J. Cardiovasc. Dev. Dis., Volume 10, Issue 12 (December 2023) – 29 articles

Endovascular therapy (EVT) has revolutionized the management of acute ischaemic strokes with large vessel occlusion, with emerging evidence suggesting its benefit also in large infarct core volume strokes. In the last two years, four randomised controlled trials have been published on this topic—RESCUE-Japan LIMIT, ANGEL-ASPECT, SELECT2 and TENSION, with overall results showing that EVT improves functional and neurological outcomes compared to medical management alone. This review aims to summarise the recent evidence presented by these four trials and highlight some of the limitations in our current understanding of this topic. Full article

Background: Chronic obstructive pulmonary disease-associated pulmonary hypertension (PH-COPD) results in a significant impact on symptoms, quality of life, and survival. There is scant and conflicting evidence about the use of pulmonary hypertension (PH) specific therapy in patients with PH-COPD. Study Design and Methods: PubMed, OVID, CINAHL, Cochrane, Embase, and Web of Science were searched using various MESH terms to identify randomized controlled trials (RCTs) or observational studies investigating PH-specific therapies in patients with severe PH-COPD, defined by mean pulmonary artery pressure (mPAP) of more than 35 mm Hg or pulmonary vascular resistance (PVR) of more than 5 woods units on right heart catheterization. The primary outcome was a change in mPAP and PVR. Secondary outcomes were changes in six-minute walk distance (6MWD), changes in the brain-natriuretic peptide (BNP), New York Heart Association (NYHA) functional class, oxygenation, and survival. Results: Thirteen studies satisfied the inclusion criteria, including a total of 328 patients with severe PH-COPD. Out of these, 308 patients received some type of specific therapy for PH. There was a significant reduction in mPAP (mean difference (MD) −3.68, 95% CI [−2.03, −5.32], p < 0.0001) and PVR (MD −1.40 Wood units, 95% CI [−1.97, −0.82], p < 0.00001). There was a significant increase in the cardiac index as well (MD 0.26 L/min/m², 95% CI [0.14, 0.39], p < 0.0001). There were fewer patients who had NYHA class III/lV symptoms, with an odds ratio of 0.55 (95% CI [0.30, 1.01], p = 0.05). There was no significant difference in the 6MWD (12.62 m, 95% CI [−8.55, 33.79], p = 0.24), PaO₂ (MD −2.20 mm Hg, 95% CI [−4.62, 0.22], p = 0.08), or BNP or NT-proBNP therapy (MD −0.15, 95% CI [−0.46, 0.17], p = 0.36). Conclusion: The use of PH-specific therapies in severe PH-COPD resulted in a significant reduction in mPAP and PVR and increased CI, with fewer patients remaining in NYHA functional class III/IV. However, no significant difference in the 6MWD, biomarkers of right ventricular dysfunction, or oxygenation was identified, demonstrating a lack of hypoxemia worsening with treatment. Further studies are needed to investigate the use of PH medications in patients with severe PH-COPD. Full article

Introduction: The prenatal diagnosis of congenital heart disease (CHD) is a traumatic event that can cause expectant parents to experience anxiety, depression, and toxic stress. Prenatal exposure to stress may impact neonatal postoperative outcomes. In addition, expectant parents may have other psychosocial stressors that may compound maternal stress. We investigated the relationship between stress in pregnancies complicated by prenatally diagnosed CHD and their neonatal outcomes. Methods: A pilot retrospective cohort study of pregnancies with prenatally diagnosed critical CHD (2019–2021) was performed. The collected data included pregnancy characteristics and neonatal and postoperative outcomes (including the need for exogenous corticosteroid treatment (ECT)). In order to quantify prenatal stressors, a composite prenatal stress score (PSS) was established and utilized. Results: In total, 41 maternal–fetal dyads were evaluated. Thirteen (32%) neonates had single-ventricle anatomy. The need for ECT after CHD surgery was associated with higher pregnant patient PSS (p = 0.01). PSS did not correlate with birthweight, infection, or hypoglycemia in the neonatal period. Conclusions: Prenatal stress is multifactorial; higher PSS is correlates with post-bypass ECT, suggesting that a stressful intrauterine environment may be associated with worse neonatal postoperative outcomes. Full article

