Intravenous infusions of mesenchymal stromal cells have cumulative beneficial effects in a porcine model of chronic ischemic cardiomyopathy.

AIMS: The development of cell therapy as a widely-available clinical option for ischemic cardiomyopathy is hindered by the invasive nature of current cell delivery methods. Furthermore, the rapid disappearance of cells after transplantation provides a cogent rationale for using repeated cell doses, which, however, has not been done thus far in clinical trials because it is not feasible with invasive approaches. The goal of this translational study was to test the therapeutic utility of the intravenous route for cell delivery. METHODS AND RESULTS: Pigs with chronic ischemic cardiomyopathy induced by myocardial infarction received one or three intravenous doses of allogeneic bone marrow mesenchymal stromal cells (MSCs) or placebo 35 days apart. Rigor guidelines, including blinding and randomization, were strictly followed. A comprehensive assessment of LV function was conducted with three independent methods (echocardiography, magnetic resonance imaging, and hemodynamic studies). The results demonstrate that three doses of MSCs improved both load-dependent and independent indices of left ventricular (LV) function and reduced myocardial hypertrophy and fibrosis; in contrast, one dose failed to produce most of these benefits. CONCLUSIONS: To our knowledge, this is the first study to show that intravenous infusion of a cell product improves LV function and structure in a large animal model of chronic ischemic cardiomyopathy and that repeated infusions are necessary to produce robust effects. This study, conducted in a clinically-relevant model, supports a new therapeutic strategy based on repeated intravenous infusions of allogeneic MSCs and provides a foundation for a first-in-human trial testing this strategy in patients with chronic ischemic cardiomyopathy.

Case 331.

HISTORY: A 43-year-old male patient with no known past medical history presented to the emergency department with new-onset bitemporal headache, dizziness, and bilateral lower extremity weakness for 1 day. The patient denied chest pain, shortness of breath, cough, or recent exposure to sick individuals. He was not on any medications and denied alcohol or illicit drug use. Vital signs were unremarkable. Physical examination was notable for a left-sided pronator drift and bilateral dysmetria that was more pronounced on the left. Results of routine laboratory workup, including complete blood count, metabolic panel, and high-sensitivity troponin level, were normal. An electrocardiogram revealed sinus tachycardia with a heart rate of 102 beats per minute, T-wave inversions in the inferior leads, left axis deviation, incomplete right bundle branch block, and frequent premature ventricular contractions. A radiograph of the chest was unremarkable. CT of the head without contrast enhancement demonstrated no acute intracranial abnormities. MRI of the brain without contrast enhancement revealed multiple acute infarcts involving left posterior inferior cerebellar artery distribution, right cerebellar hemisphere, right mesial temporal lobe, and right posterior limb of the internal capsule. CT angiography of the head and neck showed an occlusion of the right posterior cerebral artery near its origin, with a trace of distal flow. Given that these findings were concerning for a cardioembolic etiology of acute ischemic stroke, transesophageal echocardiography was performed. This showed mild left ventricular systolic dysfunction with an ejection fraction of 40%, mild global hypokinesis, and an additional finding also seen at subsequent cardiac CT and MRI that will be disclosed in part 2 of the case. The patient was started on systemic anticoagulation and guideline-directed medical therapy for heart failure with reduced ejection fraction. CT of the chest showed no evidence of lymphadenopathy or abnormalities in the lung parenchyma or interstitium. Coronary CT angiography was performed (Fig 1), followed by cardiac MRI (Fig 2).

Risk of Stroke, Dementia, and Cognitive Decline with Coronary and Arterial Calcification.

Extant research shows that following a cerebrovascular insult to the brain, patients may develop a wide range of cognitive disorders, spanning from mild cognitive impairment (CI) to advanced dementia. Several studies have shown that atherosclerosis in the carotid, coronary, and breast arteries is associated with an increased risk of stroke, CI, and dementia. In this review, we examine the association of subclinical atherosclerotic calcification detected by computed tomography (CT) in these arterial beds and the risk of stroke, CI, and dementia. A major advantage of CT is that it can accurately quantify vascular calcification in different parts of the vasculature during a single examination. However, the strength of the association between CT findings and CI and stroke varies with the location and severity of the arteries involved. Data are still limited on this topic, highlighting the need for additional investigations to further our understanding of the risk of cognitive impairment in patients with subclinical atherosclerosis. It is equally important to test preventive strategies for managing patients in whom vascular calcifications are identified incidentally in randomized controlled trials to study the effects on outcomes, including incidents of stroke and CI.

Spontaneous Bacterial Peritonitis: A Rare Complication of Pulmonary Arterial Hypertension.

