.91, p<0.001). Significant predictors of all-cause mortality regardless of HF category were increasing age, New York Heart Association functional class, N-terminal pro-brain natriuretic peptide and use of loop diuretics. CONCLUSION: Ambulatory patients with HF stratified by LVEF represent different phenotypes. However, after adjusting for a wide range of covariates, long-term survival is independent of LVEF category. Outcome significantly improved during the last two decades irrespective from type of HF.

7.
Clin Res Cardiol ; 107(11): 1040-1049, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29774407

RESUMO

BACKGROUND: Beta blockers improve survival in patients with chronic systolic heart failure (CHF). Whether physicians should aim for target dose, target heart rate (HR), or both is still under debate. METHODS AND RESULTS: We identified 1,669 patients with systolic CHF due to ischemic heart disease or idiopathic dilated cardiomyopathy from the University Hospital Heidelberg and the Clinic of Ludwigshafen, Germany. All patients were treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker and had a history of CHF known for at least 6 months. Target dose was defined as treatment with ≥ 95% of the respective published guideline-recommended dose. Target HR was defined as 51-69 bpm. All-cause mortality during the median follow-up of 42.8 months was analysed with respect to beta blocker dosing and resting HR. 201 (12%) patients met the dose target (group A), 285 (17.1%) met the HR target (group B), 627 (37.6%) met no target (group C), and 556 (33.3%) did not receive beta blockers (Group D). 5-year mortality was 23.7, 22.7, 37.6, and 55.6% for group A, B, C, and D, respectively (p < 0.001). Survival for group A patients with a HR ≥ 70 bpm was 28.8% but 14.8% if HR was 50-70 bpm (p = 0.054). CONCLUSIONS: Achieving guidelines recommended beta blocker dose or to HR control has a similar positive impact on survival. When on target dose, supplemental HR control additionally improves survival.


Assuntos
Carvedilol/uso terapêutico , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Metoprolol/uso terapêutico , Volume Sistólico/fisiologia , Antagonistas Adrenérgicos beta/uso terapêutico , Causas de Morte/tendências , Feminino , Seguimentos , Alemanha/epidemiologia , Insuficiência Cardíaca Sistólica/mortalidade , Insuficiência Cardíaca Sistólica/fisiopatologia , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Volume Sistólico/efeitos dos fármacos , Taxa de Sobrevida/tendências , Fatores de Tempo
8.
J Am Soc Echocardiogr ; 31(6): 733-742, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29402506

RESUMO

BACKGROUND: Impaired left ventricular (LV) longitudinal function (LF) is a known predictor of cardiac events in patients with heart failure, but two-dimensional strain imaging, the reference method to measure myocardial deformation, is not always feasible or available. Therefore, reliable and reproducible alternatives are needed. The aim of the present study was to evaluate unidimensional longitudinal strain (ULS) as a simple echocardiographic parameter for the assessment of LV LF. METHODS: Two hundred two patients with dilated cardiomyopathy who had their first presentation in the authors' cardiology department, as well as the same number of age- and gender-matched control subjects, were prospectively included in this study. ULS was compared with global longitudinal strain (GLS), the current gold standard for LV LF assessment by echocardiography. Uni- and multivariate Cox regression analyses were conducted to evaluate the prognostic value of ULS. RESULTS: LV LF was higher in the control group compared with patients: GLS -19.5 ± 1.7% versus -12.6 ± 4.8% and ULS -16.3 ± 1.5% versus -10.2 ± 3.9% (P < .001 for each). Correlation between ULS and GLS was excellent (r = 0.94), while Bland-Altman plots revealed lower values for ULS (bias -2.76%, limits of agreement ±3.31%). During a mean follow-up time of 39 months, the combined end point of cardiovascular death or hospitalization for acute cardiac decompensation was reached by 28 patients (13.9%). GLS (hazard ratio, 1.21; 95% CI, 1.10-1.34; P < .001) and ULS (hazard ratio, 1.24; 95% CI, 1.12-1.39; P < .001) had comparable prognostic impact on patient outcomes. CONCLUSIONS: ULS might be an alternative echocardiographic method for the assessment of LV LF, with similar diagnostic and prognostic value compared with GLS.