Background: Iatrogenic distal coronary artery perforation can be a life-threatening complication. While there are different dedicated devices for the embolization of distal perforations, there are scarce data about the embolization using the fragmented balloon catheter, the so-called cut balloon technique (CBT). Methods: We included consecutive patients with distal coronary perforations treated with CBT in four cardiac centers between 2017 and 2023. Clinical, angiographic and procedural characteristics as well as in-hospital outcomes were recorded. Results: Twenty-six patients (68% men, mean age: 71 ± 10.6 years) with 25 distal coronary perforations and one septal collateral perforation were included. Eleven patients (42%) had elective percutaneous coronary intervention, while fifteen patients (58%) were treated for acute coronary syndrome. The site of perforation was most frequently distributed in the left anterior descending artery (40%), followed by the circumflex artery (28%) and right coronary artery (24%). The diameter of balloons for CBT ranged from 1.5 to 4.0 mm, with most balloons (76%) being either 2.0 or 2.5 mm in diameter. Most balloons (88%) were previously used for lesion predilatation. The numbers of cut balloons needed to seal the perforation were 1, 2 and ≥3 in 48%, 20% and 32% of cases, respectively. The in-hospital prognosis was favorable, with cardiac tamponade requiring pericardiocentesis in only four (16%) patients. Neither emergency surgery nor cardiac death occurred. Conclusions: CBT is a safe, efficient and easy-to-implement technique for the embolization of coronary perforations. Most distal coronary perforations can be sealed with one or two fragments of cut balloons, obviating the need for additional devices. Full article

Ischemic stroke is a heterogeneous condition influenced by a combination of genetic and environmental factors. Recent advancements have explored genetics in relation to various aspects of ischemic stroke, including the alteration of individual stroke occurrence risk, modulation of treatment response, and effectiveness of post-stroke functional recovery. This article aims to review the recent findings from genetic studies related to various clinical and molecular aspects of ischemic stroke. The potential clinical applications of these genetic insights in stratifying stroke risk, guiding personalized therapy, and identifying new therapeutic targets are discussed herein. Full article

The genetic model system Drosophila has contributed fundamentally to our understanding of mammalian heart specification, development, and congenital heart disease. The relatively simple Drosophila heart is a linear muscular tube that is specified and develops in the embryo and persists throughout the life of the animal. It functions at all stages to circulate hemolymph within the open circulatory system of the body. During Drosophila metamorphosis, the cardiac tube is remodeled, and a new layer of muscle fibers spreads over the ventral surface of the heart to form the ventral longitudinal muscles. The formation of these fibers depends critically upon genes known to be necessary for mammalian second heart field (SHF) formation. Here, we review the prior contributions of the Drosophila system to the understanding of heart development and disease, discuss the importance of the SHF to mammalian heart development and disease, and then discuss how the ventral longitudinal adult cardiac muscles can serve as a novel model for understanding SHF development and disease. Full article

Over the past 50 years, there has been a major shift in age distribution of patients with congenital heart disease (CHD) thanks to significant advancements in medical and surgical treatment. Patients with CHD are, however, never cured and face unique challenges throughout their lives. In this review, we discuss the growing data suggesting accelerated aging in this population. Adults with CHD are more often and at a younger age confronted with age-related cardiovascular complications such as heart failure, arrhythmia, and coronary artery disease. These can be related to the original birth defect, complications of correction, or any residual defects. In addition, and less deductively, more systemic age-related complications are seen earlier, such as renal dysfunction, lung disease, dementia, stroke, and cancer. The occurrence of these complications at a younger age makes it imperative to further map out the aging process in patients across the spectrum of CHD. We review potential feasible markers to determine biological age and provide an overview of the current data. We provide evidence for an unmet need to further examine the aging paradigm as this stresses the higher need for care and follow-up in this unique, newly aging population. We end by exploring potential approaches to improve lifespan care. Full article