Approximately 3% of all diagnosed cases of ascites are of cardiac etiology. Although more commonly associated with heart failure, pulmonary arterial hypertension is a known but rare cause of cardiac ascites, which has not been associated with spontaneous bacterial peritonitis. We present a case of a 75-year-old male with known pulmonary arterial hypertension and new-onset ascites, the fluid analysis of which was consistent with both cardiac ascites and spontaneous bacterial peritonitis. He was successfully managed with antibiotics, loop diuretics, and mineralocorticoid receptor antagonists.

The role of artificial intelligence in cardiovascular magnetic resonance imaging.

Cardiovascular magnetic resonance (CMR) imaging is the gold standard test for myocardial tissue characterization and chamber volumetric and functional evaluation. However, manual CMR analysis can be time-consuming and is subject to intra- and inter-observer variability. Artificial intelligence (AI) is a field that permits automated task performance through the identification of high-level and complex data relationships. In this review, we review the rapidly growing role of AI in CMR, including image acquisition, sequence prescription, artifact detection, reconstruction, segmentation, and data reporting and analysis including quantification of volumes, function, myocardial infarction (MI) and scar detection, and prediction of outcomes. We conclude with a discussion of the emerging challenges to widespread adoption and solutions that will allow for successful, broader uptake of this powerful technology.

Artificial Intelligence in Coronary Artery Calcium Scoring.

Cardiovascular disease (CVD), particularly coronary heart disease (CHD), is the leading cause of death in the US, with a high economic impact. Coronary artery calcium (CAC) is a known marker for CHD and a useful tool for estimating the risk of atherosclerotic cardiovascular disease (ASCVD). Although CACS is recommended for informing the decision to initiate statin therapy, the current standard requires a dedicated CT protocol, which is time-intensive and contributes to radiation exposure. Non-dedicated CT protocols can be taken advantage of to visualize calcium and reduce overall cost and radiation exposure; however, they mainly provide visual estimates of coronary calcium and have disadvantages such as motion artifacts. Artificial intelligence is a growing field involving software that independently performs human-level tasks, and is well suited for improving CACS efficiency and repurposing non-dedicated CT for calcium scoring. We present a review of the current studies on automated CACS across various CT protocols and discuss consideration points in clinical application and some barriers to implementation.

The Role of Lipoprotein(a) in Peripheral Artery Disease.

Lipoprotein(a) is a low-density-lipoprotein-like particle that consists of apolipoprotein(a) bound to apolipoprotein(b). It has emerged as an established causal risk factor for atherosclerotic cardiovascular disease, stroke, and aortic valve stenosis through multifactorial pathogenic mechanisms that include inflammation, atherogenesis, and thrombosis. Despite an estimated 20% of the global population having elevated lipoprotein(a) levels, testing remains underutilized due to poor awareness and a historical lack of effective and safe therapies. Although lipoprotein(a) has a strong association with coronary artery disease and cerebrovascular disease, its relationship with peripheral artery disease is less well established. In this article, we review the epidemiology, biology, and pathogenesis of lipoprotein(a) as it relates to peripheral artery disease. We also discuss emerging treatment options to help mitigate major adverse cardiac and limb events in this population.

Environmental Pollution and Cardiovascular Disease: Part 2 of 2: Soil, Water, and Other Forms of Pollution.

With a growing body of evidence that now links environmental pollution to adverse cardiovascular disease (CVD) outcomes, pollution has emerged as an important risk factor for CVD. There is thus an urgent need to better understand the role of pollution in CVD, key pathophysiological mechanisms, and to raise awareness among health care providers, the scientific community, the general population, and regulatory authorities about the CV impact of pollution and strategies to reduce it. This article is part 2 of a 2-part state-of-the-art review on the topic of pollution and CVD-herein we discuss major environmental pollutants and their effects on CVD, highlighting pathophysiological mechanisms, and strategies to reduce CVD risk.

Environmental Pollution and Cardiovascular Disease: Part 1 of 2: Air Pollution.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Over the past 50 years, there has been a substantial decline in the incidence of CVD and related mortality in high-income countries, largely due to the mitigation of modifiable risk factors such as smoking, hypertension, and diabetes. However, a significant burden of CVD remains in low- to middle-income countries, despite their lower prevalence of traditional risk factors; other environmental factors, particularly pollution, play a significant role in this attributable risk. Mounting evidence underscores a strong association between pollution and adverse health effects, including CVD. This article is part 1 of a 2-part state-of-the-art review and discusses air pollution and its adverse effects on CVD, highlighting pathophysiological mechanisms and methods to reduce air pollution and exposure to these pollutants.

Meta-Analysis of the Safety and Efficacy of Direct Oral Anticoagulants for the Treatment of Left Ventricular Thrombus.

