Jin Kyung Kim

Aortic regurgitation (AR) in young adults (aged 18–44 years) is often under‐ or misdiagnosed and is not always benign. As in older populations, prognosis depends on the severity of regurgitation, the underlying cause, early left ventricular dysfunction, and the chosen intervention strategy. Prompt diagnosis and timely treatment improve outcomes, yet the optimal timing for surgery in asymptomatic chronic AR remains uncertain. Recent studies have proposed new thresholds for left ventricular structural and functional assessment to better evaluate the impact of AR on prognosis and guide intervention timing. Echocardiography remains the primary imaging modality, but a multimodality approach is essential to accurately assess AR severity and subtle left ventricular changes. Transesophageal echocardiography with 3‐dimensional imaging is crucial for evaluating valve repair feasibility, particularly when valve‐sparing root repair, reintervention, or transcatheter procedures are considered. Additional tools such as cardiac magnetic resonance, global longitudinal strain, and biomarkers may further enhance disease monitoring. Assessment can be challenging, especially with eccentric jets or complex valve anatomy, and current surgical cut‐offs remain debated. Aortic valve repair is preferred in young patients, including those with concomitant proximal aortic aneurysm, but it remains underutilized. Here, we propose a treatment algorithm for severe AR in young adults, integrating the underlying cause, valve anatomy, and left ventricular function, with a special focus on multimodality imaging to guide monitoring and therapeutic strategies.

Cardiac masses are complex clinical conditions that frequently pose diagnostic challenges in cardiology practice. These masses can form within heart chambers or near the pericardium and are generally categorized as either non-neoplastic or neoplastic. These latter are further classified into benign and malignant (primary and secondary or metastatic). Diagnosing these conditions often requires a multiparametric approach that includes both clinical features, such as the patient’s and associated clinical conditions, and multimodality imaging. However, histological examination of the resected specimen is often necessary to ascertain the nature of the mass. Given their heterogeneity and the rarity of many cardiac masses, there are no guidelines or consensus on the best diagnostic approach. Modern imaging protocols must be tailored to the specific clinical issues and patient characteristics, given the rapid advancements in technology. Thus, it is imperative to use a multimodality approach, combining different imaging techniques and multidisciplinary teamwork. Hereby, we propose a practical algorithm for evaluating cardiac lesions using a step-by-step implementation of multimodal imaging. Ultimately, the goal is to tailor the most suitable imaging technique to the patient’s needs.

BACKGROUND: Obesity is a well-established risk factor for both adverse pregnancy outcomes (APOs) and cardiovascular disease (CVD). However, it is not known whether APOs are mediators or markers of the obesity-CVD relationship. This study examined the association between body mass index, APOs, and postpartum CVD risk factors. METHODS: The sample included adults from the nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be) Heart Health Study who were enrolled in their first trimester (6 weeks–13 weeks 6 days gestation) from 8 United States sites. Participants had a follow-up visit at 3.7 years postpartum. APOs, which included hypertensive disorders of pregnancy, preterm birth, small-for-gestational-age birth, and gestational diabetes, were centrally adjudicated. Mediation analyses estimated the association between early pregnancy body mass index and postpartum CVD risk factors (hypertension, hyperlipidemia, and diabetes) and the proportion mediated by each APO adjusted for demographics and baseline health behaviors, psychosocial stressors, and CVD risk factor levels. RESULTS: Among 4216 participants enrolled, mean±SD maternal age was 27±6 years. Early pregnancy prevalence of overweight was 25%, and obesity was 22%. Hypertensive disorders of pregnancy occurred in 15%, preterm birth in 8%, small-for-gestational-age birth in 11%, and gestational diabetes in 4%. Early pregnancy obesity, compared with normal body mass index, was associated with significantly higher incidence of postpartum hypertension (adjusted odds ratio, 1.14 [95% CI, 1.10–1.18]), hyperlipidemia (1.11 [95% CI, 1.08–1.14]), and diabetes (1.03 [95% CI, 1.01–1.04]) even after adjustment for baseline CVD risk factor levels. APOs were associated with higher incidence of postpartum hypertension (1.97 [95% CI, 1.61–2.40]) and hyperlipidemia (1.31 [95% CI, 1.03–1.67]). Hypertensive disorders of pregnancy mediated a small proportion of the association between obesity and incident hypertension (13% [11%–15%]) and did not mediate associations with incident hyperlipidemia or diabetes. There was no significant mediation by preterm birth or small-for-gestational-age birth. CONCLUSIONS: There was heterogeneity across APO subtypes in their association with postpartum CVD risk factors and mediation of the association between early pregnancy obesity and postpartum CVD risk factors. However, only a small or nonsignificant proportion of the association between obesity and CVD risk factors was mediated by any of the APOs, suggesting APOs are a marker of prepregnancy CVD risk and not a predominant cause of postpartum CVD risk.

