[Heart failure care in a digitalized future : A discourse on resource-sparing structures and self-determined patients]. / Herzinsuffizienzversorgung in einer digitalisierten Zukunft : Ein Diskurs zu ressourcenschonenden Strukturen und selbstbestimmten Patienten.

Digital health solutions, applications of artificial intelligence (AI) and new technologies, such as cardiac magnetic resonance imaging and cardiac human genetics are currently being validated in cardiac healthcare pathways. They show promising approaches for improving existing healthcare structures in the future by strengthening the focus on predictive, preventive and personalized medicine. In addition, the accompanying use of digital health applications will become increasingly more important in the future healthcare, especially in patients with chronic diseases. In this article, the authors describe a case of chronic heart failure (HF) as an example to provide an overview of how digitalized healthcare can be efficiently designed across sectors and disciplines in the future. Moreover, the importance of a self-determined patient management for the treatment process itself is underlined. Since HF is frequently accompanied by various comorbidities during the course of the disease that are often recognized only after a delay, the necessity for a timely simultaneous and preventive treatment of multiple comorbidities in cardiovascular diseases is emphasized. Against this background the currently separately applied disease management programs (DMP) are critically questioned. The development of a holistic DMP encompassing all indications for the treatment of chronic diseases may pave the way to a more efficient medical care system.

Mortality and morbidity 1 year after stopping a remote patient management intervention: extended follow-up results from the telemedical interventional management in patients with heart failure II (TIM-HF2) randomised trial.

BACKGROUND: The Telemedical Interventional Management in Heart Failure II (TIM-HF2) trial showed that, compared with usual care, a structured remote patient management (RPM) intervention done over 12-months reduced the percentage of days lost due to unplanned cardiovascular hospitalisations and all-cause death. The aim of the study was to evaluate whether this clinical benefit seen for the RPM group during the initial 12 month follow-up of the TIM-HF2 trial would be sustained 1 year after stopping the RPM intervention. METHODS: TIM-HF2 was a prospective, randomised, multicentre trial done in 43 hospitals, 60 cardiology practices, and 87 general practitioners in Germany. Patients with heart failure, New York Heart Association functional class II or III, and who had been hospitalised for heart failure within 12 months before randomisation were randomly assigned to either the RPM intervention or usual care. At the final study visit (main trial), the RPM intervention was stopped and the 1 year extended follow-up period started, which lasted 1 year. The primary outcome was percentage of days lost due to unplanned cardiovascular hospitalisations and all-cause mortality. Analyses were done using the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01878630. FINDINGS: Between Aug 13, 2013, and May 12, 2017, 1538 patients were enrolled (765 to the remote patient management group and 773 to the usual care group) in the main trial. 671 of 765 patients in the remote patient management group and 673 of 773 in the usual care group completed the main trial and started the extended follow-up period up to 1 year later. In the extended follow-up period, the percentage of days lost due to unplanned cardiovascular hospital admissions and all-cause mortality did not differ significantly between groups weighted mean 5·95% [95% CI 4·59-7·31] in the RPM group vs 6·64% [95% CI 5·19-8·08] in the usual care group [rate ratio 0·79; 95% CI 0·78-1·21]). However, when data from the main trial and the extended follow-up period were combined, the percentage of days lost due to unplanned cardiovascular hospitalisation or all-cause death was significantly less in patients allocated to the RPM group (382 [50%] of 765; weighted mean 9·28%; 95% CI 7·76-10·81) than in the UC group (398 [51%] of 773; 11·78%; 95% CI 10·08-13·49; ratio of weighted average 0·79; 95% CI 0·62-1·00; p=0·0486). INTERPRETATION: The positive effect of our RPM intervention on morbidity and mortality over the course of the main trial was no longer observed 1 year after stopping the RPM intervention. However, because the TIM-HF2 trial was not powered to show significance during the extended follow-up period, our results are exploratory and require further research. FUNDING: German Federal Ministry of Education and Research.

