J. Cardiovasc. Dev. Dis., Volume 8, Issue 6 (June 2021) – 13 articles

We present the case of a 45-year-old woman admitted to our unit with acute heart failure and cardiogenic shock, requiring an intra-aortic balloon pump insertion and inotropes and vasopressors infusion. Despite such treatment, the patient developed multi organ failure and intravascular disseminated coagulation with haemolysis. The initial diagnosis of acute myocarditis was subsequently denied by the finding of bilateral adrenal masses by MRI scan, and urine and plasma metanephrines measurements confirmed a pheochromocytoma (PCC). Genetic analysis revealed a mutation in the neurofibromatosis type 1 (NF1) gene, and an accurate physical examination drew attention to small cafè-au-lait spots, usually associated with this syndrome. PCC diagnosis should be promptly considered in patients presenting with unexplained acute heart failure and cardiogenic shock of unknown origin, considering its life-threatening complications and the good prognosis after radical surgery. Full article

The electrophysiological signatures of the myocardium in cardiac structures, such as the atrioventricular node, pulmonary veins or the right ventricular outflow tract, are established during development by the spatial and temporal expression of transcription factors that guide expression of specific ion channels. Genome-wide association studies have shown that small variations in genetic regions are key to the expression of these transcription factors and thereby modulate the electrical function of the heart. Moreover, mutations in these factors are found in arrhythmogenic pathologies such as congenital atrioventricular block, as well as in specific forms of atrial fibrillation and ventricular tachycardia. In this review, we discuss the developmental origin of distinct electrophysiological structures in the heart and their involvement in cardiac arrhythmias. Full article

Transcatheter left atrial appendage occlusion (LAAO) is non-inferior to vitamin K antagonists (VKAs) in preventing thromboembolic events in atrial fibrillation (AF). Non-vitamin K antagonists (NOACs) have an improved safety profile over VKAs; however, evidence regarding their effect on cardiovascular and neurological outcomes relative to LAAO is limited. Up-to-date randomized trials or propensity-score-matched data comparing LAAO vs. NOACs in high-risk patients with AF were pooled in our study. A total of 2849 AF patients (LAAO: 1368, NOACs: 1481, mean age: 75 ± 7.5 yrs, 63.5% male) were enrolled. The mean CHA2DS2-VASc score was 4.3 ± 1.7, and the mean HAS-BLED score was 3.4 ± 1.2. The baseline characteristics were comparable between the two groups. In the LAAO group, the success rate of device implantation was 98.8%. During a mean follow-up of 2 years, as compared with NOACs, LAAO was associated with a significant reduction of ISTH major bleeding (p = 0.0002). There were no significant differences in terms of ischemic stroke (p = 0.61), ischemic stroke/thromboembolism (p = 0.63), ISTH major and clinically relevant minor bleeding (p = 0.73), cardiovascular death (p = 0.63), and all-cause mortality (p = 0.71). There was a trend toward reduction of combined major cardiovascular and neurological endpoints in the LAAO group (OR: 0.84, 95% CI: 0.64–1.11, p = 0.12). In conclusion, for high-risk AF patients, LAAO is associated with a significant reduction of ISTH major bleeding without increased ischemic events, as compared to “contemporary NOACs”. The present data show the superior role of LAAO over NOACs among high-risk AF patients in terms of reduction of major bleeding; however, more randomized controlled trials are warranted. Full article

Society and medical practice have been restructured dramatically to avoid further spread of the COVID-19 virus; telehealth/telemedicine, mask wearing, and nationwide social distancing practices have become widespread. However, we still face unprecedented challenges in fields where patients require frequent and active follow-up visits for monitoring, including that of solid-organ transplant, and in particular, heart transplant. Adherence to immunosuppression remains a unique challenge in heart transplantation, especially during the COVID-19 pandemic. Failure to adhere to immunosuppression can have disastrous consequences, including graft rejection and death. In this article, we discuss challenges related to adherence to immunosuppression medications among heart transplant recipients, as well as opportunities to leverage digital approaches and interventions to monitor and optimize adherence behavior and health outcomes in this population. Full article

Both cannabis and amphetamine are the most commonly used illegal substances worldwide and are associated with a number of adverse cardiovascular effects including transient coronary vasospasm. Here, we present the case of a 39-year-old male admitted to our institution with a 6-h history of severe chest pain and ST-segment elevation on the ECG. Coronary angiography on admission showed normal coronary arteries. The patient had a 14-year history of substance abuse, primarily amphetamine and cannabis, and was prescribed lisdexamfetamin (Aduvanz^®) for attention deficit hyperactivity disorder (ADHD) for the past 2 years. A cardiac magnetic resonance (CMR) the following day showed widely distributed focal lesions of late gadolinium enhancement in mid- and sub-epicardial myocardium in the anterior, lateral and inferior walls, suggestive of chronic fibrotic lesions. There was no sign of acute myocardial edema. No viral cause was identified during a thorough investigation, including negative SARS-COV-2 and endomyocardial biopsy. Substance-abuse-induced coronary vasospasm leading to ST-segment elevation, myocardial damage with a rise and fall of cardiac TnT, as well as a slightly reduced left ventricular ejection fraction (48%) and regional wall motion abnormalities on echocardiography, was the most likely diagnosis. Full article

