The genetics of spontaneous coronary artery dissection: a scoping review.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a multifactorial process that involves predisposing factors and precipitating stressors. Genetic abnormality has been implicated to play a mechanistic role in the development of SCAD. This systematic review aims to summarize the current evidence concerning the link between SCAD and genetic abnormalities. METHODS: We reviewed original studies published until May 2023 that reported SCAD patients with a genetic mutation by searching PubMed, Embase Ovid, and Google Scholar. Registries, cohort studies, and case reports were included if a definitive SCAD diagnosis was reported, and the genetic analysis was performed. Exclusion criteria included editorials, reviews, letters or commentaries, animal studies, meeting papers, and studies from which we were unable to extract data. Data were extracted from published reports. RESULTS: A total of 595 studies were screened and 55 studies were identified. Among 116 SCAD patients with genetic abnormalities, 20% had mutations in the COL gene, 13.70% TLN1 gene, and 8.42% TSR1 gene. Mutations affecting the genes encoding COL and TLN1 were most frequently reported (20 and 13.7%, respectively). Interestingly, 15 genes of this collection were also reported in patients with thoracic aortic diseases as well. The genetic commonality between fibromuscular dysplasia (FMD) and SCAD was also included. CONCLUSION: In this review, the inherited conditions and reported genes of undetermined significance from case reports associated with SCAD are collected. A brief description of the encoded protein and the clinical features associated with pathologic genes is provided. Current data suggested that the diagnostic yield of genetic studies for patients with SCAD would be low and routine genetic screening of such patients with no clinical features indicative of associated disorders remains debatable. This review can be used as a guide for clinicians to recognize inherited syndromic and nonsyndromic disorders associated with SCAD.

Evaluation of Cardiac Troponin and Adverse Outcomes After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis.

Several studies have demonstrated the usefulness of cardiac troponin I (cTn) levels in predicting adverse clinical outcomes of patients with anerusmal subarachnoid hemorrhage (aSAH). However, it remains unclear whether cTn levels can be a useful factor in predicting adverse neurologic and cardiovascular outcomes regarding follow-up duration. The study aimed to evaluate the clinical value of cTn elevation among patients with aSAH. A systematic literature search was performed in PubMed and Cochrane to collect original studies that compared the adverse outcomes in patients with aSAH who had elevated cTn levels and those who did not have elevated cTn levels. Data on patient demographics and outcome measurements (mortality, major disability, delayed cerebral ischemia, cardiac dysfunction, and pulmonary edema) were extracted. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were computed by fitting a random effects model. A total of 4,117 patients with aSAH were included in the meta-analysis. Elevated cTn levels was associated with a higher all-cause mortality (OR 3.64; 95% CI 2.68-4.94; I2 = 22.05%), poor major disability (OR 2.27; 95% CI 1.5-3.37; I2 = 52.07%), delayed cerebral ischemia (OR 2.10; 95% CI 1.46-3.03; I2 = 13.80%), cardiac dysfunction (OR 9.20; 95% CI 4.31-19.60; I2 = 39.89), and pulmonary edema (OR 10.32; 95% CI 5.64-18.90; I2 = 0.00%). Additionally, elevated cTn levels was associated with higher mortality in prospective studies (OR 3.66; 95% CI 2.61-5.14) as well as when compared with studies with short-term and long-term follow-up periods. Patients with aSAH who had elevated cTn levels also tended to experience poor short-term major disability (OR 2.36; 95% CI 1.48-3.76). Among patients with aSAH, elevated cTn levels was associated with higher mortality and adverse neurologic and cardiovascular outcomes. Given its clinical value, cardiac troponin levels may be included in the assessment of patients withs aSAH.

Clinical outcomes of pharmacological thromboprophylaxis among patients with intracerebral hemorrhage: Systematic review and meta-analysis.