Efficacy of telemedical interventional management in patients with heart failure (TIM-HF2): a randomised, controlled, parallel-group, unmasked trial.

BACKGROUND: Remote patient management in patients with heart failure might help to detect early signs and symptoms of cardiac decompensation, thus enabling a prompt initiation of the appropriate treatment and care before a full manifestation of a heart failure decompensation. We aimed to investigate the efficacy of our remote patient management intervention on mortality and morbidity in a well defined heart failure population. METHODS: The Telemedical Interventional Management in Heart Failure II (TIM-HF2) trial was a prospective, randomised, controlled, parallel-group, unmasked (with randomisation concealment), multicentre trial with pragmatic elements introduced for data collection. The trial was done in Germany, and patients were recruited from hospitals and cardiology practices. Eligible patients had heart failure, were in New York Heart Association class II or III, had been admitted to hospital for heart failure within 12 months before randomisation, and had a left ventricular ejection fraction (LVEF) of 45% or lower (or if higher than 45%, oral diuretics were being prescribed). Patients with major depression were excluded. Patients were randomly assigned (1:1) using a secure web-based system to either remote patient management plus usual care or to usual care only and were followed up for a maximum of 393 days. The primary outcome was percentage of days lost due to unplanned cardiovascular hospital admissions or all-cause death, analysed in the full analysis set. Key secondary outcomes were all-cause and cardiovascular mortality. This study is registered with ClinicalTrials.gov, number NCT01878630, and has now been completed. FINDINGS: Between Aug 13, 2013, and May 12, 2017, 1571 patients were randomly assigned to remote patient management (n=796) or usual care (n=775). Of these 1571 patients, 765 in the remote patient management group and 773 in the usual care group started their assigned care, and were included in the full analysis set. The percentage of days lost due to unplanned cardiovascular hospital admissions and all-cause death was 4·88% (95% CI 4·55-5·23) in the remote patient management group and 6·64% (6·19-7·13) in the usual care group (ratio 0·80, 95% CI 0·65-1·00; p=0·0460). Patients assigned to remote patient management lost a mean of 17·8 days (95% CI 16·6-19·1) per year compared with 24·2 days (22·6-26·0) per year for patients assigned to usual care. The all-cause death rate was 7·86 (95% CI 6·14-10·10) per 100 person-years of follow-up in the remote patient management group compared with 11·34 (9·21-13·95) per 100 person-years of follow-up in the usual care group (hazard ratio [HR] 0·70, 95% CI 0·50-0·96; p=0·0280). Cardiovascular mortality was not significantly different between the two groups (HR 0·671, 95% CI 0·45-1·01; p=0·0560). INTERPRETATION: The TIM-HF2 trial suggests that a structured remote patient management intervention, when used in a well defined heart failure population, could reduce the percentage of days lost due to unplanned cardiovascular hospital admissions and all-cause mortality. FUNDING: German Federal Ministry of Education and Research.

[Indications and Clinical Implications of the Use of the Cardiac Markers BNP and NT-proBNP]. / Einsatzgebiete und praktischer Nutzen der kardialen Marker BNP und NT-proBNP.

B-type natriuretic peptides are markers of myocardial wall stress. BNP or NT-proBNP are used for the differential diagnosis of acute dyspnoe where normal serum concentrations make a cardiac cause unlikely. New data show their importance for risk prediction in different stages of heart failure and in primary prevention. Natriuretic peptide guided therapy improves titration of heart failure medications. Compared to BNP, NT-proBNP is better suited during therapy with the new angiotensin-rezeptor-neprilysin-inhibitor Sacubitril/Valsartan. This review article summarizes current data on the importance of B-type natriuretic peptides for the interface of ambulatory and hospital care and presents recommendations for their practical use in patient care.

Predicting hospitalization and mortality in patients with heart failure: The BARDICHE-index.

