Revascularization and long-term outcomes in high-acuity spontaneous coronary artery dissection.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is often treated conservatively due to revascularization risks. Yet, an important number of SCAD patients have high acuity characteristics necessitating revascularization, with uncertain long-term outcomes. OBJECTIVES: Document revascularization utilization and long-term outcomes in high acuity SCAD. METHODS: Prospective/retrospective analysis of consecutive patients with acute myocardial infarction (AMI) due to first SCAD event presenting directly to the Minneapolis Heart Institute 2002-2021, median follow-up 3.8 years. RESULTS: Among 139 patients (age 49 ± 12 years, 96% female), revascularization was performed in 60 (43%), utilizing percutaneous coronary intervention (PCI) (n = 56, successful in 80%) or coronary artery bypass graft (n = 4). In the entire cohort, 90 (65%) unique patients had one or more high acuity characteristic: ST-elevation (38%), proximal dissection (38%), cardiogenic shock (6.5%), cardiac arrest (9.4%), left main dissection (6.5%), peripartum dissection (7.2%). High acuity patients accounted for 51 of 60 (85%) revascularizations. Revascularization rates were: ST-elevation (60%), proximal dissection (62%), cardiogenic shock (89%), cardiac arrest (62%), left main dissection (100%), peripartum dissection (70%). Survival was 97% (revascularized) vs 100% (nonrevascularized); p = 0.2. Adverse outcomes (revascularized vs. nonrevascularized) included recurrent AMI:16.7% versus 8.9%; p = 0.2, SCAD recurrence: 13.3% versus 6.3%; p = 0.1, stroke: 5% versus 2.5%; p = 0.44, implantable cardioverter-defibrillator: 6.7% versus 6.3%; p > 0.9. Reintervention was necessary in 21% of PCI-treated patients. CONCLUSIONS: High-acuity characteristics were present in nearly two-thirds of this SCAD cohort; the vast majority of revascularizations were performed in high-acuity patients. Despite high acuity, long-term survival was favorable in revascularized patients.

Sex-based differences in quality of care and outcomes in a health system using a standardized STEMI protocol.

BACKGROUND: Recent data from the National Cardiovascular Data Registry indicate that women with ST-segment-elevation myocardial infarction (STEMI) continue to have higher mortality and reported delays in treatment compared with men. We aimed to determine whether the sex difference in mortality exists when treatment disparities are reduced. METHODS: Using a prospective regional percutaneous coronary intervention (PCI)-based STEMI system database with a standardized STEMI protocol, we evaluated baseline characteristics, treatment, and clinical outcomes of STEMI patients stratified by sex. RESULTS: From March 2003 to January 2016, 4,918 consecutive STEMI patients presented to the Minneapolis Heart Institute at Abbott Northwestern Hospital regional STEMI system including 1,416 (28.8%) women. Compared with men, women were older (68.4 vs 60.9 years) with higher rates of hypertension (66.7% vs 55.7%), diabetes (21.7% vs 17.4%), and cardiogenic shock (11.5% vs 8.0%) (all P < .001). Pre-revascularization medications and PCI were performed with same frequencies, but women were less likely to receive statin or antiplatelet therapy at discharge. After age adjustment, women had similar in-hospital mortality to men (5.1% vs 4.8%, P = .60) despite slightly longer door-to-balloon time (95 vs 92 minutes, P = .004). Five-year follow-up confirmed absence of a sex disparity in age-adjusted survival post-STEMI. CONCLUSIONS: Previously reported treatment disparities between men and women are diminished in a regional PCI-based STEMI system using a standardized STEMI protocol. No sex differences in short-term or long-term age-adjusted mortality are present in this registry despite some treatment disparities. These results suggest that STEMI health care disparities and mortality in women can be improved using STEMI protocols and systems.

Eliminating untimely deaths of women from heart disease: highlights from the Minnesota Women's Heart Summit.

Despite national campaigns to increase awareness and reduce cardiovascular disease (CVD) mortality in women, CVD remains their leading cause of death, annually killing more women than men. Although some progress has been made in our understanding and treatment of CVD in women, the causes, extent, and demographic trends of observed sex differences and disparities remain uncertain, and the growing burden of CVD and its risk factors among younger women is concerning. The Minnesota Women's Heart Summit was convened to chart a course to eliminate premature deaths of women from heart disease. The multidisciplinary summit was hosted by the Minneapolis Heart Institute, Minneapolis Heart Institute Foundation, University of Minnesota, and Mayo Clinic. Presentations highlighted sex-based differences in symptoms, treatment, and outcomes, and panel experts provided commentary. Invited faculty and summit participants worked in small-group sessions to identify strategies to dissolve barriers, improve primary and secondary prevention, and enhance women's care and outcomes. This report summarizes strategies identified during the conference to serve as springboards for more substantive future initiatives. These include, for example, standardized data collection and use of existing data sets to inform perspectives on sex-related cardiovascular issues, mandatory reporting of sex-specific data, and increased attention to underserved/high-risk women. Participants acknowledged that implementing these ideas would be challenging and recommended key priorities/next action steps such as providing services close to "point-of-life" rather than "point-of-care" and creation of policies and regulations so that resources and environmental modifications encouraging healthier lifestyle choices are promoted. Additional research is needed to improve identification, treatment, and health behaviors and to address continued lack of awareness, symptom recognition delays, barriers to care, and outcome disparities-especially in diverse populations.

IL-2 availability regulates the tissue specific phenotype of murine intra-hepatic Tregs.

