J. Cardiovasc. Dev. Dis., Volume 9, Issue 9 (September 2022) – 29 articles

Ankle-brachial index and arterial stiffness are associated with leg function in the elderly and in patients with peripheral arterial disease. Little is known about the meaning of these parameters in young and trained subjects and how they are related to physical performance. The main objective was to evaluate the mediating role of arterial stiffness and ankle-brachial index in physical performance. In a cross-sectional, case-control study, 240 male athletes were consecutively enrolled from the Laboratory of Cardiology and Sports Medicine, “G. d’Annunzio” University (Italy). All the subjects underwent the examination protocol for the annual medical evaluation for sport participation. Soccer (football) players compared to runners showed a lower level of ankle-brachial index, higher arterial stiffness, and lower systolic and diastolic blood pressure. In the treadmill stress test, soccer players compared to runners showed a greater maximal aerobic capacity. Differences in cardiovascular performance between soccer players and runners were mediated by better arterial stiffness and low level of ankle-brachial index; the estimated effect was 0.11 ± 0.05 and 0.24 ± 0.06, respectively. Vigorous strength training drops blood pressure and increases arterial stiffness. Taken together, our findings would seem to suggest that ABI and CAVI could be used as markers for athletes’ performance. Full article

Background: Existing prediction models for post-transplant mortality in patients bridged to heart transplantation with temporary mechanical circulatory support (tMCS) perform poorly. A more reliable model would allow clinicians to provide better pre-operative risk assessment and develop more targeted therapies for high-risk patients. Methods: We identified adult patients in the United Network for Organ Sharing database undergoing isolated heart transplantation between 01/2009 and 12/2017 who were supported with tMCS at the time of transplant. We constructed a machine learning model using extreme gradient boosting (XGBoost) with a 70:30 train:test split to predict 1-year post-operative mortality. All pre-transplant variables available in the UNOS database were included to train the model. Shapley Additive Explanations was used to identify and interpret the most important features for XGBoost predictions. Results: A total of 1584 patients were included, with a median age of 56 (interquartile range: 46–62) and 74% male. Actual 1-year mortality was 12.1%. Out of 498 available variables, 43 were selected for the final model. The area under the receiver operator characteristics curve (AUC) for the XGBoost model was 0.71 (95% CI: 0.62–0.78). The most important variables predictive of 1-year mortality included recipient functional status, age, pulmonary capillary wedge pressure (PCWP), cardiac output, ECMO usage, and serum creatinine. Conclusions: An interpretable machine learning model trained on a large clinical database demonstrated good performance in predicting 1-year mortality for patients bridged to heart transplantation with tMCS. Machine learning may be used to enhance clinician judgement in the care of markedly high-risk transplant recipients. Full article

Background: Current guideline-based implantable cardioverter-defibrillator (ICD) implants fail to meet the demands for precision medicine. Machine learning (ML) designed for survival analysis might facilitate personalized risk stratification. We aimed to develop explainable ML models predicting mortality and the first appropriate shock and compare these to standard Cox proportional hazards (CPH) regression in ICD recipients. Methods and Results: Forty-five routine clinical variables were collected. Four fine-tuned ML approaches (elastic net Cox regression, random survival forests, survival support vector machine, and XGBoost) were applied and compared with the CPH model on the test set using Harrell’s C-index. Of 887 adult patients enrolled, 199 patients died (5.0 per 100 person-years) and 265 first appropriate shocks occurred (12.4 per 100 person-years) during the follow-up. Patients were randomly split into training (75%) and test (25%) sets. Among ML models predicting death, XGBoost achieved the highest accuracy and outperformed the CPH model (C-index: 0.794 vs. 0.760, p < 0.001). For appropriate shock, survival support vector machine showed the highest accuracy, although not statistically different from the CPH model (0.621 vs. 0.611, p = 0.243). The feature contribution of ML models assessed by SHAP values at individual and overall levels was in accordance with established knowledge. Accordingly, a bi-dimensional risk matrix integrating death and shock risk was built. This risk stratification framework further classified patients with different likelihoods of benefiting from ICD implant. Conclusions: Explainable ML models offer a promising tool to identify different risk scenarios in ICD-eligible patients and aid clinical decision making. Further evaluation is needed. Full article

Children and adults with single ventricle congenital heart disease (CHD) develop many sequelae during staged surgical palliation. Universal pulmonary vascular sequelae in this patient population include two inter-related but distinct complications: pulmonary arteriovenous malformations (PAVMs) and aortopulmonary collaterals (APCs). This review highlights what is known and unknown about these vascular sequelae focusing on diagnostic testing, pathophysiology, and areas in need of further research. Full article