BACKGROUND: Prediction of events in chronic heart failure (CHF) patients is still difficult and available scores are often complex to calculate. Therefore, we developed and validated a simple-to-use, multidimensional prognostic index for such patients. METHODS: A theoretical model was developed based on known prognostic factors of CHF that are easily obtainable: Body mass index (B), Age (A), Resting systolic blood pressure (R), Dyspnea (D), N-termInal pro brain natriuretic peptide (NT-proBNP) (I), Cockroft-Gault equation to estimate glomerular filtration rate (C), resting Heart rate (H), and Exercise performance using the 6-min walk test (E) (the BARDICHE-index). Scores were given for all components and added, the sum ranging from 1 (lowest value) to 25 points (maximal value), with estimated risk being highest in patients with highest scores. Scores were categorized into three groups: a low (≤8 points); medium (9-16 points), or high (>16 points) BARDICHE-score. The model was validated in a data set of 1811 patients from two prospective CHF-cohorts (median follow-up 887days). The primary outcome was 5-year all-cause survival. Secondary outcomes were 5-year survival without all-cause hospitalization and 5-year survival without CHF-related hospitalization. RESULTS: There were significant differences between BARDICHE-risk groups for mortality (hazard ratio=3.63 per BARDICHE-group, 95%-CI 3.10-4.25), mortality or all-cause hospitalization (HR=2.00 per BARDICHE-group, 95%-CI 1.83-2.19), and mortality or CHF-related hospitalization (HR=3.43 per BARDICHE-group, 95%-CI 3.01-3.92; all P<10-50). Outcome was predicted independently of left ventricular ejection fraction (LVEF) and gender. CONCLUSIONS: The BARDICHE-index is a simple multidimensional prognostic tool for patients with CHF, independently of LVEF.

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.

Long-term outcome of patients with and without super-response to CRT-D.

OBJECTIVE: To compare outcome between patients with and without super-response to cardiac resynchronization therapy-defibrillator (CRT-D). METHODS AND RESULTS: In this cohort study, 167 consecutive CRT-D candidates were included. Super-response to CRT-D was defined clinically [improvement of ≥1 New York Heart Association (NYHA) class or ≥50 m in six-minute walk distance (6MWD)] and echocardiographically [increase of left ventricular ejection fraction (LVEF) ≥1 category (LVEF <30 to 30-40 % or 30-40 to 41-51 %) or reduction of left ventricular end-diastolic diameter (LVEDD) ≥10 mm]. Clinical outcome (death, cardiac transplantation and appropriate shock therapy) was compared between super-responders (n = 32) and non-super-responders (n = 135). During follow-up (616 patient-years; median 3.3 years), all-cause mortality was significantly lower in super-responders compared to non-super-responders (log rank p < 0.05). At least one appropriate shock was noted in 22 % of super-responders and 39 % of non-super-responders (p = 0.069). Time to appropriate shock therapy was significantly longer in super-responders (log rank p < 0.05). Event-free survival from death or cardiac transplantation was comparable between the two groups. CONCLUSION: Super-response to CRT-D is associated with improved survival and lower risk of appropriate shock therapy compared to non-super-responders. Further information about the mechanisms of super-response and its long-term consequences are needed to foresee favorable outcome after implantation of CRT-D.

Etiology-specific assessment of predictors of long-term survival in chronic systolic heart failure.

