J. Cardiovasc. Dev. Dis., Volume 9, Issue 8 (August 2022) – 52 articles

Background: Tei index (TI) is a combined myocardial performance index, which was found to be more sensitive for overall cardiac dysfunction than systolic or diastolic parameters alone. Currently, there is only limited evidence for this measure in the context of myocarditis. Thus, TI could add additional benefits to conventional diagnostic workup. Methods: TI of patients with myocarditis (n = 40), acute coronary syndrome (n = 29) and controls (n = 50) was retrospectively analyzed concerning its discriminatory ability for myocarditis. Results: TI was most pathological in patients with myocarditis (median 0.41 vs. 0.35 vs. 0.31, p < 0.0001). Its discriminatory ability was better than that of EF or E/e’ (AUCs: TI: 0.71, p < 0.0001; EF: 0.57, p = 0.112; E/e’: 0.64, p = 0.983), which was also verified in logistic regression analysis (B(SE) = 0.81(0.23), p = 0.0004). The association of TI with myocarditis remained significant even after correction for confounders in propensity score weighted analysis. Conclusions: The TI showed a better discriminatory ability for myocarditis than conventional echocardiographic parameters. Since TI is easily conducted, it might be a helpful adjunctive tool to supplement conventional diagnostic modalities in patients with suspected myocarditis. Full article

Aortic stenosis is the most common valve disease requiring surgery or percutaneous treatment. Since the first-in-man implantation in 2002 we have witnessed incredible progress in transcatheter aortic valve implantation (TAVI). In this article, we review the technical aspects of TAVI development with a look at the future. Durability, low thrombogenicity, good hydrodynamics, biocompatibility, low catheter profile, and deployment stability are the attributes of an ideal TAVI device. Two main design types exist—balloon-expandable and self-expanding prostheses. Balloon-expandable prostheses use a cobalt-chromium alloy frame providing high radial strength and radiopacity, while the self-expanding prostheses use a nickel-titanium (Nitinol) alloy frame, which expands to its original shape once unsheathed and heated to the body temperature. The valve is sewn onto the frame and consists of the porcine or bovine pericardium, which is specially treated to prevent calcinations and prolong durability. The lower part of the frame can be covered by polyethylene terephthalate fabric or a pericardial skirt, providing better sealing between the frame and aortic annulus. The main future challenges lie in achieving lower rates of paravalvular leaks and new pacemaker implantations following the procedure, lower delivery system profiles, more precise positioning, longer durability, and a good hemodynamic profile. Patient-specific design and the use of autologous tissue might solve these issues. Full article

Patients with advanced heart failure (HF) have reduced cardiac output and impaired peripheral blood flow, which diminishes endothelial shear stress and consequently flow-mediated dilatation (FMD). The aim of our study was to find out whether endothelial dysfunction is associated with the number of CD34⁺ cells and TNF-α levels in patients with ischemic and non-ischemic HF after stimulation with granulocyte colony-stimulating factor (G-CSF). We included 56 patients with advanced HF (LVEF < 35%). Eighteen patients (32.14%) had ischemic and 38 (67.86%) patients had non-ischemic HF. FMD of the brachial artery was performed before the patients underwent 5-day bone marrow stimulation with daily subcutaneous injections of G-CSF (5 μg/kg bid). On the fifth day peripheral blood CD34⁺ cell count was measured. No statistically significant differences were found between the patient groups in NT-proBNP levels ((1575 (425–2439) vs. 1273 (225–2239)) pg/mL; p = 0.40), peripheral blood CD34⁺ cell count ((67.54 ± 102.32 vs. 89.76 ± 71.21) × 10⁶; p = 0.32), TNF-α ((8.72 ± 10.30 vs. 4.96 ± 6.16) ng/mL; p = 0.13) and FMD (6.7 ± 5.4 vs. 7.2 ± 5.9%; p = 0.76). In a linear regression model, only FMD (p = 0.001) and TNF-α (p = 0.003) emerged as statistically significant predictors of CD34⁺ cells counts. Our study suggests that TNF-α is a good predictor of impaired endothelial function and of CD34⁺ cells mobilization after G-CSF stimulation in patients with advanced HF of ischemic and non-ischemic origin. Full article