BACKGROUND: Literature on the preferred anticoagulant for treating left ventricular thrombus (LVT) is lacking. Thus, our objective was to compare the efficacy of DOACs versus warfarin in treating LVT. METHODS: Databases were searched for RCTs and adjusted observational studies that compared DOAC versus warfarin through March 2024. The primary efficacy outcomes of interest were LVT resolution, systemic embolism, composite of stroke, and TIA. The primary safety outcomes encompassed all-cause mortality and bleeding events. RESULTS: Our meta-analysis including 31 studies demonstrated that DOAC use was associated with higher odds of thrombus resolution (OR: 1.08, 95% CI: 0.86-1.31, p: 0.46). A statistically significant reduction in the risk of stroke/TIA was observed in the DOAC group versus the warfarin group (OR: 0.65, 95% CI: 0.48-0.89, p: 0.007). Furthermore, statistically significant reduced risks of all-cause mortality (OR: 0.68, 95% CI: 0.47-0.98, p: 0.04) and bleeding events (OR: 0.70, 95% CI: 0.55-0.89, p: 0.004) were observed with DOAC use as compared to warfarin use. CONCLUSION: Compared to VKAs, DOACs are noninferior as the anticoagulant of choice for LVT treatment. However, further studies are warranted to confirm these findings.

Sleep Apnea and Heart Failure-Current State-of-The-Art.

Sleep-disordered breathing (SDB), including obstructive and central sleep apnea, significantly exacerbates heart failure (HF) through adverse cardiovascular mechanisms. This review aims to synthesize existing literature to clarify the relationship between SDB and HF, focusing on the pathophysiological mechanisms, diagnostic challenges, and the effectiveness of treatment modalities like continuous positive airway pressure (CPAP) and adaptive servo-ventilation ASV. We analyzed peer-reviewed articles from 2003 to 2024 sourced from PubMed, EMBASE, Scopus, and Web of Science databases. The prevalence of SDB in HF patients is high, often underdiagnosed, and underappreciated. Management strategies, including CPAP and ASV, have been shown to mitigate symptoms and improve cardiac function. However, despite the availability of effective treatments, significant challenges in screening and diagnosis persist, affecting patient management and outcomes. DB significantly impacts HF prognosis. Enhanced screening strategies and broader utilization of therapeutic interventions like CPAP and ASV are essential to improve the management and outcomes of HF patients with concomitant SDB. Future research should focus on refining diagnostic and treatment protocols to optimize care for HF patients with SDB.

Hydropneumopericardium Due to a Traumatic Esophageal-Pericardial Fistula.

Esophago-pericardial fistula is a rare, life-threatening condition, usually arising as a complication of benign esophageal disorders or iatrogenic causes. Prompt diagnosis via multimodality imaging is crucial, with computed tomography being the most sensitive. Management varies based on severity, with a growing trend toward early endoscopic interventions, which result in improved outcomes.

Wide Complex Tachycardia in a Middle-Aged Woman With Diarrhea.

A woman in her mid-60s with a history of paroxysmal atrial fibrillation and hypertension presents with 3 days of nausea, vomiting, and diarrhea. What would you do next?

Role of circadian clock system in the mitochondrial trans-sulfuration pathway and tissue remodeling.

Previous studies from our laboratory revealed that the gaseous molecule hydrogen sulfide (H2S), a metabolic product of epigenetics, involves trans-sulfuration pathway for ensuring metabolism and clearance of homocysteine (Hcy) from body, thereby mitigating the skeletal muscle's pathological remodeling. Although the master circadian clock regulator that is known as brain and muscle aryl hydrocarbon receptor nuclear translocator like protein 1 (i.e., BMAL 1) is associated with S-adenosylhomocysteine hydrolase (SAHH) and Hcy metabolism but how trans-sulfuration pathway is influenced by the circadian clock remains unexplored. We hypothesize that alterations in the functioning of circadian clock during sleep and wake cycle affect skeletal muscle's biology. To test this hypothesis, we measured serum matrix metalloproteinase (MMP) activities using gelatin gels for analyzing the MMP-2 and MMP-9. Further, employing casein gels, we also studied MMP-13 that is known to be influenced by the growth arrest and DNA damage-45 (GADD45) protein during sleep and wake cycle. The wild type and cystathionine ß synthase-deficient (CBS-/+) mice strains were treated with H2S and subjected to measurement of trans-sulfuration factors from skeletal muscle tissues. The results suggested highly robust activation of MMPs in the wake mice versus sleep mice, which appears somewhat akin to the "1-carbon metabolic dysregulation", which takes place during remodeling of extracellular matrix during muscular dystrophy. Interestingly, the levels of trans-sulfuration factors such as CBS, cystathionine γ lyase (CSE), methyl tetrahydrofolate reductase (MTHFR), phosphatidylethanolamine N-methyltransferase (PEMT), and Hcy-protein bound paraoxonase 1 (PON1) were attenuated in CBS-/+ mice. However, treatment with H2S mitigated the attenuation of the trans-sulfuration pathway. In addition, levels of mitochondrial peroxisome proliferator-activated receptor-gamma coactivator 1-α (PGC 1-α) and mitofusin-2 (MFN-2) were significantly improved by H2S intervention. Our findings suggest participation of the circadian clock in trans-sulfuration pathway that affects skeletal muscle remodeling and mitochondrial regeneration.