Assuntos
Ecocardiografia/métodos , Insuficiência Cardíaca Sistólica/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Contração Miocárdica/fisiologia , Função Ventricular Esquerda/fisiologia , Idoso , Feminino , Seguimentos , Insuficiência Cardíaca Sistólica/diagnóstico , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
9.
Eur J Cardiovasc Nurs ; 17(2): 170-177, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28718661

RESUMO

BACKGROUND: While comprehensive evidence exists regarding negative effects of depression on self-care behaviours in patients with chronic heart failure (CHF), the relation between anxiety and self-care behaviours in patients with CHF is not clear. The aim of this study was to analyse the interactions between anxiety, depression and self-care behaviours in patients with CHF. METHODS: The self-care behaviour of CHF outpatients was measured using the European Heart Failure Self-care Behaviour Scale (EHFScBS). The Patient Health Questionnaire (PHQ) was used to assess anxiety, the PHQ-9 was used to measure depression severity. Differences between patients with and without anxiety were assessed with the respective tests. Associations between anxiety, self-care and other predictors were analysed using linear regressions. RESULTS: Of the 308 participating patients, 35 (11.4%) fulfilled the PHQ criteria for an anxiety disorder. These patients took antidepressants more frequently (11.8% versus 2.3%, p = .02), had had more contacts with their general practitioner within the last year (11.8 ± 16.1 versus 6.7 ± 8.6, p = .02), and had a higher PHQ-9 depression score (12.9 ± 5.7 versus 6.5 ± 4.7, p < .01) than patients without anxiety disorder. Anxiety and self-care were negatively associated (ß = -0.144, r2 = 0.021, p = 0.015). The explanation of variance was augmented in a multivariate regression with the predictors age, sex, education, living with a partner, and New York Heart Association (NYHA) class ( r2 = 0.098) when anxiety was added ( r2 = 0.112). Depression further increased the explanation of variance (ß = -0.161, r2 = 0.131, p = 0.019). CONCLUSIONS: Anxiety is negatively associated with self-care behaviour in patients with CHF. However, this effect disappears behind the stronger influence of depression on self-care. The consideration of mental comorbidities in patients with CHF is important.


Assuntos
Transtornos de Ansiedade/psicologia , Transtorno Depressivo/psicologia , Comportamentos Relacionados com a Saúde , Insuficiência Cardíaca Sistólica/psicologia , Insuficiência Cardíaca Sistólica/terapia , Autocuidado , Adulto , Idoso , Transtornos de Ansiedade/complicações , Doença Crônica , Comorbidade , Transtorno Depressivo/complicações , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade
10.
Eur Heart J Cardiovasc Pharmacother ; 4(2): 82-92, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28475676

RESUMO

Aims: Angiotensin-converting enzyme inhibitors (ACEIs) are recommended as first-line therapy in patients with heart failure with reduced ejection fraction (HFrEF). The comparative effectiveness of different ACEIs is not known. Methods and results: A total of 4723 outpatients with stable HFrEF prescribed enalapril, lisinopril, or ramipril were identified from three registries in Norway, England, and Germany. In three separate matching procedures, patients were individually matched with respect to both dose equivalents and their respective propensity scores for ACEI treatment. During a follow-up of 21 939 patient-years, 360 (49.5%), 337 (52.4%), and 1119 (33.4%) patients died among those prescribed enalapril, lisinopril, and ramipril, respectively. In univariable analysis of the general sample, enalapril and lisinopril were both associated with higher mortality when compared with ramipril treatment [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.30-1.65, P < 0.001 and HR 1.38, 95% CI 1.22-1.56, P < 0.001, respectively). Patients prescribed enalapril or lisinopril had similar mortality (HR 1.06, 95% CI 0.92-1.24, P = 0.41). However, there was no significant association between ACEI choice and all-cause mortality in any of the matched samples (HR 1.07, 95% CI 0.91-1.25, P = 0.40; HR 1.12, 95% CI 0.96-1.32, P = 0.16; and HR 1.10, 95% CI 0.93-1.31, P = 0.25 for enalapril vs. ramipril, lisinopril vs. ramipril, and enalapril vs. lisinopril, respectively). Results were confirmed in subgroup analyses with respect to age, sex, left ventricular ejection fraction, New York Class Association functional class, cause of HFrEF, rhythm, and systolic blood pressure. Conclusion: Our results suggest that enalapril, lisinopril, and ramipril are equally effective in the treatment of patients with HFrEF when given at equivalent doses.


