Tobias Täger

Long-term changes of renal function in relation to ace inhibitor/angiotensin receptor blocker dosing in patients with heart failure and chronic kidney disease.

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.

Peritoneal ultrafiltration in end-stage chronic heart failure

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.

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

Background—&bgr;-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 &bgr;-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.

Anxiety and self-care behaviour in patients with chronic systolic heart failure: A multivariate model:

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.

Periodontitis in Chronic Heart Failure

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.

Biological variation of the cardiac index in patients with stable chronic heart failure: inert gas rebreathing compared with impedance cardiography†

In chronic heart failure (CHF), changes in cardiac function define the course of the disease. The cardiac index (CI) is the most adequate indicator of cardiac function. Interpretation of serial CI measurements, however, requires knowledge of the biological variation of CI. Because measurements of CI can be confounded by the clinical situation or the method applied, biological variation might be subject to the same confounders.

Comparative effectiveness of enalapril, lisinopril, and ramipril in the treatment of patients with chronic heart failure: a propensity score-matched cohort study

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.

Hemodynamic Determinants of the Biologic Variation of N-Terminal Pro–B-Type Natriuretic Peptide in Patients With Stable Systolic Chronic Heart Failure

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.

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

Background—&bgr;-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 &bgr;-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.

Carvedilol Compared With Metoprolol Succinate in the Treatment and Prognosis of Patients With Stable Chronic Heart FailureCLINICAL PERSPECTIVE

Background—&bgr;-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 &bgr;-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.