BACKGROUND: We sought to identify prognostic factors of long-term mortality, specific for the underlying etiology of chronic systolic heart failure (CHF). METHODS AND RESULTS: Between 1995 and 2009 baseline characteristics, treatment and follow-up data from 2318 CHF-patients due to ischemic (ICM; 1100 patients) or dilated cardiomyopathy (DCM; 1218 patients) were prospectively compared. To calculate hazard ratios with 95%-confidence intervals cox regression was used. We respectively established etiology-specific multivariable models of independent prognostic factors. During the follow-up period of up to 14.8 years (mean = 53.1 ± 43.5 months; 10,264 patient-years) 991 deaths (42.8%) occurred. In the ICM-cohort, 5-year-survival was 53.4% (95% CI: 49.9-56.7%), whereas in DCM-patients it was higher (68.1% (95% CI: 65.1-71.0%)). Age, ejection fraction, or hyponatremia were independent predictors for mortality in both cohorts, whereas diabetes, COPD, atrial fibrillation and a heart rate of ≥ 80/min carried independent predictive power only in ICM-patients. CONCLUSION: This study demonstrates the disparity of prognostic value of clinically derived risk factors between the two main causes of CHF. The effects of covariables in DCM-patients were lower, suggesting a less modifiable disease through risk factors considering mortality risk. An etiology-specific prognostic model may improve accuracy of survival estimations in CHF.

Gender aspects in clinical presentation and prognostication of chronic heart failure according to NT-proBNP and the Heart Failure Survival Score.

AIMS: We performed a prospective multi-center study to assess gender-specific differences in the predictive value of the measured level of NT-proBNP and the calculated Heart Failure Survival Score (HFSS). METHODS: Baseline characteristics and follow-up data up to 5 years from 2,019 men and 530 women diagnosed with chronic heart failure (CHF) due to ischemic heart disease or dilated cardiomyopathy were prospectively compared. Death from any cause constituted the endpoint of the study. NT-proBNP was measured and HFSS calculated according to standard methods. Survival of men and women according to level of NT-proBNP and HFSS was analyzed in logistic regression models. RESULTS: Median NT-proBNP level in men was 1,394 ng/l (IQR 516-3,406 ng/l) and 1,168 ng/l (IQR 444-2,830 ng/l) in women (p = n.s.). Median HFSS value was 8.4 (IQR 7.7-9.1) and 8.5 (8.0-9.1) in men and women, respectively. NT-proBNP levels and HFSS score correlated well with survival rates in both genders (p for interaction = 0.22 for NT-proBNP and 0.93 for HFSS). The all-cause death rates were similar in men and women. CONCLUSION: Despite a number of gender-specific differences in CHF and the general predominance of men measured levels of NT-proBNP and HFSS score can be utilized for risk stratification with similar informative value in men and women.

Ivabradine treatment in a chronic heart failure patient cohort: symptom reduction and improvement in quality of life in clinical practice.

INTRODUCTION: In the prospective, open-label multicenter INTENSIFY study, the effectiveness and tolerability of ivabradine as well as its impact on quality of life (QOL) in chronic systolic heart failure (CHF) patients were evaluated over a 4-month period. METHODS: In CHF patients with an indication for treatment with ivabradine, resting heart rate (HR), heart failure symptoms [New York Heart Association (NYHA) class, signs of decompensation], left ventricular ejection fraction, brain natriuretic peptide (BNP) values, QOL, and concomitant medication with focus on beta-blocker therapy were documented at baseline, after 4 weeks, and after 4 months. The results were analyzed using descriptive statistical methods. RESULTS: Thousand nine hundred and fifty-six patients with CHF were included. Their mean age was 67 ± 11.7 years and 56.9% were male. 77.8% were receiving beta-blockers. Other concomitant medications included angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (83%), diuretics (61%), aldosterone antagonists (18%), and cardiac glycosides (8%). At baseline, the mean HR of patients was 85 ± 11.8 bpm, 51.1% and 37.2% of patients were classified as NYHA II and III, respectively, and 22.7% showed signs of decompensation. BNP concentrations were tracked in a subgroup, and values exceeding 400 pg/mL were noted in 53.9% of patients. The mean value of the European quality of life-5 dimensions (EQ-5D) QOL index was 0.64 ± 0.28. After 4 months of treatment with ivabradine, HR was reduced to 67 ± 8.9 bpm. Furthermore, the proportion of patients presenting with signs of decompensation decreased to 5.4% and the proportion of patients with BNP levels >400 pg/mL dropped to 26.7%, accompanied by a shift in NYHA classification towards lower grading (24.0% and 60.5% in NYHA I and II, respectively). EQ-5D index improved to 0.79 ± 0.21. CONCLUSION: Over 4 months of treatment, ivabradine effectively reduced HR and symptoms in CHF patients in this study reflecting daily clinical practice. These benefits were accompanied by improved QOL and good general tolerability.