Background: Depression and anxiety occur more frequently in women and are associated with an increased risk of cardiovascular disease. Objectives: Data on the association between these psychiatric conditions and the incidence of acute heart failure (HF) and how they influence heart failure outcomes in women are lacking. We investigated this potential relationship using data from the National Inpatient Sample. Methods: We used ICD-10 codes to extract encounters for acute heart failure and/or the acute exacerbation of chronic heart failure, anxiety, and depression from the discharge data of the NIS from 2019 to 2020. We compared baseline characteristics and length of stay (LOS), cost of care (COC) and acute HF by depression/anxiety status for males and females and employed regression models to assess the influence of these psychiatric conditions on the outcomes. Results: There were 6,394,136 encounters involving females, which represented 56.6% of the sample. The prevalence of depression and anxiety were 15.7% and 16.8%, respectively. Among females, the occurrence of acute CHF did not differ by depression or anxiety status. However, Takostubo cardiomyopathy was more prevalent in those with depression (0.3% vs. 0.2%, p = 0.003) and anxiety (0.3% vs. 0.2%, p = 0.03) compared to those without these conditions. Among those with depression, LOS was significantly longer (3 days IQR: 2–6, vs. 3 days IQR:2–5 days, p < 0.001). The COC was USD 1481 more in patients with depression. On the contrary, LOS and COC were significantly lower in those without anxiety. Conclusions: Depression was associated with an increased LOS among both men and women and an increased cost of care among women. Anxiety was associated with a decreased LOS and cost of care among women, which may be related to an increased rate of against medical advice (AMA) discharges among this population. Further research is necessary to identify optimal management strategies for depression and anxiety among patients hospitalized with HF. Full article

Electroporation is used in medicine for drug and gene delivery, and as a nonthermal ablation method in tumor treatment and cardiac ablation. Electroporation involves delivering high-voltage electric pulses to target tissue; however, this can cause effects beyond the intended target tissue like nerve stimulation, muscle contractions and pain, requiring use of sedatives or anesthetics. It was previously shown that adjusting pulse parameters may mitigate some of these effects, but not how these adjustments would affect electroporation’s efficacy. We investigated the effect of varying pulse parameters such as interphase and interpulse delay while keeping the duration and number of pulses constant on nerve stimulation, muscle contraction and assessing pain and electroporation efficacy, conducting experiments on human volunteers, tissue samples and cell lines in vitro. Our results show that using specific pulse parameters, particularly short high-frequency biphasic pulses with short interphase and long interpulse delays, reduces muscle contractions and pain sensations in healthy individuals. Higher stimulation thresholds were also observed in experiments on isolated swine phrenic nerves and human esophagus tissues. However, changes in the interphase and interpulse delays did not affect the cell permeability and survival, suggesting that modifying the pulse parameters could minimize adverse effects while preserving therapeutic goals in electroporation. Full article

Trastuzumab is the primary treatment for all stages of HER2-overexpressing breast cancer in patients. Though discovered over 20 years ago, trastuzumab-induced cardiotoxicity (TIC) remains a research topic in cardio-oncology. This review explores the pathophysiological basis of TIC and its clinical manifestations. Their understanding is paramount for early detection and cardioprotective treatment. Trastuzumab renders cardiomyocytes susceptible by inhibiting the cardioprotective NRG-1/HER2/HER4 signaling pathway. The drug acts on HER2-receptor-expressing cardiomyocytes, endothelium, and cardiac progenitor cells (see the Graphical Abstract). The activation of immune cells, fibroblasts, inflammation, and neurohormonal systems all contribute to the evolution of TIC. A substantial amount of research demonstrates that trastuzumab induces overt and subclinical left ventricular (LV) systolic failure. Data suggest the development of right ventricular damage, LV diastolic dysfunction, and heart failure with preserved ejection fraction. Further research is needed to define a chronological sequence of cardiac impairments to guide the proper timing of cardioprotection implementation. Full article

Heart failure (HF) is a global pandemic affecting over 64 million people worldwide. Its prevalence is on an upward trajectory, with associated increasing healthcare expenditure. Organizations including the American College of Cardiology (ACC) and the American Heart Association (AHA) have identified HF prevention as an important focus. Recently, the ACC/AHA/Heart Failure Society of America (HFSA) Guidelines on heart failure were updated with a new Class IIa, Level of Evidence B recommendation for biomarker-based screening in patients at risk of developing heart failure. In this review, we evaluate the studies that have assessed the various roles and contributions of biomarkers in the prediction and prevention of heart failure. We examined studies that have utilized biomarkers to detect cardiac dysfunction or abnormality for HF risk prediction and screening before patients develop clinical signs and symptoms of HF. We also included studies with biomarkers on prognostication and risk prediction over and above existing HF risk prediction models and studies that address the utility of changes in biomarkers over time for HF risk. We discuss studies of biomarkers to guide management and assess the efficacy of prevention strategies and multi-biomarker and multimodality approaches to improve risk prediction. Full article