Sparse data are available on the female-specific features of chronic thromboembolic pulmonary hypertension (CTEPH). We prospectively enrolled 160 consecutive female patients who were firstly diagnosed with CTEPH between 2013 and 2019 to explore their clinical phenotypes, treatment patterns, and long-term survival. The patients’ mean age was 54.7 ± 13.8 years, 70.6% provided a confirmed history of venous thromboembolism, 46 (28.8%) patients underwent pulmonary endarterectomy (PEA), 65 (40.6%) received balloon pulmonary angioplasty (BPA), and 49 (30.6%) were treated with medical therapy alone. The patients were followed for a median of 51 (34–70) months; three patients were lost to follow-up, and twenty-two patients died. The estimated survival rates at 1, 3, 5, and 7 years were 98.1% (95% CI 96.0–100), 96.9% (95% CI 94.2–99.6), 85.1% (95% CI 78.1–92.2), and 76.2% (95% CI 65.2–87.2), respectively. After adjusting for the confounders, the results of the multivariate Cox analysis showed that the presence of anemia (5.56, 95% CI 1.6–19.22) was associated with an increased risk of all-cause death, and compared with medical treatment, receiving PEA and BPA decreased the risk of death by 74% (0.26, 95% CI 0.07–0.97) and 86% (0.14, 95% CI 0.04–0.57), respectively. In conclusion, in the modern era of CTEPH treatment, invasive revascularization combined with targeted therapy display good clinical outcomes for females; anemia should be actively modified, which may lead to clinical improvements. (ClinicalTrials.gov Identifier: NCT05360992). Full article

The global evolution of the SARS-CoV-2 virus is known to all. The diagnosis of SARS-CoV-2 pneumonia is expected to worsen, and mortality will be higher when combined with myocardial injury (MI). The combination of novel coronavirus infections in patients with MI can cause confusion in diagnosis and assessment, with each condition exacerbating the other, and increasing the complexity and difficulty of treatment. It would be a formidable challenge for clinical practice to deal with this situation. Therefore, this review aims to gather literature on the progress in managing MI related to SARS-CoV-2 pneumonia. This article reviews the definition, pathogenesis, clinical evaluation, management, and treatment plan for MI related to SARS-CoV-2 pneumonia based on the most recent literature, diagnosis, and treatment trial reports. Many studies have shown that early diagnosis and implementation of targeted treatment measures according to the different stages of disease can reduce the mortality rate among patients with MI related to SARS-CoV-2 pneumonia. The reviewed studies show that multiple strategies have been adopted for the management of MI related to COVID-19. Clinicians should closely monitor SARS-CoV-2 pneumonia patients with MI, as their condition can rapidly deteriorate and progress to heart failure, acute myocardial infarction, and/or cardiogenic shock. In addition, appropriate measures need to be implemented in the diagnosis and treatment to provide reasonable care to the patient. Full article

Background: Left atrial spontaneous echo contrast (LASEC) can be detected by transesophageal echocardiography (TEE) before the catheter ablation of atrial fibrillation (AF), especially in patients with left atrial (LA) dilation. Whether LASEC has prognostic value in predicting the procedure outcomes in patients with an enlarged atrium is unknown. The prognostic implications of LASEC with the catheter ablation of AF patients with LA dilation will be evaluated in this study. Methods: AF patients scheduled to undergo catheter ablation in Ruijin Hospital, Shanghai, China, between January 2018 and June 2020 were screened for this prospective study. All patients underwent TEE before the procedure. Patients with a left atrial diameter (LAD; 45 mm ≤ LAD < 50 mm) and left atrial volume (LAV ≥ 120 mL) were enrolled in this study. The endpoint was AF/atrial tachycardia (AT) recurrence-free survival following a 3-month blanking period after the catheter ablation. All patients were followed up for 18 months. Results: This study included 123 AF patients, who were divided into the LASEC (n = 73) and no LASEC (n = 50) groups. Baseline patient characteristics were similar in the two groups. At the end of 18 months of follow-up, AF/AT recurrence-free survival was achieved in 33 (45.2%) and 34 (68.0%) patients in the LASEC and no LASEC groups, respectively (p = 0.013). In survival analysis, the LASEC group was also associated with a poor outcome of catheter ablation (log-rank test, p = 0.011; Cox regression, p = 0.015, HR = 2.058, 95%CI = 1.151–3.679). Meanwhile, during the follow-up AF/AT recurrence was observed in 30 (57.7%) and 15 (71.4%) cases in the mild and severe SEC groups, respectively. Ischemic stroke occurred in two patients in the LASEC group. Conclusions: LASEC could be a predictor of the recurrence of AF/AT after catheter ablation in AF patients with LA dilation. The higher the degree of LASEC, the worse the prognosis. Full article

