Wassim Mosleh

The Role of SGLT-2 Inhibitors as Part of Optimal Medical Therapy in Improving Cardiovascular Outcomes in Patients with Diabetes and Coronary Artery Disease

The optimal treatment approach to patients with coronary artery disease (CAD), including those with type 2 diabetes mellitus (T2DM), has been extensively evaluated. Several trials of stable ischemic heart disease including patients with T2DM have demonstrated that medical management is comparable to revascularization in terms of mortality and rates of major adverse cardiovascular events (MACE). There has been a growing appreciation for optimal medical therapy’s (OMT) role in improving clinical outcomes. It is vital to target T2DM patients to prevent or delay MACE events through advanced OMT, ultimately delaying if not avoiding the need for revascularization. There has been significant evolution in the development of pharmacologic management of T2DM patients. Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a new pharmacologic therapy with tremendous potential to alter clinical practice and influence practice guidelines. SGLT2-inhibitors have great potential in reducing MACE in patients with T2DM and CAD. Empagliflozin should be considered as a part of OMT among these patients. If results similar to the EMPA-REG OUTCOMES trial are replicated in other trials, the use of these pharmacologic agents as a part of OMT may narrow the gap between revascularization and OMT alone in patients with T2DM and multi-vessel disease. Future studies on the role of SLGT-2 inhibitors with regard to heart failure outcomes are needed to elucidate the mechanisms and clinical effects in this vulnerable population.

Myocardial and Serum Galectin-3 Expression Dynamics Marks Post-Myocardial Infarction Cardiac Remodelling

BACKGROUND Acute myocardial infarction (MI) causes significant changes in cardiac morphology and function. Galectin-3 is a novel and potentially therapeutically important mediator of cardiac remodelling. Myocardial and serum galectin-3 expression dynamics in response to the early cardiovascular outcomes after acute MI are not fully elucidated. METHODS We first performed a comprehensive longitudinal microarray analyses in mice after acute MI. We then measured the serum levels of galectin-3 in a translational porcine model of coronary microembolism-induced post-ischaemic cardiac remodelling. We validated our pre-clinical studies in humans by measuring serum galectin-3 levels of 52 patients with acute ST-elevation MI (STEMI) and 11 healthy controls. We analysed galectin-3 data in relation to the development of major adverse cardiovascular outcomes (MACO). RESULTS Of the 9,753 genes profiled at infarcted and remote myocardium at eight different time points, dynamic myocardial overexpression of galectin-3 mRNA was detected. In a pig model of diffuse myocardial damage and cardiac remodelling, galectin-3 localised to the areas of tissue damage and myocardial fibrosis, with proportionate increase of their serum galectin-3 expression levels. In humans, increased serum galectin-3 level was associated with in-hospital MACO. CONCLUSIONS In this translational study, we demonstrated that galectin-3 is dynamically overexpressed in response to acute MI-induced cardiac remodelling. Elevated galectin-3 levels are associated with the development of in-hospital MACO.

Mono versus Dual Antiplatelet Therapy after Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis

ABSTRACT Background: Dual antiplatelet therapy (DAPT) is routinely prescribed after transcatheter aortic valve replacement (TAVR) despite the lack of definitive data demonstrating its superiority over mono-antiplatelet therapy (MAPT). We aim to investigate the benefits of DAPT versus MAPT and at different follow-up time points post TAVR. Methods: A systematic search was conducted for studies investigating DAPT versus MAPT in patients who underwent TAVR. The primary outcome was net adverse clinical events (NACE) at longest reported follow-up, defined as a composite end-point of all-cause mortality, major stroke, myocardial infarction (MI), and combined life threatening and major bleeding. Secondary endpoints included each outcome individually. We performed subgroup analysis according to study type (randomized control trials vs. observational studies) and follow-up duration post-TAVR (≤ 30 days, between 3 and 6 months, and ≥ 1 year). Results: Twelve studies with 9,650 patients were included. Post-TAVR MAPT was associated with significantly reduced NACE (0.60 [0.45, 0.81], p < 0.001), all-cause mortality (OR 0.54 [0.33, 0.88], p = 0.01), and combined life threatening and major bleeding (0.57 [0.39, 0.84], p = 0.005) in the first 30 days after the procedure when compared to DAPT. The difference in outcomes diminishes with longer-term follow up durations (3–6 month or ≥ 6-month). No differences were seen with other secondary endpoints. Conclusion: MAPT is associated with improved outcomes compared to DAPT in the first 30 days post-TAVR with no difference in outcomes on longer-term follow up. Future prospective, adequately powered, multicenter, placebo-controlled, randomized double-blinded cohort studies are warranted to confirm our findings.