Left atrial appendage occlusion in atrial fibrillation after intracranial hemorrhage.

OBJECTIVE: To evaluate the safety and feasibility of percutaneous left atrial appendage occlusion (LAAO) in patients with atrial fibrillation (AF) and previous intracranial hemorrhage (ICH). METHODS: In an explorative, prospective, single-center, observational study, LAAO was performed in patients with previous ICH and AF using the Amplatzer Cardiac Plug device. Risks of ischemic strokes and hemorrhagic complications were estimated using the CHA2DS2Vasc score and the HAS-BLED score. Before and 1, 6, 12, and 24 months after the procedure, clinical status and complications were recorded. Major complications were predefined as periprocedural stroke, death, pericardial effusion, and device embolism. RESULTS: LAAO was performed in 20 patients. Based on CHA2DS2Vasc score (mean 4.5 ± 1.4) and HAS-BLED score (mean 4.7 ± 1.0), annual risks of stroke and hemorrhagic complications were 4.0%-6.7% and 8.7%-12.5%, respectively. No patient had a procedure-related complication. Minor postprocedural complications were observed in 4/20 patients (2 inguinal hematoma, 1 self-limiting asystole, and 1 thrombus formation on device). No ischemic or hemorrhagic stroke occurred during a mean follow-up of 13.6 ± 8.2 months. CONCLUSIONS: In this first study of LAAO in patients with previous ICH, LAAO appears feasible and safe. A larger, controlled trial is needed to assess the efficacy and safety of the procedure compared to other preventive measures. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in patients with a history of previous ICH and AF, percutaneous LAAO is safe and feasible.

A genome-wide association study identifies 6p21 as novel risk locus for dilated cardiomyopathy.

AIMS: Dilated cardiomyopathy (DCM) is one of the leading causes for cardiac transplantations and accounts for up to one-third of all heart failure cases. Since extrinsic and monogenic causes explain only a fraction of all cases, common genetic variants are suspected to contribute to the pathogenesis of DCM, its age of onset, and clinical progression. By a large-scale case-control genome-wide association study we aimed here to identify novel genetic risk loci for DCM. METHODS AND RESULTS: Applying a three-staged study design, we analysed more than 4100 DCM cases and 7600 controls. We identified and successfully replicated multiple single nucleotide polymorphism on chromosome 6p21. In the combined analysis, the most significant association signal was obtained for rs9262636 (P = 4.90 × 10(-9)) located in HCG22, which could again be replicated in an independent cohort. Taking advantage of expression quantitative trait loci (eQTL) as molecular phenotypes, we identified rs9262636 as an eQTL for several closely located genes encoding class I and class II major histocompatibility complex heavy chain receptors. CONCLUSION: The present study reveals a novel genetic susceptibility locus that clearly underlines the role of genetically driven, inflammatory processes in the pathogenesis of idiopathic DCM.

Clinical characteristics, morbidity, and prognostic value of concomitant coronary artery disease in idiopathic dilated cardiomyopathy.