Assuntos
Enalapril/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Lisinopril/uso terapêutico , Pontuação de Propensão , Ramipril/uso terapêutico , Volume Sistólico/fisiologia , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Resultado do Tratamento
11.
J Card Fail ; 23(12): 835-842, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28757153

RESUMO

BACKGROUND CONTEXT: Biologic variation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in chronic heart failure (CHF) may affect blood levels and risk stratification. The sources of NT-proBNP variation are unknown. METHODS AND RESULTS: We performed NT-proBNP measurements and clinical and hemodynamic assessments in 50 patients with heart failure with reduced ejection fraction (HFrEF) who met criteria for clinical stability over 2 time intervals. Hemodynamic variables were measured with the use of inert gas rebreathing and impedance cardiography. Heart rhythm was monitored with the use of external electrocardiographic event recorders throughout the study. Determinants of NT-proBNP-levels and both absolute (ΔNT-proBNPabs) and relative (ΔNT-proBNP%) changes at 1-week and 2-week intervals were identified with the use of univariable and multivariable linear mixed-effects models and linear regression analyses, respectively. Clinical and hemodynamic variables did not significantly change between study visits. The individual variation of NT-proBNP at 2 weeks was 9.2% (range 3.9%-18.6%). Weight and glomerular filtration rate were independently associated with baseline NT-proBNP concentrations (P = .01 and P = .005, respectively). There was no relationship between absolute and relative changes of NT-proBNP at 1-week intervals and changes in clinical and hemodynamic variables. Absolute change of NT-proBNP at 2-week intervals was associated with absolute change in left cardiac work index (P = .008), and relative change in NT-proBNP at 2-week intervals was determined by relative change of thoracic fluid content index (P = .008) and diastolic blood pressure (P = .01). The coefficients of determination (R2) for the multivariable models with Δ1wkNT-proBNPabs, Δ2-weeksNT-proBNPabs, Δ1wkNT-proBNP%, and Δ2wksNT-proBNP% as dependent variables were 0.21, 0.19, 0.10, and 0.32, respectively. CONCLUSIONS: In patients with stable HFrEF, changes in clinical and hemodynamic variables only marginally contribute to the variation of NT-proBNP.


Assuntos
Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica/fisiologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Idoso , Doença Crônica , Eletrocardiografia/métodos , Feminino , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
12.
Clin Res Cardiol ; 106(12): 974-985, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28779229

RESUMO

BACKGROUND: Extracellular matrix (ECM) biomarkers such as matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are pathophysiological key, prognostic marker and therapeutic target in chronic heart failure (HF). Serial measurements of MMPs and TIMPs may be useful for guidance of these applications. However, interpretation of time-dependent changes requires knowledge about the biological variation of ECM biomarkers. METHODS: We performed measurements of MMP-2, MMP-9, TIMP-1, and TIMP-4 in 50 patients with chronic HF who met rigid criteria for clinical stability at 3-h, 6-h, 1-week and 2-week time intervals. In addition, clinical and haemodynamic assessment was performed at baseline, at 1- and 2-week intervals. Haemodynamic variables were measured using inert gas rebreathing and impedance cardiography. Heart rhythm was monitored with external ECG event recorders throughout the complete study. Reference change values (RCVs) and minimal important differences (MIDs) were determined for MMP-2, MMP-9, TIMP-1, and TIMP-4. RESULTS: Clinical and haemodynamic variables were stable over time. Depending on the time-interval, RCVs ranged between 4.9 and 11.7% for MMP-2, 26.4 and 56.7% for MMP-9, 10.8 and 30.7% for TIMP-1, and 16.0 and 47.4% for TIMP-4, respectively. The MIDs varied between 43.38 and 65.22 ng/ml for MMP-2, 28.71 and 40.96 ng/ml for MMP-9, 52.32 and 156.07 ng/ml for TIMP-1, and 293.92 and 798.04 pg/ml for TIMP-4, respectively. CONCLUSION: The biological variation of ECM biomarkers differs with respect to individual biomarkers and time intervals. MMP-2 may be most suitable for serial biomarker measurements, as the biological variation is low irrespective of the time interval between measurements.


