Electrical Stimulation Increases the Secretion of Cardioprotective Extracellular Vesicles from Cardiac Mesenchymal Stem Cells.

Clinical trials have shown that electric stimulation (ELSM) using either cardiac resynchronization therapy (CRT) or cardiac contractility modulation (CCM) approaches is an effective treatment for patients with moderate to severe heart failure, but the mechanisms are incompletely understood. Extracellular vesicles (EV) produced by cardiac mesenchymal stem cells (C-MSC) have been reported to be cardioprotective through cell-to-cell communication. In this study, we investigated the effects of ELSM stimulation on EV secretion from C-MSCs (C-MSCELSM). We observed enhanced EV-dependent cardioprotection conferred by conditioned medium (CM) from C-MSCELSM compared to that from non-stimulated control C-MSC (C-MSCCtrl). To investigate the mechanisms of ELSM-stimulated EV secretion, we examined the protein levels of neutral sphingomyelinase 2 (nSMase2), a key enzyme of the endosomal sorting complex required for EV biosynthesis. We detected a time-dependent increase in nSMase2 protein levels in C-MSCELSM compared to C-MSCCtrl. Knockdown of nSMase2 in C-MSC by siRNA significantly reduced EV secretion in C-MSCELSM and attenuated the cardioprotective effect of CM from C-MSCELSM in HL-1 cells. Taken together, our results suggest that ELSM-mediated increases in EV secretion from C-MSC enhance the cardioprotective effects of C-MSC through an EV-dependent mechanism involving nSMase2.

Atrial fibrillation ablation with advanced radiofrequency catheter versus second-generation cryoballoon catheter.

Aim: To compare cost and readmissions among atrial fibrillation (AF) patients undergoing ablation using the THERMOCOOL SMARTTOUCH™ SF (STSF) radiofrequency catheter versus the Arctic Front Advance™ (AFA) cryoballoon catheter. Patients & methods: The Premier Healthcare Database was used for the study purposes. Propensity score matching was used to match patients in the two groups. Costs and readmissions were assessed. A regression model was used for outcome assessment. Results: After propensity matching, 2767 patients were identified in each of the STSF and AFA cohorts. In the matched cohort, STSF patients had significantly lower supply costs than AFA patients. STSF patients had significantly lower 4-12-month AF-related inpatient readmissions compared with AFA patients (2.58% vs 3.99%; p = 0.0402). Costs of care summing index procedure and readmission costs were also lower for the STSF patients versus AFA patients. Conclusions: Patients who underwent AF ablation using the STSF catheter versus the AFA catheter had lower cost and AF-related readmissions.

Potential Financial Impact of Incidental Cardiac Pathology Detected During Lung Cancer Screening.

BACKGROUND: Lung cancer screening (LCS) is broadly accepted. Screening also identifies incidental cardiac findings (S findings) that need follow-up. We report the magnitude of the potential downstream revenue generated by appropriate S finding management after 4 years of our free LCS program. MATERIALS AND METHODS: A retrospective database and chart review of a single-center free LCS program in the underserved southeast were performed. All patients who were enrolled in the screening required a primary care physician (PCP) as part of the decision-making model. Referrals to cardiac specialists for S findings found on LCS were recorded. Cost analysis was performed to track potential downstream revenue generated for the institution based upon Medicare allowable or Diagnosis-related group calculations. RESULTS: One thousand one hundred thirty-two scans were reviewed with 262 (23%) yielding positive S findings for 1 or more organ systems. 181/262 (69%) patients had cardiac findings, only 64/181 (35%) of these patients were referred to cardiology specialists by the PCP. The total Medicare billable amount for all cardiac referrals/interventions was $284 379, representing 35% of the potential billable amount of $804 260. Percutaneous coronary intervention (PCI) was the highest billable amount at $18 568. Eight percent of the patients undergoing appropriate cardiac evaluation required a PCI. If not for the screening and cardiac specialist referral, this patient group may not have received appropriate cardiovascular diagnosis and treatment. DISCUSSION: Lung cancer screening also identifies patients with significant cardiac disease, many of whom may not be appropriately referred. Identification and treatment of incidentally noted cardiovascular findings may both improve patient care and justify supporting free LCS programs.

Elective cardiovascular care in the era of the COVID-19 pandemic: managing tragic choices.