Preventive Therapies in Peripheral Arterial Disease.

Atherosclerosis, while initially deemed a bland proliferative process, is now recognized as a multifactorial-lipoprotein-mediated inflammation-driven pathway. With the rising incidence of atherosclerotic disease of the lower extremity arteries, the healthcare burden and clinical morbidity and mortality due to peripheral artery disease (PAD) are currently escalating. With a healthcare cost burden of over 21 billion USD and 200 million patients afflicted worldwide, accurate knowledge regarding the pathophysiology, presentation, and diagnosis of the disease is crucial. The role of lipoproteins and their remnants in atherosclerotic vessel occlusion and plaque formation and progression has been long established. This review paper discusses the epidemiology, pathophysiology, and presentation of PAD. PAD has been repeatedly noted to portend to poor cardiovascular and limb outcomes. We discuss major therapeutic avenues for the prevention of major cardiovascular adverse events and major limb adverse events in patients with PAD.

Intensive Cardiac Rehabilitation Outcomes in Patients with Heart Failure.

INTRODUCTION: Cardiac rehabilitation (CR) has proven to be beneficial for patients with heart failure (HF), potentially reducing morbidity and mortality while improving fitness and psychological outcomes. Intensive cardiac rehabilitation (ICR) represents an emerging form of CR that has demonstrated advantages for patients with various cardiovascular diseases. Nevertheless, the specific outcomes of ICR in patients with HF remain unknown. OBJECTIVES: The purpose of this study is to assess the effectiveness of ICR in patients with HF. METHODS: This retrospective study involved 12,950 patients who participated in ICR at 46 centers from January 2016 to December 2020. Patients were categorized into two groups: the HF group, comprising 1400 patients (11%), and the non-HF group, consisting of 11,550 patients (89%). The primary endpoints included the ICR completion rate, changes in body mass index (BMI), exercise minutes per week (EMW), and depression scores (CESD). A t-test was employed to compare variables between the two groups. RESULTS: The HF group comprises older patients, with 37% being females (compared to 44% in the non-HF group). The ICR completion rate was higher in the non-HF group. After ICR completion, adjusted analyses revealed that patients without HF demonstrated a greater improvement in BMI. There were no differences in fitness, as measured via EMW, or in depression scores, as measured via CESD, between the two groups. CONCLUSIONS: Despite the lower baseline functional status and psychosocial scores of HF patients compared to non-HF patients, patients with HF were able to attain similar or even better functional and psychosocial outcomes after ICR.

Artificial intelligence in cardiac computed tomography.

Artificial Intelligence (AI) is a broad discipline of computer science and engineering. Modern application of AI encompasses intelligent models and algorithms for automated data analysis and processing, data generation, and prediction with applications in visual perception, speech understanding, and language translation. AI in healthcare uses machine learning (ML) and other predictive analytical techniques to help sort through vast amounts of data and generate outputs that aid in diagnosis, clinical decision support, workflow automation, and prognostication. Coronary computed tomography angiography (CCTA) is an ideal union for these applications due to vast amounts of data generation and analysis during cardiac segmentation, coronary calcium scoring, plaque quantification, adipose tissue quantification, peri-operative planning, fractional flow reserve quantification, and cardiac event prediction. In the past 5 years, there has been an exponential increase in the number of studies exploring the use of AI for cardiac computed tomography (CT) image acquisition, de-noising, analysis, and prognosis. Beyond image processing, AI has also been applied to improve the imaging workflow in areas such as patient scheduling, urgent result notification, report generation, and report communication. In this review, we discuss algorithms applicable to AI and radiomic analysis; we then present a summary of current and emerging clinical applications of AI in cardiac CT. We conclude with AI's advantages and limitations in this new field.

Dyslipidemia in Human Immunodeficiency Virus Disease: JACC Review Topic of the Week.

The advent of newer and better tolerated antiretroviral therapy has progressively shortened the life expectancy gap between people living with HIV (PWH) and the general population. However, in this aging cohort, cardiovascular disease is now a significant cause of morbidity and mortality despite advances in cardiac care. Therefore, it is critical to assess and treat all cardiovascular disease risk factors, including dyslipidemia, early and aggressively in PWH. Data are not as robust regarding the pathogenesis and management of dyslipidemia in PWH, with most evidence being extrapolated from the general uninfected population. In this review the authors describe the current understanding of the pathophysiology of HIV and antiretroviral therapy-induced dyslipidemia, and the approach to risk assessment and management, given that drug-drug interactions remain an important consideration in this population.