Background: There is evidence that monocyte chemoattractant protein-1 (MCP-1) levels reflect the intensity of the inflammatory response in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI) and have a predictive value for clinical outcomes. However, little is known about the effect of mild therapeutic hypothermia (MTH) on the inflammatory response in patients with CS complicating AMI. Therefore, we conducted a biomarker study to investigate the effect of MTH on MCP-1 levels in patients with CS complicating AMI. Methods: In the randomized mild hypothermia in cardiogenic shock (SHOCK-COOL) trial, 40 patients with CS complicating AMI were enrolled and assigned to MTH (33 °C) for 24 h or normothermia at a 1:1 ratio. Blood samples were collected at predefined time points at the day of admission/day 1, day 2 and day 3. Differences in MCP-1 levels between and within the MTH and normothermia groups were assessed. Additionally, the association of MCP-1 levels with the risk of all-cause mortality at 30 days was analyzed. Missing data were accounted for by multiple imputation as sensitivity analyses. Results: There were differences in MCP-1 levels over time between patients in MTH and normothermia groups (P for interaction = 0.013). MCP-1 levels on day 3 were higher than on day 1 in the MTH group (day 1 vs day 3: 21.2 [interquartile range, 0.25–79.9] vs. 125.7 [interquartile range, 87.3–165.4] pg/mL; p = 0.006) and higher than in the normothermia group at day 3 (MTH 125.7 [interquartile range, 87.3–165.4] vs. normothermia 12.3 [interquartile range, 0–63.9] pg/mL; p = 0.011). Irrespective of therapy, patients with higher levels of MCP-1 at hospitalization tended to have a decreased risk of all-cause mortality at 30 days (HR, 2.61; 95% CI 0.997–6.83; p = 0.051). Conclusions: The cooling phase of MTH had no significant effect on MCP-1 levels in patients with CS complicating AMI compared to normothermic control, whereas MCP-1 levels significantly increased after rewarming. Trial registration: NCT01890317. Full article

Hypoplastic left heart syndrome (HLHS) is a collective term applied to severe congenital cardiac malformations, characterised by a combination of abnormalities mainly affecting the left ventricle, associated valves, and ascending aorta. Although in clinical practice HLHS is usually sub-categorised based on the patency of the mitral and aortic (left-sided) valves, it is also possible to comprehensively categorise HLHS into defined sub-groups based on the left ventricular morphology. Here, we discuss the published human-based studies of the ventricular myocardium in HLHS, evaluating whether the available evidence is in keeping with this ventricular morphology concept. Specifically, we highlight results from histological studies, indicating that the appearance of cardiomyocytes can be different based on the sub-group of HLHS. In addition, we discuss the histological appearances of endocardial fibroelastosis (EFE), which is a common feature of one specific sub-group of HLHS. Lastly, we suggest investigations that should ideally be undertaken using HLHS myocardial tissues at early stages of HLHS development to identify biological pathways and aid the understanding of HLHS aetiology. Full article

Background: Circumferential pulmonary vein isolation (PVI) using radiofrequency ablation (RFA) is a standard of care intervention for patients with symptomatic atrial fibrillation (AF). During follow-up, a substantial number of patients need a redo procedure due to reconnections on the basis of insufficient non-transmural ablation lesions. High-power short-duration ablation (HPSD) is expected to create efficient lesions while causing fewer complications than in conventional RFA settings. The aim of this study was to compare one-year outcome data of very HPSD (90 Watt, 4 s) to a strategy using 50 Watt HPSD ablation guided by the CLOSE protocol using the Ablation Index (AI), an arbitrary unit composed of power, contact force and ablation time. Methods: We retrospectively analyzed short and long-term (median follow-up 23.2 ± 9.9 months) outcome data from 52 patients that were scheduled for first-do-symptomatic PVI. A very HPSD ablation protocol with 90 Watt and a 4 s duration cut-off was compared to an HPSD CLOSE approach (50 Watts; AI 550 at the anterior LA wall; AI 400 at the posterior LA wall, the roof and the floor) in terms of freedom from AF recurrence in a long-term electrocardiogram (ECG) over a five days surveillance period. To gain an impression of the subjective sense of wellbeing, the Atrial Fibrillation Effects on QualiTy-of-Life (AFEQT) score was recorded. Results: Overall freedom from AF was found in 81% (90 W 4 s) vs. 87.5% (50 W), (p = 0.52). There were 3 AF recurrences during the blanking period (90 W 4 s) vs. 1 (50 W). Within each population, one patient was scheduled for a redo-PVI-procedure. The AFEQT score was in favor of the 90 Watt 4 s approach (86.1 vs. 77.5; p = 0.37). Conclusion: Within our relatively small studied population, we found hints that in addition to shortening ablation times and radiation exposure without significantly increasing the rate of relevant intraprocedural complications, very high power short-duration ablation (90 W 4 s) provides comparable efficacy rates after one year. Full article

Tissue inhibitor of metalloproteinase 3 (TIMP3) is a protease with high expression levels in the heart and plays an essential role in extracellular matrix turnover by maintaining equilibrium with matrix metalloproteinases. Considerable data in experimental models have demonstrated a protective role of TIMP3 in coronary artery disease (CAD) and myocardial infarction (MI). However, causality remains unexplored in population studies. Here, we sought to decipher the potential causality between TIMP3 and CAD/MI using the Mendelian randomization (MR) method. We extracted summary−level datasets for TIMP3 and CAD/MI from the genome−wide association studies performed in the KORA study and CARDIoGRAMplusC4D consortium, respectively. Seven independent SNPs were obtained as instrumental variables for TIMP3. The MR analyses were replicated using FinnGen datasets, and the main results were combined in meta−analyses. Elevated genetically predicted serum TIMP3 levels were causally associated with a lower risk of CAD [odds ratio (OR), 0.97; 95% confidence interval (CI), 0.95, 0.98; p = 5.29 × 10⁻⁵] and MI (OR, 0.96; 95% CI, 0.95, 0.98; p = 3.85 × 10⁻⁵). The association patterns persisted in the meta−analyses combining the different datasets (CAD: OR, 0.97; 95% CI, 0.96, 0.99; p = 4.37 × 10⁻⁵; MI: OR, 0.97; 95% CI, 0.96, 0.99; p = 9.96 × 10⁻⁵) and was broadly consistent across a set of complementary analyses. Evidence of heterogeneity and horizontal pleiotropy was limited for all associations considered. In conclusion, this MR study supports inverse causal associations between serum TIMP3 and the risk of CAD and MI. Strategies for raising TIMP3 levels may offer new avenues for the prevention strategies of atherosclerotic cardiovascular diseases. Full article