This work aimed to study the efficacy and safety of the class III antiarrhythmic agent cavutilide (Niferidil, Refralon) for pharmacological cardioversion in patients with paroxysmal and persistent atrial fibrillation (AF) and heart failure (HF). Methods and Results: In this retrospective cohort study, 58 patients with stable HF (aged 69 [61;73] years, 30 males, 78% with persistent AF) and 274 patients without HF (aged 63 [57;70] years, 196 males, 56% with persistent AF) were included. The median AF duration in the group with HF was 35.5 [10.6;124] days, and that in the group without HF was 14.5 [3.6;90] days. All patients received 5–30 µg/kg cavutilide intravenously in one to four (if needed) boluses of 5–5–10–10 µg/kg at 15 min intervals. Subsequent boluses were not administered if the patient’s sinus rhythm (SR) was restored or if bradycardia, QT prolongation > 500 ms or evidence of proarrhythmia was observed. Holter electrocardiogram monitoring was started before infusion and was continued for 24 h. The main criterion for an antiarrhythmic effect was sinus rhythm restoration within 24 h of the initial bolus. Results: Cavutilide converted AF to SR in 37.9% of patients with HF after bolus 1 (5 µg/kg), in 58.6% after bolus 2 (cumulative dose = 10 µg/kg), in 74% of cases after bolus 3 (cumulative dose = 20 µg/kg) and in 92.8% of cases after bolus 4 (cumulative dose = 30 µg/kg). Cavutilide was effective in 89% of cases with persistent AF with a median duration of 70.5 [30;159] days and in 92% of cases with paroxysmal AF with a median duration of 36 [24;102] h. In the group of patients without HF, the effectiveness of bolus 1 was 36.9%, that of the bolus 2 was 58%, that of the bolus 3 was 77% and that of the bolus 4 was 90.1%. Cavutilide restored SR in 90% of patients with persistent AF with a median duration of 82.5 [28;180] days and in 90% of cases with paroxysmal AF with a median duration of 50 [24;120] h. No statistically significant difference in the probability of SR restoration or the effectiveness of each bolus of cavutilide was found between patients with and without HF. The median time to restoration of SR in patients with HF was 23 [11;55] min, and that in patients without HF was 22 [10;45] min (p = 0.424). No cases of symptomatic/severe bradycardia were observed in either group. QT prolongation over 500 ms after cavutilide injection was registered in 19% of patients without HF and in 15.5% of those with HF (p = 0.58). Short runs of Torsade de pointes tachycardia occurred in one patient (0.4%) without HF after 10 µg cavutilide administration and were successfully treated with MgSO₄. Conclusions: Cavutilide demonstrated a high likelihood of AF conversion to SR in paroxysmal (92%) and persistent (89%) arrhythmia and HF. Concomitant HF and its severity do not affect the efficacy and safety of cavutilide. Full article

The healthcare sector generates approximately 30% of all the world’s data volume, mostly for record keeping, compliance and regulatory requirements, and patient care. Healthcare data often exist in silos or on different systems and platforms due to decentralised storage and data protection laws, limiting accessibility for health service research. Thus, both the lack of access to data and more importantly the inability to control data quality and explore post-trial (phase IV) data or data with translational relevance have an impact on optimising care and research of congestive heart failure (CHF). We highlight that for some diseases, such as CHF, generating non-traditional data has significant importance, but is hindered by the logistics of accessing chronic disease data from separate health silos and by various levels of data quality. Modern multidisciplinary healthcare management of cardiovascular diseases—especially when spanning across community hubs to tertiary healthcare centres—increases the complexities involved between data privacy and access to data for healthcare and health service research. We call for an increased ability to leverage health data across systems, devices, and countries. Full article

