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Item A Preliminary Study of Short-Term Sexual Function and Satisfaction among Men Post-Myocardial Infarction(Sage, 2022) Smith, Asa B.; Barton, Debra L.; Davis, Matthew; Jackson, Elizabeth A.; Smith, Jacqui; Wittmann, Daniela; School of NursingSexuality is an important component of holistic quality of life, and myocardial infarction (MI) negatively influences many aspects of sexuality, including sexual function. However, there is limited literature that examines sexuality beyond the most basic physical components. This pilot study aimed to describe the relationships between the physical, psychologic, and social domains of holistic sexuality at an early timepoint post-MI. Adult men post-MI were mailed self-report surveys at two weeks post discharge. Physical domains of sexuality were measured with the arousal, orgasm, erection, lubrication, and pain subscales of the Male Sexual Function Index, (MSFI). The social domain utilized the sexual satisfaction subscale of the MSFI. The psychologic domain included the desire subscale of the MSFI and sexual fear (Multidimensional Sexuality Questionnaire (MSQ)). Spearman correlations were estimated to examine associations among the different measurement subscales. Twenty-four men post-MI were analyzed. Average scores on the MSFI were 9.2 (SD 7.7). Desire and satisfaction were the highest scoring subscales among men when compared with other subscales (i.e., erection, lubrication). There was minimal evidence supporting a relationship between sexual fear and function. Additional research is also needed with larger samples, and among women post-MI.Item Absence of cardiomyocyte differentiation following transplantation of adult cardiac-resident Sca-1+ cells into infarcted mouse hearts(American Heart Association, 2018-12-18) Soonpaa, Mark H.; Lafontant, Pascal J.; Reuter, Sean; Scherschel, John A.; Srour, Edward F.; Zaruba, Marc-Michael; Rubart-von der Lohe, Michael; Field, Loren J.; Medicine, School of MedicineAlthough several lines of evidence suggest that the glycosyl phosphatidylinositol-anchored cell surface protein Sca-1 marks cardiac-resident stem cells, a critical analysis of the literature raises some concerns regarding their cardiomyogenic potential.1 Here, isolated adult cardiac-resident Sca-1+ cells were engrafted into infarcted hearts and monitored for cardiomyogenic differentiation. Donor cells were prepared from ACT-EGFP; MHC-nLAC double-transgenic mice ([C57/Bl6J x DBA/2J]F1 genetic background; all procedures followed were in accordance with Institutional Guidelines). The ACT-EGFP transgene targets ubiquitous expression of an enhanced green fluorescent protein reporter, and the MHC-nLAC transgene targets cardiomyocyte-restricted expression of a nuclear-localized β-galactosidase reporter. Donor cell survival was monitored via EGFP fluorescence, while cardiomyogenic differentiation was monitored by reacting with the chromogenic β-galactosidase substrate 5-bromo-4-chloro-3-indolyl-β-D-galactoside (X-GAL), which gives rise to a blue product.2 Double-transgenic hearts were dispersed with Blendzyme and the resulting cells reacted with an APC-conjugated anti-Sca-1 antibody and a PE-conjugated cocktail of antibodies recognizing hematopoietic lineage markers.3 Sca-1+, EGFP+, lineage- cells were then isolated via fluorescence-activated cell sorting (FACS; characterization of the donor cells is provided in Figure 1A), and 100,000 cells were injected into the infarct border zone of non-transgenic [C57/Bl6J x DBA/2J]F1 mice immediately following permanent coronary artery occlusion.Item Aortic root thrombosis leading to STEMI in a Heartmate 3 patient(Springer, 2023-03) Ilonze, Onyedika J.; Torabi, Asad; Guglin, Maya; Saleem, Kashif; Rao, Roopa; Medicine, School of MedicineDespite left ventricular assist device (LVAD) therapy becoming established for end-stage heart failure (HF), complications remain. Thromboembolic complications are rare with the newest iteration of LVADs. We managed a case of a continuous-flow LVAD-related thromboembolic event that presented as an acute myocardial infarction. A 64-year-old male who underwent Heartmate III® LVAD implantation had crushing substernal