Irisin, as one of the myokines induced by exercise, has attracted much attention due to its important physiological functions such as white fat browning, the improvement in metabolism, and the alleviation of inflammation. Despite the positive role that irisin has been proven to play in the prevention and treatment of cardiovascular diseases, whether it can become a biomarker and potential target for predicting and treating cardiovascular diseases remains controversial, given the unreliability of its detection methods, the uncertainty of its receptors, and the species differences between animals and humans. This paper was intended to review the role of irisin in the diagnosis and treatment of cardiovascular diseases, the potential molecular mechanism, and the urgent problems to be solved in hopes of advancing our understanding of irisin as well as providing data for the development of new and promising intervention strategies by discussing the causes of contradictory results. Full article

There is increasing recognition of the value of four-dimensional flow cardiovascular magnetic resonance (4D-flow MRI) as a potential means to detect and measure abnormal flow behaviour that occurs during early left ventricular (LV) dysfunction. We performed a systematic review of current literature on the role of 4D-flow MRI-derived flow parameters in quantification of LV function with a focus on potential clinical applicability. A comprehensive literature search was performed in March 2022 on available databases. A total of 1186 articles were identified, and 30 articles were included in the final analysis. All the included studies were ranked as “highly clinically applicable”. There was considerable variability in the reporting of methodologies and analyses. All the studies were small-scale feasibility or pilot studies investigating a diverse range of flow parameters. The most common primary topics of investigation were energy-related flow parameters, flow components and vortex analysis which demonstrated potentials for quantifying early diastolic dysfunction, whilst other parameters including haemodynamic forces, residence time distribution and turbulent kinetic energy remain in need of further evaluation. Systematic quantitative comparison of study findings was not possible due to this heterogeneity, therefore limiting the collective power of the studies in evaluating clinical applicability of the flow parameters. To achieve broader clinical application of 4D-flow MRI, larger scale investigations are required, together with standardisation of methodologies and analytical approach. Full article

Congenital heart disease (CHD) affects about 1 in 100 newborns and its causes are multifactorial. In the embryo, blood flow within the heart and vasculature is essential for proper heart development, with abnormal blood flow leading to CHD. Here, we discuss how blood flow (hemodynamics) affects heart development from embryonic to fetal stages, and how abnormal blood flow solely can lead to CHD. We emphasize studies performed using avian models of heart development, because those models allow for hemodynamic interventions, in vivo imaging, and follow up, while they closely recapitulate heart defects observed in humans. We conclude with recommendations on investigations that must be performed to bridge the gaps in understanding how blood flow alone, or together with other factors, contributes to CHD. Full article

Electrical isolation of pulmonary veins (PVI) is the cornerstone of invasive treatment of atrial fibrillation (AF). However, arrhythmia-free survival of a PVI only approach is suboptimal in patients with persistent and long-term persistent AF. Hybrid AF ablation has been developed with the aim of combining the advantages of a thoracoscopic surgical ablation (direct visualization of anatomical structures to be spared and the possibility to perform epicardial lesions) and endocardial ablation (possibility to check line block, confirm PVI, and possibility to perform cavotricuspid isthmus ablation). Patient selection is of utmost importance. In persistent and long-term persistent AF, hybrid AF ablation demonstrated promising results in terms of AF free survival. It has been associated with a relatively low complication rate if performed in centers with expertise in hybrid procedures and experience with both surgical and endocardial ablation. Different techniques have been described, with different approaches and lesion sets. The aim of this review is to provide a state-of-the-art overview of hybrid AF ablation. Full article

Arrhythmogenic cardiomyopathy (ACM) is a heritable myocardial disease characterized by life-threatening ventricular arrhythmias and sudden cardiac death. Cardiomyocyte death is an essential pathogenic mechanism in ACM, but the cell death landscape has never been elucidated. Our study aimed to address this problem based on RNA-sequencing (RNA-seq) data. Myocardial RNA-seq data from arrhythmogenic right ventricular cardiomyopathy (ARVC) patients and normal controls were obtained from the Gene Expression Omnibus database (GSE107475, GSE107311, GSE107156, GSE107125). Signature gene sets of cell death processes, immune cells, and pathways were collected. Single-sample gene-set enrichment analysis calculated the enrichment scores for these signature gene sets. The RNA-seq data of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) derived from an ACM patient were used for validation (GSE115621). Weighted gene coexpression network analysis (WGCNA) was applied to identify coexpression modules. Immunogenic cell death, apoptosis, necroptosis, and pyroptosis were significantly up-regulated in ARVC. Positive correlations of these four up-regulated cell death processes with immune cells and pathways were found within the ARVC myocardium. In the ARVC sample cluster with higher cell death levels, central memory CD4 T cell, memory B cell, type 1 T helper cell, mast cell, natural killer T cell, and plasmacytoid dendritic cell were more substantially infiltrated. Similarly, immune pathways were more up-regulated in this cluster. Positive linear correlations were found between cell death, immune responses, and myocardial fibrosis within the ARVC samples. Eventually, WGCNA identified a shared coexpression module related to these mechanisms. This study first demonstrated the landscape of cell death processes in the ACM (ARVC) myocardium and their positive correlations with immune responses and myocardial fibrosis. These mechanisms have potential interactions and jointly contribute to the pathogenesis of ACM. Full article