OBJECTIVE: Efficacy and safety of pharmacologic thromboprophylaxis after an episode of intracerebral hemorrhage remains unclear. This meta-analysis aimed at comparing the clinical outcomes of intracerebral hemorrhage patients with or without pharmacologic thromboprophylaxis. METHODS: We performed a comprehensive literature review of PubMed to identified relevant studies. The primary and secondary endpoints included venous thromboembolism, deep venous thrombosis, pulmonary emboli, rebleeding, hematoma enlargement (defined as increase in hematoma volume of ≥33%), major disability (defined as modified Rankin score of 3-5), and death. Pooled outcomes were estimated by fitting random effects model with restricted maximum likelihood method. A total of 8 original studies including 3893 patients were analyzed. RESULT: Compared to the control group, pharmacologic thromboprophylaxis was associated with a lower risk of pulmonary embolism (odds ratio [OR]: 0.34, 95% CI: 0.15-0.80, P = 0.01). There was no significant difference in the risk of DVT (OR: 0.75; [95% CI: 0.37-1.53], P = 0.44) and VTE (OR: 0.65; [95% CI: 0.34-1.25], P = 0.20). Finally, anticoagulation was not associated with an increase rate of major disability (OR:1.36; [95% CI: 0.57 - 3.23], P = 0.48), rebleeding (OR: 0.35; [95% CI: 0.10-1.19], P = 0.09), hematoma enlargement (OR:1.34; [95% CI: 0.58-3.12], P = 0.49), or death (OR:0.90; [95% CI: 0.68-1.19], P = 0.46). CONCLUSION: Among patients with intracerebral hemorrhage, pharmacologic thromboprophylaxis was associated with a significant reduction in pulmonary embolism, without an increase in rebleeding or hematoma enlargement. The results of this meta-analysis need to be further validated in large scale clinical trials.

Effect of azithromycin and hydroxychloroquine in patients hospitalized with COVID-19: Network meta-analysis of randomized controlled trials.

Chloroquine or its derivative hydroxychloroquine (HCQ) combined with or without azithromycin (AZ) have been widely investigated in observational studies as a treatment option for coronavirus 2019 (COVID-19) infection. The network meta-analysis aims to summarize evidence from randomized controlled trials (RCTs) to determine if AZ or HCQ is associated with improved clinical outcomes. PubMed and Embase were searched from inception to March 7, 2021. We included published RCTs that investigated the efficacy of AZ, HCQ, or its combination among hospitalized patients with COVID-19 infection. The outcomes of interest were all-cause mortality and the use of mechanical ventilation. The pooled odds ratio was calculated using a random-effect model. A total of 10 RCTs were analyzed. Participant's mean age ranged from 40.4 to 66.5 years. There was no significant effect on mortality associated with AZ plus HCQ (odds ratio [OR] = 0.562 [95% confidence interval {CI}: 0.168-1.887]), AZ alone (OR = 0.965 [95% CI: 0.865-1.077]), or HCQ alone (OR = 1.122 [95% CI: 0.995-1.266]; p = 0.06). Similarly, based on pooled effect sizes derived from direct and indirect evidence, none of the treatments had a significant benefit in decreasing the use of mechanical ventilation. No heterogeneity was identified (Cochran's Q = 1.68; p = 0.95; τ2 = 0; I2 = 0% [95% CI: 0%-0%]). Evidence from RCTs suggests that AZ with or without HCQ was not associated with a significant effect on the mortality or mechanical ventilation rates in hospitalized patients with COVID-19. More research is needed to explore therapeutics agents that can effectively reduce the mortality or severity of COVID-19.

Current Opinion on the use of Direct Oral Anticoagulants for the Prophylaxis of Venous Thromboembolism among Medical Inpatients.

Venous thromboembolism (VTE) is a known cause of morbidity and mortality, especially among acutely ill medical patients. Although VTE prophylaxis is part of post-discharge clinical care in surgical patients, there is controversy regarding its use in acutely ill medical patients and the current guideline statements suggest against its routine use. Recent clinical trials (APEX, MAGELLAN and MARINER) compared the safety and efficacy of direct oral anticoagulants (including betrixaban and rivaroxaban) with the standard of the care, enoxaparin, to identify the risk-benefit tradeoff. In this review, we summarized the key findings from these trials and substudies and recent updates in society guidelines regarding VTE prevention. In addition, we discussed the potential barriers, cost-effectiveness, and COVID-19 with respect to the implementation of extended-duration or post-discharge usage of direct oral anticoagulants.

COVID-19-associated coagulopathy: a concise review on pathogenesis and clinical implications.

In this review, we summarize the possible mechanisms of COVID-19-associated coagulopathy and compare its features to other similar conditions. The recent COVID-19 pandemic has caused enormous mortality and morbidity worldwide. It is important to note that COVID-19-associated thrombotic events play a huge role in the morbidity of this disease. Interestingly, it has been observed that this complication may occur despite prophylactic anticoagulant therapy. Recent studies on COVID-19-associated coagulopathy revealed that the COVID-19-associated hypercoagulability is more frequently observed among those with a severe course of the disease. Various mechanisms have been suggested as explanations for this condition and possible underlying etiologies.

COVID-19: A double threat to takotsubo cardiomyopathy and spontaneous coronary artery dissection?

