Mortality in ST-Segment Elevation Myocardial Infarction With Nonobstructive Coronary Arteries and Mimickers.

Importance: The clinical characteristics and prognosis of patients with ST-segment elevation myocardial infarction (STEMI) with nonobstructive coronaries (MINOCA) are largely unknown. Objective: To assess differences in 5-year mortality in patients presenting with STEMI due to MINOCA and MINOCA mimickers as compared with obstructive disease. Design, Setting, and Participants: A retrospective analysis of a prospective registry-based cohort study of consecutive STEMI activations at 3 regional Midwest STEMI programs. STEMI without a culprit artery and elevated troponin levels were categorized as MINOCA (absence of coronary artery stenosis >50% and confirmed or suspected coronary artery plaque disruption, epicardial coronary spasm, or coronary embolism/thrombosis) or MINOCA mimickers (takotsubo cardiomyopathy, myocarditis, or nonischemic cardiomyopathy). Data were analyzed from March 2003 to December 2020. Main Outcomes and Measures: Adjusted Cox regression analysis was used to assess 5-year mortality risk in STEMI presenting with MINOCA and MINOCA mimickers in comparison with obstructive disease. Results: Among 8560 consecutive patients with STEMI, mean (SD) age was 62 (14) years, 30% were female (2609 participants), and 94% were non-Hispanic White (4358 participants). The cohort included 8151 patients with STEMI due to obstructive disease (95.2%), 120 patients with MINOCA (1.4%), and 289 patients with MINOCA mimickers (3.8%). Patients were followed up for a median (IQR) of 7.1 (3.6-10.7) years. Patients with MINOCA and MINOCA mimickers were less likely to be discharged with cardiac medications compared with obstructive disease. At 5-year follow-up, mortality in STEMI presenting with obstructive disease (1228 participants [16%]) was similar to MINOCA (20 participants [18%]; χ21 = 1.1; log-rank P = .29) and MINOCA mimickers (52 participants [18%]; χ21 = 2.3; log-rank P = .13). In adjusted Cox regression analysis compared with obstructive disease, the 5-year mortality hazard risk was 1.93 times higher in MINOCA (95% CI, 1.06-3.53) and similar in MINOCA mimickers (HR, 1.08; 95% CI, 0.79-1.49). Conclusions and Relevance: In this large multicenter cohort study of consecutive clinical patients with STEMI, presenting with MINOCA was associated with a higher risk of mortality than obstructive disease; the risk of mortality was similar in patients with MINOCA mimickers and obstructive disease. Further investigation is necessary to understand the pathophysiologic mechanisms involved in this high-risk STEMI population.

COVID-19 STEMI related to microthrombi may lead to coronary microvascular dysfunction.

Coronavirus disease 2019 (COVID-19) increases the risk of ST-segment elevation myocardial infarction (STEMI), and is associated with a higher occurrence of nonobstructive coronary artery disease. We present a unique case of STEMI with concomitant COVID-19 infection in a young female found to have slow flow in multiple vessels on angiography, likely due to microvascular thrombi. Three months later, the patient developed coronary microvascular dysfunction (CMD), suggesting an evolution of microvascular thrombi and injury into subsequent CMD.

Characteristics and Long-term Mortality in Patients with ST-Segment Elevation Myocardial Infarction with Non-Obstructive Coronary Arteries (STE-MINOCA): A High Risk Cohort.