chest pain and ventricular tachycardia with acute anterolateral myocardial infarction on electrocardiogram on post-operative day 9. Echocardiography showed closed aortic valve and mild aortic regurgitation, but CT angiography showed thrombus within the left coronary cusp despite full anticoagulation. Continuous suction of blood from the left ventricle despite pulsatile flow into the ascending aorta resulted in a minimally opening aortic valve and stagnation of blood leading to thrombosis on the coronary cusp. Apart from post-operative ventricular tachycardia and right ventricular failure, he had adequate body size (body surface area 2.13 m2) and no post-operative or coagulopathy which could predispose him to thrombosis. Coronary angiography revealed stable severe three-vessel disease and thrombus in left main and proximal circumflex artery, and he had aspiration thrombectomy, and international normalized ratio target was increased to 3–3.5 with aspirin 325 mg daily. He survived to discharge but died 60 days after LVAD implant with multiple low flow alarms, and cardiac arrest. We review the literature and propose a management algorithm for patients with impaired AV opening and aortic root thrombosis.Item Atypical depression and double depression predict new-onset cardiovascular disease in U.S. adults(Wiley, 2018-01) Case, Stephanie M.; Sawhney, Manisha; Stewart, Jesse C.; Psychology, School of ScienceBACKGROUND: Although depression is a risk factor for cardiovascular disease (CVD), it is unknown whether this risk varies across depressive disorder subtypes. Thus, we investigated atypical major depressive disorder (MDD) and double depression as predictors of new-onset CVD in a nationally representative sample of U.S. adults. METHODS: Prospective data from 28,726 adults initially free of CVD who participated in Wave 1 (2001-2002) and Wave 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were examined. Lifetime depressive disorder subtypes (Wave 1) and incident CVD (Wave 2) were determined by structured interviews. RESULTS: We identified 1,116 incident CVD cases. In demographics adjusted models, the atypical MDD group had a higher odds of incident CVD than the no depression history (OR = 2.19, 95% CI: 1.71-2.81, P < .001), dysthymic disorder only (OR = 1.61, 95% CI: 1.08-2.39, P = .019), and nonatypical MDD (OR = 1.46, 95% CI: 1.11-1.91, P = .006) groups. Likewise, the double depression group had a higher odds of incident CVD than the no depression history (OR = 2.17, 95% CI: 1.92-2.45, P < .001), dysthymic disorder only (OR = 1.59, 95% CI: 1.16-2.19, P = .004), and MDD only (OR = 1.46, 95% CI: 1.20-1.77, P < .001) groups. Relationships were similar but attenuated after adjustment for CVD risk factors and anxiety disorders. CONCLUSIONS: Adults with atypical MDD or double depression may be subgroups of the depressed population at particularly high risk of new-onset CVD. Thus, these subgroups may (a) be driving the overall depression-CVD relationship and (b) be in need of earlier and/or more intense CVD primary prevention efforts to reduce their excess CVD burden.Item Chronic heart failure following hemorrhagic myocardial infarction: mechanism, treatment and outlook(Shared Science Publishers, 2023-02-13) Chan, Shing Fai; Vora, Keyur; Dharmakumar, Rohan; Medicine, School of MedicineMyocardial infarction (MI), the blockage of arterial blood supply of the heart, is among the most common causes of death worldwide. Even when patients receive immediate treatment by re-opening blocked arteries, they often develop chronic heart failure (CHF) in the aftermath of MI events. Yet, the factors that contribute to the development of MI-associated CHF are poorly understood. In our recent study (Nat Commun 13:6394), we link intramyocardial hemorrhage, an injury which can occur during reperfusion of areas affected by MI, to an increased risk of CHF. Mechanistically, our data suggest that an iron-induced adverse cascade of events after hemorrhagic MI drives fatty degeneration of infarcted tissue, which ultimately contributes to negative cardiac remodeling. In this Microreview, we discuss the implications of our findings regarding the molecular mechanism, more targeted treatment