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Vaccination is considered the best measure to overcome the Sars-Cov2 pandemic. However, changing national recommendations on sequence and time frame necessitate the collection of real-word data on adverse events of Sars-CoV2 vaccination protocols outside of pivotal trials. We report results from a survey on the adverse events and the operational consequences of a Sars-CoV2 vaccination campaign with partly mixed vaccination protocol as well as booster vaccination. While the spectrum of adverse effects in our cohort appeared to be similar to pivotal studies, there were substantial differences in both frequency and distribution with only 3 out of 10 participants staying symptom-free. In over 26% of vaccinees symptoms were so severe, that they stayed at home with mean days on sick leave being 1.5 per person using mixed vaccination protocol. Being aware, that these results might partially be attributable to nocebo effects they are of importance for future vaccination campaigns., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Study Objectives: Aim of the study was to investigate the association between obstructive sleep apnoea (OSA) and cardiovascular morbidity and mortality in a cohort of patients with cardiovascular risk factors., Methods: In this prospective study, 378 patients of the DIAST-CHF cohort were screened for OSA by home polygraphy. Inclusion criteria were risk factors for diastolic heart failure, such as hypertension, diabetes mellitus, atherosclerotic disease, or history of chronic heart failure. Patients were followed up after 1, 2, 5, 9 and 10 years for the occurrence of major adverse cardiac and cerebrovascular events (MACE and MACCE)., Results: 344 patients were included in the analysis, of which 60% were diagnosed with OSA (apnoea-hypopnoea index ≥5/h). Overall mortality was higher in the OSA group (14.9% vs. 5.9%; p = 0.007), but significance disappeared after adjustment for age and sex (hazard ratio (HR) 1.89, 95% confidence interval (CI) 0.86-4.16, p = 0.12). There was no significant difference in the occurrence of MACE or MACCE in patients with OSA compared to those without OSA (MACE: 31% vs. 30%; p = 0.61; MACCE: 32% vs. 30%; p = 0.53)., Conclusion: We did not find evidence of an adverse effect of OSA on cardiovascular morbidity and mortality in a cohort of patients with cardiovascular risk factors., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: We investigated the modifying role and prognostic importance of diastolic dysfunction (DD) in patients with heart failure and systolic dysfunction (SD)., Hypothesis: The echocardiographic evaluation of diastolic function in patients with SD provides further prognostic information., Methods: From the German Competence Network Heart Failure, 1046 heart failure patients with reduced left ventricular ejection fraction (LVEF; <50%) were echocardiographically studied and followed for a median of 5 years. SD was subdivided into nonsevere (LVEF 36%-49%) and severe (LVEF ≤35%); DD was subdivided into nonsevere (E/E' <15) and severe (E/E' ≥15)., Results: In general, severe SD was associated with higher hazard ratios (HRs; 2-fold to 3.5-fold) for all endpoints (all-cause death, cardiac death, cardiovascular hospitalization, duration of hospitalization). Patients with severe SD had a 2.5-fold risk of death (95% confidence interval [CI]: 1.84-3.47, P < 0.001), and patients with severe DD showed a 1.8-fold risk (95% CI: 1.17-2.61, P = 0.004). Furthermore, we observed a strong interaction of SD and DD: concomitant severe DD in patients with moderate SD increased risk substantially (HR: 1.73, 95% CI: 1.16-2.6, P = 0.007); by contrast, in patients with severe SD, additional presence of severe DD added little or no risk (HR for interaction: 0.5-1.2)., Conclusions: In heart failure patients with reduced LVEF, the evaluation of diastolic function provides additional prognostic information. Although severe SD generally increased the risk for all endpoints, the degree of DD and its impact as a prognostic marker for overall and cardiovascular mortality appeared of particular relevance in subjects with nonsevere SD., (© 2017 Wiley Periodicals, Inc.)

