@article{NolteHermannLingenPlatscheketal.2019,
  author    = {Nolte, Kathleen and Hermann-Lingen, Christoph and Platschek, Lars and Holzendorf, Volker and Pilz, Stefan and Tomaschitz, Andreas and D{\"u}ngen, Hans-Dirk and Angermann, Christiane E. and Hasenfuß, Gerd and Pieske, Burkert and Wachter, Rolf and Edelmann, Frank},
  title     = {Vitamin D deficiency in patients with diastolic dysfunction or heart failure with preserved ejection fraction},
  series = {ESC Heart Failure},
  volume    = {6},
  journal   = {ESC Heart Failure},
  doi       = {10.1002/ehf2.12413},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232303},
  pages     = {262-270},
  year      = {2019},
  abstract  = {Aims Vitamin D deficiency is prevalent in heart failure (HF), but its relevance in early stages of heart failure with preserved ejection fraction (HFpEF) is unknown. We tested the association of 25-hydroxyvitamin D [25(OH)D] serum levels with mortality, hospitalizations, cardiovascular risk factors, and echocardiographic parameters in patients with asymptomatic diastolic dysfunction (DD) or newly diagnosed HFpEF. Methods and results We measured 25(OH)D serum levels in outpatients with risk factors for DD or history of HF derived from the DIAST-CHF study. Participants were comprehensively phenotyped including physical examination, echocardiography, and 6 min walk test and were followed up to 5 years. Quality of life was evaluated by the Short Form 36 (SF-36) questionnaire. We included 787 patients with available 25(OH)D levels. Median 25(OH)D levels were 13.1 ng/mL, mean E/e′ medial was 13.2, and mean left ventricular ejection fraction was 59.1\%. Only 9\% (n = 73) showed a left ventricular ejection fraction <50\%. Fifteen per cent (n = 119) of the recruited participants had symptomatic HFpEF. At baseline, participants with 25(OH)D levels in the lowest tertile (≤10.9 ng/L; n = 263) were older, more often symptomatic (oedema and fatigue, all P ≤ 0.002) and had worse cardiac [higher N-terminal pro-brain natriuretic peptide (NT-proBNP) and left atrial volume index, both P ≤ 0.023], renal (lower glomerular filtration rate, P = 0.012), metabolic (higher uric acid levels, P < 0.001), and functional (reduced exercise capacity, 6 min walk distance, and SF-36 physical functioning score, all P < 0.001) parameters. Increased NT-proBNP, uric acid, and left atrial volume index and decreased SF-36 physical functioning scores were independently associated with lower 25(OH)D levels. There was a higher risk for lower 25(OH)D levels in association with HF, DD, and atrial fibrillation (all P ≤ 0.004), which remained significant after adjusting for age. Lower 25(OH)D levels (per 10 ng/mL decrease) tended to be associated with higher 5 year mortality, P = 0.05, hazard ratio (HR) 1.55 [1.00; 2.42]. Furthermore, lower 25(OH)D levels (per 10 ng/mL decrease) were related to an increased rate of cardiovascular hospitalizations, P = 0.023, HR = 1.74 [1.08; 2.80], and remained significant after adjusting for age, P = 0.046, HR = 1.63 [1.01; 2.64], baseline NT-proBNP, P = 0.048, HR = 1.62 [1.01; 2.61], and other selected baseline characteristics and co-morbidities, P = 0.043, HR = 3.60 [1.04; 12.43]. Conclusions Lower 25(OH)D levels were associated with reduced functional capacity in patients with DD or HFpEF and were significantly predictive for an increased rate of cardiovascular hospitalizations, also after adjusting for age, NT-proBNP, and selected baseline characteristics and co-morbidities.},
  language  = {en}
}
@article{EdelmannMusialBrightGelbrichetal.2016,
  author    = {Edelmann, Frank and Musial-Bright, Lindy and Gelbrich, Goetz and Trippel, Tobias and Radenovic, Sara and Wachter, Rolf and Inkrot, Simone and Loncar, Goran and Tahirovic, Elvis and Celic, Vera and Veskovic, Jovan and Zdravkovic, Marija and Lainscak, Mitja and Apostolović, Svetlana and Neskovic, Aleksandar N. and Pieske, Burkert and D{\"u}ngen, Hans-Dirk},
  title     = {Tolerability and feasibility of beta-blocker titration in HFpEF versus HFrEF: Insights from the CIBIS-ELD trial},
  series = {JACC: Heart Failure},
  volume    = {4},
  journal   = {JACC: Heart Failure},
  number    = {2},
  doi       = {10.1016/j.jchf.2015.10.008},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-191022},
  pages     = {140-149},
  year      = {2016},
  abstract  = {OBJECTIVES: This study evaluated the tolerability and feasibility of titration of 2 distinctly acting beta-blockers (BB) in elderly heart failure patients with preserved (HFpEF) and reduced (HFrEF) left ventricular ejection fraction. BACKGROUND: Broad evidence supports the use of BB in HFrEF, whereas the evidence for beta blockade in HFpEF is uncertain. METHODS: In the CIBIS-ELD (Cardiac Insufficiency Bisoprolol Study in Elderly) trial, patients >65 years of age with HFrEF (n = 626) or HFpEF (n = 250) were randomized to bisoprolol or carvedilol. Both BB were up-titrated to the target or maximum tolerated dose. Follow-up was performed after 12 weeks. HFrEF and HFpEF patients were compared regarding tolerability and clinical effects (heart rate, blood pressure, systolic and diastolic functions, New York Heart Association functional class, 6-minute-walk distance, quality of life, and N-terminal pro-B-type natriuretic peptide). RESULTS: For both of the BBs, tolerability and daily dose at 12 weeks were similar. HFpEF patients demonstrated higher rates of dose escalation delays and treatment-related side effects. Similar HR reductions were observed in both groups (HFpEF: 6.6 beats/min; HFrEF: 6.9 beats/min, p = NS), whereas greater improvement in NYHA functional class was observed in HFrEF (HFpEF: 23\% vs. HFrEF: 34\%, p < 0.001). Mean E/e' and left atrial volume index did not change in either group, although E/A increased in HFpEF. CONCLUSIONS: BB tolerability was comparable between HFrEF and HFpEF. Relevant reductions of HR and blood pressure occurred in both groups. However, only HFrEF patients experienced considerable improvements in clinical parameters and Left ventricular function. Interestingly, beta-blockade had no effect on established and prognostic markers of diastolic function in either group. Long-term studies using modern diagnostic criteria for HFpEF are urgently needed to establish whether BB therapy exerts significant clinical benefit in HFpEF. (Comparison of Bisoprolol and Carvedilol in Elderly Heart Failure HF] Patients: A Randomised, Double-Blind Multicentre Study CIBIS-ELD]; ISRCTN34827306).},
  language  = {en}
}