While mortality in patients with hypertensive emergency has significantly improved over the past decades, the incidence and complications associated with acute hypertension-mediated organ damage have not followed a similar trend. Hypertensive emergency is characterized by an abrupt surge in blood pressure, mostly occurring in people with pre-existing hypertension to result in acute hypertension-mediated organ damage. Acute hypertension-mediated organ damage commonly affects the cardiovascular system, and present as acute heart failure, myocardial infarction, and less commonly, acute aortic syndrome. Elevated cardiac troponin with or without myocardial infarction is one of the major determinants of outcome in hypertensive emergency. Despite being an established entity distinct from myocardial infarction, myocardial injury has not been systematically studied in hypertensive emergency. The current guidelines on the evaluation and management of hypertensive emergencies limit the cardiac troponin assay to patients presenting with features of myocardial ischemia and acute coronary syndrome, resulting in underdiagnosis, especially of atypical myocardial infarction. In this narrative review, we aimed to give an overview of the epidemiology and pathophysiology of hypertensive emergencies, highlight challenges in the evaluation, classification, and treatment of hypertensive emergency, and propose an algorithm for the evaluation and classification of cardiac acute hypertension-mediated organ damage. Full article

1. Introduction: Pulmonary vein isolation (PVI) is an established procedure used to achieve rhythm control in atrial fibrillation (AF). In obese patients (pts), in whom AF occurs more frequently, a reduced effectiveness of PVI has been observed. Therefore, this study’s aim was to compare the long-term efficacy of PVI between obese and non-obese patients. 2. Methods: We enrolled 111 consecutive pts with a body mass index (BMI) of >30 kg/m² undergoing PVI from our large registry. Procedural data and outcomes were compared with a matched group of 115 non-obese PVI pts and the long-term outcomes were analyzed. 3. Results: Overall follow-up duration was 314 patient-years in the obese and 378 patient-years in the non-obese group. The follow-up rate was 71% in the obese and 76% in the non-obese group. In both groups, their AF-characteristics did not differ significantly, while known risk factors were significantly more prevalent in the obese group. Procedural characteristics were similar in both groups. During follow-up, the obese pts demonstrated significant weight loss compared to the non-obese pts, while at the same time, the overall recurrence rate during follow-up did not differ significantly between both groups (obese: 39.2% and non-obese: 43.7%). PVI related and long-term complications were comparable between both groups. In the univariate analysis, obesity was not found to be associated with an increased AF recurrence risk. 4. Conclusion: These real-life data demonstrate that obese pts may not show higher AF recurrence rates after PVI compared to pts with normal body weight. Furthermore, PVI was found to be safe and effective in obese patients; thus, a BMI alone may not be a criterion for refusal of PVI. Full article

The study investigates the prognostic role of treatment with carvedilol as compared to metoprolol in patients with ventricular tachyarrhythmias. A large retrospective registry was used including consecutive patients on beta-blocker (BB) treatment with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2015. Patients treated with carvedilol were compared to patients with metoprolol. The primary prognostic outcome was all-cause mortality at three years. Secondary endpoints comprised a composite arrhythmic endpoint (i.e., recurrences of ventricular tachyarrhythmias, appropriate implantable cardioverter defibrillator (ICD) therapies) and cardiac rehospitalization. Kaplan–Meier survival curves, multivariable Cox regression analyses, and propensity score matching were applied for statistics. There were 1098 patients included, 80% treated with metoprolol and 20% with carvedilol. Patients with carvedilol were older, more often presenting with VT (78% vs. 62%; p = 0.001) and with more advanced stages of heart failure. Treatment with carvedilol was associated with comparable all-cause mortality compared to metoprolol (20% vs. 16%, log rank p = 0.234; HR = 1.229; 95% CI 0.874–1.728; p = 0.235). However, secondary endpoints (i.e., composite arrhythmic endpoint: 32% vs. 17%; p = 0.001 and cardiac rehospitalization: 25% vs. 14%; p = 0.001) were more frequently observed in patients with carvedilol, which was still evident after multivariable adjustment. After propensity score matching (n = 194 patients with carvedilol and metoprolol), no further differences regarding the distribution of baseline characteristics were observed. Within the propensity-score-matched cohort, higher rates of the composite arrhythmic endpoint were still observed in patients treated with carvedilol, whereas the risk of cardiac rehospitalization was not affected by the type of beta-blocker treatment. In conclusion, carvedilol and metoprolol are associated with comparable all-cause mortality in patients with ventricular tachyarrhythmias, whereas the risk of the composite arrhythmic endpoint was increased in patients with carvedilol therapy. Full article