Background and Motivation: Coronary artery disease (CAD) has the highest mortality rate; therefore, its diagnosis is vital. Intravascular ultrasound (IVUS) is a high-resolution imaging solution that can image coronary arteries, but the diagnosis software via wall segmentation and quantification has been evolving. In this study, a deep learning (DL) paradigm was explored along with its bias. Methods: Using a PRISMA model, 145 best UNet-based and non-UNet-based methods for wall segmentation were selected and analyzed for their characteristics and scientific and clinical validation. This study computed the coronary wall thickness by estimating the inner and outer borders of the coronary artery IVUS cross-sectional scans. Further, the review explored the bias in the DL system for the first time when it comes to wall segmentation in IVUS scans. Three bias methods, namely (i) ranking, (ii) radial, and (iii) regional area, were applied and compared using a Venn diagram. Finally, the study presented explainable AI (XAI) paradigms in the DL framework. Findings and Conclusions: UNet provides a powerful paradigm for the segmentation of coronary walls in IVUS scans due to its ability to extract automated features at different scales in encoders, reconstruct the segmented image using decoders, and embed the variants in skip connections. Most of the research was hampered by a lack of motivation for XAI and pruned AI (PAI) models. None of the UNet models met the criteria for bias-free design. For clinical assessment and settings, it is necessary to move from a paper-to-practice approach. Full article

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition characterized by the presence of low levels of a monoclonal protein in the serum and a low percentage of clonal plasma cells in the bone marrow. MGUS may progress to multiple myeloma or other plasma cell disorders at a rate of 1% annually. However, MGUS may also have adverse effects on the cardiovascular system independent of its malignant potential. Emerging data have shown that MGUS is associated with cardiovascular disease. The mechanisms underlying this association are not fully understood but may involve genetic abnormalities, vascular calcification, cryoglobulinemia, cold agglutinin disease, autoantibodies and the direct or indirect effects of the monoclonal protein on the vascular endothelium. Herein, we review current evidence in this field and we suggest that patients with MGUS may benefit from regular cardiovascular risk assessment to prevent severe cardiovascular complications, in parallel with close hematological follow-up to monitor potential disease progression. Full article

The transforming growth factor beta (TGFβ) and Hippo signaling pathways are evolutionarily conserved pathways that play a critical role in cardiac fibroblasts during embryonic development, tissue repair, and fibrosis. TGFβ signaling and Hippo signaling are also important for cardiac cushion remodeling and septation during embryonic development. Loss of TGFβ2 in mice causes cardiac cushion remodeling defects resulting in congenital heart disease. In this study, we used in vitro molecular and pharmacologic approaches in the cushion mesenchymal cell line (tsA58-AVM) and investigated if the Hippo pathway acts as a mediator of TGFβ2 signaling. Immunofluorescence staining showed that TGFβ2 induced nuclear translocation of activated SMAD3 in the cushion mesenchymal cells. In addition, the results indicate increased nuclear localization of Yes-associated protein 1 (YAP1) following a similar treatment of TGFβ2. In collagen lattice formation assays, the TGFβ2 treatment of cushion cells resulted in an enhanced collagen contraction compared to the untreated cushion cells. Interestingly, verteporfin, a YAP1 inhibitor, significantly blocked the ability of cushion cells to contract collagen gel in the absence or presence of exogenously added TGFβ2. To confirm the molecular mechanisms of the verteporfin-induced inhibition of TGFβ2-dependent extracellular matrix (ECM) reorganization, we performed a gene expression analysis of key mesenchymal genes involved in ECM remodeling in heart development and disease. Our results confirm that verteporfin significantly decreased the expression of α-smooth muscle actin (Acta2), collagen 1a1 (Col1a1), Ccn1 (i.e., Cyr61), and Ccn2 (i.e., Ctgf). Western blot analysis indicated that verteporfin treatment significantly blocked the TGFβ2-induced activation of SMAD2/3 in cushion mesenchymal cells. Collectively, these results indicate that TGFβ2 regulation of cushion mesenchymal cell behavior and ECM remodeling is mediated by YAP1. Thus, the TGFβ2 and Hippo pathway integration represents an important step in understanding the etiology of congenital heart disease. Full article

