Impact of cavotricuspid isthmus ablation for typical atrial flutter and heart failure in the elderly—results of a retrospective multi-center study

IntroductionWhile in the CASTLE-AF trial, in patients with atrial fibrillation and heart failure with reduced ejection fraction, interventional therapy using pulmonary vein isolation was associated with outcome improvement, data on cavotricuspid isthmus ablation (CTIA) in atrial flutter (AFL) in the elderly is rare.MethodsWe included 96 patients between 60 and 85 years with typical AFL and heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF) treated in two medical centers. 48 patients underwent an electrophysiological study with CTIA, whereas 48 patients received rate or rhythm control and guideline-compliant heart failure therapy. Patients were followed up for 2 years, with emphasis on left ventricular ejection fraction (LVEF) over time. Primary endpoints were cardiovascular mortality and hospitalization for cardiac causes.ResultsPatients with CTIA showed a significant increase in LVEF after 1 (p < 0.001) and 2 years (p < 0.001) in contrast to baseline LVEF. Improvement of LVEF in the CTIA group was associated with significantly lower 2-year mortality (p = 0.003). In the multivariate regression analysis, CTIA remained the relevant factor associated with LVEF improvement (HR: 2.845 CI:95% 1.044–7.755; p = 0.041). Elderly patients (≥ 70 years) further benefited from CTIA, since they showed a significantly reduced rehospitalization (p = 0.042) and mortality rate after 2 years (p = 0.013).ConclusionsCTIA in patients with typical AFL and HFrEF/HFmrEF was associated with significant improvement of LVEF and reduced mortality rates after 2 years. Patient age should not be a primary exclusion criterion for CTIA, since patients ≥70 years also seem to benefit from intervention in terms of mortality and hospitalization

Prophylactic rivaroxaban in the early post-discharge period reduces the rates of hospitalization for atrial fibrillation and incidence of sudden cardiac death during long-term follow-up in hospitalized COVID-19 survivors

Introduction: While acute Coronavirus disease 2019 (COVID-19) affects the cardiovascular (CV) system according to recent data, an increased CV risk has been reported also during long-term follow-up (FU). In addition to other CV pathologies in COVID-19 survivors, an enhanced risk for arrhythmic events and sudden cardiac death (SCD) has been observed. While recommendations on post-discharge thromboprophylaxis are conflicting in this population, prophylactic short-term rivaroxaban therapy after hospital discharge showed promising results. However, the impact of this regimen on the incidence of cardiac arrhythmias has not been evaluated to date.Methods: To investigate the efficacy of this therapy, we conducted a single center, retrospective analysis of 1804 consecutive, hospitalized COVID-19 survivors between April and December 2020. Patients received either a 30-day post-discharge thromboprophylaxis treatment regimen using rivaroxaban 10 mg every day (QD) (Rivaroxaban group (Riva); n = 996) or no thromboprophylaxis (Control group (Ctrl); n = 808). Hospitalization for new atrial fibrillation (AF), new higher-degree Atrioventricular-block (AVB) as well as incidence of SCD were investigated in 12-month FU [FU: 347 (310/449) days].Results: No differences in baseline characteristics (Ctrl vs Riva: age: 59.0 (48.9/66.8) vs 57 (46.5/64.9) years, p = n.s.; male: 41.5% vs 43.7%, p = n.s.) and in the history of relevant CV-disease were observed between the two groups. While hospitalizations for AVB were not reported in either group, relevant rates of hospitalizations for new AF (0.99%, n = 8/808) as well as a high rate of SCD events (2.35%, n = 19/808) were seen in the Ctrl. These cardiac events were attenuated by early post-discharge prophylactic rivaroxaban therapy (AF: n = 2/996, 0.20%, p = 0.026 and SCD: n = 3/996, 0.30%, p < 0.001) which was also observed after applying a logistic regression model for propensity score matching (AF: χ2-statistics = 6.45, p = 0.013 and SCD: χ2-statistics = 9.33, p = 0.002). Of note, no major bleeding complications were observed in either group.Conclusion: Atrial arrhythmic and SCD events are present during the first 12 months after hospitalization for COVID-19. Extended prophylactic Rivaroxaban therapy after hospital discharge could reduce new onset of AF and SCD in hospitalized COVID-19 survivors

Impact of Ivabradine on Inflammatory Markers in Chronic Heart Failure

Background. Inflammation plays a crucial role in the progression of chronic heart failure (CHF). Ivabradine is known to reduce the morbidity and mortality of patients with CHF under certain conditions. Beyond the reduction of heart rate, only limited knowledge exists about potential anti-inflammatory effects of ivabradine that might contribute to its benefit in CHF. Thus, the present study aimed to investigate the effect of ivabradine on systemic inflammation. Methods. In the present study, 33 patients with CHF due to dilated, ischemic, and hypertensive cardiomyopathy were treated with ivabradine according to the guidelines of the European Society of Cardiology (ESC). A number of circulating dendritic cells as well as inflammatory mediators were investigated using FACS analysis and ELISA, respectively, before and during ivabradine therapy. Results. Treatment with ivabradine resulted in a significant improvement of CHF symptoms as well as an increase in left ventricular ejection fraction. Moreover, ivabradine treatment led to a significant reduction of TNF-alpha (TNF-α) serum levels and a reconstitution of circulating dendritic cells which are known to be reduced in patients with CHF. Conclusion. We show that treatment with ivabradine in patients with CHF resulted in an improvement of HF symptoms and ejection fraction as well as a normalization of inflammatory mediators