Introduction: Currently, the deployment of human–computer interactive technologies to provide personalized care has grown and immensely taken shape in most healthcare settings. With the increasing growth of the internet and technology, personalized health interventions including smartphones, associated apps, and other interventions demonstrate prowess in various health fields, including cardiovascular management. This systematic review thus examines the effectiveness of various human–computer interactions technologies through telehealth (mainly eHealth) towards optimizing the outcomes in cardiovascular treatment. Methods: A comprehensive search of MEDLINE, EMBASE, and CINAHL databases using key terms was conducted from 2000 to November 2021 to identify suitable studies that explored the use of human–computer interaction technologies to provide a personalized care approach to facilitate bolstered outcomes for cardiovascular patients, including the elderly. The included studies were assessed for quality and risk of bias, and the authors undertook a data extraction task. Results: Ten studies describing the use of a mix of personalized health app (mHealth) interventions were identified and included in the study. Among the included studies, nine of them were randomized trials. All of the studies demonstrated the effectiveness of various personalized health interventions in maximizing the benefits of cardiovascular disease treatment. Conclusions: Personalized health application interventions through precision medicine has great potential to boost cardiovascular disease management outcomes, including rehabilitation. Fundamentally, since each intervention’s focus might differ based on the disease and outcome preference, it is recommended that more research be done to tailor the interventions to specific disease and patient outcome expectations. Full article

Calcific aortic valve disease (CAVD) is a common cardiac defect, particularly in the aging population. While several risk factors, such as bi-leaflet valve structure and old age, have been identified in CAVD pathogenesis, molecular mechanisms resulting in this condition are still under active investigation. Bone morphogenetic protein signaling via the activin type I receptor (AcvRI) plays an important role during physiological and pathological processes involving calcification, e.g., bone formation and heterotopic ossification. In addition, AcvRI is required for normal cardiac valve development, yet its role in aortic valve disease, if any, is currently unknown. Here, we induced the expression of constitutively active AcvRI in developing mouse embryos in the endocardium and in cells at the valve leaflet–wall junction that are not of endocardium origin using the Nfac1Cre transgene. The mutant mice were born alive, but showed thickened aortic and pulmonary valve leaflets during the early postnatal period. Adult mutant mice developed aortic stenosis with high frequency, sclerotic aortic valves, and displayed Alcian Blue-positive hypertrophic chondrocyte-like cells at the leaflet–wall junction. Calcification was only seen with low penetrance. In addition, we observed that the expression levels of gene sets associated with inflammation-related cytokine signaling, smooth muscle cell contraction, and cGMP signaling were altered in the mutants when compared with those of the controls. This work shows that, in a mouse model, such continuous AcvRI activity in the Nfatc1Cre recombination domain results in pathological changes in the aortic valve structure and function. Full article

Background: Myocardial T2* mapping at 1.5T remains the gold standard, but the use of 3T scanners is increasing. We aimed to determine the conversion equations in different scanners with clinically available, vendor-provided T2* mapping sequences using a phantom and evaluated the feasibility of the phantom-based conversion method. Methods: T2* of a phantom with FeCl₃ (five samples, 3.53–20.09 mM) were measured with 1.5T (MR-A1) and 3T scanners (MR-A2, A3, B), and the site-specific equation was determined. T2* was measured in the interventricular septum of three healthy volunteers at 1.5T (T2*_1.5T, MR-A1) and 3T (T2*_3.0T, MR-B). T2*_3.0T was converted based on the equation derived from the phantom (T2*_eq). Results: R2* at 1.5T and 3T showed linear association, but a different relationship was observed according to the scanners (MR-A2, R2*_1.5T = 0.76 × R2*_3.0T − 2.23, R² = 0.999; MR-A3, R2*_1.5T = 0.95 × R2*3.0T − 34.28, R² = 0.973; MR-B, R2*_1.5T = 0.76 × R2*_3.0T − 3.02, R² = 0.999). In the normal myocardium, T2*_eq and T2*_1.5T showed no significant difference (35.5 ± 3.5 vs. 34.5 ± 1.2, p = 0.340). The mean squared error between T2*_eq and T2*_1.5T was 16.33, and Bland–Altman plots revealed a small bias (−0.94, 95% limits of agreement: −8.86–6.99). Conclusions: a phantom-based, site-specific equation can be utilized to estimate T2* values at 1.5T in centers where only 3T scanners are available. Full article

Catheter ablation for persistent atrial fibrillation (PeAF) is particularly challenging, as the clinical outcomes are modest. Pulmonary vein isolation (PVI) plus linear ablation is one of the main strategies for PeAF ablation. Completely durable transmural lesions are difficult to achieve by catheter ablation during mitral isthmus ablation. The ligament of Marshall contains the vein of Marshall (VOM), myocardial tracts and innervation, and serves as arrhythmogenic foci that make it an attractive target in catheter ablation of atrial fibrillation. Additionally, it co-localizes with the mitral isthmus, and may serve as a part of the perimitral isthmus reentrant circuit. Ethanol infusion into the VOM results in rapid ablation of the neighboring myocardium and its innervation. Its incorporation into PVI significantly increases the success rate of mitral isthmus block and the clinical outcome of PeAF ablation. Full article