Assuntos
Matriz Extracelular/enzimologia , Insuficiência Cardíaca/sangue , Frequência Cardíaca/fisiologia , Metaloproteinases da Matriz/sangue , Inibidores Teciduais de Metaloproteinases/biossíntese , Biomarcadores/sangue , Cardiografia de Impedância , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
13.
Clin Res Cardiol ; 106(9): 711-721, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28434020

RESUMO

AIMS: Beta-blockers are recommended for the treatment of chronic heart failure (CHF). However, it is disputed whether beta-blockers exert a class effect or whether there are differences in efficacy between agents. METHODS AND RESULTS: 6010 out-patients with stable CHF and a reduced left ventricular ejection fraction prescribed either bisoprolol, carvedilol or metoprolol succinate were identified from three registries in Norway, England, and Germany. In three separate matching procedures, patients were individually matched with respect to both dose equivalents and the respective propensity scores for beta-blocker treatment. During a follow-up of 26,963 patient-years, 302 (29.5%), 637 (37.0%), and 1232 (37.7%) patients died amongst those prescribed bisoprolol, carvedilol, and metoprolol, respectively. In univariable analysis of the general sample, bisoprolol and carvedilol were both associated with lower mortality as compared with metoprolol succinate (HR 0.80, 95% CI 0.71-0.91, p < 0.01, and HR 0.86, 95% CI 0.78-0.94, p < 0.01, respectively). Patients prescribed bisoprolol or carvedilol had similar mortality (HR 0.94, 95% CI 0.82-1.08, p = 0.37). However, there was no significant association between beta-blocker choice and all-cause mortality in any of the matched samples (HR 0.90; 95% CI 0.76-1.06; p = 0.20; HR 1.10, 95% CI 0.93-1.31, p = 0.24; and HR 1.08, 95% CI 0.95-1.22, p = 0.26 for bisoprolol vs. carvedilol, bisoprolol vs. metoprolol succinate, and carvedilol vs. metoprolol succinate, respectively). Results were confirmed in a number of important subgroups. CONCLUSION: Our results suggest that the three beta-blockers investigated have similar effects on mortality amongst patients with CHF.


Assuntos
Bisoprolol/uso terapêutico , Carbazóis/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Metoprolol/uso terapêutico , Propanolaminas/uso terapêutico , Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Carvedilol , Doença Crônica , Inglaterra , Feminino , Seguimentos , Alemanha , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Sistema de Registros , Resultado do Tratamento
14.
Int J Cardiol ; 238: 97-104, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28342630

RESUMO

BACKGROUND: In patients with chronic heart failure (CHF) increasing levels of total serum cholesterol are associated with improved survival - while statin usage is not. The impact of statin treatment on the "reverse epidemiology" of cholesterol is unclear. METHODS: 2992 consecutive patients with non-ischemic CHF due to left ventricular systolic dysfunction from the Norwegian CHF Registry and the CHF Registries of the Universities of Hull, UK, and Heidelberg, Germany, were studied. 1736 patients were individually double-matched on both cholesterol levels and the individual propensity scores for statin treatment. All-cause mortality was analyzed as a function of baseline cholesterol and statin use in both the general and the matched sample. RESULTS: 1209 patients (40.4%) received a statin. During a follow-up of 13,740 patient-years, 360 statin users (29.8%) and 573 (32.1%) statin non-users died. When grouped according to total cholesterol levels as low (≤3.6mmol/L), moderate (3.7-4.9mmol/L), high (4.8-6.2mmol/L), and very high (>6.2mmol/L), we found improved survival with very high as compared with low cholesterol levels. This association was present in statin users and non-users in both the general and matched sample (p<0.05 for each group comparison). The negative association of total cholesterol and mortality persisted when cholesterol was treated as a continuous variable (HR 0.83, 95%CI 0.77-0.90, p<0.001 for matched patients), but it was less pronounced in statin users than in non-users (F-test p<0.001). CONCLUSIONS: Statins attenuate but do not eliminate the reverse epidemiological association between increasing total serum cholesterol and improved survival in patients with non-ischemic CHF.


Assuntos
Colesterol/sangue , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Seguimentos , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Taxa de Sobrevida/tendências
15.
Am Heart J ; 178: 28-36, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27502849