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic that has affected millions of individuals worldwide. Prior studies suggest that COVID-19 may be associated with an increased risk for various cardiovascular disorders, such as myocardial injury, arrhythmia, acute coronary syndrome, and venous thromboembolism. Early reports of non-COVID-19 patients have described the concurrence of takotsubo cardiomyopathy (TTC) and spontaneous coronary artery dissection (SCAD). However, the interplay between COVID-19, TTC and SCAD has not been well established. We herein propose two sets of two-hit hypotheses for the development of SCAD and TTC in the context of COVID-19. The first two-hit hypothesis explains the development of SCAD, in which TTC-associated formation of vulnerable coronary substrate serves as the first hit (predisposing factor), and COVID-19-associated inflammation and vascular disruption serves as the second hit (precipitating factor). The second two-hit hypothesis is proposed to explain the development of TTC, in which SCAD-associated formation of vulnerable myocardial substrate serves as the first hit, and COVID-19-associated sympathetic overactivity serves as the second hit. Under this conceptual framework, COVID-19 poses a double threat for the development of SCAD (among patients with underlying TTC) as well as TTC (among patients with underlying SCAD), thereby forming a reciprocal causation. This hypothesis provides a rationale for the joint assessment of TTC and SCAD in COVID-19 patients with pertinent cardiovascular manifestations.

Prognostic Value of Biomarkers in Cardiac Allograft Vasculopathy following Heart Transplantation: A Literature Review.

Cardiac allograft vasculopathy (CAV), also known as cardiac transplant vasculopathy, is a major determinant of long-term survival among cardiac transplantation recipients. Histologically, CAV is featured by diffuse, concentric thickening of the vascular wall, and primarily affects large and small epicardial coronary arteries, intramyocardial arteries, and veins. Owing to graft denervation, CAV typically follows an insidious course, and patients may not experience classic angina symptoms but instead present with progressive heart failure or ventricular arrhythmias. Recent studies on biomarkers have furthered the knowledge concerning the prediction and prognosis of CAV. Given its association with metabolic, thrombotic, inflammatory, and immunologic markers, CAV is likely to represent a complex multifactorial process that involves both immune-mediated and non-immune-mediated pathways. In order to identify the high-risk patients that would benefit from early intervention, future research is warranted to examine the usefulness of a biomarker panel in CAV risk stratification.

Venous Thromboembolism among Hospitalized Patients with COVID-19 Undergoing Thromboprophylaxis: A Systematic Review and Meta-Analysis.

BACKGROUND: Preliminary evidence indicates that prophylactic-dose thromboprophylaxis may be inadequate to control the increased risk of venous thromboembolism (VTE) in patients hospitalized for coronavirus disease 2019 (COVID-19) infection. Additionally, it remains unclear whether the D-dimer measurement is useful for VTE risk stratification among COVID-19 patients. This study aimed to offer benchmark data on the incidence of VTE and to examine the difference in D-dimer levels among anticoagulated COVID-19 patients with and without VTE incident. METHODS: A comprehensive literature review of PubMed from inception to May 2020 was performed for original studies that reported the frequency of VTE and death among COVID-19 patients who received thromboprophylaxis on hospitalization. The endpoints included VTE (a composite of pulmonary embolism (PE) or deep vein thrombosis (DVT)), PE, DVT, and mortality. RESULTS: A total of 11 cohort studies were included. Among hospitalized COVID-19 patients, 23.9% (95% confidence interval (CI), 16.2% to 33.7%; I2 = 93%) developed VTE despite anticoagulation. PE and DVT were detected in 11.6% (95% CI, 7.5% to 17.5%; I2 = 92%) and 11.9% (95% CI, 6.3% to 21.3%; I2 = 93%) of patients, respectively. Patients in the intensive care unit (ICU) had a higher risk for VTE (30.4% )95% CI, 19.6% to 43.9%)) than those in the ward (13.0% (95% CI, 5.9% to 26.3%)). The mortality was estimated at 21.3% (95% CI, 17.0% to 26.4%; I2 = 53%). COVID-19 patients who developed VTE had higher D-dimer levels than those who did not develop VTE (mean difference, 2.05 µg/mL; 95% CI, 0.30 to 3.80 µg/mL; P = 0.02). CONCLUSIONS: The heightened and heterogeneous risk of VTE in COVID-19 despite prophylactic anticoagulation calls into research on the pathogenesis of thromboembolic complications and strategy of thromboprophylaxis and risk stratification. Prominent elevation of D-dimer may be associated with VTE development and can be used to identify high-risk subsets.

Effect of Vitamins and Dietary Supplements on Cardiovascular Health.