Echocardiography, CT and MRI have a crucial role in the management of congenital heart disease (CHD) patients. All of these modalities can be presented in a 2D or a 3D rendered format. The aim of this paper is to review the key advantages and potential limitations, as well as the future challenges of a 3D approach in each imaging modality. The focus of this review is on anatomic rather than functional assessment. Conventional 2D echocardiography presents limitations when imaging complex lesions, whereas 3D imaging depicts the anatomy in all dimensions. CT and MRI can visualise extracardiac vasculature and guide complex biventricular repair. Three-dimensional printed models can be used in depicting complex intracardiac relationships and defining the surgical strategy in specific lesions. Extended reality imaging retained dynamic cardiac motion holds great potential for planning surgical and catheter procedures. Overall, the use of 3D imaging has resulted in a better understanding of anatomy, with a direct impact on the surgical and catheter approach, particularly in more complex cases. Full article

The SARS-CoV-2 virus has caused a pandemic, infecting nearly 80 million people worldwide, with mortality exceeding six million. The average survival span is just 14 days from the time the symptoms become aggressive. The present study delineates the deep-driven vascular damage in the pulmonary, renal, coronary, and carotid vessels due to SARS-CoV-2. This special report addresses an important gap in the literature in understanding (i) the pathophysiology of vascular damage and the role of medical imaging in the visualization of the damage caused by SARS-CoV-2, and (ii) further understanding the severity of COVID-19 using artificial intelligence (AI)-based tissue characterization (TC). PRISMA was used to select 296 studies for AI-based TC. Radiological imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound were selected for imaging of the vasculature infected by COVID-19. Four kinds of hypotheses are presented for showing the vascular damage in radiological images due to COVID-19. Three kinds of AI models, namely, machine learning, deep learning, and transfer learning, are used for TC. Further, the study presents recommendations for improving AI-based architectures for vascular studies. We conclude that the process of vascular damage due to COVID-19 has similarities across vessel types, even though it results in multi-organ dysfunction. Although the mortality rate is ~2% of those infected, the long-term effect of COVID-19 needs monitoring to avoid deaths. AI seems to be penetrating the health care industry at warp speed, and we expect to see an emerging role in patient care, reduce the mortality and morbidity rate. Full article

In vertebrates, the coordinated beat of the early heart tube drives cardiogenesis and supports embryonic growth. How the heart pumps at this valveless stage marks a fascinating problem that is of vital significance for understanding cardiac development and defects. The developing heart achieves its function at the same time as continuous and dramatic morphological changes, which in turn modify its pumping dynamics. The beauty of this muti-time-scale process also highlights its complexity that requires interdisciplinary approaches to study. High-resolution optical imaging, particularly fast, four-dimensional (4D) imaging, plays a critical role in revealing the process of pumping, instructing numerical modeling, and enabling biomechanical analyses. In this review, we aim to connect the investigation of valveless pumping mechanisms with the recent advancements in embryonic cardiodynamic imaging, facilitating interactions between these two areas of study, in hopes of encouraging and motivating innovative work to further understand the early heartbeat. Full article

Background: The present study investigated whether angiotensin II type 1 receptor blocker irbesartan (ARB) and partial agonist of PPAR-γ prevents heart apoptosis by suppressing cardiac Fas/FasL-mediated to mitochondria-mediated apoptosis in the hearts of hypertensive rat model. Methods: Cardiac function using echocardiography, H&E staining, TUNEL assay, and Western blotting were measured in the excised hearts from three groups, i.e., an untreated hypertensive group (SHR), an ARB-treated hypertensive group (50 mg/kg/day, S.C., SHR-ARB), and untreated normotensive Wistar-Kyoto rats (WKY). Results: Fas Ligand, Fas death receptors, FADD, active caspase-8, active caspase-3 (Fas/FasL-mediated apoptotic pathway), as well as Bax, cytochrome c, active caspase-9 and -3 (mitochondria-mediated apoptotic pathway), IGF-II, and p-JNK were decreased in SHR-ARB group when compared with the SHR group. SIRT1, PGC-1α, Bcl2, and Bcl-xL (SIRT1/PGC-1α pro-survival pathway) were increased in the SHR-ARB group when compared with the SHR group. Conclusions: Our findings suggested that the ARB might prevent cardiac Fas/FasL-mediated to mitochondria-mediated apoptosis pathway in the hypertensive model associated with IGF-II, p-JNK deactivation, and SIRT1/PGC-1α pro-survival pathway upregulation. ARB prevents hypertension-enhanced cardiac apoptosis via enhancing SIRT1 longevity signaling and enhances the mitochondrial biogenetic survival pathway. Full article