BACKGROUND: Patients with idiopathic dilated cardiomyopathy (dCMP) might present coronary artery disease (CAD) concomitant to dCMP and prognostic differences between ischemic heart disease and non-ischemic cardiomyopathy have been described. Clinical characteristics and prognostic implications of concomitant CAD in patients with dCMP are largely unknown. METHODS: A total of 1,263 patients with chronic systolic dysfunction from dCMP-of these 67.1 % (n = 847; 72.3 % men) without and 32.9 % (n = 416; 80.8 % men) with concomitant CAD were included and baseline clinical characteristics noted. They were followed prospectively for 36.3 (20.8-65.0) months, representing 5,168 patient-years. All-cause mortality was the primary endpoint; and decompensation requiring hospitalisation as well as the combined endpoint thereof were secondary endpoints. RESULTS: Independent significant predictors of CAD were smoking status (current smoker: OR 2.68, 95 % CI 1.61-4.46; p < 0.001; past smoker: OR 2.52, 95 % CI 1.40-4.52; p < 0.005; each vs. non-smoker), presence of dyslipidemia (OR 3.46, 95 % CI 2.23-5.35; p < 0.001), age (OR 1.06, 95 % CI 1.04-1.08; p < 0.001), and female sex (OR 0.49, 95 % CI 0.29-0.81; p = 0.005). The presence of CAD was not a significant predictor of all-cause mortality (adjusted HR 0.74, 95 % CI 0.36-1.54; p = 0.42), morbidity (adjusted HR 1.48, 95 % CI 0.55-3.99; p = 0.44), or the combined endpoint (HR 0.65, 95 % CI 0.24-1.78; p = 0.40). CONCLUSION: Concomitant CAD is common in patients with dCMP. Clinical predictors of its presence are largely coincident with classic risk factors in the general population. The presence of concomitant CAD appears not to be associated with adverse prognosis (morbidity or mortality) in patients with dCMP.

Incidence rates and predictors of major and minor depression in patients with heart failure.

AIMS: Depression is common in heart failure (HF) and associated with adverse outcomes. This study aimed to investigate incidence rates and predictors of depression in patients sampled from four subprojects of the German Competence Network Heart Failure. METHODS: Eight hundred thirty nine symptomatic HF patients free of depression at baseline underwent repeat depression screening (Patient Health Questionnaire, PHQ-9) after 12 months. Ordered logistic regression analysis was employed to search for predictors of incident depression. RESULTS: Incident minor (major) depression was observed in 61 (7.3%) and 47 (5.6%) of the population. Depression was recurrent in 15 (25%) and 16 (34%), respectively. Multiple regression analysis revealed seven variables predicting minor or major depression: Previous depressive episode (odds ratio [OR] 4.04, 95% confidence interval [CI] 2.37-6.89, p ≤ 0.001), previous resuscitation (OR 2.44, CI 1.23-4.81, p=0.010), current smoking (OR 2.06, CI 1.08-3.50, p=0.008), >4 visits/year to general practitioner (OR 1.67, CI 1.06-2.63, p=0.026), New York Heart Association class (OR 1.54/class, 95% CI 1.05-2.25, p=0.027), PHQ-9 baseline sum-score (OR 1.18/point, CI 1.11-1.27, p<0.001), and SF-36 physical functioning (OR 1.08/-5 points, CI 1.03-1.13, p=0.002). CONCLUSIONS: In these HF patients initially free of depression annual incidence rates were high. Several independent predictors allowed identification of patients at particular risk. Although obtained in a selected cohort these findings call, in view of the grave prognosis of HF patients with comorbid depression, for regular depression screening and development of specific supportive strategies to improve patient care and outcomes in HF.

Optimization of pharmacotherapy in chronic heart failure: is heart rate adequately addressed?

