Homozygous familial hypercholesterolemia (HoFH) is a genetic disease characterized by high levels of low-density lipoprotein cholesterol (LDL-C) present from birth, leading to early-onset and progressive atherosclerotic cardiovascular disease. Early treatment initiation is crucial for cardiovascular risk reduction; however, many patients do not reach LDL-C treatment goals. Inclisiran, a small interfering RNA targeting hepatic PCSK9 (proprotein convertase subtilisin/kexin type 9), is effective and well tolerated in adult patients with hyperlipidemia; however, it has not yet been studied in pediatric patients.

Stereotactic arrhythmia radiotherapy (STAR) has emerged as a potential therapy for treatment-refractory ventricular tachycardia (VT). However, the mechanisms underlying STAR efficacy, such as scar or other electromechanical changes, are still unclear. The goal of this study was to develop a translational porcine model of ischemic monomorphic VT treated with STAR to examine the physiological changes after a typical clinical STAR treatment.

Sarcoidosis is characterized by noncaseating granulomatous inflammation that involves the lungs or lymph nodes in 90% of cases. The prevalence of cardiac involvement in patients with sarcoidosis is thought to be between 5% and 25%. However, cardiac sarcoidosis can also present without extracardiac disease (known as clinically isolated cardiac sarcoidosis) or with previously unrecognized extracardiac disease. The principal manifestations of cardiac sarcoidosis are heart failure or left ventricular systolic dysfunction, high-grade atrioventricular nodal disease, or ventricular arrhythmia. Cardiovascular imaging plays a crucial role in making the diagnosis, partly due to the low yield of endomyocardial biopsy in cardiac sarcoidosis. Cardiovascular imaging is also used for risk stratification for ventricular arrhythmia, to identify patients who may benefit from immunosuppressive therapy, and for longitudinal follow-up on and off therapy. It can also be used to identify alternative diagnoses to cardiac sarcoidosis. This review will discuss how to use imaging in the diagnosis and management of patients with suspected or known cardiac sarcoidosis.

Background: The sex-related prognosis of patients with cardiogenic shock (CS) undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) remains unclear. Our analyses aim to assess sex-specific outcomes in patients with CS receiving VA-ECMO and explored whether the effect of moderate hypothermia (MH) on clinical outcomes was modified by sex. Methods: In this post-hoc analysis of the HYPO-ECMO trial, clinical outcomes were compared by sex. The primary outcome was 30-day all-cause mortality (ACM). Key secondary outcomes included ACM and a composite outcome of ACM, heart transplant, escalation to left ventricular assist device implantation, or stroke at 30, 60 and 180 days. Results: Among the 334 patients enrolled in the trial, 81 (24%) were female. At 30 days, 45.7% of female and 46.6% of male patients experienced the primary outcome, with no sex differences (adjusted OR, 1.01 [0.57 - 1.78], p=0.98 and log-rank test, p=0.93). No significant sex differences were observed in all-cause mortality at 60 and 180 days (adjusted OR, 0.87 [0.49 - 1.52], p=0.61 and 0.83 [0.47 - 1.46], p=0.51, respectively) or in the composite outcome up to 180 days (p>0.2 for all). The effect of MH on the primary outcome (aOR, 0.73 [0.43 - 1.25], p=0.25 and 0.67 [0.26 - 1.76], p=0.41, in male and female respectively, interaction p-value = 0.88) and secondary outcomes (interaction p-value >0.3 for all) was not modified by sex. Conclusions: In this post-hoc analysis of the HYPO-ECMO trial, male and female experienced similar outcomes in CS treated with VA-ECMO. Sex did not significantly modify the effect of moderate hypothermia on outcomes. Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02754193.

Heart valve replacement in children is fraught with long-term morbidity and mortality rates, largely because conventional implants lack the capacity to grow with the child. Partial heart transplantation presents a potential solution by transplanting only specific segments of a donor heart, thereby providing a living and growing heart valve implant. This approach harnesses the full spectrum of cardiac tissues, which, when freshly procured and supported by immunosuppression, can integrate as functional and potentially growth-capable tissue. This state-of-the-art review discusses the history and development of partial heart transplantation, its indications, recent clinical experiences, regulation, and future directions.

