Cardiovascular Management of Patients Undergoing Hematopoietic Stem Cell Transplantation: From Pretransplantation to Survivorship: A Scientific Statement From the American Heart Association.

Hematopoietic stem cell transplantation can cure various disorders but poses cardiovascular risks, especially for elderly patients and those with cardiovascular diseases. Cardiovascular evaluations are crucial in pretransplantation assessments, but guidelines are lacking. This American Heart Association scientific statement summarizes the data on transplantation-related complications and provides guidance for the cardiovascular management throughout transplantation. Hematopoietic stem cell transplantation consists of 4 phases: pretransplantation workup, conditioning therapy and infusion, immediate posttransplantation period, and long-term survivorship. Complications can occur during each phase, with long-term survivors facing increased risks for late effects such as cardiovascular disease, secondary malignancies, and endocrinopathies. In adults, arrhythmias such as atrial fibrillation and flutter are the most frequent acute cardiovascular complication. Acute heart failure has an incidence ranging from 0.4% to 2.2%. In pediatric patients, left ventricular systolic dysfunction and pericardial effusion are the most common cardiovascular complications. Factors influencing the incidence and risk of complications include pretransplantation therapies, transplantation type (autologous versus allogeneic), conditioning regimen, comorbid conditions, and patient age. The pretransplantation cardiovascular evaluation consists of 4 steps: (1) initial risk stratification, (2) exclusion of high-risk cardiovascular disease, (3) assessment of cardiac reserve, and (4) optimization of cardiovascular reserve. Clinical risk scores could be useful tools for the risk stratification of adult patients. Long-term cardiovascular management of hematopoietic stem cell transplantation survivors includes optimizing risk factors, monitoring, and maintaining a low threshold for evaluating cardiovascular causes of symptoms. Future research should prioritize refining risk stratification and creating evidence-based guidelines and strategies to optimize outcomes in this growing patient population.

Evaluation of the Levels of Selected Cytokines and Their Possible Influence on the Development of Cardiovascular and Pulmonary Complications in Patients after COVID-19.

Background and Objectives: The aim of this study was to evaluate the levels of selected cytokines and their possible influence on the development of cardiovascular and pulmonary complications in patients hospitalized at the Silesian Centre for Heart Disease in Zabrze after having undergone COVID-19. Materials and methods: The study included 76 randomly selected patients from the SILCOVID-19 database. The median time from symptom onset to the study visit was 102 (86-118) days. The median age of the study group was 53 (44-60) years. Assays of a panel of 30 cytokines were carried out in the serum of patients on a Luminex100 platform using the Milliplex MAP kit from Merck KGaA Germany. Results: There were no statistically significant differences in most of the cytokines analyzed between patients with confirmed or excluded lung lesions or cardiac abnormalities. Additionally, no statistically significant differences in cytokine concentrations according to gender, age, comorbidity of diabetes, renal disease, hypertension, increased risk of thrombotic disease, or psychological disorders were demonstrated. There were high concentrations of cytokines such as platelet-derived growth actor-AA (PDGF-AA), monocyte chemoattractant protein-1 (MCP-1), monokine-induced gamma interferon (MIG), and vascular endothelial growth factor-A (VEGF-A). Conclusions: No direct impact of the dependencies between a panel of cytokines and the incidence of cardiovascular and pulmonary complications in patients hospitalized at the Silesian Centre for Heart Disease in Zabrze after having undergone COVID-19 was demonstrated. The demonstration of high levels of certain cytokines (PDGF-AA, VEGF, MIG, and IP10) that are of significance in the development of many lung diseases, as well as cytokines (MCP-1) that influence the aetiopathogenesis of cardiovascular diseases seems to be highly concerning in COVID-19 survivors. This group of patients should receive further monitoring of these cytokine levels and diagnostic imaging in order to detect more severe abnormalities as early as possible and administer appropriate therapy.

Atrial fibrillation-induced cardiomyopathy presenting with bilateral intermittent claudication associated with intracardiac thrombi.