Background: Primary aldosteronism (PA) is a common cause of secondary hypertension and confers a higher risk of stroke. The treatment strategies of PA mainly include medical and adrenalectomy treatment, while there is still no solid conclusion on how these two different treatment strategies mitigate the detrimental effect of PA on stroke. Methods: PubMed, Embase, and Cochrane Library were searched for studies comparing stroke events in patients with PA receiving medical treatment versus adrenalectomy treatment published up to 19 March 2022, including patients with essential hypertension as a control group. We used either fixed or random effect models according to the heterogeneities. Sensitivity analysis was conducted by deleting each study one at a time. Results: We reviewed 201 articles, and three studies met the final criteria, including 3244 PA patients with medical treatment, 1611 PA patients with adrenalectomy treatment, and 20,568 EH patients. Patients with PA post adrenalectomy were observed with a significantly decreased risk of stroke compared to patients receiving medical treatment (OR: 0.57, 95% CI: 0.35–0.93, p = 0.03), and with no difference when compared to patients with essential hypertension. Patients with PA receiving medical treatment were still observed with higher stroke risks (OR: 1.88, 95% CI: 1.68–2.11, p < 0.00001) than patients with essential hypertension. Conclusion: PA is a critical modifiable risk factor for stroke. Adrenalectomy has a superior performance in the mitigation of stroke risks among patients with PA. Full article

Depression is one of the world’s most common and mentally disabling illnesses. Post-partum depression is a subtype of depression that affects one in seven women worldwide. Successful pharmacological treatment must consider the consequences for both, since the mother–child bond is fundamental for the well-being of both mother and infant as well as the general development of the newborn. Changes in maternal physiology and/or behavior can significantly influence the development of breastfed infants. Ketamine has been extensively studied for use as an antidepressant due to its mixed mechanisms of action. Safety and efficacy studies in the cardiovascular and urinary systems of a lactating postpartum depression animal model are essential for contributing toward ketamine’s clinical use in the respective patient population. Thus, this project aimed to study the implications of postpartum maternal exposure to ketamine during lactation on the cardiovascular system of female rats submitted to the depression induction model by maternal separation. This model promotes depressive effects through stress caused by the interruption of mother–infant bond early in the offspring’s life. To achieve depression, each dam was separated from her offspring for 3 h per day, from post-natal day 2 (PND2) to PND12. Experimental groups received daily treatment with either 5, 10, or 20 mg/kg of ketamine intraperitoneally during the lactation period, from PND2 to PND21. Behavioral tests consisted of the maternal and aggressive maternal behavior tests, the olfactory preference test, and the forced swim test. A technique for the detection of catecholamines and indoleamines in the heart muscle was developed for the experimental model groups. The histopathological evaluation was performed on these animals’ cardiac muscles and urinary bladders. Our findings suggest that ketamine is safe for use in postpartum depression and does not induce cardiovascular and/or urinary systems toxicity. Full article

Introduction: No previous studies comparing the outcomes between off-pump coronary artery bypass grafting (off-pump CABG, OPCAB) and on-pump CABG (ONCAB) have been performed in patients with severe left ventricular dysfunction (LVD) and a giant left ventricle. We aimed to investigate whether such patients could benefit from OPCAB. Methods: From January 2011 to January 2021, a total of 98 patients with severe LVD and a giant left ventricle underwent isolated CABG (ONCAB 46, OPCAB 52) in Wuhan Union Hospital. The clinical data were collected retrospectively and propensity score matching was performed to adjust baseline characteristics. Results: After propensity matching, the two groups were comparable in baseline variables. The OPCAB group had a higher rate of incomplete revascularization than the ONCAB group (25.0% vs. 9.1%; p = 0.047). The 30-day mortality was similar between the matched groups (4.5% vs. 4.5%; p = 1.000) but the OPCAB group had a lower risk of postoperative IABP usage (9.1% vs. 25.0%; p = 0.047) and renal insufficiency (11.4% vs. 29.5%; p = 0.034). The long-term probability of survival (log-rank test, p = 0.450) was similar between the two groups but the OPCAB group had a lower probability of major adverse cardiovascular events (log-rank test, p = 0.038). Conclusions: For patients with severe LVD and a giant left ventricle, OPCAB reduced early postoperative complications while sacrificing long-term quality of life compared to those having ONCAB. Full article