Patients hospitalized with symptoms of acute coronary syndrome remain at high risk for adverse events postdischarge, highlighting a need for modifiable therapeutic targets. The role of sedentary behavior in this risk and the potential benefits of replacing sedentary time with other activities remain unclear. This study examined the association between sedentary behavior and 1-year cardiac events/mortality among patients evaluated for acute coronary syndrome and estimated risk reductions from substituting alternative activities for sedentary time.

Background: Vascular smooth muscle cells (vSMCs), the predominant cell type in the aortic wall, play a crucial role in maintaining aortic integrity, blood pressure, and cardiovascular function. vSMC contractility and function depend on smooth muscle alpha-actin 2 (ACTA2). The pathogenic variant ACTA2 c.536G>A (p. R179H) causes multisystemic smooth muscle dysfunction syndrome (MSMDS), a severe disorder marked by widespread smooth muscle abnormalities, resulting in life-threatening aortic disease and high-risk early mortality from aneurysms or stroke. No effective treatments exist for MSMDS. Methods: To develop a comprehensive therapy for MSMDS, we utilized CRISPR-Cas9 adenine base editing to correct the ACTA2 R179H mutation. We generated isogenic human induced pluripotent stem cell (iPSC) lines and humanized mice carrying this pathogenic missense mutation. iPSC-SMCs were evaluated for key functional characteristics, including proliferation, migration, and contractility. The adenine base editor (ABE) ABE8e-SpCas9-VRQR under control of either a SMC-specific promoter or a CMV promoter, and an optimized single guide RNA (sgRNA) under control of U6 promoter were delivered intravenously to humanized R179H mice using adeno-associated virus serotype 9 (AAV9) and phenotypic outcomes were evaluated. Results: The R179H mutation causes a dramatic phenotypic switch in human iPSC-SMCs from a contractile to a synthetic state, a transition associated with aneurysm formation. Base editing prevented this pathogenic phenotypic switch and restored normal SMC function. In humanized mice, the ACTA2R179H/+ mutation caused widespread smooth muscle dysfunction, manifesting as decreased blood pressure, aortic dilation and dissection, bladder enlargement, gut dilation, and hydronephrosis. In vivo base editing rescued these pathological abnormalities, normalizing smooth muscle function. Conclusions: This study demonstrates the effectiveness of adenine base editing to treat MSMDS and restore aortic smooth muscle function. By correcting the ACTA2 R179H mutation, the pathogenic phenotypic shift in SMCs was prevented, key aortic smooth muscle functions were restored, and life-threatening aortic dilation and dissection were mitigated in humanized mice. These findings underscore the promise of gene-editing therapies in addressing the underlying genetic causes of smooth muscle disorders and offer a potential transformative treatment for patients facing severe vascular complications.

Inflammation suppresses right ventricular (RV) function in pulmonary arterial hypertension (PAH). In particular, we showed GP130 (glycoprotein-130) signaling promotes pathological microtubule remodeling and RV dysfunction in rodent PAH. Emerging data demonstrate the intestinal microbiome regulates systemic inflammation, but the impact of modulating the gut microbiome on the GP130-microtubule axis in RV failure is unknown.

Heart failure (HF) is associated with high mortality rates and substantial health care costs. While there is growing emphasis on integrating palliative care for patients with HF, limited data exist on the locations where adults with HF spend their final days. The study aimed to analyze the location and circumstances of death among adults with HF in the United States using Centers for Disease Control and Prevention's Wide-ranging Online Data for epidemiological Research data.

Aortic valve calcium score (AVCa) measured on noncontrast computed tomography (CT) is well-established for grading aortic stenosis (AS) severity. However, thresholds for AVCa measured on contrast CT remain uncertain. We evaluated correlations, associated factors, and severity thresholds of AVCa measured on contrast CT against transthoracic echocardiography (TTE) measures of AS.