There is emerging evidence that the cardiac interatrial septum has an important role as a thromboembolic source for ischemic strokes. There is little consensus on treatment of patients with different cardiac interatrial morphologies or pathologies who have had stroke. In this paper, we summarize the important background, diagnostic, and treatment considerations for this patient population as presented during the Federation of American Societies for Experimental Biology (FASEB) Virtual Catalytic Conference on the Cardiac Interatrial Septum and Stroke Risk, held on December 7, 2022. During this conference, many aspects of the cardiac interatrial septum were discussed. Among these were the embryogenesis of the interatrial septum and development of anatomic variants such as patent foramen ovale and left atrial septal pouch. Also addressed were various mechanisms of injury such as shunting physiologies and the consequences that can result from anatomic variants, as well as imaging considerations in echocardiography, computed tomography, and magnetic resonance imaging. Treatment options including anticoagulation and closure were addressed, as well as an in‐depth discussion on whether the left atrial septal pouch is a stroke risk factor. These issues were discussed and debated by multiple experts from neurology, cardiology, and radiology.

Background: Although it is critically important to understand the underlying molecular and electrophysiological changes that predispose to the induction and maintenance of atrial fibrillation (AF), the underlying mechanism of AF is still poorly defined. AF is characterized as the electrophysiological and membrane integrity abnormality of the atrial cells, and claudin-5 (Cldn5), a tight junction protein, may be involved in the pathophysiology of AF, however, the role of Cldn5 in AF is unknown. Methods: Left atrial appendages from the enlarged left atrium were obtained from AF patients undergoing modified radiofrequency ablation maze procedure and normal left atrial appendages were obtained from non-AF donors. Western blot, immunofluorescence, transmission electron microscope (TEM), and proteomics analysis were performed to screen the specific protein expression and signal pathway changes in AF heart tissue vs. non-AF heart tissue. In addition, Cldn5 shRNA or siRNA adeno-associated virus (AAV) were then injected into the mouse left ventricle or added into HL1 cells respectively to knockdown claudin-5 in cardiomyocytes to observe whether the change of Cldn5 influences electrophysiology and affects those protein expressions stem from the proteomic analysis. Mitochondrial density and membrane potential were also measured by Mito tracker staining and JC-1 staining under the confocal microscope in vitro . Results: The protein level of claudin-5 was significantly decreased in cardiomyocytes from the left atrium of AF patients compared to non-AF donors. Proteomics analysis showed that 83 proteins were downregulated and 102 proteins were upregulated in the left atrial appendage of AF patients. Among them, CACNA2D2, CACNB2, MYL2 and MAP6 were dramatically downregulated. KEGG pathway analysis showed these changes would lead to hypertrophic and/or dilated cardiomyopathy. Cldn5 shRNA AAV infection induced-Cldn5 deficiency caused severe cardiac atrophy and arrhythmias in mice. The decreases in both mitochondrial numbers and mitochondrial membrane potential (MMP) were also observed in vitro after Cldn5 knockdown by siRNA. Finally, western blot analysis confirmed the protein level of CACNA2D2, CACNB2, MYL2 and MAP6 were downregulated after Cldn5 knockdown in vivo and in vitro . Conclusions: We demonstrated for the first time the deficiency of Cldn5 in cardiomyocytes in the left atrium of AF patients. The mechanism of AF might be associated with Cldn5 deficiency- associated downregulation of CACNA2D2, CACNB2, MYL2 and MAP6, and mitochondrial dysfunction in cardiomyocytes. Clinical Perspective: What Is New?: This is the first study to find the decreased expression of claudin-5 (Cldn5) with prominent muscle atrophy in the left atrial appendage of atrial fibrillation (AF) patients. Knockdown of Cldn5 in the left ventricle via shRNA adeno-associated virus (AAV) infection caused myocardial atrophy and arrhythmia including ST elevation, replacement of P-waves with f-waves, and absence of P-waves prior to QRS. The protein levels of CACNA2D2, CACNB2, MYL2 and MAP6 were significantly downregulated after Cldn5 deficiency. What Are the Clinical Implications?: The present findings may improve our understanding of the role of Cldn5 in the pathophysiology of AF and provide a new therapeutic target for preventing AF.