Neurally mediated syncope (NMS) is a common clinical problem. The underlying genetic factors of NMS remain controversial. We hypothesized that cardiac syncope-related genes may contribute to NMS in patients with previous frequent syncopal episodes and/or a family history of syncope. A total of 54 consecutive patients diagnosed with NMS were prospectively enrolled between 2013 and 2016. Inclusion criteria were more than five syncopal episodes with a family history of syncope (n = 17) or more than five syncopal episodes with no family history of syncope (n = 37). Ninety-eight cardiac syncope-related genes (channelopathy: 43 genes, cardiomyopathy: 50 genes, primary pulmonary hypertension: 5 genes) were screened by exome sequencing. All identified variants were classified according to the standards and guidelines by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Of the 54 patients, 17 patients (31.5%) had a family history of syncope. Two patients (3.7%) had pathogenic and likely pathogenic variants (PV/LPV) in cardiac syncope-related genes TTN and MYH7. We investigated genetic variation in patients with frequent NMS with a positive family history of syncope in Korea. PV/LPVs in genes related to cardiomyopathy were associated with recurrent NMS in Korean patients. Closer follow-up of these patients might be needed. Full article

(1) Background: Radiofrequency catheter ablation (RFCA) is an essential treatment for ventricular arrhythmia (VA). However, high impedance in the transitional area of the distal great cardiac vein (TAODGCV) often leads to ablation failure. This study aimed to explore the factors influencing impedance and identify effective ways to reduce impedance. (2) Methods: A total of 156 patients with VA arising from the TAODGCV received RFCA therapy at our center from October 2009 to August 2021 and were retrospectively analyzed. Local impedance variation during RFCA was monitored, recorded, and analyzed. (3) Results: The impedance increased from the proximal to distal portions of the TAODGCV and decreased by increasing the saline flow rate at the same site. To overcome high impedance, we implemented the following strategies: (1) Reset the upper limit impedance to 300 Ω and accelerate the saline flow rate to 60 mL/min (effective in 118 of 144 patients); (2) turn off the upper limit impedance (effective in eleven of 21 patients); (3) use high-flow-rate irrigation devices (effective in five of 15 patients); and (4) increase the upper limit temperature (effective in six of ten patients). (4) Conclusions: In the TAODGCV, local impedance is mainly influenced by the target site location and saline flow rate. We concluded several methods to overcome the high impedance and contribute to a successful ablation. Full article

(1) Background: The present study aims to investigate the effect of administration of Levosimendan and Exenatide in various concentrations, as well as of the coadministration of those agents in an ischemia–reperfusion injury isolated heart model. (2) Methods: After 30 min of perfusion, the hearts underwent a 30 min period of regional ischemia followed by a 120 min period of reperfusion. All animals were randomly divided into 12 experimental groups of nine animals in each group: (1) Control, (2) Sham, (3) Digox (Negative control, Digoxin 1.67 μg/min), (4) Levo 1 (Levosimendan 0.01 μg/min), (5) Levo 2 (Levosimendan 0.03 μg/mL), (6) Levo 3 (Levosimendan 0.1 μg/min), (7) Levo 4 (Levosimendan 0.3 μg/min), (8) Levo 5 (Levosimendan 1 μg/min), (9) Exen 1 (Exenatide 0.001 μg/min), (10) Exen 2 (Exenatide 0.01 μg/min), (11) Exen 3 (Exenatide 0.1 μg/min) and (12) Combi (Levosimendan 0.1 µg/mL + Exenatide 0.001 μg/min). The hemodynamic parameters were recorded throughout the experiment. Arrhythmias and coronary flow were also evaluated. After every experiment the heart was suitably prepared and infarct size was measured. Markers of myocardial injury were also measured. Finally, oxidative stress was evaluated measuring reactive oxygen species. (3) Results: A dose-dependent improvement of the haemodynamic response was observed after the administration of both Levosimendan and Exenatide. The coadministration of both agents presented an even greater effect, improving the haemodynamic parameters further than the two agents separately. Levosimendan offered an increase of the coronary flow and both agents offered a reduction of arrhythmias. A dose-dependent reduction of the size of myocardial infarction and myocardial injury was observed after administration of Levosimendan and Exenatide. The coadministration of both agents offered a further improving the above parameters. Levosimendan also offered a significant reduction of oxidative stress. (4) Conclusions: The administration of Levosimendan and Exenatide offers a significant benefit by improving the haemodynamic response, increasing the coronary flow and reducing the occurrence of arrhythmias, the size of myocardial injury and myocardial oxidative stress in isolated rat hearts. Full article

Abnormal aortic arches (AAAs) cover a spectrum of malformations, including abnormal laterality, branching patterns, and flow-limiting narrowing, which themselves vary from tubular hypoplasia, through discrete coarctation, to complete interruption of the arch. Neonatal surgery within the first days of life is necessary for most of these morphologies. Patch aortoplasty is widely used as it can offer a good haemodynamic result, being tailored to each combination of presenting pathologies. Our study hypothesis was that arch malformations are frequent in DORV and exhibit a plethora of phenotypes. We reviewed 54 post-mortem heart specimens from the UCL Cardiac Archive, analysing morphological features that would potentially influence the surgical repair, and taking relevant measurements of surgical importance. AAAs were found in half of the specimens, including 22.2% with aortic arch narrowing. In total, 70% and 30% of narrow arches had a subpulmonary and subaortic interventricular defect, respectively. Z-scores were significantly negative for all cases with tubular hypoplasia. We concluded that arch malformations are a common finding among hearts with DORV. Surgery on the neonatal aortic arch in DORV, performed in conjunction with other interventions that aim to balance pulmonary to systemic flow (Qp/Qs), should be anticipated and form an important part of multi-modal imaging. Full article