options as well as perspectives in the clinical care of CHF after hemorrhagic MI.Item Depression and Anxiety Screens as Predictors of 8-Year Incidence of Myocardial Infarction and Stroke in Primary Care Patients(American Psychosomatic Society, 2016-06) Stewart, Jesse C.; Hawkins, Misty A. W.; Khambaty, Tasneem; Perkins, Anthony J.; Callahan, Christopher M.; Psychology, School of ScienceBecause depression and anxiety are typically studied in isolation, our purpose was to examine the relative importance of these overlapping emotional factors in predicting incident cardiovascular disease (CVD). Methods We examined depression and anxiety screens, and their individual items, as predictors of incident hard CVD events, myocardial infarction, and stroke over eight years in a diverse sample of 2,041 older primary care patients initially free of CVD. At baseline, participants completed self-report depression and anxiety screens. Data regarding CVD events were obtained from an electronic medical record system and the Centers for Medicare and Medicaid Services analytic files. Results During follow-up, 683 (33%) experienced a CVD event. Cox proportional hazards models – adjusted for demographic and CVD risk factors – revealed that a positive anxiety screen, but not a positive depression screen, was associated with an increased risk of a hard CVD event in separate models (Years 0–3: Anxiety HR=1.54, p<.001; Years 3+: Anxiety HR=0.99, p=.93; Depression HR=1.10, p=.41), as well as when entered into the same model (Years 0–3: Anxiety HR=1.53, p<.001; Years 3+: Anxiety HR=0.99, p=.99; Depression HR=1.03, p=.82). Analyses examining individual items and secondary outcomes showed that the anxiety-CVD association was largely driven by the feeling anxious item and the myocardial infarction outcome. Conclusions Anxiety, especially feeling anxious, is a unique risk factor for CVD events in older adults, independent of conventional risk factors and depression. Anxiety deserves increased attention as a potential factor relevant to CVD risk stratification and a potential target of CVD primary prevention efforts.Item E2F1 Suppresses Oxidative Metabolism and Endothelial Differentiation of Bone Marrow Progenitor Cells(American Heart Association, 2018-03-02) Xu, Shiyue; Tao, Jun; Yang, Liu; Zhang, Eric; Boriboun, Chan; Zhou, Junlan; Sun, Tianjiao; Cheng, Min; Huang, Kai; Shi, Jiawei; Dong, Nian-Guo; Liu, Qinghua; Zhao, Ting C.; Qiu, Hongyu; Harris, Robert A.; Chandel, Navdeep S.; Losordo, Douglas W.; Qin, Gangjian; Biochemistry and Molecular Biology, School of MedicineRATIONALE: The majority of current cardiovascular cell therapy trials use bone marrow progenitor cells (BM PCs) and achieve only modest efficacy; the limited potential of these cells to differentiate into endothelial-lineage cells is one of the major barriers to the success of this promising therapy. We have previously reported that the E2F transcription factor 1 (E2F1) is a repressor of revascularization after ischemic injury. OBJECTIVE: We sought to define the role of E2F1 in the regulation of BM PC function. METHODS AND RESULTS: Ablation of E2F1 (E2F1 deficient) in mouse BM PCs increases oxidative metabolism and reduces lactate production, resulting in enhanced endothelial differentiation. The metabolic switch in E2F1-deficient BM PCs is mediated by a reduction in the expression of pyruvate dehydrogenase kinase 4 and pyruvate dehydrogenase kinase 2; overexpression of pyruvate dehydrogenase kinase 4 reverses the enhancement of oxidative metabolism and endothelial differentiation. Deletion of E2F1 in the BM increases the amount of PC-derived endothelial cells in the ischemic myocardium, enhances vascular growth, reduces infarct size, and improves cardiac function after myocardial infarction. CONCLUSION: Our results suggest a novel mechanism by which E2F1 mediates the metabolic control of BM PC differentiation, and strategies that inhibit E2F1 or enhance oxidative metabolism in BM PCs may improve the effectiveness of cell therapy.Item Effects of smoke-free air law on acute myocardial infarction hospitalization in Indianapolis and Marion County, Indiana(BMC Public Health, 2018-02-09) Weaver, Anne M.; Wang, Yi; Rupp, Katelin; Watson, Dennis