Objectives: To assess whether competing risks help explain why regions with initially high serum cholesterol have higher mortality from coronary heart disease (CHD) and lower mortality from stroke and other major heart diseases, while the reverse is found for those with initially lower serum cholesterol. Material and Methods. Ten cohorts of men (N = 9063) initially aged 40–59 in six countries were examined and followed for fatal outcomes for 60 years. Major cardiovascular disease (CVD) groups were CHD, stroke, and other Heart Diseases of Uncertain Etiology (HDUE), or the combination of stroke and HDUE (STHD), along with all other causes of death. Fine-Gray competing risk analysis was applied with CHD versus all other causes of death or STHD (direct mode) and all other causes of death or STHD versus CHD (inverse mode), and the effects of 19 covariates (of which 3 references) on the cause-specific hazard of the outcomes were assessed, thus investigating potential etiologic roles. A systematic comparison with results obtained by running the Cox model in direct and inverse modes with the same end-point results was also performed and illustrated graphically. Results. CHD mortality is bound to different risk factor relationships when compared with all other causes of death and with STHD. The role of serum cholesterol is crucial since, in both comparisons, by Fine-Gray, its coefficients are positive and significant for CHD and negative and significant for all other causes of death and STHD. Risk factor capabilities in specific outcome types of the CVD domain (CHD versus STHD) are different depending on the outcome types considered. Risk factor coefficients are smaller in Fine-Gray modelling and larger in the Cox model. Fine-Gray detects different risk factors whose coefficients may have opposite algebraic signs. Conclusions. This is the first report whereby a large group of risk factors are investigated in connection with life-long CVD outcomes by Fine-Gray competing risk analysis, and a systematic comparison is performed with results obtained by Cox models in both direct and inverse modes. Subtypes of CVD mortality should be summed with full awareness that some risk factors vary by pathology, and they should at least be disentangled into CHD and STHD. Full article

Background: Hypertension challenges arise in part from poor adherence due to inadequate patient education. VR offers immersive learning to improve hypertension knowledge. Objective: To compare VR education with traditional verbal education to improve hypertension knowledge. Methods: In this randomised trial, 182 patients with hypertension were assigned to receive either traditional physician-led education (n = 88) or VR education (n = 94) with equivalent content. The VR group experienced a 3D video using Oculus Quest 2 headsets. Knowledge was assessed post-intervention using a 29-item questionnaire. The primary outcome was the objective score. Subjective satisfaction and responder characteristics were secondary outcomes. Results: Median objective scores were significantly higher for VR (14, IQR 3) versus traditional education (10, IQR 5), p < 0.001, indicating superior hypertension knowledge acquisition with VR. Subjective satisfaction was high in both groups. Participants were categorized into low (first quartile) and medium-high (second to fourth quartiles) responders based on their scores. Low responders had a significantly higher prevalence of older women than medium-high responders (57% vs. 40% female, p = 0.024; 68 vs. 65 years), p = 0.036). Conclusions: VR outperforms traditional education. Tailoring to groups such as older women can optimise learning. Full article

Blood pressure (BP) dynamics during graded exercise testing provide important insights into cardiovascular health, particularly in athletes. These measurements, taken during intense physical exertion, complement and often enhance our understanding beyond traditional resting BP measurements. Historically, the challenge has been to distinguish ‘normal’ from ‘exaggerated’ BP responses in the athletic environment. While basic guidelines have served their purpose, they may not fully account for the complex nature of BP responses in today’s athletes, as illuminated by contemporary research. This review critically evaluates existing guidelines in the context of athletic performance and cardiovascular health. Through a rigorous analysis of the current literature, we highlight the multifaceted nature of exercise-induced BP fluctuations in athletes, emphasising the myriad determinants that influence these responses, from specific training regimens to inherent physiological nuances. Our aim is to advocate a tailored, athlete-centred approach to BP assessment during exercise. Such a paradigm shift is intended to set the stage for evidence-based guidelines to improve athletic training, performance and overall cardiovascular well-being. Full article