Almost 30 years after the first endoscopic mitral valve repair, Minimally Invasive Mitral Valve Surgery (MIMVS) has become the standard at many institutions due to optimal clinical results and fast recovery. The question that arises is can already good results be further improved by an Institutional Risk Management Performance (IRMP) system in decreasing risks in minimally invasive mitral valve surgery (MIMVS)? As of yet, there are no reports on IRMP and learning systems in the literature. (2) Methods: We described and appraised our five-year single institutional experience with MIMVS in isolated valve surgery included in the Netherlands Heart Registry (NHR) and investigated root causes of high-impact complications. (3) Results: The 120-day and 12-month mortality were 1.1% and 1.9%, respectively, compared to the average of 4.3% and 5.3% reported in the NHR. The regurgitation rate was 1.4% compared to 5.2% nationwide. The few high-impact complications appeared not to be preventable. (4) Discussion: In MIMVS, freedom from major and minor complications is a strong indicator of an effective IRMP but remains concealed from physicians and patients, despite its relevance to shared decision making. Innovation adds to the complexity of MIMVS and challenges surgical competence. An IRMP system may detect and control new risks earlier. (5) Conclusion: An IRMP system contributes to an effective reduction of risks, pain and discomfort; provides relevant input for shared decision making; and warrants the safe introduction of new technology. Crossroads conclusions: investment in machine learning and AI for an effective IRMP system is recommended and the roles for commanding and operating surgeons should be considered. Full article

Pulmonary arterial hypertension (PAH) is a vasoconstrictive disease of the distal pulmonary vasculature resulting in adverse right heart remodeling. Pregnancy in PAH patients is associated with high maternal morbidity and mortality as well as neonatal and fetal complications. Pregnancy-associated changes in the cardiovascular, pulmonary, hormonal, and thrombotic systems challenge the complex PAH physiology. Due to the high risks, patients with PAH are currently counseled against pregnancy based on international consensus guidelines, but there are promising signs of improving outcomes, particularly for patients with mild disease. For patients who become pregnant, multidisciplinary care at a PAH specialist center is needed for peripartum monitoring, medication management, delivery, postpartum care, and complication management. Patients with PAH also require disease-specific counseling on contraception and breastfeeding. In this review, we detail the considerations for reproductive planning, pregnancy, and delivery for the multidisciplinary care of a patient with PAH. Full article

Cardiotoxicity is a significant complication of chemotherapeutic agents in cancer patients. Cardiovascular incidents including LV dysfunction, heart failure (HF), severe arrhythmias, arterial hypertension, and death are associated with high morbidity and mortality. Risk stratification of cancer patients prior to initiation of chemotherapy is crucial, especially in high-risk patients for cardiotoxicity. The early identification and management of potential risk factors for cardiovascular side effects seems to contribute to the prevention or minimization of cardiotoxicity. Screening of cancer patients includes biomarkers such as cTnI and natriuretic peptide and imaging measurements such as LV function, global longitudinal strain, and cardiac MRI. Cardioprotective strategies have been investigated over the last two decades. These strategies for either primary or secondary prevention include medical therapy such as ACE inhibitors, ARBs, b-blockers, aldosterone antagonists, statins and dexrazoxane, physical therapy, and reduction of chemotherapeutic dosages. However, data regarding dosages, duration of medical therapy, and potential interactions with chemotherapeutic agents are still limited. Collaboration among oncologists, cardiologists, and cardio-oncologists could establish management cardioprotective strategies and approved follow-up protocols in patients with cancer receiving chemotherapy. Full article

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a crucial factor in the development and progression of cardiovascular diseases. PCSK9 has been demonstrated to modify LDL plasma levels and increase platelet activation, which promotes atherosclerosis, a defining feature of nearly all cardiovascular diseases. Platelet activation has been shown to promote and maintain the response to atherosclerosis development, from beginning to progression and exacerbation, which can lead to advanced cardiovascular events including myocardial infarction (MI) or death. Research on PCSK9 and platelet activation is currently underway with the main goal of reducing the risk of advanced cardiovascular events by preventing or slowing down atherosclerosis progression. Both in vitro and in vivo studies have been used to explore PCSK9 functions to develop new drugs targeting PCSK9. Finding the most suitable study models that represent the pathological and physiological systems found in humans is very important to achieving the goal. This review aimed to present a current and comprehensive overview of the experimental models that have been used to investigate the role of PCSK9 in platelet activation-induced atherosclerotic cardiovascular diseases. Full article