The COVID-19 pandemic has led to significant morbidity and mortality globally. As health systems grapple with caring for patients affected with COVID-19, cardiovascular procedures that are deemed 'elective' have been postponed. Guidelines concerning which cardiac procedures should be performed during the pandemic vary by specialty and geography in the USA. We propose a clinical heuristic to guide individual physicians and governing bodies in their decision making regarding which cardiac procedures should be performed during the COVID-19 pandemic using the behavioural economics concept of heuristics and ecological rationality.

Global, Regional, and National Burden of Calcific Aortic Valve and Degenerative Mitral Valve Diseases, 1990-2017.

BACKGROUND: Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017. METHODS: Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations. Geospatial statistical methods were used to estimate disease for all countries, because data on nonrheumatic valvular diseases are extremely limited for some regions of the world, such as Sub-Saharan Africa and South Asia. Results accounted for estimated level of disease severity as well as the estimated availability of valve repair or replacement procedures. DALYs and other measures of health-related burden were generated for both sexes and each 5-year age group, location, and year from 1990 to 2017. RESULTS: Globally, CAVD and degenerative mitral valve disease caused 102 700 (95% uncertainty interval [UI], 82 700-107 900) and 35 700 (95% UI, 30 500-42 500) deaths, and 12.6 million (95% UI, 11.4 million-13.8 million) and 18.1 million (95% UI, 17.6 million-18.6 million) prevalent cases existed in 2017, respectively. A total of 2.5 million (95% UI, 2.3 million-2.8 million) DALYs were estimated as caused by nonrheumatic valvular diseases globally, representing 0.10% (95% UI, 0.09%-0.11%) of total lost health from all diseases in 2017. The number of DALYs increased for CAVD and degenerative mitral valve disease between 1990 and 2017 by 101% (95% UI, 79%-117%) and 35% (95% UI, 23%-47%), respectively. There is significant geographic variation in the prevalence, mortality rate, and overall burden of these diseases, with highest age-standardized DALY rates of CAVD estimated for high-income countries. CONCLUSIONS: These global and national estimates demonstrate that CAVD and degenerative mitral valve disease are important causes of disease burden among older adults. Efforts to clarify modifiable risk factors and improve access to valve interventions are necessary if progress is to be made toward reducing, and eventually eliminating, the burden of these highly treatable diseases.

How to prevent and manage radiation-induced coronary artery disease.

Radiation-induced coronary heart disease (RICHD) is the second most common cause of morbidity and mortality in patients treated with radiotherapy for breast cancer, Hodgkin's lymphoma and other prevalent mediastinal malignancies. The risk of RICHD increases with radiation dose. Exposed patients may present decades after treatment with manifestations ranging from asymptomatic myocardial perfusion defects to ostial, triple-vessel disease and sudden cardiac death. RICHD is insidious, with a long latency and a tendency to remain silent late into the disease course. Vessel involvement is often diffuse and is preferentially proximal. The pathophysiology is similar to that of accelerated atherosclerosis, characterised by the formation of inflammatory plaque with high collagen and fibrin content. The presence of conventional risk factors potentiates RICHD, and aggressive risk factor management should ideally be initiated prior to radiation therapy. Stress echocardiography is more sensitive and specific than myocardial perfusion imaging in the detection of RICHD, and CT coronary angiography shows promise in risk stratification. Coronary artery bypass grafting is associated with higher risks of graft failure, perioperative complications and all-cause mortality in patients with RICHD. In most cases, the use of drug-eluting stents is preferable to surgical intervention, bare metal stenting or balloon-angioplasty alone.

A novel high throughput approach to screen for cardiac arrhythmic events following stem cell treatment.

Although stem cell therapy is promising for repairing damaged cardiac tissue and improving heart function, there are safety concerns, especially regarding the risk of arrhythmias, which can be life threatening. To address this issue, we propose to develop a novel screening system to evaluate arrhythmic risk associated with stem cell therapy using a high-throughput multielectrode array system that can measure conduction velocity and action potential duration in cardiomyocytes co-cultured with different types of stem cells, such as mesenchymal stem cells, skeletal myoblasts, and resident cardiac stem cells. We will assess the arrhythmic potential of each of these types of stem cells under normoxic and hypoxic conditions, with/without application of oxidative stress or catecholamines. We hypothesize that these methods will prove to be an effective way to screen for arrhythmic risk of cardiac stem cell therapy. Ultimately, our approach can potentially be personalized to develop a robust screening protocol in order to identify which stem cell type carries the least amount of risk for arrhythmia. This system will have great clinical benefit to improve the risk/benefit ratio of human stem cell therapy for heart disease.