Males and females differ in the basic anatomy and physiology of the heart. Sex differences are evident in cardiac repolarization in humans; women have longer corrected QT and JT intervals. However, the molecular mechanisms that lead to these differences are incompletely understood. Here, we present that, like in humans, sex differences in QT and JT intervals exist in mouse models; female mice had longer corrected QT and JT intervals compared with age-matched males. To further understand the molecular underpinning of these sex differences, we developed a novel technology using fluorescent confocal microscopy that allows the simultaneous visualization of action potential, Ca²⁺ transients, and contractions in isolated cardiomyocytes at a high temporal resolution. From this approach, we uncovered that females at baseline have increased action potential duration, decreased Ca²⁺ release and reuptake rates, and decreased contraction and relaxation velocities compared with males. Additionally, males had a shorter overall time from action potential onset to peak contraction. In aggregate, our studies uncovered male and female differences in excitation-contraction coupling that account for differences observed in the EKG. Overall, a better understanding of sex differences in electrophysiology is essential for equitably treating cardiac disease. Full article

The coronavirus disease (COVID)-19 has turned into a pandemic causing a global public health crisis. While acute COVID-19 mainly affects the respiratory system and can cause acute respiratory distress syndrome, an association with persistent inflammatory stress affecting different organ systems has been elucidated in long COVID syndrome (LCS). Increased severity and mortality rates have been reported due to cardiophysiological and metabolic systemic disorders as well as multiorgan failure in COVID-19, additionally accompanied by chronic dyspnea and fatigue in LCS. Hence, novel therapies have been tested to improve the outcomes of LCS of which one potential candidate might be sodium–glucose cotransporter 2 (SGLT2) inhibitors. The aim of this narrative review was to discuss rationales for investigating SGLT2 inhibitor therapy in people suffering from LCS. In this regard, we discuss their potential positive effects—next to the well described “cardio-renal-metabolic” conditions—with a focus on potential anti-inflammatory and beneficial systemic effects in LCS. However, potential beneficial as well as potential disadvantageous effects of SGLT2 inhibitors on the prevalence and long-term outcomes of COVID-19 will need to be established in ongoing research. Full article

Objective: To conduct a systematic review to determine if there are exercise mobile applications (apps) that can produce evidence-based, individualized exercise plans. Materials and Methods: We searched the Apple Store and Google Play for exercise apps with terms related to exercise and health. Exercise apps were eligible if they: (1) had a ≥4 out of 5 overall rating with ≥1000 reviews; (2) were free to download; and (3) were not gender specific. Exercise apps were evaluated via the evidence-based exercise prescription (ExRx) standards of the American College of Sports Medicine (ACSM) and American Heart Association. For the exercise app evaluation criteria, an app was included if it (1) was evidence-based; (2) contained a preparticipation health screening protocol; (3) built a cardiovascular disease (CVD) risk factor profile; (4) prioritized one chronic disease or health condition to focus on; (5) framed the exercise plan by the frequency, intensity, time, and type principle (FITT) of ExRx; and (6) specified special considerations. Results: Of the 531 potentially qualifying apps, 219 qualified. The qualifying apps were rarely evidenced-based (0.5%) or had a preparticipation screening protocol (3.7%). Only 27.7% built CVD risk factor profiles. Most apps (64.8%) focused on body image and/or athletic performance. Only 4.3% focused on chronic diseases or health conditions, while the remainder (34.5%) did not disclose a focus. No app framed the exercise plans by the FITT of ExRx. Only 1.4% of the apps specified special considerations. Conclusion: There are no commercially available exercise apps that generate an evidence-based, individualized exercise plan for adults with CVD risk factors. Full article

Persistent patent ductus arteriosus is a very common condition in preterm infants. Although there is no management agreed by consensus, despite numerous randomized controlled trials, hemodynamically significant patent ductus arteriosus increases morbidity and mortality in these vulnerable patients. Medical treatment is usually offered as first-line therapy, although it carries a limited success rate and potential severe adverse events. In recent years, transcatheter patent ductus arteriosus closure has fast developed and become widely accepted as a safe and efficient alternative to surgical ductal ligation in extremely low birth weight infants >700 g, using most often the dedicated Amplatzer Piccolo Occluder device. This article aims to provide an appraisal of the patients’ selection process, and a step-by-step description of the procedure as well as a comprehensive review of its outcomes. Full article