Evaluation of cardiac function during periods of stress is of key importance for the perioperative setting. Non-invasive hemodynamic monitors provide markers of cardiac function. This pilot study sought to evaluate the ability of a non-invasive hemodynamic monitor to detect cardiac stress during formal stress echocardiography testing. The primary goal was to compare the change in hemodynamic values during the pre/during/post phases of stress echocardiography testing in patients who had results negative versus positive for myocardial ischemia. Adult patients scheduled for outpatient cardiac stress testing were screened. Only patients scheduled for stress-echocardiography testing were consented. Patients with history of arrhythmias were excluded. During the testing, patients wore a cuff-based hemodynamic sensor (Nexfin system, Edwards Lifesciences). Data from the hemodynamic sensor were compared to the findings of the stress study. A total of 37 patients were enrolled, with 31 patients included for analysis. Five patients had stress studies positive for coronary ischemia. Comparison of the hemodynamic variables between patients who had a positive stress study versus negative showed a significant reduction in the percentage change in dP/dt and stroke volume from baseline (p < 0.05). This pilot study indicates that patients who have abnormal stress echocardiograms also have significantly reduced values from a noninvasive hemodynamic monitor. Further evaluation of the clinical utility of this technology, to assist in the care of patients at risk for cardiac ischemia, should be carried out.

A collective body of evidence indicates that estrogen protects the heart from myocardial ischemia/reperfusion (I/R) injury, but the underlying mechanism remains incompletely understood. We have previously delineated a novel mechanism of how 17β-estradiol (E2) protects cultured neonatal rat cardiomyocytes from hypoxia/reoxygenation (H/R) by identifying a functionally active mitochondrial pool of p38β and E2-driven upregulation of manganese superoxide dismutase (MnSOD) activity via p38β, leading to the suppression of reactive oxygen species (ROS) and apoptosis. Here we investigate these cytoprotective actions of E2 in vivo. Left coronary artery ligation and reperfusion was used to produce I/R injury in ovariectomized (OVX) female mice and in estrogen receptor (ER) null female mice. E2 treatment in OVX mice reduced the left ventricular infarct size accompanied by increased activity of mitochondrial p38β and MnSOD. I/R-induced infarct size in ERα knockout (ERKO), ERβ knockout (BERKO) and ERα and β double knockout (DERKO) female mice was larger than that in wild type (WT) mice, with little difference among ERKO, BERKO, and DERKO. Loss of both ERα and ERβ led to reduced activity of mitochondrial p38β and MnSOD at baseline and after I/R. The physical interaction between mitochondrial p38β and MnSOD in the heart was detected by co-immunoprecipitation (co-IP). Threonine 79 (T79) and serine 106 (S106) of MnSOD were identified to be phosphorylated by p38β in kinase assays. Overexpression of WT MnSOD in cardiomyocytes reduced ROS generation during H/R, while point mutation of T79 and S106 of MnSOD to alanine abolished its antioxidative function. We conclude that the protective effects of E2 and ER against cardiac I/R injury involve the regulation of MnSOD via posttranslational modification of the dismutase by p38β.