Although cardiovascular complications are common in hospitalized COVID-19 patients, those with milder cases who recovered at home are less studied. Here, we report the case of a young woman who recently recovered from COVID-19 at home. A week after recovery, she was admitted to our institution with acute chest pain, signs of ischemia on the electrocardiogram and elevated cardiac troponins. Coronary angiography showed normal epicardial coronary arteries, but the cardiac magnetic resonance showed transmural late gadolinium enhancement (LGE) in the mid-ventricular level of the lateral wall. The findings were strongly suggestive of a minor transmural myocardial infarction. This case report highlights the role of multimodality imaging in detecting cardiac injury in COVID-19 patients as well as the fact that mild COVID-19 cases who recovered at home are also exposed to thromboembolic events during the convalescent period. Full article

Current prognostic risk scores for transcatheter aortic valve implantation (TAVI) do not benefit yet from modern machine learning techniques, which can improve risk stratification of one-year mortality of patients before TAVI. Despite the advancement of machine learning in healthcare, data sharing regulations are very strict and typically prevent exchanging patient data, without the involvement of ethical committees. A very robust validation approach, including 1300 and 631 patients per center, was performed to validate a machine learning model of one center at the other external center with their data, in a mutual fashion. This was achieved without any data exchange but solely by exchanging the models and the data processing pipelines. A dedicated exchange protocol was designed to evaluate and quantify the model’s robustness on the data of the external center. Models developed with the larger dataset offered similar or higher prediction accuracy on the external validation. Logistic regression, random forest and CatBoost lead to areas under curve of the ROC of 0.65, 0.67 and 0.65 for the internal validation and of 0.62, 0.66, 0.68 for the external validation, respectively. We propose a scalable exchange protocol which can be further extended on other TAVI centers, but more generally to any other clinical scenario, that could benefit from this validation approach. Full article

The heart is laterally asymmetric. Not only is it positioned on the left side of the body but the organ itself is asymmetric. This patterning occurs across scales: at the organism level, through left–right axis patterning; at the organ level, where the heart itself exhibits left–right asymmetry; at the cellular level, where gene expression, deposition of matrix and proteins and cell behaviour are asymmetric; and at the molecular level, with chirality of molecules. Defective left–right patterning has dire consequences on multiple organs; however, mortality and morbidity arising from disrupted laterality is usually attributed to complex cardiac defects, bringing into focus the particulars of left–right patterning of the heart. Laterality defects impact how the heart integrates and connects with neighbouring organs, but the anatomy of the heart is also affected because of its asymmetry. Genetic studies have demonstrated that cardiac asymmetry is influenced by left–right axis patterning and yet the heart also possesses intrinsic laterality, reinforcing the patterning of this organ. These inputs into cardiac patterning are established at the very onset of left–right patterning (formation of the left–right organiser) and continue through propagation of left–right signals across animal axes, asymmetric differentiation of the cardiac fields, lateralised tube formation and asymmetric looping morphogenesis. In this review, we will discuss how left–right asymmetry is established and how that influences subsequent asymmetric development of the early embryonic heart. In keeping with the theme of this issue, we will focus on advancements made through studies using the zebrafish model and describe how its use has contributed considerable knowledge to our understanding of the patterning of the heart. Full article

Background and aims: Chronic inflammation associated with the uncontrolled activation of innate and acquired immunity plays a fundamental role in all stages of atherogenesis. Monocytes are a heterogeneous population and each subset contributes differently to the inflammatory process. A high level of lipoprotein(a) (Lp(a)) is a proven cardiovascular risk factor. The aim of the study was to investigate the association between the increased concentration of Lp(a) and monocyte subpopulations in patients with a different severity of coronary atherosclerosis. Methods: 150 patients (124 males) with a median age of 60 years undergoing a coronary angiography were enrolled. Lipids, Lp(a), autoantibodies, blood cell counts and monocyte subpopulations (classical, intermediate, non-classical) were analyzed. Results: The patients were divided into two groups depending on the Lp(a) concentration: normal Lp(a) < 30 mg/dL (n = 82) and hyperLp(a) ≥ 30 mg/dL (n = 68). Patients of both groups were comparable by risk factors, autoantibody levels and blood cell counts. In patients with hyperlipoproteinemia(a) the content (absolute and relative) of non-classical monocytes was higher (71.0 (56.6; 105.7) vs. 62.2 (45.7; 82.4) 10³/mL and 17.7 (13.0; 23.3) vs. 15.1 (11.4; 19.4) %, respectively, p < 0.05). The association of the relative content of non-classical monocytes with the Lp(a) concentration retained a statistical significance when adjusted for gender and age (r = 0.18, p = 0.03). The severity of coronary atherosclerosis was associated with the Lp(a) concentration as well as the relative and absolute (p < 0.05) content of classical monocytes. The high content of non-classical monocytes (OR = 3.5, 95% CI 1.2–10.8) as well as intermediate monocytes (OR = 8.7, 2.5–30.6) in patients with hyperlipoproteinemia(a) were associated with triple-vessel coronary disease compared with patients with a normal Lp(a) level and a low content of monocytes. Conclusion: Hyperlipoproteinemia(a) and a decreased quantity of classical monocytes were associated with the severity of coronary atherosclerosis. The expansion of CD16+ monocytes (intermediate and non-classical) in the presence of hyperlipoproteinemia(a) significantly increased the risk of triple-vessel coronary disease. Full article