Unstable and symptomatic complete atrioventricular block represents a potentially fatal condition that requires prompt therapy while waiting for definitive pacemaker implantation. Although transcutaneous pacing is included in acute management, it could be a difficult approach due to its painfulness and the occasional failure of mechanical capture. Drug therapy is a feasible choice, and current guidelines encompass the use of atropine, dopamine, or epinephrine. Isoprenaline has never been investigated in this setting, and no specific indication of its use has been provided despite its potentially more favorable pharmacological profile. The study population included a consecutive series of patients who presented to the emergency department because of unstable third-degree atrioventricular block and were treated with either isoprenaline or dopamine infusion while waiting for definitive pacemaker implantation. Asymptomatic patients or those with reversible causes of complete atrioventricular block were excluded. The clinical response to the drug was deemed poor if, despite achieving a full drug dose, patients remained symptomatic and/or with hemodynamic instability, ventricular rate and rhythm did not improve or worsened, including if ventricular arrhythmias or asystolic pauses and/or irrepressible nausea/vomiting occurred. Isoprenaline infusion has proved to be safe and tolerated with no arrhythmia induction or hypotensive issues. Isoprenaline has also proven to be more satisfactory in achieving an effective clinical response in 84% of patients rather than dopamine (31%, p < 0.001), reducing the need for temporary artificial pacing. Our data point out the efficacy and safety of isoprenaline infusion and its greater tolerability over dopamine in the acute management of unstable third-degree AV block while waiting for definitive pacemaker implantation. Full article

Background: Regional functional left ventricular (LV) assessment using current imaging techniques remains limited. Inward displacement (InD) has been developed as a novel technique to assess regional LV function via measurement of the regional displacement of the LV endocardial border across each of the 17 LV segments. Currently, normal ranges for InD are not available for clinical use. The aim of this study was to validate the normal reference limits of InD in healthy adults across all LV segments. Methods: InD was analyzed in 120 healthy subjects with a normal LV ejection fraction, using the three standard long-axis views obtained during cardiac MRI that quantified the degree of inward endocardial wall motion towards the true LV center of contraction. For all LV segments, InD was measured in mm and expressed as a percentage of the theoretical degree of maximal segment contraction towards the true LV centerline. The arithmetic average InD was obtained for each of the 17 segments. The LV was divided into three regions, obtaining average InD at the LV base (segments 1–6), mid-cavity (segments 7–12) and apex (segments 13–17). Results: Average InD was 33.4 ± 4.3%. InD was higher in basal and mid-cavity LV segments (32.8 ± 4.1% and 38.1 ± 5.8%) compared to apical LV segments (28.6 ± 7.7%). Interobserver variability correlations for InD were strong (R = 0.80, p < 0.0001). Conclusions: We provide clinically meaningful reference ranges for InD in subjects with normal LV function, which will emerge as an important screening and assessment imaging tool for a range of HFrEF therapies. Full article

Background: Coronary collateral flow in angiography has been linked with lower mortality rates in patients with coronary artery disease. However, the relevance of the underlying mechanism is sparse. Therefore, we tested the hypothesis that in patients with acute myocardial infarction (AMI), relevant coronary collateral flow is associated with more salvaged myocardium and lower risk of developing heart failure. Methods and Results: Patients with first AMI who received a percutaneous coronary intervention within 24 h after symptom onset were classified visually by assigning a Cohen–Rentrop Score (CRS) ranging between 0 (no collaterals) and 3 (complete retrograde filling of the occluded vessel). All 36 patients included in the analysis underwent cardiac magnetic resonance examination within 3 to 5 days after myocardial infarction and after 12 weeks. Patients with relevant collateral flow (CRS 2–3) to the infarct-related artery had significantly smaller final infarct size compared to those without (7 ± 4% vs. 20 ± 12%, p < 0.001). In addition, both groups showed improvement in left ventricular ejection fraction early after AMI, whereas the recovery was greater in CRS 2–3 (+8 ± 5% vs. +3 ± 5%, p = 0.015). Conclusion: In patients with first AMI, relevant collateral flow to the infarct-related artery was associated with more salvaged myocardium at 12 weeks, translating into greater improvement of systolic left ventricular function. The protective effect of coronary collaterals and the variance of infarct location should be further investigated in larger studies. Full article