Cardiac intensive care units are witnessing a demographic shift, characterized by patients with increasingly complex or end-stage cardiovascular disease with a greater burden of concomitant comorbid noncardiovascular disease. Despite technical advances in care that may be offered, many critically ill cardiovascular patients will nevertheless experience significant morbidity and mortality during the acute decompensation, including physical and psychological suffering. Palliative care, with its specialized focus on alleviating suffering, aligns treatments with patient and caregiver values and improves overall care planning. Integrating palliative care into cardiovascular disease management extends the therapeutic approach beyond life-sustaining measures to encompass life-enhancing goals, addressing the physical, emotional, psychosocial, and spiritual needs of critically ill patients. This American Heart Association scientific statement aims to explore the definitions and conceptual framework of palliative care and to suggest strategies to integrate palliative care principles into the management of patients with critical cardiovascular illness.

Much work has been done on developing hierarchical composite end point analysis methods, which meaningfully measure the effect of a treatment for patients with heart failure. Two motivations for this work have been as follows: (1) trying to ensure that more severe outcomes are weighted more heavily in the analysis; (2) combining different types of end points such as death, number of recurrent hospitalizations, and continuous functional or biologic end points. Such methods include the win ratio, the win odds, and the proportion in favor of treatment. In this article, our focus is when all components are clinical end points such as death or hospitalizations and do not include continuous end points. We review these methods using HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training). We also describe recent methods for combining different clinical end points, which take into account the time a subject is in a particular clinical state. These include the pairwise win time, the restricted mean time in favor of treatment, the expected win time, and the expected win time against reference. We discuss the US Food and Drug Administration guidances and make general recommendations.

Induction therapy is the use of potent immunosuppression in the perioperative period with the intent to diminish rejection rates in at-risk patients or as a renal-protective strategy. The potent immunomodulatory effects of these agents must be balanced against the recipient's risk of infectious or malignant complications, among others. There is a notable lack of clinically useful risk stratification models that integrate these competing risks and guide the clinician in the use of these therapies. This review integrates the existing evidence on the utility and safety of various induction regimens and highlights the gaps of knowledge in the field. In addition, we frame the discussion in view of the changing landscape of heart transplantation where many unknowns remain, such as the impact of induction immunosuppression on patients bridged with mechanical circulatory devices or receiving organs from hepatitis C-positive or donation after circulatory death donors, among others.

Thresholds to define prognosis with hs-cTnI (high-sensitivity cardiac troponin I) have not been systematically addressed in wild-type transthyretin amyloid cardiomyopathy, in part because of the multiplicity of hs-cTnI assays. The aims of this study were, first, to assess the prognostic performance of hs-cTnI measured with different assays in patients with wild-type transthyretin amyloid cardiomyopathy and, second, to identify assay-specific hs-cTnI thresholds for prognosis that could be integrated into staging systems for risk stratification.

Hypertrophic cardiomyopathy (HCM) is associated with significant morbidity and mortality, including sudden cardiac death in the young. Its prevalence is estimated to be 1 in 500, although many people are undiagnosed. The ability to screen electrocardiograms for its presence could improve detection and enable earlier diagnosis. This study evaluated the accuracy of an artificial intelligence device (viz HCM) in detecting HCM based on a 12-lead electrocardiogram.

Imaging markers of atherosclerotic inflammation are needed to enhance cardiovascular risk assessment and evaluate the impact of therapies. We sought to test the hypothesis that treatments impacting arterial inflammation can be evaluated using a simplified measure of periaortic fat attenuation (FA) assessed on noncontrast, nongated computed tomography (CT) of the descending thoracic aorta.

Hemodynamic response to escalation of vasoactive drugs has not been well-characterized in patients with cardiogenic shock (CS). We tested the hypothesis that lower diastolic perfusion pressure (DPP=diastolic blood pressure-right atrial pressure) was associated with more limited hemodynamic response to uptitration of vasoactive drugs and with possible benefit from early mechanical circulatory support in patients with CS.

A functionally significant myocardial bridge (MB) is an important cause of angina with nonobstructive coronary arteries. However, distinguishing a functionally significant versus incidental MB remains challenging. Resting and hyperemic intracoronary functional indices are available, but no studies have compared their diagnostic performance in MBs.

The effects of the aspirin-free strategy on bleeding and cardiovascular events were unknown in patients with high bleeding risk (HBR), with or without acute coronary syndrome (ACS), undergoing percutaneous coronary intervention.

Mortality due to ischemic heart disease (IHD) has declined in countries with high socioeconomic development. Whether these declines extend to other settings, and whether socioeconomic development influences IHD mortality among men and women differently, is unknown.