RESUMO

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have become cornerstones of therapy for chronic heart failure (CHF). Guidelines advise high target doses for ACEIs/ARBs, but fear of worsening renal function may limit dose titration in patients with concomitant chronic kidney disease (CKD). METHODS: In this retrospective observational study, we identified 722 consecutive patients with systolic CHF, stable CKD stage III/IV (estimated glomerular filtration rate [eGFR] 15-60 mL min(-1) 1.73 m(-2)) and chronic ACEI/ARB treatment from the outpatient heart failure clinics at the Universities of Hull, UK, and Heidelberg, Germany. Change of renal function, worsening CHF, and hyperkalemia at 12-month follow-up were analyzed as a function of both baseline ACEI/ARB dose and dose change from baseline. RESULTS: ΔeGFR was not related to baseline dose of ACEI/ARB (P = .58), or to relative (P = .18) or absolute change of ACEI/ARB dose (P = .21) during follow-up. Expressing change of renal function as a categorical variable (improved/stable/decreased) as well as subgroup analyses with respect to age, sex, New York Heart Association functional class, left ventricular ejection fraction, diabetes, concomitant aldosterone antagonists, CKD stage, hypertension, ACEI vs ARB, and congestion status yielded similar results. There was no association of dose/dose change with incidence of either worsening CHF or hyperkalemia. CONCLUSIONS: In patients with systolic CHF and stable CKD stage III/IV, neither continuation of high doses of ACEI/ARB nor up-titration was related to adverse changes in longer-term renal function. Conversely, down-titration was not associated with improvement in eGFR. Use of high doses of ACEI/ARB and their up-titration in patients with CHF and CKD III/IV may be appropriate provided that the patient is adequately monitored.


Assuntos
Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Disfunção Ventricular Esquerda/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Taxa de Filtração Glomerular , Insuficiência Cardíaca/complicações , Humanos , Hiperpotassemia/epidemiologia , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Insuficiência Renal Crônica/complicações , Estudos Retrospectivos , Volume Sistólico , Disfunção Ventricular Esquerda/complicações
16.
Tex Heart Inst J ; 43(4): 297-304, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27547136

RESUMO

Periodontal disease has been associated with an increased risk of cardiovascular events. The purpose of our study was to investigate whether a correlation between periodontitis and chronic heart failure exists, as well as the nature of the underlying cause. We enrolled 71 patients (mean age, 54 ± 13 yr; 56 men) who had stable chronic heart failure; all underwent complete cardiologic and dental evaluations. The periodontal screening index was used to quantify the degree of periodontal disease. We compared the findings to those in the general population with use of data from the 4th German Dental Health Survey. Gingivitis, moderate periodontitis, and severe periodontitis were present in 17 (24%), 17 (24%), and 37 (52%) patients, respectively. Severe periodontitis was more prevalent among chronic heart failure patients than in the general population. In contrast, moderate periodontitis was more prevalent in the general population (P <0.00001). The severity of periodontal disease was not associated with the cause of chronic heart failure or the severity of heart failure symptoms. Six-minute walking distance was the only independent predictor of severe periodontitis. Periodontal disease is highly prevalent in chronic heart failure patients regardless of the cause of heart failure. Prospective trials are warranted to clarify the causal relationship between both diseases.


Assuntos
Insuficiência Cardíaca/epidemiologia , Periodontite/epidemiologia , Adulto , Idoso , Doença Crônica , Tolerância ao Exercício , Feminino , Alemanha/epidemiologia , Nível de Saúde , Inquéritos Epidemiológicos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Índice Periodontal , Periodontite/diagnóstico , Prevalência , Prognóstico , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Teste de Caminhada
17.
Stroke ; 47(2): 336-41, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26742800

RESUMO

BACKGROUND AND PURPOSE: Whether newly diagnosed atrial fibrillation (nAF) after stroke reflects underlying heart disease and represents an increased risk of cardioembolic stroke, or whether it is triggered by neurogenic mechanisms remains uncertain. We investigated, whether cardiovascular risk factors and echocardiographic parameters in patients with nAF are similar to patients with known AF (kAF) and differ from patients without AF. METHODS: Consecutive acute ischemic stroke patients were enrolled into a prospective stroke database. All patients with echocardiography were included and univariable and multivariable testing was applied to compare clinical characteristics and echocardiographic findings among patients with nAF, kAF, and no AF. RESULTS: A total of 1397 patients were included (male, 62.3%; median age, 71 years). AF was present in 320 (22.9%) patients. Of those, nAF was present in 36.2% (116/320) and kAF in 63.8% (204/320). No clinical or echocardiographic factor was independently associated with detection of nAF compared with kAF but a trend toward larger left atrial diameters in patients with kAF was observed (P=0.070). In contrast, patients with nAF were more often female (P<0.001), older (P<0.001) and had a larger left atrial diameters (P<0.001) compared with patients without AF. While stroke severity in patients with nAF and kAF was similar, patients without AF had less severe strokes. CONCLUSIONS: Stroke patients with nAF and with kAF share common cardiovascular risk factors, have similar echocardiographic findings and suffer equally severe strokes. We conclude that preexisting heart disease is the major cause of AF that is first diagnosed after stroke.