Decrease in Circulating Dendritic Cell Precursors in Patients with Peripheral Artery Disease

Peripheral artery disease (PAD) is a common manifestation of atherosclerosis. Inflammation is important for initiation and progression of the disease. Dendritic cells (DCs) as antigen-presenting cells play an important role in the immune system. Therefore, we hypothesize that, in patients with PAD, DCPs might be reduced in blood due to their recruitment into the vascular wall and induce a proinflammatory response. The numbers of myeloid DCPs, plasmacytoid DCPs, and total DCPs were analyzed by flow cytometry in blood of patients with PAD (n=52) compared to controls (n=60). Femoralis plaques (n=12) of patients who underwent surgery were immunostained for CD209 and CD83 (mDCs) as well as CD304, CD123 (pDCs), and HLA-DR. In patients with PAD, a significant decrease in mDCPs, pDCPs, and tDCPs was observed. In immunostaining, markers indicative for mDCs (CD209: 16 versus 8 cells/0.1 mm2, P=0.02; CD83: 19 versus 5 cells/0.1 mm2, P=0.03) were significantly elevated in femoralis plaques compared to control vessels. We show for the first time that mDCPs, pDCPs, and tDCPs are significantly reduced in patients with PAD. Immunohistochemical analysis unraveled that the decrease in DCPs might be due to their recruitment into atherosclerotic plaques

Decreased Regulatory T Cells in Vulnerable Atherosclerotic Lesions: Imbalance between Pro- and Anti-Inflammatory Cells in Atherosclerosis

Atherosclerosis is a chronic inflammatory disease of the arterial wall in which presentation of autoantigens by dendritic cells (DCs) leads to the activation of T cells. Anti-inflammatory cells like Tregs counterbalance inflammation in atherogenesis. In our study, human carotid plaque specimens were classified as stable (14) and unstable (15) according to established morphological criteria. Vessel specimens (n=12) without any signs of atherosclerosis were used as controls. Immunohistochemical staining was performed to detect different types of DCs (S100, fascin, CD83, CD209, CD304, and CD123), proinflammatory T cells (CD3, CD4, CD8, and CD161), and anti-inflammatory Tregs (FoxP3). The following results were observed: in unstable lesions, significantly higher numbers of proinflammatory cells like DCs, T helper cells, cytotoxic T cells, and natural killer cells were detected compared to stable plaques. Additionally, there was a significantly higher expression of HLA-DR and more T cell activation (CD25, CD69) in unstable lesions. On the contrary, unstable lesions contained significantly lower numbers of Tregs. Furthermore, a significant inverse correlation between myeloid DCs and Tregs was shown. These data suggest an increased inflammatory state in vulnerable plaques resulting from an imbalance of the frequency of local pro- and anti-inflammatory immune cells

Analysis of Metabolic Markers in Patients with Chronic Heart Failure before and after LVAD Implantation

Chronic heart failure (HF) is a clinical syndrome characterized by functional impairments of the myocardium. Metabolic and clinical changes develop with disease progression. In an advanced state, left ventricular assist devices (LVADs) are implanted for mechanical unloading. Our study aimed to assess the effects of LVAD implantation on the metabolic phenotypes and their potential to reverse the latter in patients with advanced HF. Plasma metabolites were analyzed by LC–MS/MS in 20 patients with ischemic cardiomyopathy (ICM), 20 patients with dilative cardiomyopathy (DCM), and 20 healthy controls. Samples were collected in HF patients before, 30 days after, and >100 days after LVAD implantation. Out of 188 measured metabolites, 63 were altered in HF. Only three metabolites returned to pre-LVAD concentrations 100 days after LVAD implantation. Pre-LVAD differences between DCM and ICM were mainly observed for amino acids and biogenic amines. This study shows a reversal of metabolite abnormalities in HF as a result of LVAD implantation. The etiology of the underlying disease plays an essential role in defining which specific metabolic parameter is altered in HF and reversed by LVAD implantation. Our findings provide a detailed insight into the disease pattern of ICM and DCM and the potential for reversibility of metabolic abnormalities in HF

Classic and Novel Biomarkers as Potential Predictors of Ventricular Arrhythmias and Sudden Cardiac Death