Background: The prognosis of ST-segment elevation myocardial infarction with non-obstructive coronaries (STE-MINOCA) is largely unknown. Methods: The objective of this study is to evaluate the prevalence, characteristics, and 5-year mortality of patients with STE-MINOCA compared to STEMI with coronary artery obstruction (STEMI-Obstruction) using a multicenter cohort of consecutive STEMI patients at 3 regional Midwest STEMI programs from 2003 to 2020. STE-MINOCA was defined based on (1) coronary stenosis < 60% by visual estimation, (2) ischemia with elevated troponin, and (3) no alternative diagnosis. STE-MINOCA was further classified based on American Heart Association (AHA) definition as AHA STE-MINOCA and AHA STE-MINOCA Mimicker. Results: 8,566 STEMI patients, including 420 (4.9%) STE-MINOCA (26.9% AHA STE-MINOCA and 73.1% AHA STE-MINOCA Mimicker) were followed for a median of 7.1 years. Compared to STEMI-Obstruction, STE-MINOCA were younger, more often female, had fewer cardiovascular risk factors, and were less likely to be discharged on cardiac medications. At five years, mortality was higher in STE-MINOCA compared with STEMI-Obstruction (18% vs. 15%, p=0.033). In propensity score-matched analysis, STE-MINOCA had a 1.4-fold (95% CI: 1.04-1.89, p=0.028) higher risk of 5-year all-cause mortality compared with STEMI-Obstruction. Furthermore, 5-year mortality risk was significantly higher in AHA STE-MINOCA Mimicker (19% vs. 15%, p=0.043) but similar in AHA STE-MINOCA (17% vs. 15%, p=0.42) compared with STEMI-Obstruction. Conclusions: In this large multicenter STEMI cohort, nearly 5% of patients presented with STE-MINOCA. At five years, mortality approached 20% among patients with STE-MINOCA. Despite the lower risk profile, STE-MINOCA patients were at 40% higher risk of 5-year all-cause mortality compared with STEMI-Obstruction. Additionally, 5-year all-cause mortality risk was higher in AHA STE-MINOCA Mimicker but similar in AHA STE-MINOCA compared to STEMI-Obstruction.

Long-term sequelae of adverse pregnancy outcomes.

A growing body of literature highlights the importance of recognizing adverse pregnancy outcomes (APOs) as cardiovascular risk factors when risk stratifying women for cardiovascular disease (CVD). We conducted a comprehensive review of the long term cardiovascular consequences associated with APOs including hypertensive disorders of pregnancy (HDP), preterm delivery, gestational diabetes (GDM), low birth weight and fetal growth restriction during pregnancy using electronic databases, PubMed and the Cochrane Library. Women with pregnancies complicated by HDP, preterm birth, and low birth weight are at higher risk of developing CVD than were women without APOs in the years following pregnancy. Among women with a history of multiple APOs, HDP and GDM are independent risk factors for atherosclerotic CVD. The pathophysiology leading to CVD is multifactorial, and includes both physiologic and environmental factors. APOs should be accounted for in a women's CVD risk assessment and stratification as recommended by prevention guidelines. Further research is needed to determine the underlying mechanisms that lead to the increased risk of CVD in women with APOs.

Histological experimental study on the effect of stem cell therapy on adriamycin induced chemobrain.

BACKGROUND AND OBJECTIVES: Negative consequences of chemotherapy on brain function were suggested and were addressed in animal models as the clinical phenomenon of chemobrain .It was postulated that adriamycin (ADR) induce changes in behaviour and in brain morphology. Human umbilical cord mesenchymal stem cells (HUCMSCs) could be induced to differentiate into neuron-like cells .The present study aimed at investigating the possible therapeutic effect of HUCMSC therapy on adriamycin induced chemobrain in rat. METHODS AND RESULTS: Twenty five female albino rats were divided into control group, ADR group where rats were given single intraperitoneal (IP) injection of 5 mg/kg ADR. The rats were sacrificed two and four weeks following confirmation of brain damage. In stem cell therapy group, rats were injected with HUCMSCs following confirmation of brain damage and sacrificed two and four weeks after therapy. Brain sections were exposed to histological, histochemical, immunohistochemical and morphometric studies. In ADR group, multiple shrunken neurons exhibiting dark nuclei and surrounded by vacuoles were seen .In response to SC therapy ,multiple normal pyramidal nerve cells were noted. The area of shrunken nerve cells exhibiting dark nuclei, Prussion blue and CD105 positive cells were significantly different in ADR group in comparison to SC therapy group. CONCLUSIONS: ADR induced progressive duration dependant cerebral degenerative changes. These changes were ameliorated following cord blood human mesenchymal stem cell therapy. A reciprocal relation was recorded between the extent of regeneration and the existence of undifferentiated mesenchymal stem cells.

A comparison between two strategies for monitoring hepatic function during antituberculous therapy.