Systemic thromboembolism associated with atrial fibrillation (AF) is usually caused by thrombi in the left atrial appendage and acute onset. We experienced an unusual case of a woman in her 60s who presented to the outpatient district having bilateral intermittent claudication for more than 1 month, which turned out to be multiple thromboembolism from asymptomatic AF with tachycardia. She was also complicated with non-ischaemic dilated cardiomyopathy with reduced ejection fraction, consistent with arrhythmia-induced cardiomyopathy (AiCM), along with left atrial and left ventricular thrombi and thromboembolism in multiple organs. Rate control with beta-blockers was not effective. With the administration of amiodarone after adequate anticoagulation therapy, she returned to sinus rhythm, and the ejection fraction was restored. This case is instructive in that AiCM with AF can cause thrombosis in the left ventricle, and the patient may present with worsening intermittent claudication as a result of systemic embolism.

Association between Immune Checkpoint Inhibitors and Atherosclerotic Cardiovascular Disease Risk: Another Brick in the Wall.

In recent years, immune checkpoint inhibitors have significantly changed the field of oncology, emerging as first-line treatment, either alone or in combination with other regimens, for numerous malignancies, improving overall survival and progression-free survival in these patients. However, immune checkpoint inhibitors might also cause severe or fatal immune-related adverse events, including adverse cardiovascular events. Initially, myocarditis was recognized as the main immune checkpoint inhibitor-related cardiac event, but our knowledge of other potential immune-related cardiovascular adverse events continues to broaden. Recently, preclinical and clinical data seem to support an association between immune checkpoint inhibitors and accelerated atherosclerosis as well as atherosclerotic cardiovascular events such as cardiac ischemic disease, stroke, and peripheral artery disease. In this review, by offering a comprehensive overview of the pivotal role of inflammation in atherosclerosis, we focus on the potential molecular pathways underlying the effects of immune checkpoint inhibitors on cardiovascular diseases. Moreover, we provide an overview of therapeutic strategies for cancer patients undergoing immunotherapy to prevent the development of cardiovascular diseases.

Blood group AB is associated with reduced blood loss but also elevated cardiovascular mortality in aortocoronary bypass surgery.

Patient blood group (BG) is predictive for von-Willebrand-factor (VWF) and Factor VIII variation. The clinical impact of this ABO-effect on blood loss, cardiovascular complications and outcome has been described for several patient cohorts. The aim of this study was to investigate the impact of patient BG on blood loss and outcome after coronary artery bypass surgery (CABG). Patient records, intraoperative data and perioperative transfusion records of 5713 patients receiving an on-pump CABG procedure between 05/2004 and 12/2018 were analyzed. A logistic regression model for death due to perioperative myocardial ischaemia (PMI) was developed from initially 24 variables by using an univariate and multivariate selection process. BG AB patients required less blood transfusions as compared to the other blood groups, especially in case of emergency operations. However, BG AB patients also had a higher mortality which was due to secondary cardiovascular complications. The impact of blood type on the rate of cardiovascular mortality was confirmed in the logistic regression model. BG AB patients have a worse outcome after CABG surgery due to an increased incidence of fatal cardiovascular complications. As perioperative myocardial ischemia due to graft occlusion appears to be the most likely explanation, stricter anticoagulation for BG AB patients should be discussed.

Long-term post-transplantation outcomes in patients with hypertrophic cardiomyopathy: Single-center 35-year experience.

BACKGROUND: Heart transplantation (HT) is the only option for most patients with end-stage heart failure and hypertrophic cardiomyopathy (HCM) who fail medical therapy. Data on the long-term outcomes post-transplant in HCM individuals remain scarce. METHODS: We analyzed data of 319 adult patients who underwent HT between 1984 and 2019. Patients were followed for cardiac allograft rejection, cardiac allograft vasculopathy (CAV), death, or re-transplantation. RESULTS: Outcomes of 24 patients with HCM, 160 with ischemic, and 135 with dilated cardiomyopathy were compared. During a mean follow-up of 11.6 ± 7.2 (max 27.8), 16.7 ± 8.2 (max 32.7), and 16.1 ± 9.7 (max 34.6) years after HT in hypertrophic, ischemic, and dilated cardiomyopathy groups, respectively: 10-year survival rate was 67%, 62%, 69%, respectively (p = .04). Post-transplantation, HCM individuals more often than the other two studied groups required prolonged inotropic support (37%, 12%, 17%, respectively, p = .02), temporary mechanical circulatory support (45%, 13%, 14%, respectively, p < .01), and renal replacement therapy immediately post-HT (55%, 19%, 24%, respectively, p < .01). No significant inter-group differences were noted in the 10-year freedom from acute allograft rejection (38%, 46%, 43%, respectively, p = .38) or 10-year freedom from CAV (88%, 78%, 81%, respectively, p = .57). CONCLUSIONS: The long-term post-transplant prognosis of adult patients with hypertrophic cardiomyopathy is favorable despite more challenging immediate post-HT course.