Sudden cardiac death (SCD), most often induced by ventricular arrhythmias, is one of the main reasons for cardiovascular-related mortality. While coronary artery disease remains the leading cause of SCD, other pathologies like cardiomyopathies and, especially in the younger population, genetic disorders, are linked to arrhythmia-related mortality. Despite many efforts to enhance the efficiency of risk-stratification strategies, effective tools for risk assessment are still missing. Biomarkers have a major impact on clinical practice in various cardiac pathologies. While classic biomarkers like brain natriuretic peptide (BNP) and troponins are integrated into daily clinical practice, inflammatory biomarkers may also be helpful for risk assessment. Indeed, several trials investigated their application for the prediction of arrhythmic events indicating promising results. Furthermore, in recent years, active research efforts have brought forward an increasingly large number of “novel and alternative” candidate markers of various pathophysiological origins. Investigations of these promising biological compounds have revealed encouraging results when evaluating the prediction of arrhythmic events. To elucidate this issue, we review current literature dealing with this topic. We highlight the potential of “classic” but also “novel” biomarkers as promising tools for arrhythmia prediction, which in the future might be integrated into clinical practice

A Comparative Analysis of Novel Biomarkers in Sepsis and Cardiovascular Disease

(1) Background: Sepsis still represents a major health care challenge, with mortality rates exceeding 25% in the western world. To further improve outcomes in this patient collective, new cardiovascular biomarkers present a promising opportunity as they target the paramount prognostic processes in sepsis: inflammation and ischemia. However, in contrast to cardiovascular diseases, a detailed analysis of novel biomarkers in sepsis is still lacking. (2) Objective: In this project, we aimed to perform a comparative analysis of biomarker levels in ischemic cardiovascular disease and sepsis. Analyzed markers comprised soluble suppression of tumorigenicity 2 (sST2; hemodynamics and inflammation), growth-differentiation factor 15 (GDF-15; injury, remodelling), soluble urokinase-type plasminogen activator receptor (suPAR; inflammation and remodeling) and heart-type fatty acid binding protein (H-FABP; myocardial ischemia). (3) Methods: In total, 311 patients were included in the study: 123 heart-failure (HF) patients, 60 patients with ST-segment elevation myocardial infarction (STEMI) and 53 sepsis patients. A total of 75 patients without coronary artery disease or signs of heart failure served as a control group. Plasma samples were analyzed by use of ELISA after informed consent. (4) Results: Patients with sepsis showed significantly increased plasma levels in all tested biomarkers compared to cardiovascular disease entities (sST2, suPAR, GDF-15: p p p p p p p < 0.001). (5) Conclusions: All tested novel cardiac biomarkers showed significantly elevated levels in sepsis patients. Interestingly, a secretion pattern similar to STEMI was observed with regards to sST2 and HFABP. Thus, by providing an assessment tool especially covering the cardiovascular component of the disease, novel biomarkers offer a promising tool in sepsis patients

A Comparative Analysis of Novel Biomarkers in Sepsis and Cardiovascular Disease

(1) Background: Sepsis still represents a major health care challenge, with mortality rates exceeding 25% in the western world. To further improve outcomes in this patient collective, new cardiovascular biomarkers present a promising opportunity as they target the paramount prognostic processes in sepsis: inflammation and ischemia. However, in contrast to cardiovascular diseases, a detailed analysis of novel biomarkers in sepsis is still lacking. (2) Objective: In this project, we aimed to perform a comparative analysis of biomarker levels in ischemic cardiovascular disease and sepsis. Analyzed markers comprised soluble suppression of tumorigenicity 2 (sST2; hemodynamics and inflammation), growth-differentiation factor 15 (GDF-15; injury, remodelling), soluble urokinase-type plasminogen activator receptor (suPAR; inflammation and remodeling) and heart-type fatty acid binding protein (H-FABP; myocardial ischemia). (3) Methods: In total, 311 patients were included in the study: 123 heart-failure (HF) patients, 60 patients with ST-segment elevation myocardial infarction (STEMI) and 53 sepsis patients. A total of 75 patients without coronary artery disease or signs of heart failure served as a control group. Plasma samples were analyzed by use of ELISA after informed consent. (4) Results: Patients with sepsis showed significantly increased plasma levels in all tested biomarkers compared to cardiovascular disease entities (sST2, suPAR, GDF-15: p &lt; 0.001; H-FABP: compared to HF p &lt; 0.001) and controls (sST2: 7.4-fold, suPAR: 3.4-fold, GDF-15: 6.5-fold and H-FABP: 15.3-fold increased plasma levels, p &lt; 0.001). Moreover, in patients with sepsis, serum concentrations of sST2 and suPAR were significantly elevated in patients with HF and patients with STEMI (sST2: HF: 1.6-fold increase and STEMI: 2.5-fold increase, p &lt; 0.001; suPAR: HF: 1.4-fold increase, p &lt; 0.001 and STEMI: 1.4-fold increase, p &lt; 0.01), whereas plasma levels of GDF-15 and H-FABP were markedly elevated in patients with STEMI only (GDF-15: 1.6-fold increase, H-FABP: 6.4-fold increase, p &lt; 0.001). (5) Conclusions: All tested novel cardiac biomarkers showed significantly elevated levels in sepsis patients. Interestingly, a secretion pattern similar to STEMI was observed with regards to sST2 and HFABP. Thus, by providing an assessment tool especially covering the cardiovascular component of the disease, novel biomarkers offer a promising tool in sepsis patients