The aim of the study is to evaluate the use of beta-blockers in chronic heart failure (CHF) and the extent of heart rate reduction achieved in clinical practice and to determine differences in outcome of patients who fulfilled select inclusion criteria of the SHIFT study according to resting heart rate modulated by beta-blocker therapy. We evaluated an all-comer population of our dedicated CHF outpatient clinic between 2006 and 2010. For inclusion, individually optimized doses of guideline-recommended pharmacotherapy including beta-blockers had to be maintained for at least 3 months and routine follow-up performed at our outpatient CHF-clinic thereafter. Treatment dosages of beta-blockers, and demographic and clinical profiles including resting heart rate were assessed. The outcome of patients who fulfilled select inclusion criteria of the SHIFT study (left-ventricular ejection fraction (LVEF) ≤35 %, sinus rhythm, NYHA II-IV) and were followed-up for at least 1 year was stratified according to resting heart rates: ≥75 versus <75 bpm and ≥70 versus <70 bpm. The composite primary endpoint was defined as all-cause death or hospital admission for worsening heart failure during 12-month follow-up. In total, 3,181 patients were assessed in regard to treatment dosages of beta-blockers, and demographic and clinical profiles including resting heart rate. Of the overall studied population, 443 patients fulfilled all inclusion criteria and entered outcome analysis. Median observation time of survivors was 27.5 months with 1,039.7 observation-years in total. Up-titration to at least half the evidence-based target dose of beta-blockers was achieved in 69 % and full up-titration in 29 % of these patients. Patients with increased heart rates were younger, more often male, exhibited a higher NYHA functional class and lower LVEF. The primary endpoint occurred in 21 % of patients in the ≥70 bpm group versus 9 % of patients in the group with heart rates <70 bpm (p <0.01). Likewise, comparing the groups ≥75 and <75 bpm, the primary endpoint was significantly increased in the group of patients with heart rates ≥75 bpm 27 vs. 12.2 %; p < 0.01). 5-year event-free survival was significantly lower among patients with heart rates ≥70 bpm as compared to those with <70 bpm (log-rank test p < 0.05) and among patients in the ≥75 bpm group versus <75 bpm group (log-rank test p < 0.01). In conclusion, in clinical practice, 53 % of CHF patients have inadequate heart rate control (heart rates ≥75 bpm) despite concomitant beta-blocker therapy. In this non-randomized cohort, adequate heart rate control under individually optimized beta-blocker therapy was associated with improved mid- and long-term clinical outcome up to 5 years. As further up titration of beta-blockers is not achievable in many patients, the administration of a selective heart rate lowering agent, such as ivabradine adjuvant to beta-blockers may pose an opportunity to further modulate outcome.

Immunosuppression with tacrolimus early after orthotopic heart transplantation: a comparison of prograf and advagraf.

BACKGROUND: We compared trough levels and clinical outcomes in patients who received Prograf or Advagraf (tacrolimus) de novo following heart transplantation surgery. METHODS: Eighty-two patients were included in this follow-up study. Biopsy results were controlled for the first 3 months after orthotopic heart transplantation. Trough levels were monitored for 4 weeks: daily during the first 7 days and once every week thereafter. The lengths of stay in the hospital and in intensive care were compared. The end point of the study was the 1-year mortality rate. RESULTS: We found significant differences between the groups for both biopsy results and trough levels. Trough levels differed for the first 5 days and then converged on the sixth day. The levels remained comparable throughout the monitoring period. The 1-year mortality rates for Prograf and Advagraf were 20% and 15%, respectively. CONCLUSIONS: Trough levels were comparable after an adjustment period. There were no differences between the 2 groups in their 1-year mortality rates. These results suggest that Advagraf is a safe alternative to Prograf for patients who have undergone heart transplantation.

Transfemoral biopsy--a routine procedure after orthotopic heart transplantation for dilated cardiomyopathy in a patient with persistent left superior vena cava and hypoplastic right superior vena cava.

INTRODUCTION: The increasing number of end stage heart failure patients has caused a high number of transplant candidates, including patients with concomitant other cardiac abnormalities. Congenital heart failure can exhibit changes in a variety of anatomic landmarks, and performing heart transplantation in this setting can be challenging. Monitoring for possible rejection is done via intramyocardial biopsies. Here the difficulties arise from variations in anatomic structures. BACKGROUND: We present a case of a persistent left superior vena cava discovered intraoperatively during heart transplantation. The patient was a 45-year-old man who underwent transplantation for a severely reduced left ventricular function, along with a high left ventricular end-diastolic pressure and and end stage heart failure. DISCUSSION: In previous cases, the biopsy was performed by means of left-sided transjugular venous access. Bearing the well-known complications in mind, we chose the transfemoral access so we could take biopsies postoperatively. Biopsies in patients with persistent left vena cava should routinely be performed using the transfemoral access.