Primordial Drivers of Diabetes Heart Disease: Comprehensive Insights into Insulin Resistance.

Insulin resistance has been regarded as a hallmark of diabetes heart disease (DHD). Numerous studies have shown that insulin resistance can affect blood circulation and myocardium, which indirectly cause cardiac hypertrophy and ventricular remodeling, participating in the pathogenesis of DHD. Meanwhile, hyperinsulinemia, hyperglycemia, and hyperlipidemia associated with insulin resistance can directly impair the metabolism and function of the heart. Targeting insulin resistance is a potential therapeutic strategy for the prevention of DHD. Currently, the role of insulin resistance in the pathogenic development of DHD is still under active research, as the pathological roles involved are complex and not yet fully understood, and the related therapeutic approaches are not well developed. In this review, we describe insulin resistance and add recent advances in the major pathological and physiological changes and underlying mechanisms by which insulin resistance leads to myocardial remodeling and dysfunction in the diabetic heart, including exosomal dysfunction, ferroptosis, and epigenetic factors. In addition, we discuss potential therapeutic approaches to improve insulin resistance and accelerate the development of cardiovascular protection drugs.

Cardiac involvement and its clinical significance in patients with anorexia nervosa.

Cardiac complications are a major concern in patients with anorexia nervosa (AN) which contribute to morbidity and mortality. However, limited information exists regarding risk factors for the development of these complications. Our objective was to investigate the prevalence and associated risk factors of cardiac involvement among children and adolescents with AN admitted to a tertiary pediatric hospital. We collected demographic, clinical, and laboratory data from individuals with AN hospitalized between 2011 and 2020 in Schneider Children's Medical Center in Israel. Diagnosis was based on established criteria (DSM-5). Patients with other co-morbidities were excluded. Cardiac investigations included electrocardiograms (ECG) and echocardiograms. We conducted correlation tests between cardiac findings and clinical and laboratory indicators. A total of 403 AN patients (81.4% were females) with a median age of 15 ± 2 years were included in the study. Sinus bradycardia was the most common abnormality, observed in 155 (38%) participants. Echocardiogram was performed in 170 (42.2%) patients, of whom 37 (22%) demonstrated mild cardiac aberrations. Among those aberrations, 94.6% could be attributed to the current metabolic state, including pericardial effusion (15.3%) and valve dysfunction (8.8%). Systolic or diastolic cardiac dysfunction, tachyarrhythmias, or conduction disorders were not observed. Patients with new echocardiographic aberration had significantly lower body mass index (BMI) at admission, and the prevalence of amenorrhea and hypotension was higher in this group. CONCLUSIONS: The prevalence of cardiac involvement, except for sinus bradycardia, was notably low in our cohort. The presence of cardiac aberrations is correlated with several clinical variables: lower body mass index (BMI) and the presence of amenorrhea and hypotension at admission. Patients presenting with these variables may be at high risk for cardiac findings per echocardiography. Dividing the patients into high and low risk groups may enable targeted evaluation, while avoiding unnecessary cardiac investigations in low-risk patients. WHAT IS KNOWN: • Cardiac involvement in anorexia nervosa (AN) patients is a major concern, which contributes to morbidity and mortality. • It is unknown which patients are prone to develop this complication. WHAT IS NEW: • Cardiac complications in our cohort are less frequent compared to previous studies, and it is correlated with lower body mass index (BMI) at admission, and the prevalence of amenorrhea and hypotension.

The Association of Incidental Radiation Dose to the Heart Base with Overall Survival and Cardiac Events after Curative-intent Radiotherapy for Non-small Cell Lung Cancer: Results from the NI-HEART Study.