Cardiovascular disease marks the leading cause of mortality and morbidity in the United States. Pharmacological therapies have been developed to reduce the burden of cardiovascular diseases in the setting of large-scale randomized controlled trials. In contrast, vitamins and minerals have not undergone an equal level of scrutiny, and the evidence of cardiovascular benefit remains elusive. Multivitamins are the most popular over-the-counter supplements in the United States, despite the lack of clear benefit as a means of primary or secondary cardiovascular prevention. Recent studies indicate a potential role of multivitamins in secondary prevention when concomitantly administered with chelation therapy. Additionally, preclinical and observational studies have shown preliminary evidence of cardiovascular protection with dietary supplements such as carnitine, arginine, and coenzyme Q10. This review summarizes the currently available data about the effect of vitamins and other dietary supplements on the cardiovascular system.

The AngelMed Guardian® System in the Detection of Coronary Artery Occlusion: Current Perspectives.

Total ischemic time, which specifies the time from the onset of chest pain to initiation of reperfusion during percutaneous coronary intervention, consists of two intervals: symptom to door time and door to balloon time. A door to balloon time of 90 mins or less has become a quality-of-care metric in the management of ST elevation myocardial infarction (STEMI). While national efforts made by the American College of Cardiology (ACC) and American Heart Association (AHA) have curtailed in-hospital door to balloon time over the years, a reduction in pre-hospital symptoms to door time presents a challenge in modern interventional Cardiology. Early and complete revascularization has been associated with improved clinical outcomes in MI and strategies that may help reduce symptom to door time, and thus the total ischemic time, are crucial. Rapidly evolving ST-segment changes commonly develop prior to ischemia-related symptom onset, and are detectable even in patients with clinically unrecognized silent MIs. Therefore, a highly intelligent ischemia detection system that alerts patients of ST segment deviation may allow for rapid identification of acute coronary occlusion. The AngelMed Guardian® System is a cardiac activity monitoring and alerting system designed for rapid identification of intracardiac ST-segment changes among patients at a high risk for recurrent ACS events. This article reviews the clinical studies evaluating the design, safety and efficacy of the AngelMed Guardian System and discusses the clinical implications of the device.

Spontaneous coronary artery dissection managed with a conservative or revascularization approach: a meta-analysis.

BACKGROUND: The optimal treatment approach for spontaneous coronary artery dissection (SCAD) remains unclear. OBJECTIVES: The study aims to compare in-hospital and long-term clinical outcomes of SCAD patients initially managed with medical therapy (conservative approach) versus percutaneous coronary intervention or coronary artery bypass grafting (revascularization approach) based on published data. METHODS: We identified relevant studies by performing a systematic search in the Ovid MEDLINE and Embase databases. Studies with N at least 10 that report in-hospital outcomes [death, myocardial infarction (MI) and revascularization] or long-term outcomes (death, MI, revascularization, SCAD recurrence, and heart failure) were included. Risk difference between conservative and revascularization approach was estimated with the inverse variance-weighted method in a fixed-effect or random-effect model. RESULTS: A total of 22 nonrandomized, observational studies were analyzed (N = 1435). Compared with the initial revascularization approach, the conservative approach was associated with a comparable risk of in-hospital outcomes [risk difference: death, -0.61% (95% confidence interval, -2.13-0.91%), P = 0.43; MI, -0.99% (-4.65-2.67%), P = 0.60; revascularization, -3.02% (-8.79-2.75%), P = 0.31] and long-term outcomes [death, -0.06% (-2.33-2.20%), P = 0.96; MI, 0.96% (-2.35-4.27%), P = 0.57; revascularization, -3.31% (-7.63-1.02%), P = 0.13; SCAD recurrence, 3.75% (-2.05-9.55%), P = 0.21; heart failure, -0.01% (-3.13-3.11%), P = 0.99]. There was no significant heterogeneity across these studies. CONCLUSION: Pooled results suggest that SCAD patients initially managed with a conservative strategy may have similar in-hospital and long-term outcomes compared with those who received revascularization in the absence of ongoing ischemia or left main artery involvement. More data from prospective studies are warranted to validate these findings.

Smartwatch for the Detection of Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia and poses a substantial economic burden due to associated thromboembolic complications. Screening for AF may theoretically be effective, but there is no consensus regarding the optimal screening method because the available tools are either invasive or not cost-effective. Recently, smartwatch industry has received a surge of interest for this purpose by introducing technologies such as photoplethysmography, artificial intelligence, and actual electrodes taking an electrocardiogram to measure and analyze heart rate and rhythm with relatively acceptable accuracy. Combined with other features such as ease of use and connectivity, smartwatches can potentially be used for large-scale AF screening and might eventually replace the current gold standards. In this review, we discuss the feasibility of this approach and summarize the current evidence on AF detection with smartwatches.