We investigated whether obstructive sleep apnoea (OSA) independently affects diastolic function in a primary care cohort of patients with cardiovascular risk factors. 378 study participants with risk factors for diastolic dysfunction were prospectively included and a polygraphy was performed in all patients. Diastolic dysfunction was assessed by comprehensive echocardiography including tissue Doppler. Sleep apnoea was classified according to apnoea/hypopnoea index (AHI) as none (AHI <5 events·h(-1)), mild (AHI ≤5 to <15 events·h(-1)) or moderate-to-severe (AHI ≥15 events·h(-1)). Patients with central sleep apnoea (n=14) and patients with previously diagnosed sleep apnoea (n=12) were excluded. In the remaining 352 subjects, 21.6% had an AHI ≥15 events·h(-1). The prevalence of diastolic dysfunction increased with the severity of sleep apnoea from 44.8% (none) to 56.8% (mild) to 69.7% (moderate-to-severe sleep apnoea) (p=0.002). The degree of diastolic dysfunction also increased with sleep apnoea severity (p=0.004). In univariate regression analysis, age, desaturation index, AHI, cardiac frequency, angiotensin receptor 1 antagonist therapy, body mass index (BMI) and left ventricular mass were associated with diastolic dysfunction. In multivariate regression analysis, only age, BMI, AHI and cardiac frequency were independently associated with diastolic dysfunction. Moderate-to-severe OSA is independently associated with diastolic dysfunction in patients with classical risk factors for diastolic dysfunction.

Background: To assess heart failure therapies in diabetic patients with preserved as compared to impaired systolic ventricular function., Methods: 3304 patients with heart failure from 9 different studies were included (mean age 63 ± 14 years); out of these, 711 subjects had preserved left ventricular ejection fraction (≥ 50%) and 994 patients in the whole cohort suffered from diabetes., Results: The majority (>90%) of heart failure patients with reduced ejection fraction (SHF) and diabetes were treated with an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) or with beta-blockers. By contrast, patients with diabetes and preserved ejection fraction (HFNEF) were less likely to receive these substance classes (p < 0.001) and had a worse blood pressure control (p < 0.001). In comparison to patients without diabetes, the probability to receive these therapies was increased in diabetic HFNEF patients (p < 0.001), but not in diabetic SHF patients. Aldosterone receptor blockers were given more often to diabetic patients with reduced ejection fraction (p < 0.001), and the presence and severity of diabetes decreased the probability to receive this substance class, irrespective of renal function., Conclusions: Diabetic patients with HFNEF received less heart failure medication and showed a poorer control of blood pressure as compared to diabetic patients with SHF. SHF patients with diabetes were less likely to receive aldosterone receptor blocker therapy, irrespective of renal function.

Aims: Heart failure with normal ejection fraction (HFnEF) is an important clinical entity that remains incompletely understood. The novel biomarker growth differentiation factor 15 (GDF-15) is elevated in systolic heart failure (HFrEF) and is predictive of an adverse outcome. We investigated the clinical relevance of GDF-15 plasma levels in HFnEF., Methods and Results: A subgroup of patients from the ongoing DIAST-CHF observational trial, with a history of chronic heart failure (CHF) or positive Framingham criteria at presentation, was selected. Patients were classified as having either HFrEF (n=86) or HFnEF (n=142) and compared with healthy elderly controls (n=188) from the same cohort. Growth differentiation factor 15 levels in HFnEF were significantly higher than in controls and similar to those in HFrEF. In multivariate analysis, factors significantly associated with GDF-15 levels were age, sex, estimated glomerular filtration rate (eGFR), presence of HFrEF and HFnEF. Growth differentiation factor 15 correlated with multiple echocardiographic markers of diastolic function and was associated with 6 min walk test performance and SF-36 physical score on multivariate analysis in all patients. When using a classification for HFnEF that did not employ N-terminal pro brain natriuretic peptide (NT-proBNP) as a diagnostic criterion, the diagnostic properties of GDF-15 for detecting HFnEF tended to be superior to those of NT-proBNP, and a combination significantly improved diagnostic accuracy., Conclusion: Growth differentiation factor 15 is elevated in HFnEF to a similar degree as in HFrEF. It is independently associated with impairment in exercise capacity and in physical components of quality of life. Diagnostic precision of GDF-15 is at least as good as that of NT-proBNP and combining both markers improves diagnostic accuracy.