The L-Arginine-asymmetric dimethylarginine ratio is an independent predictor of mortality in dilated cardiomyopathy.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is associated with increased mortality in patients with chronic heart failure but it remains unclear if the etiology of heart failure influences the prognostic value of dimethylarginines. METHODS AND RESULTS: L-Arginine, ADMA, and symmetric dimethylarginine (SDMA) were measured by liquid chromatography-tandem mass spectrometry in 341 patients with chronic heart failure due to dilated cardiomyopathy (DCM; n = 226) or ischemic cardiomyopathy (ICM; n = 115). Median (interquartile range [IQR]) ADMA and SDMA plasma levels were higher, L-arginine and the L-arginine-ADMA ratio were lower in patients with severe forms of heart failure (New York Heart Association (NYHA) functional class III or IV) compared with milder forms (NYHA functional class I or II) (ADMA 0.57 (0.14) µmol/L vs 0.54 (0.12) µmol/L [P < .001]; SDMA 0.47 (0.27) µmol/L vs 0.37 (0.13) µmol/L [P < .001]; L-arginine 81.8 (39.1) µmol/L vs 92.6 (39.3) µmol/L [P < .01]), but no significant differences were observed between the different etiologies. The L-arginine-ADMA ratio was associated with outcome only in patients with DCM. In multivariate analysis, the mortality risk of DCM patients was significantly lower for those in the highest quartile compared with the lowest quartile during a median observation time of 3.3 years (hazard ratio 0.31, 95% CI 0.11-0.88; P = .028, adjusted for other risk factors). CONCLUSIONS: DCM patients with unfavourable L-arginine-ADMA ratio are at increased risk for death.

Effects of oral valganciclovir prophylaxis for cytomegalovirus infection in heart transplant patients.

BACKGROUND: Cytomegalovirus (CMV) infection is a serious complication following heart transplantation. This study (June 2003-January 2010) retrospectively assessed the effects of oral valganciclovir prophylaxis in adult heart transplant recipients during the first year after transplantation. METHODS: In patients with normal renal function, 900 mg of oral valganciclovir was administered twice daily for 14 days after heart transplant followed by 900 mg per day for following 6 months. In the event of renal insufficiency, valganciclovir was adjusted according to the manufacturer's recommendations. Antigenemia testing for pp65 antigen and simultaneous polymerase chain reaction (PCR) were used to document exposure to CMV. From 2003 to 2010, 146 patients (74.0% men) of mean age 50.7 ± 10.3 years at the time of heart transplant were included. RESULTS: A total of 16 patients (11.0% of total, 75.0% male) had a positive pp65 and PCR result (ie, CMV infection) during the year following heart transplant; three of these patients had discontinued valganciclovir prophylaxis within the first 6 months following transplant because of leukopenia, including one patient developed CMV colitis. Two further patients developed CMV pneumonia during prophylactic valganciclovir therapy. Eight patients had positive pp65 and PCR tests in the 6-12 months after heart transplant following cessation of routine prophylaxis. One of these patients developed CMV pneumonia and another developed CMV colitis and CMV pneumonia. Thirty-seven of the 146 (25.3%) patients were CMV donor-seropositive/recipient-seronegative, and seven (18.9% of this subgroup) had a positive CMV test. In patients who were CMV donor-seropositive/recipient-seronegative, the risk of a positive CMV test (ie, CMV infection) was significantly elevated (P = 0.023). CONCLUSION: CMV prophylaxis with oral valganciclovir for 6 months following heart transplant is clinically feasible. In line with previous studies, CMV donor-seropositive/recipient-seronegative patients have a significantly elevated risk of CMV infection. In patients who prematurely discontinue valganciclovir, close monitoring of CMV antigenemia appears warranted. No significantly elevated rate of CMV infection was observed after 6 months of valganciclovir prophylaxis.