Assuntos
Fibrilação Atrial/diagnóstico , Isquemia Encefálica/complicações , Doença das Coronárias/diagnóstico , Ataque Isquêmico Transitório/etiologia , Acidente Vascular Cerebral/etiologia , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estudos de Coortes , Doença das Coronárias/complicações , Bases de Dados Factuais , Ecocardiografia , Eletrocardiografia , Eletrocardiografia Ambulatorial , Feminino , Átrios do Coração/diagnóstico por imagem , Cardiopatias/complicações , Cardiopatias/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Prospectivos , Fatores de Risco
18.
Circ Heart Fail ; 8(5): 887-96, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26175538

RESUMO

BACKGROUND: ß-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. METHODS AND RESULTS: 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 ß-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. CONCLUSIONS: 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.


Assuntos
Carbazóis/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Metoprolol/administração & dosagem , Propanolaminas/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Idoso , Carvedilol , Relação Dose-Resposta a Droga , Feminino , Alemanha/epidemiologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Pontuação de Propensão , Estudos Prospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento
19.
Clin Res Cardiol ; 104(10): 822-30, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25893567

RESUMO

BACKGROUND: Despite the widespread application of measurements of respiratory muscle force (PImax) in clinical trials there is no data on biological variation, reference change value (RCV), or the minimal important difference (MID) for PImax irrespective of the target cohort. We addressed this issue for patients with chronic stable heart failure. METHODS AND RESULTS: From the outpatients' clinic of the University of Heidelberg we retrospectively selected three groups of patients with stable systolic chronic heart failure (CHF). Each group had two measurements of PImax: 90 days apart in Group A (n = 25), 180 days apart in Group B (n = 93), and 365 days apart in Group C (n = 184). Stability was defined as (a) no change in NYHA class between visits and (b) absence of cardiac decompensation 3 months prior, during, and 3 months after measurements. For each group, we determined within-subject (CVI), between-subject (CVG), and total (CVT) coefficient of variation (CV), the index of individuality (II), RCV, reliability coefficient, and MID of PImax. CVT was 8.7, 7.5, and 6.9 % for groups A, B, and C, respectively. The II and RCV were 0.21, 0.20, 0.16 and 13.6, 11.6, 10.8 %, respectively. The reliability coefficient and MID were 0.83, 0.87, 0.88 and 1.44, 1.06, 1.12 kPa, respectively. Results were similar between age, gender, and aetiology subgroups. CONCLUSION: In patients with stable CHF, measurements of PImax are highly stable for intervals up to 1 year. The low values for II suggest that evaluation of change in PImax should be performed on an individual (per patient) basis. Individually significant change can be assumed beyond 14 % (RCV) or 1.12 kPa (MID).


Assuntos
Diafragma/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Inalação , Força Muscular , Doença Crônica , Feminino , Alemanha , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
Clin Kidney J ; 8(2): 219-25, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25815181

RESUMO

BACKGROUND: Cardiorenal syndrome type 2 (CRS-2) is common in end-stage chronic heart failure (CHF). Peritoneal ultrafiltration (pUF) may entail clinical functional improvement and a reduction in hospitalizations. METHODS: Thirty-nine consecutive end-stage CHF patients with stable CRS-2 were initiated on ambulatory pUF after interdisciplinary cardiological/nephrological evaluation and prospectively followed for 1 year. All-cause hospitalization was the primary end point. Secondary end points included mortality, treatment alteration and change in weight, NYHA functional class or quality of life (QoL). Outcomes were compared both within the pUF cohort (365 prior to initiation) and with 39 matched CHF patients receiving standard medical treatment. RESULTS: Compared with pretreatment, there was a trend to a reduction in 1-year hospitalization days in the pUF group (P = 0.07). One-year mortality was 33% in the pUF group and 23% in the matched control cohort. pUF was stopped in eight patients (18%) due to recurrent peritonitis (n = 3), insufficient ultrafiltration (n = 3) or cardiac recompensation (n = 1). Compared with standard medical treatment, pUF significantly improved volume overload (P < 0.05), NYHA functional class (P < 0.001) and mental health (P < 0.05). Moreover, hospitalization days for all causes as well as cardiovascular hospitalization days were significantly reduced during the interim periods in the pUF group (P < 0.05 and P < 0.001, respectively). CONCLUSIONS: pUF is effective in improving the clinical condition of end-stage CHF patients suffering from CRS-2. Randomized controlled trials are needed to clarify the effects of pUF on hospitalization and mortality in these patients.

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