Aims: We tested the hypothesis that, in heart failure with normal ejection fraction (HFNEF), diastolic dysfunction is accentuated at increasing heart rates, and this contributes to impaired frequency-dependent augmentation of cardiac output., Methods and Results: In 17 patients with HFNEF (median age 69 years, 13 female) and seven age-matched control patients, systolic and diastolic function was analysed by pressure-volume loops at baseline heart rate and during atrial pacing to 100 and 120 min(-1). At baseline, relaxation was prolonged and end-diastolic left ventricular stiffness was higher in HFNEF, whereas all parameters of systolic function were not different from control patients. This resulted in smaller end-diastolic volumes, higher end-diastolic pressure, and a lower stroke volume and cardiac index in HFNEF vs. control patients. During pacing, frequency-dependent upregulation of contractility indices (+dP/dt(max) and Ees) occurred similarly in HFNEF and control patients, but frequency-dependent acceleration of relaxation (dP/dt(min)) was blunted in HFNEF. In HFNEF, end-diastolic volume and stroke volume decreased with higher heart rates while both remained unchanged in control patients., Conclusion: In HFNEF, frequency-dependent upregulation of cardiac output is blunted. This results from progressive volume unloading of the left ventricle due to limited relaxation reserve in combination with increased LV passive stiffness, despite preserved force-frequency relation.

Background: Screening of primary care patients at risk for left ventricular systolic dysfunction by a simple blood-test might reduce referral rates for echocardiography. Whether or not natriuretic peptide testing is a useful and cost-effective diagnostic instrument in primary care settings, however, is still a matter of debate., Methods: N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, clinical information, and echocardiographic data of left ventricular systolic function were collected in 542 family practice patients with at least one cardiovascular risk factor. We determined the diagnostic power of the NT-proBNP assessment in ruling out left ventricular systolic dysfunction and compared it to a risk score derived from a logistic regression model of easily acquired clinical information., Results: 23 of 542 patients showed left ventricular systolic dysfunction. Both NT-proBNP and the clinical risk score consisting of dyspnea at exertion and ankle swelling, coronary artery disease and diuretic treatment showed excellent diagnostic power for ruling out left ventricular systolic dysfunction. AUC of NT-proBNP was 0.83 (95% CI, 0.75 to 0.92) with a sensitivity of 0.91 (95% CI, 0.71 to 0.98) and a specificity of 0.46 (95% CI, 0.41 to 0.50). AUC of the clinical risk score was 0.85 (95% CI, 0.79 to 0.91) with a sensitivity of 0.91 (95% CI, 0.71 to 0.98) and a specificity of 0.64 (95% CI, 0.59 to 0.67). 148 misclassifications using NT-proBNP and 55 using the clinical risk score revealed a significant difference (McNemar test; p < 0.001) that was based on the higher specificity of the clinical risk score., Conclusion: The evaluation of clinical information is at least as effective as NT-proBNP testing in ruling out left ventricular systolic dysfunction in family practice patients at risk. If these results are confirmed in larger cohorts and in different samples, family physicians should be encouraged to rely on the diagnostic power of the clinical information from their patients.

Aims: To analyse the effect of diabetes (DM) on diastolic function in hypertensive patients., Methods: 439 hypertensive patients were selected for participation in this study. All participants had an echocardiographic evaluation of systolic and diastolic function. The overall degree of diastolic function and specific parameters (e.g. E/Ea ratio) were analysed., Results: We divided the cohort (63+/-10 years) into those with diabetes mellitus (DM(+), n=124) and without diabetes mellitus (DM(-), n=315). The prevalence of normal diastolic function was lower in DM(+) than DM(-) (19.4% vs. 30.8%); mild (65.3% vs. 60.0%) and moderate/ severe diastolic dysfunction were more frequent in DM(+) (15.3% vs. 9.2%, p=0.022). The E/Ea ratio, an estimate of left ventricular end-diastolic pressure, was significantly higher in DM(+) (12.3+/-4.4) as compared to DM(-) (10.8+/-3.6, p<0.001). Sex-specific analysis revealed that the effect of DM on diastolic function was mainly limited to the male subgroup. Multivariate logistic regression analysis showed that diabetes affected diastolic function in males independent of blood pressure, left ventricular mass index, concomitant medication and prevalence of coronary artery disease., Conclusion: Diabetes negatively affects diastolic function in patients with arterial hypertension. This effect is mainly confined to the male subgroup.