An association between movement behavior (MB) components (sleep time (ST), physical activity (PA) and sedentary behavior (SB)) and the state of the cardiovascular (CV) system in children has been postulated. However, it is still controversial whether MB components and/or sub-components (domains) during childhood are independently associated with aortic and peripheral blood pressure (BP), and structural or functional arterial properties. Aims: (1) to evaluate MB components and subcomponents associations with CV characteristics, (2) to analyze the explanatory capacity of interindividual variations in MB on CV properties inter-individual variations at the beginning of school age. Methods: Anthropometric, aortic and peripheral BP, hemodynamic levels (cardiac output, systemic vascular resistances), wave reflection indexes, and arterial structural (diameter, intima–media thickness) and functional (blood flow velocities, Doppler-indexes, local and regional arterial stiffness) parameters of elastic (carotids), transitional (brachial) and muscular (femoral) arteries and time spent in MB (PA questionnaires) were assessed in 816 children (5–6 years). Cardiovascular variables were standardized (z-scores), using age- and sex-related mean values and standard deviations obtained from subjects non-exposed to CV risk factors (CRFs) and who complied with 24 h MB recommendations (reference subgroup). Multiple linear regression models were constructed considering the CV z-scores as dependent variables and CRFs and MB components and subcomponents as independent variables. Results: CV variables showed independent association with MB variations. However, their explanatory capacity on CV characteristics was lesser than that of anthropometric indexes, sex and/or high BP. Conclusions: MB components and sub-components were associated with CV characteristics regardless of other factors, but their capacity to explain variations was lesser than that of anthropometric data, sex or high BP state. MB subcomponents (e.g., sedentary play and screen time in case of SB) showed different (even opposite) associations with CV parameters. ST was associated mainly with indexes of the ventricle ejective function, rather than with CV structural characteristics. SB component and subcomponents were associated with BP, but not with structural parameters. PA component and subcomponents were associated with both BP and structural parameters. The different arterial types, as well central and peripheral parameters showed independent associations with MB components and subcomponents. None of these were independently associated with arterial stiffness. Full article

Background: Transcatheter ablation is the standasrd treatment for atrioventricular nodal re-entrant tachycardia (AVNRT). However, different techniques are available. Data about the use of irrigated flexible-tip catheters and three-dimensional electroanatomical mapping (3D EAM) for AVNRT ablation are scant. The aim of this study was to evaluate in long-term follow-up efficacy and safety of a novel approach for AVNRT treatment. Methods: This is a cohort single arm study with long-term follow-up. Patients with AVNRT were treated with catheter ablation by means of irrigated flexible-tip catheters combined with 3D EAM. Results: One-hundred-and-fifty patients were enrolled and followed-up for a median of 38 months (minimum 12, maximum 74). Acute procedural success rate was 96.7% (145/150 patients). During follow-up, 11 patients had arrhythmia recurrences (7.3%). No patient developed atrioventricular conduction block with need for pacemaker implantation (0%). Fourteen patients died during follow-up (9.3%). Conclusions: Acute procedural success and long-term follow-up show that AVNRT could be safely and effectively treated with irrigated flexible-tip catheters and 3D EAM. Full article

Patent foramen ovale (PFO) is a common congenital atrial septal defect with an incidence of 15–35% in the adult population. The development of the interatrial septum is a process that begins in the fourth gestational week and is completed only after birth. During intrauterine life, the foramen ovale allows the passage of highly oxygenated blood from the right to the left atrium and into the systemic arteries, thus bypassing the pulmonary circulation. In 75% of the general population, the foramen ovale closes after birth, and only an oval depression, called fossa ovalis, remains on the right side of the interatrial septum. Patent foramen ovale can be associated with various clinically important conditions, including migraine and stroke, or decompression illness in divers. The aim of this review is to summarize the PFO developmental and anatomical features and to discuss the clinical risks associated with this atrial septal defect in adults. Full article

Patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) may demonstrate distal microvascular embolization of thrombotic materials. We retrospectively examined 20 cases displaying extensive thrombus in the infarct-related artery (IRA), treated either with a two-step procedure, with interim tirofiban infusion, or immediate stent implantation. Distal embolization tended to be more common in the latter strategy, but, overall, the outcome was comparable. Thus, a two-staged procedure may be considered in selected cases of primary PCI associated with high thrombus burden. Full article