RATIONALE: The optimum strategy for monitoring liver function during antituberculous therapy is unclear. OBJECTIVES: To assess the value of the American Thoracic Society risk-factor approach for predicting drug-induced liver injury and to compare with a uniform policy of liver function testing in all patients at 2 weeks. METHODS: We conducted an observational study of adult patients undergoing therapy for active tuberculosis at a tertiary center. All patients had alanine transferase measurement at baseline and 2 weeks following commencement of therapy. Sensitivity, specificity, and positive and negative predictive values were used to assess strategies. MEASUREMENTS AND MAIN RESULTS: There were 288 patients included, and 21 (7.3%) developed drug-induced liver injury (57.1% "early" at 2 wk and 42.9% "late," after 2 wk). There were increased rates of individuals with HIV infection in the early drug-induced liver injury group compared with no drug-induced liver injury and late drug-induced liver injury groups (33% vs. 7.1% vs. 0%; P = 0.004). The American Thoracic Society algorithm had a sensitivity and specificity of 66.7 and 65.6%, respectively, for prediction of early and 22.2% and 63.7% for late drug-induced liver injury. The uniform monitoring policy had poor sensitivity but better specificity (22.2 and 82.1%) for prediction of late drug-induced liver injury. CONCLUSIONS: In our urban, ethnically diverse population, a risk-factor approach is neither sensitive nor specific for prediction of drug-induced liver injury. A uniform policy of liver function testing at 2 weeks is useful for prompt identification of a subgroup who develop early drug-induced liver injury and may offer better specificity in ruling out late drug-induced liver injury.

Effect of stem cell therapy on amiodarone induced fibrosing interstitial lung disease in albino rat.

BACKGROUND AND OBJECTIVES: The fibrosing forms of interstitial lung disease (ILD) are associated with significant morbidity and mortality. ILD may be idiopathic, secondary to occupational, infection, complicate rheumatic diseases or drug induced. Efficacy of antifibrotic agents is as far as, limited and uncertain. No effective treatment was confirmed for pulmonary fibrosis except lung transplantation. The present study aimed at investigating the possible effect of human cord blood mesenchymal stem cell (MSC) therapy on fibrosing ILD. This was accomplished by using amiodarone as a model of induced lung damage in albino rat. METHODS AND RESULTS: Seventeen adult male albino rats were divided into 3 groups. Rats of amiodarone group were given 30 mg/kg of amiodarone orally 6 days/ week for 6 weeks. Rats of stem cell therapy group were injected with stem cells in the tail vein following confirmation of lung damage and left for 4 weeks before sacrifice. Obstructed bronchioles, thickened interalveolar septa and thickened wall of pulmonary vessels were found and proved morphometrically. Reduced type I pneumocytes and increased area% of collagen fibers were recorded. All findings regressed on stem cell therapy. CONCLUSIONS: Cord blood MSC therapy proved definite amelioration of fibrosing interstitial lung disease provided therapy starts early in the development of the pathogenesis.

TEMPOL, a membrane-permeable radical scavenger, attenuates gastric mucosal damage induced by ischemia/reperfusion: a key role for superoxide anion.

The pathogenesis of gastric mucosal injury is a multifaceted process involving reactive oxygen and nitrogen species, both of which play a crucial role in the ischemia/reperfusion model of gastric damage. Hence, several studies have evaluated the anti-ulcerogenic effect of metal chelators, antioxidative enzymes, and low-molecular-weight antioxidants. Low molecular weight superoxide dismutase (SOD) mimetics have been shown to play a protective role against oxidative damage. Therefore, the aim of the current study was to investigate the modulatory effect of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl [TEMPOL (50 mg/kg)], a SOD mimetic, and the SOD inhibitor, diethyldithiocarbamate [DETCA (100 mg/kg)] on gastric lesions induced by ischemia/reperfusion. This insult produced typical gastric lesions, a significant fall in the gastric mucosal glutathione (GSH) and nitric oxide (NO) levels, accompanied by an increase in malondialdehyde (MDA) content and myeloperoxidase (MPO) activity. TEMPOL markedly minimized gastric ulceration and restored MDA, NO, and MPO levels, but did not alter GSH level, which dropped drastically in DETCA treated group, an effect that was not reflected on gross lesions induced by ischemia/reperfusion. In conclusion, TEMPOL can confer protection from gastric ischemia/reperfusion injury possibly by reducing the level of superoxide anion (O(2)(*-)), replenishing NO, and minimizing neutrophil infiltration. Therefore, specific SOD mimetics could be beneficial as complementary agents in the management of gastric ulceration.