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Aims Heart rate was proposed as an emergent cardiovascular (CV) risk factor. Previous studies have shown associations between increased heart rate and CV risk in various populations. We aimed to evaluate the prognostic relevance of heart rate in a large contemporaneous medically optimized cohort of patients with stable chronic CV disease. Methods and results In a post hoc analysis of the ONTARGET/TRANSCEND trials, we evaluated associations between baseline and average heart rate in trial with CV risk in 31, 531 patients followed for a median of 5 years. The primary outcome, major vascular events (MVE), was a composite of CV death, myocardial infarction (MI), stroke, and congestive heart failure (CHF). Pre-specified secondary outcomes included all-cause death and the individual components of the primary outcome. Associations between heart rate and outcomes were computed with heart rate as a continuous variable, baseline heart rate >70 vs ≤70 bpm, and across heart rate quintiles, adjusting for other markers of risk, beta-blocker and non-dihydropyridine calcium channel blocker use. For each 10 bpm increase in baseline and average heart rate, we observed a significant increase in risk of MVE, CV death, CHF and all-cause death. There was a continuous relationship between MVE and baseline and, more importantly, average in-trial heart rate, with no observed threshold. MVE, CV death, stroke, CHF, and all-cause death increased across heart rate quintiles. There was no association between MI and HR. Results were consistent in clinically relevant subgroups. There were modest but significant improvements in C-statistic and in statistical measures of model calibration for models that included heart rate for MVE, CV death, CHF and all-cause death. Conclusions This large study examined and quantitated associations between heart rate and CV events in a contemporary medically optimized population with stable CV disease. Resting and, in particular, in-trial average heart rate are independently associated with significant increases in CV events and all-cause death.

Background: Impaired vascular compliance is associated with cardiovascular mortality. The effects of heart rate on vascular compliance are unclear. Therefore, we characterized effects of heart rate reduction (HRR) by I(f) current inhibition on aortic compliance and underlying molecular mechanisms in apolipoprotein E-deficient (ApoE – / – ) mice. Methods: ApoE – / – mice fed a high-cholesterol diet and wild-type (WT) mice were treated with ivabradine (20 mg/kg/d) or vehicle for 6 weeks. Compliance of the ascending aorta was evaluated by MRI. Results: Ivabradine reduced heart rate by 113 ± 31 bpm (∼19%) in WT mice and by 133 ± 6 bpm (∼23%) in ApoE – / – mice. Compared to WT controls, ApoE – / – mice exhibited reduced distensibility and circumferential strain. HRR by ivabradine increased distensibility and circumferential strain in ApoE – / – mice but did not affect both parameters in WT mice. Ivabradine reduced aortic protein and mRNA expression of the angiotensin II type 1 (AT1) receptor and reduced rac1-GTPase activity in ApoE – / – mice. Moreover, membrane translocation of p47 phox was inhibited. In ApoE – / – mice, HRR induced anti-inflammatory effects by reduction of aortic mRNA expression of IL-6, TNF-alpha and TGF-beta. Conclusion: HRR by ivabradine improves vascular compliance in ApoE – / – mice. Contributing mechanisms include downregulation of the AT1 receptor, attenuation of oxidative stress and modulation of inflammatory cytokine expression.

Background Renal replacement therapy (RRT) is frequently used in critically ill patients with acute kidney injury (AKI). Here, we provide guidelines for the management of RRT in critically ill patients on the intensive care unit (ICU). Methods We convened a systemic literature research and a Delphi process with a bi-national multidisciplinary consensus panel including 22 clinicians of 12 different German-speaking societies (Germany and Austria) with expertise in RRT. This structured guideline process was the basis for the evidence-based statements and recommendations. Results We identified seven clinical areas needing guidance: (1) start, (2) modality (diffusion and convection), (3) continuous/ intermittent, (4) anticoagulation, (5) dose (6) pharmacotherapy, (7) stopping criteria. The consensus produced 73 statements and recommendations regarding key clinical areas, the most important 47 statements and recommendations are summarized in this overview. Conclusions This evidence-based bi-national guideline should provide physicians with guidance for delivering best practice to critically ill patients with a dialysis-dependent AKI.

This article provides information and commentaries on trials which were presented at Clinical Trial Updates and Hotline Sessions presented at the Scientific Sessions 2007 of the American Heart Association in Orlando, Florida. The comprehensive summaries have been generated from the oral presentations and the webcasts of the American Heart Association. Most reports have not been published as full papers and therefore have to be considered as preliminary data, as the analysis may change in the final publications. The following papers are discussed: TRITON TIMI-38, EVA-AMI, BRIEF-PCI, RACE, MASS Stent, HF-ART, STITCH, CORONA, ILLUMINATE, CORE-64, OAT Substudy, AFCHF, MASCOT, RETHINQ, MASTER I, POISE, COUMA-GEN, HIJ-CREATE, PROVIDENCE I, CAUSMIC, IC-BMC, IC/IM BMCs.