P.Background A comprehensive smoke-free air law was enacted on June 1, 2012 in most of Marion County, Indiana, including all of the City of Indianapolis. We evaluated changes in acute myocardial infarction (AMI) admission rates in Indianapolis and Marion County before compared to after the law. Methods We collected AMI admissions from five Marion County hospitals between May 2007 and December 2014. We used Poisson regression to evaluate the overall effects of the law on monthly AMI hospitalizations, adjusting for month, seasonality, meteorology, air pollution, and hospital utilization. We tested the interactions between the law and AMI risk factors on monthly AMI admission rates to identify subpopulations for which the effects might be stronger. Results Monthly AMI admissions declined 20% (95% CI 14–25%) in Marion County and 25% (95% CI 20–29%) in Indianapolis after the law was implemented. We observed decreases among never (21%, 95% CI 13–29%), former (28%, 95% CI 21–34%), and current smokers (26%, 95% CI 11–38%); Medicaid beneficiaries (19%, 95% CI 9–29%) and non-beneficiaries (26%, 95% CI 20–31%). We observed decreases among those with a history of diabetes (Yes: 22%, 95% CI 14–29%; No: 25%, 95% CI 18–31%), congestive heart failure (Yes: 23%, 95% CI 16–30%; No: 24%, 95% CI 17–31%), and hypertension (Yes: 23%, 95% CI 17–28%: No: 26%, 95% CI 15–36%). Conclusions We observed decreases in AMI admissions comparable with previous studies. We identified subpopulations who benefitted from the law, such as former and current smokers, and those without comorbidities such as congestive heart failure and hypertension.Item Fallacy of Median Door-to-ECG Time: Hidden Opportunities for STEMI Screening Improvement(American Heart Association, 2022) Yiadom, Maame Yaa A.B.; Gong, Wu; Patterson, Brian W.; Baugh, Christopher W.; Mills, Angela M.; Gavin, Nicholas; Podolsky, Seth R.; Salazar, Gilberto; Mumma, Bryn E.; Tanski, Mary; Hadley, Kelsea; Azzo, Caitlin; Dorner, Stephen C.; Ulintz, Alexander; Liu, Dandan; Emergency Medicine, School of MedicineBackground: ST‐segment elevation myocardial infarction (STEMI) guidelines recommend screening arriving emergency department (ED) patients for an early ECG in those with symptoms concerning for myocardial ischemia. Process measures target median door‐to‐ECG (D2E) time of 10 minutes. Methods and Results: This 3‐year descriptive retrospective cohort study, including 676 ED‐diagnosed patients with STEMI from 10 geographically diverse facilities across the United States, examines an alternative approach to quantifying performance: proportion of patients meeting the goal of D2E≤10 minutes. We also identified characteristics associated with D2E>10 minutes and estimated the proportion of patients with screening ECG occurring during intake, triage, and main ED care periods. We found overall median D2E was 7 minutes (IQR:4–16; range: 0–1407 minutes; range of ED medians: 5–11 minutes). Proportion of patients with D2E>10 minutes was 37.9% (ED range: 21.5%–57.1%). Patients with D2E>10 minutes, compared to those with D2E≤10 minutes, were more likely female (32.8% versus 22.6%, P=0.005), Black (23.4% versus 12.4%, P=0.005), non‐English speaking (24.6% versus 19.5%, P=0.032), diabetic (40.2% versus 30.2%, P=0.010), and less frequently reported chest pain (63.3% versus 87.4%, P<0.001). ECGs were performed during ED intake in 62.1% of visits, ED triage in 25.3%, and main ED care in 12.6%. Conclusions: Examining D2E>10 minutes can identify opportunities to improve care for more ED patients with STEMI. Our findings suggest sex, race, language, and diabetes are associated with STEMI diagnostic delays. Moving the acquisition of ECGs completed during triage to intake could achieve the D2E≤10 minutes goal for 87.4% of ED patients with STEMI. Sophisticated screening, accounting for differential risk and diversity in STEMI presentations, may further improve timely detection.Item Fibrin clot strength measured by thrombelastography and outcomes after percutaneous coronary intervention(Thieme, 2017-01-26) Kreutz, Rolf P.; Schmeisser, Glen; Maatman, Benjamin; Schaffter, Andrea; Sinha, Anjan; von der Lohe, Elisabeth; Breall, Jeffrey A.; Medicine, School of Medicine