Due to its heterogeneous clinical picture and lengthy evolution, the management of type B aortic dissection represents a clinical challenge, often calling for complex strategies combining medical, endovascular, and open surgical strategies. We present the case of a 45-year-old female who had previously suffered a complicated type B aortic dissection requiring a femoro-femoral crossover bypass and further conservative treatment. Seven years later, due to an aneurysmal development, a staged descending aortic management was strategized, beginning with the implantation of a frozen elephant trunk device due to an insufficient proximal landing zone for endovascular repair. However, the development of a distal stent graft-induced new entry complicated the dissection and led to the formation of a second false lumen, thus prompting an expedited hybrid reconstruction. We describe a hybrid repair strategy tailored to the patient’s particular aortic anatomic conformation, combining ilio-visceral debranching and thoracic endovascular aortic repair. Due to a lack of consensus on the ideal management strategy for type B aortic dissection, an individualized approach conducted by an experienced aortic team may generate the best outcome. The appropriate timing and planning of the intervention are the keys to successful results in complex type B aortic dissection cases with an elaborate anatomic conformation. Full article

Background: Transcatheter treatments of tricuspid regurgitation (TR) have been emerging as alternatives for high-risk patients. In contrast to the immobilization of the common transcatheter tricuspid device, using a radial force-independent stent valve device at the native tricuspid annular site has several distinct advantages. Case summary: A 76-year-old patient with renal insufficiency who underwent mechanical mitral valve replacement in 2001 and transcatheter aortic valve replacement in 2021 due to severe aortic stenosis presented with chest pain and shortness of breath. Echocardiography suggested that the flow velocities of the mitral mechanical valve and aortic prosthetic valve were both within the normal range, with no significant paravalvular regurgitation; the tricuspid valve exhibited massive regurgitation (VMAX 258 cm/s, PGMAX 27 mmHg). Due to the high surgical risk, we simulated the procedure with a three-dimensional (3D)-printed model and performed transcatheter tricuspid valve replacement using a LuX-Valve (Ningbo Jenscare Biotechnology Co., Ningbo, China). Discussion: We describe transcatheter tricuspid valve replacement using the LuX-Valve and preprocedural guidance with 3D printing. Postprocedural TR was significantly reduced, indicating that 3D printing plays an important role in preprocedural guidance and that the LuX-Valve was safe and practicable for tricuspid valve replacement. Full article

This study aims to provide an overview of multivariable prognostic modelling studies developed for coronary heart disease (CHD) in the general population and to explore the optimal prognostic model by comparing the models’ performance. A systematic review was performed using Embase, PubMed, Cochrane, Web of Science, and Scopus databases until 30 November 2019. In this work, only prognostic studies describing conventional risk factors alone or a combination of conventional and genomic risk factors, being developmental and/or validation prognostic studies of a multivariable model, were included. A total of 4021 records were screened by titles and abstracts, and 72 articles were eligible. All the relevant studies were checked by comparing the discrimination, reclassification, and calibration measures. Most of the models were developed in the United States and Canada and targeted the general population. The models included a set of similar predictors, such as age, sex, smoking, cholesterol level, blood pressure, BMI, and diabetes mellitus. In this study, many articles were identified and screened for consistency and reliability using CHARM and GRIPS statements. However, the usefulness of most prognostic models was not demonstrated; only a limited number of these models supported clinical evidence. Unfortunately, substantial heterogeneity was recognized in the definition and outcome of CHD events. The inclusion of genetic risk scores in addition to conventional risk factors might help in predicting the incidence of CHDs; however, the generalizability of the existing prognostic models remains open. Validation studies for the existing developmental models are needed to ensure generalizability, improve the research quality, and increase the transparency of the study. Full article

Background: Transcatheter aortic valve implantation (TAVI) is an established therapeutic option in patients with severe aortic valve stenosis (AS) and a high surgical risk profile. Pulmonary hypertension (PH)—often co-existing with severe AS—is associated with a limited factor for prognosis and survival. The purpose of this study was to evaluate the prevalence of PH in patients undergoing TAVI, classify these patients based on right heart catheter (RHC) measurements in different PH subtypes, and analyze prognostic values on survival after TAVI. Methods: 284 patients with severe AS underwent an RHC examination for hemodynamic assessment prior to TAVI and were categorized into subtypes of PH according to the 2015 European Society of Cardiology (ESC) guidelines. TAVI patients were followed-up with for one year with regard to 30-days and 1-year mortality as primary endpoints. Results: 74 of 284 participants showed a diastolic pressure gradient (DPG) < 7 mmHg and a pulmonary vascular resistance (PVR) > 3 Wood units (WU) and could not be formally allocated to either isolated post-capillary PH (ipc-PH) or combined pre- and post-capillary PH (cpc-PH). Therefore, a new subgroup called “borderline post-capillary PH” (borderlinepc-PH) was introduced. Compared with TAVI patients with pre-capillary PH (prec-PH), ipc-PH patients suffering from borderlinepc-PH (HR 7.114; 95% CI 2.015–25.119; p = 0.002) or cpc-PH (HR 56.459; 95% CI 7.738–411.924; p < 0.001) showed a significantly increased 1-year mortality. Conclusions: Postcapillary PH was expanded to include the so-called “borderlinepc-PH” variant in addition to the ipc-PH and cpc-PH subtypes. The one-year survival after TAVI was significantly different between the subgroups, with the worst prognosis for borderlinepc-PH and cpc-PH. Full article