The implantation of cardiac devices significantly reduces morbidity and mortality in patients with cardiac arrhythmias. Arrhythmias as well as therapy delivered by the device may impact quality of life of patients concerned considerably. Therefore we aimed at conducting a systematic search and meta-analysis of trials examining the impact of the implantation of cardiac devices, namely implantable cardioverter-defibrillators (ICD), pacemakers and left-ventricular assist devices (LVAD) on quality of life. After pre-registering the trial with the PROSPERO database, we searched Medline, PsycINFO, Web of Science and the Cochrane databases for relevant publications. Study quality was assessed by two independent reviewers using standardized protocols. A total of 37 trials met our inclusion criteria. Of these, 31 trials were cohort trials while 6 trials used a randomized controlled design. We found large pre-post effect sizes for positive associations between quality of life and all types of devices. The effect sizes for LVAD, pacemaker and ICD patients were g = 1.64, g = 1.32 and g = 0.64, respectively. There was a lack of trials examining the effect of implantation on quality of life relative to control conditions. Trials assessing quality of life in patients with cardiac devices are still scarce. Yet, the existing data suggest beneficial effects of cardiac devices on quality of life. We recommend that clinical trials on cardiac devices routinely assess quality of life or other parameters of psychological well-being as a decisive study endpoint. Furthermore, improvements in psychological well-being should influence decisions about implantations of cardiac devices and be part of patient education and may impact shared decision-making. Full article

Heart failure (HF) is a significant cause of morbidity and mortality worldwide. HF with preserved ejection fraction (HFpEF) is a complex syndrome, often participated by several cardiac and extracardiac conditions, including chronic kidney disease, pulmonary disease, anaemia and advanced age. Circulating biomarkers reflecting pathophysiological pathways involved in HFpEF development and progression may assist clinicians in early diagnosis and management of this condition. Natriuretic peptides (NPs) are cardioprotective hormones released by cardiomyocytes in response to pressure or volume overload and in response to activation of neuro-endocrine-immune system. The relevance of B-type NP (BNP) and N-terminal pro-B-type NP (NT-proBNP) for diagnosis and risk stratification has been extensively demonstrated, and these biomarkers are emerging tools for population screening and as guides to the start of treatment in subclinical HF. On the contrary, conflicting evidence exists on the value of NPs to guide HF therapy. Among the other biomarkers, high-sensitivity troponins and soluble suppression of tumorigenesis-2 are the most promising biomarkers for risk stratification, predicting outcome independently from NPs. In this review, some novel biomarkers are being tested in such clinical scenario, more tightly linked to specific pathophysiological processes of cardiac damage. Full article

Background: The purpose of this study was to evaluate the risk of cardiovascular mortality (CVM) among patients with bladder cancer (BC). Methods and Materials: Data were collected from the Surveillance, Epidemiology, and End Results (SEER) database for patients who were diagnosed with BC by pathology between 2000 and 2016. The standardized mortality rate (SMR) was calculated based on reference data from the general population. Nelson–Aalen cumulative hazard curves were used to assess the risk of experiencing CVM in BC patients. Multivariate competing risk models were performed. Results: In total, data from 237,563 BC patients were obtained from the SEER database for further analysis, of which 21,822 patients experienced CVM; the overall SMR for CVM in BC patients was 1.16 (95% CI: 1.14–1.17). Age, race, sex, year of diagnosis, histologic type, summary stage, surgery, marital status, and college education level were independent predictors of CVM in patients with BC. Conclusions: Patients with BC have a significantly increased risk of experiencing CVM compared to the general population. Pre-identification of high-risk groups and cardiovascular protection interventions are important measures to effectively improve survival in this group of patients. Full article

Aim: Evaluate the influence of doxycycline, an anti-inflammatory and matrix metalloproteinase (MMP) inhibitor, on the attenuation of chronic doxorubicin-induced cardiotoxicity in rats. Methods: We allocated male Wistar rats into four groups: control (C), doxorubicin (D), doxycycline (inhibitor of MMP, IM), and Dox + doxycycline (DIM). Groups IM and DIM received doxycycline (5 mg/kg, IP) once a week for 4 weeks. In addition, 48 h after every doxycycline injection, groups D and DIM received Dox (5 mg/kg, IP). We performed echocardiogram and evaluated TIMP-4 and collagen I protein expression, MMP-2 activity, and oxidative stress and myocardial metabolism. Results: Doxorubicin promotes left atrium (LA) and left ventricle (LV) dilatation and decreases in LV fractional shortening, which was improved by doxycycline. Moreover, doxycycline attenuated the LV cardiomyocyte hypertrophy and collagen type I expression. Doxorubicin increased phosphofructokinase and decreased beta-hydroxyacyl Co-A dehydrogenase, pyruvate dehydrogenase, citrate synthase, and ATP synthase activity, which was partially attenuated by doxycycline. Lastly, doxycycline improved antioxidant enzyme activity in the DIM group. Conclusion: Doxorubicin increases oxidative stress and promotes changes in myocardial energy metabolism, accompanied by structural and functional changes. Doxycycline attenuated the doxorubicin-induced cardiotoxicity, at least in part, through changes in myocardial energy metabolism. Full article