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.

The relationship of myocardial and liver T2* values with cardiac function and laboratory findings in transfusion-dependent thalassemia major patients: A retrospective cardiac MRI study.

Introduction: Cardiac complications are the leading cause of death in thalassemia patients. It is assumed that progressive iron accumulation results in myocyte damage. Myocardial T2* measurement by cardiac MRI quantifies iron overload. We aimed to study the association between left and right ventricular (LV and RV) function and iron deposition estimation by cardiac MRI T2* in a sample of Iranian patients. Methods: Cardiac MRI exams of 118 transfusion-dependent thalassemia major patients were evaluated retrospectively. Biventricular function and volume and myocardial and liver T2* values were measured. The demographic and lab data were registered. Poisson and chi-square regression analyses investigated the correlation between the T2* value and ventricular dysfunction. Results: The study participants' mean (SD) age was 32.7y (9.02), and 47.46% were female. Forty-nine cases (41.52%) revealed at least uni-ventricular dysfunction. LV dysfunction was noted in 20 cases, whereas 47 patients revealed RV dysfunction. The risk of LV dysfunction was 5.3-fold higher in patients with cardiac T2* value less than 10msec (RR=5.3, 95% CI=1.6, 17.1, P<0.05). No association was found between age, liver T2* value, serum ferritin level, and chelation therapy with the risk of LV and RV dysfunction. Conclusion: Cardiac MRI T2* measure is a good indicator of LV dysfunction. Moreover, MRI parameters, especially RV functional measures, may have a substantial role in patient management. Therefore, cardiac MRI should be included in beta-thalassemia patients' management strategies.

Factors associated with recurrent spontaneous coronary artery dissection: a systematic review and meta-analysis.

BACKGROUND: The risk of recurrent spontaneous coronary artery dissection (SCAD) is a major concern to SCAD patients and clinicians. Identifying the high-risk subsets of recurrent SCAD remains an ongoing challenge. The meta-analysis aimed to assess the potential predictors for SCAD recurrence. METHODS: A literature search was performed in PubMed to collect studies that assessed potential factors associated with recurrence of SCAD among angiographically confirmed SCAD patients, including pregnancy, ventricular arrhythmia at presentation, history of hypertension, migraine, fibromuscular dysplasia (FMD), extracoronary vascular abnormalities (EVA), recent emotional or physical stress, and use of thienopyridine, beta-blocker, or statin. A meta-analytic approach was employed to estimate the relative risk (RR) with a 95% confidence interval (CI) by fitting random-effects models using the generic inverse variance weighted method. RESULTS: A total of 14 studies representing 4206 SCAD patients were included. Hypertension (RR, 1.49; 95% CI, 1.05-2.12; P = 0.0247) and FMD (RR, 2.02; 95% CI, 1.03-3.94; P = 0.0404) were associated with a greater risk of SCAD recurrence. The use of beta-blocker (RR, 0.51; 95% CI, 0.33-0.77; P = 0.0013) was associated with a lower risk of SCAD recurrence. Pregnancy, ventricular arrhythmia at presentation, migraine, EVA, recent emotional or physical stress, and use of thienopyridine or statin were not significantly associated with recurrent SCAD ( P > 0.05). CONCLUSION: SCAD patients with hypertension or FMD were at a higher risk of recurrence, whereas beta-blocker usage was related to a reduced risk. These findings may provide insights into risk prediction and management after the SCAD episode.

Feature-tracking cardiac magnetic resonance method: a valuable marker of replacement fibrosis in hypertrophic cardiomyopathy.

Purpose: Left ventricular (LV) replacement fibrosis is a marker of adverse cardiac events in hypertrophic cardiomyopathy (HCM). We aimed to assess the efficacy of the feature-tracking cardiac magnetic resonance (FT-CMR) in the detection of LV replacement fibrosis. Material and methods: Fifty-one patients with HCM (51% female, mean age = 21 ± 5.2 years) and significant myocardial hypertrophy, who underwent CMR between February 2018 and December 2019 were enrolled. Functional and 3D FT-CMR parameters were measured. LV global longitudinal strain, global radial strain (GRS), and global circumferential strain (GCS) were recorded. The percentage of enhanced myocardial mass was calculated. Univariate and multivariate regression analyses were performed to determine the predictors of fibrosis. A p-value of less than 0.05 was considered significant. Results: The mean enhanced mass percentage was 15.2 ± 10.53%. Among LV volumetric parameters, end-systolic and end-diastolic volume indices predicted fibrosis (fitness [F] = 8.11 and p = 0.006 vs. F = 6.6 and p = 0.012, correspondingly). The univariate linear regression demonstrated that GCS and GRS predicted total enhanced mass (%) (F = 12.29 and p = 0.001 vs. F = 7.92 and p = 0.007, respectively). After the inclusion of all volumetric and deformation parameters, the multivariate analysis identified the model of a combination of LV end-diastolic volume index (LV EDVI) and LV GCS as a robust predictor of the fibrosis percentage (F = 8.86 and p = 0.005). Conclusions: Non-contrast CMR parameters including LV GCS and LV EDVI are valuable markers of replacement fibrosis in HCM patients with notable myocardial hypertrophy.

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.

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.

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.

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.