The need for dedicated advanced heart failure units to optimize heart failure care: impact of optimized advanced heart failure unit care on heart transplant outcome in high-risk patients.

AIM: With an increasing prevalence of heart failure (HF), more patients with advanced disease have to be treated in cardiology units by sophisticated medical and interventional strategies. We therefore developed a dedicated advanced heart failure unit (AHFU) to target the specific needs of the many patients with advanced HF. We here present our concept and its impact on outcome in high-risk high-urgency (HU) heart transplant candidates. METHODS AND RESULTS: The eight-bed unit was established as an extension of the cardiologic intensive care and coronary care units in an intermediate care setting. Each bed was equipped with 24 h haemodynamic, respiratory, and arrhythmia monitoring. The unit is served 24/7 by five residents in cardiology, one staff cardiologist specializing in medical and interventional HF care, and 10 intensive care nurses. The cardiology team is supported by colleagues from cardiac surgery, sports medicine, psychosomatics, and the internal medicine departments. As an example of the intensified care on the AHFU, data from the cohorts of patients undergoing heart transplantation from HU status before (pre-AHFU 2008-11) and after establishment of the AHFU (AHFU 2012-15) were analysed. Interestingly, mortality on HU waiting list and post-heart transplant survival was comparable in both cohorts, despite significant increase in morbidity and co-morbidity as assessed by the Index for Mortality Prediction After Cardiac Transplantation model in the AHFU group. CONCLUSIONS: Our AHFU provides a unique and novel setting for the integration of modern pharmacological, interventional, surgical, and supportive HF therapy embedded in an academic heart centre. This may be a major step forward in the care of critical patients with advanced 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.

In vivo functional performance and structural maturation of decellularised allogenic aortic valves in the subcoronary position.

OBJECTIVE: Successful animal and clinical implantation of decellularised heart valves has been performed in the pulmonary position. Comparable results have not yet been achieved for the aortic position with the high haemodynamic demands of the systemic circulation and the challenging implantation procedure. METHODS: Allogenic aortic valves (n=10) were decellularised using detergents (decellularised aortic valves (dAoVs)). Five prostheses were analysed for decellularisation quality and scaffold preservation. Five valves were orthotopically implanted in juvenile sheep in a subcoronary technique. After 5 months, echocardiography, immunohistology, histology, electron microscopy and western blot (WB) were used for analysis. RESULTS: All animals survived the follow-up with increased body weight (38.8 ± 2.8kg vs 56.0 ± 2.6kg, p<0.001). After implantation, three dAoVs showed negligible and two others minor insufficiency (I), which remained unchanged at explantation. Effective orifice area increased slightly (1.1 ± 0.2cm(2) vs 1.6 ± 0.3cm(2), p=0.051). Explanted dAoVs (n=4) showed excellent macroscopy with minor soft-tissue nodules observed at the free cusp margins of only one dAoV. No valve showed any signs of thrombosis or calcification. On microscopic evaluation, the cusp architecture was preserved with an almost complete endothelial repopulation as confirmed by vimentin(+)/von Willebrand factor (vWF(+))-staining, WB of endothelial markers (eNOS/vWF) and scanning electron microscopy (SEM). Partial interstitial reseeding with vimentin(+)/alpha-smooth muscle (αsm(+))-cells was noted. Quantitative measurement of collagen-IV, collagen-I, laminin and elastin (WB) demonstrated preserved scaffold composition as compared to native tissue. CONCLUSION: The dAoVs showed excellent functional outcome at 5 months in a subcoronary model of juvenile sheep. Advanced endothelial and nascent interstitial repopulation, with preserved structural integrity under the high-shear-stress milieu of the aortic valve, encourage further long-term studies.