A 61-year-old female was referred for catheter ablation of symptomatic and frequent premature ventricular complexes presented with right bundle branch block and a prominent inferior frontal plane QRS axis. A retrograde transaortic approach was routinely performed. A sustained complete atrioventricular block was repeatedly encountered while the ablation catheter was attempting to cross the aortic valve with different curves and manipulations. The procedure was abandoned. The mechanical atrioventricular block could only have been caused by the retrograde transaortic approach. We should be cautious when performing a retrograde transaortic catheter manipulation in some patients. Full article

The World Health Organization announced that COVID-19, with SARS-CoV-2 as its pathogen, had become a pandemic on 11 March 2020. Today, the global epidemic situation is still serious. With the development of research, cardiovascular injury in patients with COVID-19, such as arrhythmia, myocardial injury, and heart failure, is the second major symptom in addition to respiratory symptoms, and cardiovascular injury is related to the prognosis and mortality of patients. The incidence of arrhythmia in COVID-19 patients ranges from 10% to 20%. The potential mechanisms include viral infection-induced angiotensin-converting enzyme 2 expression change, myocarditis, cytokine storm, cardiac injury, electrophysiological effects, hypoxemia, myocardial strain, electrolyte abnormalities, intravascular volume imbalance, drug toxicities and interactions, and stress response caused by virus infection. COVID-19 complicated with arrhythmia needs to be accounted for and integrated in management. This article reviews the incidence, potential mechanisms, and related management measures of arrhythmia in COVID-19 patients. Full article

Background: B cells and autoantibodies play an important role in the pathogenesis of abdominal aortic aneurysm (AAA). IgG glycosylations are highly valued as potential disease biomarkers and therapeutic targets. Methods: Lectin microarray was applied to analyze the expression profile of serum IgG glycosylation in 75 patients with AAA, 68 autoimmune disease controls, and 100 healthy controls. Lectin blots were performed to validate the differences. The clinical relevance of lectins binding from the microarray results was explored in AAA patients. Results: Significantly lower binding level of SBA (preferred GalNAc) was observed for the AAA group compared with DCs (p < 0.001) and HCs (p = 0.049). A significantly lower binding level of ConA (preferred mannose) was observed in patients with aneurysm diameter >5 cm. Significantly higher binding of CSA (preferred GalNAc) was present for dyslipidemia patients, whereas a lower binding level of AAL (preferred fucose) was observed for hypertensive patients. Patients with diabetes had lower binding levels of IRA (preferred GalNAc) and HPA (preferred GalNAc) compared with those not with DM. PTL-L (R = 0.36, p = 0.0015, preferred GalNAc) was positively associated with aneurysm diameters, whereas DSL (R = 0.28, p = 0.014, preferred (GlcNAc)2-4) was positively associated with patients’ age. Symptomatic patients had a lower binding level of ConA (p = 0.032), and patients with coronary heart disease had higher binding levels of STL (p = 0.0029, preferred GlcNAc). Patients with ILT bound less with black bean crude (p = 0.04, preferred GalNAc). Conclusions: AAA was associated with a decreased IgG binding level of SBA (recognizing glycan GalNAc). Symptomatic patients with aneurysm <5 cm had a higher binding level of ConA (preferred mannose). Coronary heart disease and elder age were associated with increased IgG bisecting GlcNAc. IgG O-glycosylation (GalNAc) may play an important role in AAA pathogenesis and progression. Full article