AIMS: Cardiac disease is a dose-limiting toxicity in non-small cell lung cancer radiotherapy. The dose to the heart base has been associated with poor survival in multiple institutional and clinical trial datasets using unsupervised, voxel-based analysis. Validation has not been undertaken in a cohort with individual patient delineations of the cardiac base or for the endpoint of cardiac events. The purpose of this study was to assess the association of heart base radiation dose with overall survival and the risk of cardiac events with individual heart base contours. MATERIALS AND METHODS: Patients treated between 2015 and 2020 were reviewed for baseline patient, tumour and cardiac details and both cancer and cardiac outcomes as part of the NI-HEART study. Three cardiologists verified cardiac events including atrial fibrillation, heart failure and acute coronary syndrome. Cardiac substructure delineations were completed using a validated deep learning-based autosegmentation tool and a composite cardiac base structure was generated. Cox and Fine-Gray regressions were undertaken for the risk of death and cardiac events. RESULTS: Of 478 eligible patients, most received 55 Gy/20 fractions (96%) without chemotherapy (58%), planned with intensity-modulated radiotherapy (71%). Pre-existing cardiovascular morbidity was common (78% two or more risk factors, 46% one or more established disease). The median follow-up was 21.1 months. Dichotomised at the median, a higher heart base Dmax was associated with poorer survival on Kaplan-Meier analysis (20.2 months versus 28.3 months; hazard ratio 1.40, 95% confidence interval 1.14-1.75, P = 0.0017) and statistical significance was retained in multivariate analyses. Furthermore, heart base Dmax was associated with pooled cardiac events in a multivariate analysis (hazard ratio 1.75, 95% confidence interval 1.03-2.97, P = 0.04). CONCLUSIONS: Heart base Dmax was associated with the rate of death and cardiac events after adjusting for patient, tumour and cardiovascular factors in the NI-HEART study. This validates the findings from previous unsupervised analytical approaches. The heart base could be considered as a potential sub-organ at risk towards reducing radiation cardiotoxicity.

Presurgical circulating platelet-derived microparticles level as a risk factor of blood transfusion in patients with valve heart disease undergoing cardiac surgery.

BACKGROUND: Cell-derived microparticles (MPs) are membrane vesicles that have emerged as a potential biomarker for various diseases and their clinical complications. This study investigates the role of MPs as a risk factor for blood transfusion in patients with valve heart disease undergoing cardiac surgery. METHODS: Forty adult patients undergoing heart valve surgery with cardiopulmonary bypass (CPB) were enrolled, and venous blood samples were collected prior to surgical incision. Plasma rich in MPs was prepared by double centrifugation, and the concentration of MPs was determined using the Bradford method. Flow cytometry analysis was performed to determine MPs count and phenotype. Patients were divided into "with transfusion" (n = 18) and "without transfusion" (n = 22) groups based on red blood cell (RBC) transfusion. RESULTS: There was no significant difference in MPs concentration between the "with transfusion" and "without transfusion" groups. Although the count of preoperative platelet-derived MPs (PMPs), monocyte-derived MPs (MMPs), and red cell-derived MPs (RMPs) was higher in "without transfusion" group, these differences were not statistically significant. The preoperative PMPs count was negatively correlated with RBC transfusion (P = 0.005, r = -0.65). Multivariate logistic regression analysis revealed that the count of CD41+ PMPs, Hemoglobin (Hb), and RBC count were risk factors for RBC transfusion. CONCLUSION: This study suggests that the presurgical levels of PMPs, Hb, and RBC count can serve as risk factors of RBC transfusion in patients with valve heart disease undergoing cardiac surgery. The findings provide insights into the potential use of MPs as biomarkers for blood transfusion prediction in cardiac surgery.

A nationwide trend analysis on the usage of endomyocardial biopsy.