Background: Recently identified ABCG5/8 transporters are responsible in part for the different absorption rates of campesterol, sitosterol, and cholesterol. These transporters are also expressed in the liver and might regulate biliary sterol secretion., Aims: This study was therefore conducted to determine the biliary secretion rates and hepatic clearances of campesterol, sitosterol, and cholesterol., Subjects: Six healthy, male volunteers., Methods: Deuterium labelled sitosterol and campesterol, and unlabelled sitostanol were constantly infused together with a liquid formula using a duodenal perfusion technique. Biliary secretion and hepatic clearance rates were calculated from hourly bile and plasma samples., Results: Plasma concentrations of cholesterol, campesterol, and sitosterol averaged 167.5 (50) mg/dl (SD), 0.50 (0.22) mg/dl, and 0.30 (0.10) mg/dl, respectively. Sitosterol showed a significantly higher biliary secretion rate (1.23 (0.87) mg/h) than campesterol (0.76 (0.54) mg/h, p=0.0321), but both plant sterols had significantly lower biliary secretion rates compared with cholesterol (47.7 (17.5) mg/h; p=0.001 for both). Hepatic clearance of cholesterol (0.31 (0.18) dl/h) was significantly lower compared with campesterol (2.11 (2.51) dl/h) and sitosterol (4.97 (4.70) dl/h; p=0.028 for both), and the clearance of campesterol was significant lower compared with sitosterol (p=0.028)., Conclusion: The observed inverse relation between hepatic clearance and known intestinal absorption of cholesterol, campesterol, and sitosterol supports the hypothesis that the ABCG5/8 transporters regulating intestinal sterol absorption might also be involved in biliary sterol excretion.

Background: Application of pyruvate was shown to improve contractile function in isolated animal myocardium and hemodynamics in patients with congestive heart failure. We assessed the influence of pyruvate on systolic and diastolic myocardial function and its subcellular mode of action in isolated myocardium from end-stage failing human hearts., Methods and Results: In muscle strip preparations, concentration-dependent effects of pyruvate on developed and diastolic force (n=6), aequorin light emission reflecting intracellular Ca(2+) transients (n=6), and rapid cooling contractures reflecting sarcoplasmic reticulum (SR) Ca(2+) content (n=11) were measured. Pyruvate resulted in a concentration-dependent increase in developed force and a decrease in diastolic force, with a maximum effect of 155% and 21%, respectively, at 20 mmol/L pyruvate (P<0.05). This was associated with a dose-dependent prolongation of time to peak tension and relaxation time. Pyruvate increased rapid cooling contractures by 51% and aequorin light signals by 85% (at 15 and 20 mmol/L; P<0.05). This indicates increased SR Ca(2+) content and increased intracellular Ca(2+) transients. The inotropic effect of pyruvate was still present after elimination of SR Ca(2+) storage function with 10 micromol/L cyclopiazonic acid and 1 micromol/L ryanodine (n=8). Pyruvate significantly increased intracellular pH from 7.31+/-0.03 to 7.40+/-0.04 by BCECF fluorescence (n=6)., Conclusions: The present findings indicate that pyruvate improves contractile performance of failing human myocardium by increasing intracellular Ca(2+) transients as well as myofilament Ca(2+) sensitivity. The former seem to result from increased SR Ca(2+) accumulation and release, the latter from increased intracellular pH.