Thyroid dysfunction and inflammation are individually implicated in the increased risk of heart failure. Given the regulatory role of thyroid hormones on immune cells, this study aimed to investigate their joint association in heart failure. Patients with pre-existing heart failure were enrolled when hospitalized between July 2019 and September 2021. Thyroid function and inflammatory markers were measured at the enrollment. The composite of all-cause mortality or rehospitalization for heart failure were studied in the following year. Among 451 participants (mean age 66.1 years, 69.4% male), 141 incident primary endpoints were observed during a median follow-up of 289 days. TT3 and FT3 levels were negatively correlated with BNP levels (r: −0.40, p < 0.001; r: −0.40, p < 0.001, respectively) and NT-proBNP levels (r: −0.39, p < 0.001; r: −0.39, p < 0.001). Multivariate COX regression analysis revealed that FT3 (adjusted HR: 0.677, 95% CI: 0.551–0.832) and NLR (adjusted HR: 1.073, 95% CI: 1.036–1.111) were associated with adverse event, and similar results for TT3 (adjusted HR: 0.320, 95% CI: 0.181–0.565) and NLR (adjusted HR: 1.072, 95% CI: 1.035–1.110). Restricted cubic splines analysis indicated a linear relationship between T3 level and adverse events. Mechanistically, primary cardiomyocytes showed strong resistance to TNF-α induced apoptosis under optimal T3 concentrations, as evidenced by TUNEL staining, flow cytometry analysis, and LDH release assay as well as increased expression of Bcl-2. Thyroid dysfunction and inflammation are independently associated with cardiovascular risk in heart failure patients, which may concurrently contribute to the ongoing cardiomyocyte loss in the disease progression. Full article

Although instrumental activities of daily living (IADL) are included in the outcomes of cardiac rehabilitation (CR), the relationship between IADL frequency at the end of CR and outcomes between the sexes remains unclear. We aimed to investigate the differences in frequency of IADL between the sexes and its impact on the outcomes. We retrospectively investigated 490 consecutive patients who were admitted for heart failure (HF) and participated in CR post-discharge. IADL frequency was assessed using the questionnaire-based Frenchay Activities Index (FAI). The primary endpoint was all-cause death, and the secondary endpoint was a composite of all-cause death and readmission due to HF. The cut-off values of the FAI for all-cause death in the overall cohort, females, and males were 23, 22, and 23 points, respectively. After adjusting for several factors, IADL assessed using the FAI was independently associated with all-cause mortality (hazard ratio [HR]: 0.961, 95% confidence interval [CI]: 0.937–0.986) and combined events (HR: 0.968, 95% CI: 0.952–0.985), respectively. Additionally, there was no interaction between sex and all-cause mortality. In conclusion, higher IADL frequency after CR was associated with favourable outcomes in patients with HF. Full article

Catheter ablation of ventricular tachycardia has demonstrated its important role in the treatment of ventricular tachycardia in patients with structural cardiomyopathy. Conventional mapping techniques used to define the critical isthmus, such as activation mapping and entrainment, are limited by the non-inducibility of the clinical tachycardia or its poor hemodynamic tolerance. To overcome these limitations, a voltage mapping strategy based on bipolar electrograms peak to peak analysis was developed, but a low specificity (30%) for VT isthmus has been described with this approach. Functional mapping strategy relies on the analysis of the characteristics of the electrograms but also their propagation patterns and their response to extra-stimulus or alternative pacing wavefronts to define the targets for ablation. With this review, we aim to summarize the different functional mapping strategies described to date to identify ventricular arrhythmic substrate in patients with structural heart disease. Full article

This study compared the effects of lower- versus higher-intensity isometric handgrip exercise on resting blood pressure (BP) and associated clinical markers in adults with hypertension. Thirty-nine males were randomly assigned to one of three groups, including isometric handgrip at 60% maximal voluntary contraction (IHG-60), isometric handgrip at 30% IHG-30, or a control group (CON) that had been instructed to continue with their current activities of daily living. The volume was equated between the exercise groups, with IHG-60 performing 8 × 30-s contractions and IHG-30 performing 4 × 2-min contractions. Training was performed three times per week for 8 weeks. Resting BP (median [IQR]), flow-mediated dilation, heart rate variability, and serum markers of inflammation and oxidative stress were measured pre- and post-intervention. Systolic BP was significantly reduced for IHG-60 (−15.5 mmHg [−18.75, −7.25]) and IHG-30 (−5.0 mmHg [−7.5, −3.5]) compared to CON (p < 0.01), but no differences were observed between both the exercise groups. A greater reduction in diastolic BP was observed for IHG-60 (−5.0 mmHg [−6.0, −4.25] compared to IHG-30 (−2.0 mmHg [−2.5, −2.0], p = 0.042), and for both exercise groups compared to CON (p < 0.05). Flow-mediated dilation increased for both exercise groups versus CON (p < 0.001). IHG-30 had greater reductions in interleukin-6 and tumor necrosis factor-α compared to the other groups (p < 0.05) and CON (p = 0.018), respectively. There was a reduction in Endothelin-1 for IHG-60 compared to CON (p = 0.018). Both the lower- and higher-intensity IHG training appear to be associated with reductions in resting BP and improvements in clinical markers of inflammation and oxidative stress. Full article