BACKGROUND: Endomyocardial biopsy (EMB) is a safe procedure performed in diagnostic work-up of cardiac disease. HYPOTHESIS: Data regarding temporal trends of total numbers, characteristics, in-hospital outcomes, and complications of patients undergoing EMB are sparse. METHODS: The nationwide German inpatient sample (2005-2019) was used for this analysis. Patient cases of EBM during the 5-year cycles from 2005 to 2009, 2010 to 2014, and 2015 to 2019 were compared, and temporal trends regarding total numbers and presumable major and minor EMB-associated complications were investigated. RESULTS: Overall, 67 745 EMB were performed in Germany 2005-2019. Total number of EMB increased from 3083 in 2005 to 5646 in 2019 (ß 0.40 [95% confidence interval [CI] 0.37-0.43], p < .001). Among these EMB, 19 083 (28.2%) were performed during the period 2005-2009, 22 867 (33.7%) 2010-2014, and 25 795 (38.1%) between 2015 and 2019. The proportion of patients aged ≥70 years was highest 2015-2019 (2005-2009: 9.3%; 2010-2014: 13.8%; 2015-2019: 16.1%, p < .001) and the most aggravated comorbidity profile (Charlson Comorbidity Index 2.25 ± 1.93; 2.67 ± 2.14; 3.01 ± 2.29, p < .001) was also detected 2015-2019. Major complications occurred less often in the period 2015-2019 compared to 2005-2009 (odds ratio [OR] 0.921 [95% CI 0.893-0.950], p < .001), whereas minor complications were more frequently observed between 2015 and 2019 (OR 1.067 [95% CI 1.042-1.093], p < .001). While a decrease in major complications was detected irrespective of age, an increase in minor complications was identified only in patients between 30-59 years. CONCLUSIONS: Annual numbers of EMB increased significantly in Germany 2005-2019. Patients who underwent EMB in recent years were older and showed an aggravated comorbidity profile accompanied by fewer major complications, underscoring safety of the procedure.

Cardiac disease in Cushing's syndrome. Emphasis on the role of cardiovascular magnetic resonance imaging.

BACKGROUND: Cushing's Syndrome (CS) is associated with increased cardiovascular morbidity and mortality. In endogenous CS, cardiovascular mortality remains increased for up to 15 years post remission of hypercortisolism. Similarly, patients with exogenous CS have 4-fold increased incidence of cardiovascular events, regardless of pre-existing cardiovascular disease (CVD). OBJECTIVE: To present the pathophysiology, prognosis, clinical and imaging phenotype of cardiac disease in CS. METHODS: A Pubmed search for cardiac disease in CS over the last 20 years was conducted using combinations of relevant terms. Preclinical and clinical studies, as well as review papers reporting on subclinical heart failure (HF), cardiomyopathy, coronary heart disease (CHD), and cardiovascular imaging were selected. RESULTS: Cardiac disease in CS is associated with direct mineralocorticoid and glucocorticoid receptor activation, increased responsiveness to angiotensin II, ectopic epicardial adiposity, arterial stiffness and endothelial dysfunction, as well as with diabetes mellitus, hypertension, hyperlipidemia, obesity and prothrombotic diathesis. Subclinical HF and cardiomyopathy are principally related to direct glucocorticoid (GC) effects and markedly improve or regress post hypercortisolism remission. In contrast, CHD is related to both direct GC effects and CS comorbidities and persists post cure. In patients without clinical evidence of CVD, echocardiography and cardiac magnetic resonance (CMR) imaging reveal left ventricular hypertrophy, fibrosis, diastolic and systolic dysfunction, with the latter being underestimated by echocardiography. Finally, coronary microvascular disease is encountered in one third of cases. CONCLUSION: Cardiovascular imaging is crucial in evaluation of cardiac involvement in CS. CMR superiority in terms of reproducibility, operator independency, unrestricted field of view and capability of tissue characterisation makes this modality ideal for future studies.

[Beating heart surgical treatment of atrio-esophageal fistula after radiofrequency ablation of atrial fibrillation]. / Trattamento chirurgico a cuore battente di una fistola atrio-esofagea post-ablazione tramite radiofrequenza di fibrillazione atriale.

Atrio-esophageal fistula (AEF) is a rare (0.02-0.1%) complication of radiofrequency ablation for atrial fibrillation and is associated with high mortality. It typically presents between 2 and 6 weeks after catheter ablation. AEF was reported to be the second complication as cause of death after radiofrequency ablation with a mortality rate of 71%. Common clinical features of AEF include dysphagia, nausea, heartburn, hematemesis or melena, high fever, sepsis, pericardial or pleural effusions, mediastinitis, seizures, and stroke. Once the diagnosis of AEF is made, early surgical repair is mandatory. Herein, we report a case of a AEF treated surgically without extracorporeal circulation.