The use of cardiac-CT alone to exclude left atrial thrombus before atrial fibrillation ablation: Efficiency, safety, and cost analysis

Atrial fibrillation (AF) is a growing financial burden on the healthcare system. Cardiac computed tomographic angiography (CCTA) is needed for pulmonary vein mapping before AF ablation (AFA). CCTA has shown to be an alternative to transesophageal echocardiogram (TEE) to rule out left atrial appendage thrombus (LAAT) pre‐AFA. We aim to examine the safety, cost‐effectiveness, and time‐efficiency of utilizing CCTA alone to rule out LAAT before AFA.

Automation, machine learning, and artificial intelligence in echocardiography: A brave new world

Automation, machine learning, and artificial intelligence (AI) are changing the landscape of echocardiography providing complimentary tools to physicians to enhance patient care. Multiple vendor software programs have incorporated automation to improve accuracy and efficiency of manual tracings. Automation with longitudinal strain and 3D echocardiography has shown great accuracy and reproducibility allowing the incorporation of these techniques into daily workflow. This will give further experience to nonexpert readers and allow the integration of these essential tools into more echocardiography laboratories. The potential for machine learning in cardiovascular imaging is still being discovered as algorithms are being created, with training on large data sets beyond what traditional statistical reasoning can handle. Deep learning when applied to large image repositories will recognize complex relationships and patterns integrating all properties of the image, which will unlock further connections about the natural history and prognosis of cardiac disease states. The purpose of this review article was to describe the role and current use of automation, machine learning, and AI in echocardiography and discuss potential limitations and challenges of in the future.

Elevated end-diastolic wall stress after acute myocardial infarction predicts adverse cardiovascular outcomes and longer hospital length of stay

Acute myocardial infarction (MI) leads to ventricular remodeling in response to oxygen demand. Such changes include left ventricular (LV) dilatation and increased myocardial wall stress. Prior studies showed that wall stress is a vital parameter of cardiac remodeling. However, outcome data are lacking. We aim to investigate wall stress post‐MI in relation to biomarkers of cardiac remodeling and cardiovascular outcomes.

A Partial Anomalous Pulmonary Venous Connection in a Severely Symptomatic Patient, Is Surgery Always Recommended?

Partial anomalous pulmonary venous connection (PAPVC) is a rare cardiac anomaly occurring when a pulmonary vein drains into the right atrium, coronary sinus or a systemic vein creating a left-to-right shunt. Symptoms develop from right-sided fluid overload and pulmonary vascular disease. We report a rare case of a severely symptomatic patient with an incidentally discovered PAPVC in the setting of underlying severe pulmonary hypertension from multifactorial severe restrictive lung disease. Despite his worsening symptoms, a multi-disciplinary meeting decided against surgical intervention. Nine months after the decision was made, the patient showed no signs or symptoms of clinical deterioration. Prior studies recommend surgery for PAPVCs with evidence of right ventricular dilation, mild-to-moderate tricuspid regurgitation, or early stages of pulmonary vascular disease. However, our case demonstrates how decision making should consider the shunt’s contribution to the overall clinical picture and underlying comorbidities. If a decision is made to defer surgical intervention, strict follow up and repeat re-evaluations for possible risk re-stratification and surgery reconsideration are warranted.