Background and aims Wearable cardioverter defibrillator (WCD) can protect patients from sudden cardiac death due to ventricular tachyarrhythmias and serve as a bridge to decision of definite defibrillator implantation. The aim of this analysis from an international, multicenter WCD registry was to identify predictors of sustained ventricular tachycardia (VT) and/or ventricular fibrillation (VF) in this population. Methods One thousand six hundred seventy-five patients with WCD were included in a multicenter registry from 9 European centers, with a median follow-up of 440 days (IQR 120–893). The primary study end point was the occurrence of sustained VT/VF. Results Sustained VT was detected by WCD in 5.4% and VF in 0.9% of all patients. Of the 30.3% of patients receiving ICD implantation during follow-up, sustained VT was recorded in 9.3% and VF in 2.6%. Non-ischemic cardiomyopathy (HR 0.5, p  < 0.001), and medication with angiotensin-converting enzyme inhibitors (HR 0.7, p  = 0.027) and aldosterone antagonists (HR 0.7, p  = 0.005) were associated with a significantly lower risk of VT/VF. Conclusions Patients who received WCD due to a transient increased risk of sudden cardiac death have a comparatively lower risk of VT/VF in the presence of non-ischemic cardiomyopathy. Of note, optimal medical treatment for heart failure not only results in an improvement in left ventricular ejection fraction but also in a reduction in the risk for VT/VF. Graphical Abstract

COVID-19 comprises several severity stages ranging from oligosymptomatic disease to multi-organ failure and fatal outcomes. The mechanisms why COVID-19 is a mild disease in some patients and progresses to a severe multi-organ and often fatal disease with respiratory failure are not known. Biomarkers that predict the course of disease are urgently needed. The aim of this study was to evaluate a large spectrum of established laboratory measurements. Patients from the prospective PULMPOHOM and CORSAAR studies were recruited and comprised 35 patients with COVID-19, 23 with conventional pneumonia, and 28 control patients undergoing elective non-pulmonary surgery. Venous blood was used to measure the serum concentrations of 79 proteins by Luminex multiplex immunoassay technology. Distribution of biomarkers between groups and association with disease severity and outcomes were analyzed. The biomarker profiles between the three groups differed significantly with elevation of specific proteins specific for the respective conditions. Several biomarkers correlated significantly with disease severity and death. Uniform manifold approximation and projection (UMAP) analysis revealed a significant separation of the three disease groups and separated between survivors and deceased patients. Different models were developed to predict mortality based on the baseline measurements of several protein markers. A score combining IL-1ra, IL-8, IL-10, MCP-1, SCF and CA-9 was associated with significantly higher mortality (AUC 0.929). Several newly identified blood markers were significantly increased in patients with severe COVID-19 (AAT, EN-RAGE, myoglobin, SAP, TIMP-1, vWF, decorin) or in patients that died (IL-1ra, IL-8, IL-10, MCP-1, SCF, CA-9). The use of established assay technologies allows for rapid translation into clinical practice.

Myocardial calcification after prolonged highly dosed catecholamine treatment has been described experimentally. Here, we demonstrate myocardial calcifications by high-dose catecholamine treatment leading to chronic heart failure in patients. A 62-year-old Caucasian woman presented with central pulmonary embolism, developing acute heart failure, and cardiogenic shock. Twenty-six days of high-dose norepinephrine treatment had to be administered to maintain circulation. After 74 days of intensive care treatment, the patient fortunately recovered but was readmitted to emergency ward because of dyspnoea and congestion. Computed tomography pulmonary angiography ruled out recurrence of pulmonary embolism, but depicted massive intramural cardiac calcifications, which were not present before treatment. Coronary angiography showed normal coronary arteries, and myocardial biopsy excluded infectious myocarditis. There was no evidence for sarcoidosis, thyroid disease, tuberculosis, or hyperparathyroidism. Oral heart failure treatment was initiated and at the 7 week follow-up the patient remained symptomatic with New York Heart Association functional Class III, while right and left ventricular function had recovered. Prolonged activation of the heart by catecholamines leading to myocardial calcifications has first been examined experimentally by Fleckenstein . Herein, we are able to show, that this can occur in clinical situations. Careful dosing of catecholamines and early use of non-catecholamine-based haemodynamic support is recommended to avoid consecutive impairment of heart function and heart failure.

Background High resting heart rate (RHR) predicts cardiovascular outcomes in patients with vascular disease and heart failure. We evaluated the prognostic value of RHR in a large contemporary population-based, prospective cohort of individuals without known coronary artery disease. Methods and results Resting heart rate (RHR) was determined in 4091 individuals (mean age 59.2 ± 7.7; 53 % women) from the Heinz Nixdorf RECALL study, of whom, 3348 were free of heart rate lowering medication. During 10.5 years of follow-up (median), 159 (3.9 %) individuals developed a coronary event and 398 (9.7 %) died of any cause. Persons without any event ( n  = 3603) had similar heart rates as persons with coronary events (69.5 ± 11 versus 69.9 ± 11 bpm, p  = 0.51) but lower heart rates than persons who died (72.3 ± 13 bpm, p  < 0.0001). In individuals without heart rate lowering medication, an increase in heart rate by 5 bpm was associated with an increased hazard ratio (HR) for all-cause mortality of 13 % in unadjusted analysis and also upon adjustment for traditional cardiovascular risk factors, including coronary artery calcification [full model: HR (95 % CI) 1.13 (1.07–1.20), p  < 0.0001], but not for coronary events [HR 1.02 (0.94–1.11), p  = 0.60]. In individuals without heart rate lowering medication, the HR (full model) for heart rate ≥70 versus <70 bpm with regard to all-cause mortality and coronary events was 1.68 (1.30–2.18), p  < 0.0001, and 1.20 (0.82–1.77), p  = 0.35. Analysis of the entire cohort revealed a continuous relationship of heart rate with all-cause mortality [HR for lowest to highest heart rate quartile 1.64 (1.22–2.22), p  = 0.001, full model] but not with coronary events [HR 1.04 (0.65–1.66), p  = 0.86]. Conclusions In the general population without known coronary artery disease and heart rate lowering medication, elevated RHR is an independent risk marker for all-cause mortality but not for coronary events.