Interplay of inflammatory biomarkers in heart disease patients with depressive symptoms: An update.

The pathophysiological mechanisms that connect heart disease and depressive disorders have been identified as abnormal endothelial function, dysregulation of the Hypothalamic Pituitary Adrenal (HPA) axis and abnormal platelet activities. Among these mechanisms, both endothelial dysfunction and HPA axis dysregulation are influenced by low grade inflammation and play significant roles in both conditions. Consequently, it is hypothesized that inflammation is an integral part of the formation of atherosclerotic plaques, linking the occurrence of heart diseases to the activation and shedding of intercellular adhesion molecules (ICAMs), especially soluble ICAM-1. This process is accompanied by the local and systemic secretion of various inflammatory markers like interleukin-6, Tumour Necrosis Factor, and C-reactive protein. Therefore, this review primarily focuses on defining the potential role of different inflammatory biomarkers in depression and heart disease and assessing whether mediators could serve as predictive biomarkers for detecting depressive symptoms in patients with heart disease.

Transvenous lead extraction safety and efficacy in infected and noninfected patients using mechanical-only tools: Prospective registry from a high-volume center.

BACKGROUND: Transvenous lead extraction (TLE) is a well-established treatment option for patients with cardiac implantable electronic devices (CIED) complications. OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of TLE in CIED infection and non-CIED infection patients. METHODS: Consecutive patients who underwent TLE between 2016 and 2022 entered the EXTRACT Registry. Models of prediction were constructed for periprocedural clinical and procedural success and the incidence of major complications, including death in 30 days. RESULTS: The registry enrolled 504 patients (mean age 66.6 ± 12.8 years; 65.7% male). Complete procedural success was achieved in 474 patients (94.0%) and clinical success in 492 patients (97.6%). The total number of major and minor complications was 16 (3.2%) and 51 (10%), respectively. Three patients (0.6%) died during the procedure. New York Heart Association functional class IV and C-reactive protein levels defined before the procedure were independent predictors of any major complication, including death in 30 days in CIED infection patients. The time since the last preceding procedure and platelet count before the procedure were independent predictors of any major complication, including death in 30 days in non-CIED infection patients. CONCLUSIONS: TLE is safe and successfully performed in most patients, with a low major complication rate. CIED infection patients demonstrate better periprocedural clinical success and complete procedural success. However, CIED infection predicts higher 30-day mortality compared with non-CIED infection patients. Predictors of any major complication, including death in 30 days, differ between CIED infection and non-CIED infection patients.

Impact of repeat ablation of ventricular tachycardia in patients with structural heart disease.

AIMS: Recurrences of ventricular tachycardia (VT) after initial catheter ablation is a significant clinical problem. In this study, we report the efficacy and risks of repeat VT ablation in patients with structural heart disease (SHD) in a tertiary single centre over a 7-year period. METHODS AND RESULTS: Two hundred ten consecutive patients referred for repeat VT ablation after previous ablation in our institution were included in the analysis (53% ischaemic cardiomyopathy, 91% males, median age 65 years, mean left ventricular ejection fraction 35%). After performing repeat ablation, the clinical VTs were acutely eliminated in 82% of the patients, but 46% of the cohort presented with VT recurrence during the 25-month follow-up. Repeat ablation led to a 73% reduction of shock burden in the first year and 61% reduction until the end of follow-up. Similarly, VT burden was reduced 55% in the first year and 36% until the end of the study. Fifty-two patients (25%) reached the combined endpoint of ventricular assist device implantation, heart transplantation, or death. Advanced New York Heart Association functional class, anteroseptal substrate, and periprocedural complication after repeat ablation were associated with worse prognosis independently of the type of cardiomyopathy. CONCLUSION: While complete freedom from VT after repeat ablation in SHD was difficult to achieve, ablation led to a significant reduction in VT and shock burden. Besides advanced heart failure characteristics, anteroseptal substrate and periprocedural complications predicted a worse outcome.