Pulmonary Arterial Enlargement is Associated With Acute Chest Pain in Patients Without Obstructive Coronary Artery Disease

Background: Pulmonary hypertension (PH) is an underdiagnosed cause for chest pain in patients without significant coronary artery disease (CAD). Studies showed that enlarged pulmonary arterial (PA) and right ventricular chamber sizes correlate with the severity of PH. Therefore, we studied the association between chest pain, right ventricular dimensions (RVDs), and PA size on coronary coronary tomographic angiography (CCTA). Methods: The CCTA of 87 patients presenting with chest pain without evidence of obstructive CAD was examined. The PA diameter (PAD), right atrial dimension (RAD), and RVD were measured. A comparative control cohort included 31 patients who presented without cardiopulmonary complaints and underwent thoracic CT. The risk for obstructive sleep apnea (OSA) was assessed using STOP-BANG questionnaires. Results: Patients with chest pain without obstructive CAD showed markedly dilated right atrial and ventricular chambers compared with standard parameters (right atrium: 48 ± 6.4 mm; right ventricle long axis: 61 ± 9.5 mm). When comparing chest pain vs non-chest pain group, respectively, the mean PAD measured 25.92 ± 0.43 mm vs 22.89 ± 0.38 mm (P < .001), RAD2 measured 40.1423 ± 0.7108 mm vs 34.8800 ± 1.0245 mm (P = .0048), and RVD2 measured 31.7729 ± 0.7299 mm vs 27.6379 ± 1.6178 mm (P = .034). Chest pain was associated with higher PAD (odds ratio [OR]: 11.11, P < .05) after adjusting for age, sex, body mass index, history of hypertension, hyperlipidemia, congestive heart failure, chronic obstructive pulmonary disease, OSA, and smoking. The chest pain group had a mean STOP-BANG score of 3.9 ± 1.8 in all patients, and 3.62 ± 0.20 in patients without known history of OSA, representing an elevated risk index for the disease. Conclusions: In patients presenting with chest pain without obstructive CAD on CCTA, there is a strong association between the presence of chest pain and enlarged PAD. They also represent a high-risk group for OSA.

The Therapeutic Potential of Blocking Galectin-3 Expression in Acute Myocardial Infarction and Mitigating Inflammation of Infarct Region: A Clinical Outcome-Based Translational Study

Introduction: Increased galectin-3 is associated with ischemic cardiomyopathy, although its role in early remodeling post-myocardial infarction (MI) has not been fully elucidated. There are no data demonstrating that blocking galectin-3 expression would have an impact on the heart and that its relationship to remodeling is not simply an epiphenomenon. The direct association between galectin-3 and myocardial inflammation, dysfunction, and adverse cardiovascular outcomes post-MI was examined using clinical and translational studies. Methods: We performed expression analysis of 9753 genes in murine model of acute MI. For galectin-3 loss of function studies, homozygous galectin-3 knock-out (KO) mice were subjected to coronary artery ligation procedure to induce acute MI (MI, N = 6; Sham, N = 6). For clinical validation, serum galectin-3 levels were measured in 96 patients with ST-elevation MI. Echocardiographic and angiographic parameters of myocardial dysfunction and 3-month composite outcome including mortality, recurrent MI, stroke, and heart failure hospitalization were measured. Results: In the infarct regions of murine models, galectin-3 was a robustly expressed gene. Elevated galectin-3 expression strongly correlated with macrophage-mediated genes. Galectin-3 KO mice showed reduced myocardial macrophage infiltration after acute MI. Galectin-3 levels were higher in patients with early systolic dysfunction, and predicted 3-month major adverse cardiovascular events (area under the curve [AUC]: 0.917 ± 0.063; P = .001). Conclusions: Galectin-3 is directly associated with early myocardial inflammation post-MI and may represent a potential target for therapeutic inhibition.

IMPROVEMENT IN COST AND EFFICIENCY IN ELECTROPHYSIOLOGY LABORATORY BY CARDIAC COMPUTED TOMOGRAPHY TO EXCLUDE LEFT ATRIAL APPENDAGE THROMBUS PRIOR TO ATRIAL FIBRILLATION ABLATION

Background: Atrial fibrillation (AF) is an ever-increasing problem with growing financial burden on the healthcare system.