Non-obstructive coronary artery disease occurs in 3.5–15% of patients presenting with acute myocardial infarction. This group of patients has a poor prognosis. Identification of factors that predict worse outcomes in myocardial infarction with non-obstructive coronary arteries (MINOCA) is therefore important. Patients with a diagnosis of MINOCA (n = 110) were enrolled in this single-center, retrospective registry. Follow-up was performed 12, 24 and 36 months after discharge. The primary composite endpoint was defined as myocardial infarction, coronary revascularization, stroke or TIA, all-cause death, or hospital readmission due to any cardiovascular event. The mean age of the study group was 64.9 (± 13.5) years and 38.2% of patients were male. The occurrence of the primary composite endpoint was 36.4%. In a COX proportional hazards model analysis, older age (p = 0.027), type 2 diabetes (p = 0.013), history of neoplasm (p = 0.004), ST-segment depression (p = 0.018) and left bundle branch block/right bundle branch block (p = 0.004) by ECG on discharge, higher Gensini score (p = 0.022), higher intraventricular septum (p = 0.007) and posterior wall thickness increases (p = 0.001) were shown to be risk factors for primary composite endpoint occurrence. Our study revealed that several factors such as older age, type 2 diabetes, ST-segment depression and LBBB/RBBB in ECG on discharge, higher Gensini score, and myocardial hypertrophy and history of neoplasm may contribute to worse clinical outcomes in MINOCA patients. Full article

Objective: Little is known about the fate of bypass grafts to the right coronary system. To investigate the long-term patency of venous bypass grafts directed to the right coronary artery (RCA) based on postoperative angiograms and to identify predictors of graft occlusion. Methods: In this single-center study, all patients who underwent coronary angiography from 2005 to 2021 after previously undergoing isolated coronary artery bypass grafting (CABG) were included. The primary endpoint was graft occlusion over a median follow-up of 9.1 years. Results: Among a total of 1106 patients (17.0% women, 64 (57–71) years median age), 289 (26.1%) received a sequential vein graft and 798 (72.2%) a single graft. Multivariate regression revealed age (HR 1.019, CI 95% 1.007–1.032), the urgency of CABG (HR 1.355, CI 95% 1.108–1.656), and severely impaired left ventricular function (HR 1.883, CI 95% 1.290–2.748), but not gender and chronic total occlusion (CTO) as predictive factors for graft occlusion. Single conduits were found to be a predictor of graft patency (HR 0.575 CI 95% 0.449–0.737). The angiographic outcome showed an overall 10-year freedom from graft occlusion of 73.4% ± 1.6%. The 5-year (10-year) freedom from graft occlusion was 76.9% ± 2.8% (57.8% ± 4.0%) for sequential grafts and 90.4% ± 1.1% (77.8% ± 1.7%) for single grafts (log-rank p < 0.001). Conclusions: In symptomatic patients with renewed angiography, venous bypass grafting of the RCA showed acceptable long-term patency rates. Single bypass grafting of the RCA was superior to sequential grafting, which needs to be further investigated. Full article

Introduction: The optimal freeze duration in cryoballoon pulmonary vein isolation (PVI) is unknown. TTI-based titration of cryoenergy allows individualized freeze duration and has emerged as a favorable ablation strategy in PV cryoablation. In a recent study, we demonstrated that omission of a bonus freeze and reduction in freeze duration to a minimum of 2 min in the case of short TTI led to comparable arrhythmia recurrence rates. Whereas clinical outcome seems to be comparable to fixed freeze duration, evidence of long-term PV reconnection rates in patients undergoing TTI-based cryoballoon ablation is sparse. Aim of the study: To evaluate the procedural efficacy of a single 2-min freeze for PVI, we assessed PV conduction recovery after cryoballoon PVI with a TTI-guided titration of freeze duration compared to a fixed ablation protocol. Methods and Results: We included consecutive patients with atrial fibrillation (AF) recurrence undergoing a second ablation procedure after the initial cryoballoon procedure. The second AF ablation procedure was performed by the 3D-mapping system and radiofrequency ablation technique. A total of 219 patients (age: 66.2 ± 10.8 years, 53% female, paroxysmal AF: 53%) treated with the TTI-guided protocol (174 patients, 685 PV) or fixed protocol (45 patients, 179 PV) showed comparable total reconnection rates (TTI: 36.9% vs. fixed: 31.8%, p = 0.21). The PV reconnection rate was not statistically different for PVs treated with a 2-min freeze in case of short TTI, compared to longer freeze duration. Interestingly, the PV reconnection rate was lower in LIPVs treated with the fixed protocol (13% vs. 31%, p = 0.029). In the TTI group, 17 out of 127 patients (15%) had durable isolation of all PVs, whereas in 8 out of 40 patients (20%) in the fixed group, all PVs were still isolated (p = 0.31). Conclusions: overall reconnection rate was not different using a TTI-guided ablation protocol compared to a fixed ablation protocol, whereas the LIPV reconnection rate was significantly lower in patients treated with a fixed ablation protocol. Full article