CD4+CD25+Foxp3+ Tregs are known to acquire tissue-specific features and exert cytoprotective and regenerative functions. The extent to which this applies to liver-resident Tregs is unknown. In this study, we aimed to explore the phenotypic and functional characteristics of adult murine liver resident Tregs during homeostasis. Additionally, we investigated their role in ameliorating liver inflammation and tissue damage. Quantification of Foxp3+CD4+CD25+ cells comparing different tissues showed that the liver contained significantly fewer resident Tregs. A combination of flow cytometry phenotyping and microarray analysis of intra-hepatic and splenic Tregs under homeostatic conditions revealed that, although intra-hepatic Tregs exhibited the core transcriptional Treg signature, they expressed a distinct transcriptional profile. This was characterized by reduced CD25 expression and increased levels of pro-inflammatory Th1 transcripts Il1b and Ifng. In vivo ablation of Tregs in the Foxp3-DTR mouse model showed that Tregs had a role in reducing the magnitude of systemic and intra-hepatic inflammatory responses following acute carbon tetrachloride (CCl4) injury, but their absence did not impact the development of hepatocyte necrosis. Conversely, the specific expansion of Tregs by administration of IL-2 complexes increased the number of intra-hepatic Tregs and significantly ameliorated tissue damage following CCl4 administration in C57BL/6 mice. The cytoprotective effect observed in response to IL-2c was associated with the increased expression of markers known to regulate Treg suppressive function. Our results offer insight into the transcriptome and complex immune network of intra-hepatic Tregs and suggest that strategies capable of selectively increasing the pool of intra-hepatic Tregs could constitute effective therapies in inflammatory liver diseases.

Revascularization in Patients With Spontaneous Coronary Artery Dissection and ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of myocardial infarction (MI) in younger women, often treated conservatively due to revascularization risks. Revascularization outcomes are largely unknown in SCAD presenting with ST-segment elevation myocardial infarction (STEMI). OBJECTIVES: The purpose of this study was to compare revascularization strategies and outcomes of STEMI-SCAD with STEMI atherosclerosis (STEMI-ATH). METHODS: Consecutive STEMI patients were retrospectively analyzed (2003 to 2017) at 2 regional STEMI programs (Minneapolis Heart Institute and Cedars-Sinai Smidt Heart Institute) with 3-year outcomes. RESULTS: Among 5,208 STEMI patients, SCAD was present in 53 (1%; 93% female). SCAD prevalence was 19% in female STEMI patients age ≤50 years. Compared with STEMI-ATH, STEMI-SCAD patients were younger (age 49 ± 10 years vs. 63 ± 13 years), were more often female (93% vs. 27%), and had more frequent cardiogenic shock (19% vs. 9%); all p ≤ 0.03. In STEMI-SCAD, the culprit artery was more commonly left main (13% vs. 1%) or left anterior descending (47% vs. 38%); both p = 0.003. Acute revascularization was lower in STEMI-SCAD (70% vs. 97%); p < 0.001. In STEMI-SCAD, acute revascularization included percutaneous coronary intervention (PCI), n = 33 (62%), or bypass grafting, n = 4 (8%); PCI success was 91%. Those with revascularization were more likely to have shock, left main culprit, proximal dissection, and initial TIMI (Thrombolysis In Myocardial Infarction) flow grade 0 to 1. The 3-year survival was 98% for STEMI-SCAD versus 84% for STEMI-ATH; p < 0.001. CONCLUSIONS: STEMI-SCAD represents an important STEMI subset, particularly among younger women, characterized by significantly greater frequency of left main or left anterior descending culprit and cardiogenic shock than STEMI-ATH. Primary PCI is successful in most STEMI-SCAD patients, with low 3-year mortality.

Reduced small artery but not large artery elasticity is an independent risk marker for cardiovascular events.

BACKGROUND: Atherosclerosis begins in the arterial wall, with endothelial dysfunction accompanied by functional and structural changes that influence arterial stiffness. Pulse contour analysis provides an assessment of compliance or elasticity of the large conduit arteries (C(1)) and small microcirculatory arteries (C(2)). In this study, the predictive value of reduced elasticity of these arteries was evaluated by follow-up of subjects who underwent pulse contour analysis at the University of Minnesota. METHODS: Questionnaires were sent to 870 subjects who had radial artery pulse wave analysis performed between 1993 and 1999 using a noninvasive sensor, parameter estimating algorithm and modified Windkessel model of the circulation. Responses from 419 subjects >19 years of age reported on any cardiovascular events including death, myocardial infarction, stroke, transient ischemic attacks, angina, or coronary or peripheral vascular interventional procedures. RESULTS: Of the subjects, 168 (41%) reported one or more cardiovascular events. Events were more common in those with elevated blood pressure, elevated cholesterol, diabetes, and family history of events. Age, reduced C(1), and reduced C(2) were univariate predictors of events. After adjusting for age, a 2-unit decrease in C(2) remained a significant predictor (odds ratio 1.50, P <.001), whereas C(1) was no longer predictive. CONCLUSION: Reduced small artery elasticity, which is a measure of endothelial dysfunction, is significantly associated with cardiovascular events independent of age.

Comparison of functional recovery following percutaneous coronary intervention for ST elevation myocardial infarction in three age groups (<70, 70 to 79, and ≥80 years).

Functional outcomes of elderly patients ≥80 years who undergo percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI) are unknown. Registry data indicate that up to 55% of elderly patients with STEMI do not receive reperfusion therapy despite a suggested mortality benefit, and only limited data are available regarding outcomes in elderly patients treated with primary PCI. Therefore, prospective data from a regional STEMI transfer program were analyzed to determine major adverse cardiac events, length of stay, and discharge status of consecutive patients with STEMI ≥80 years from March 2003 to November 2006. Of the 1,323 consecutive patients with STEMI treated in this regional STEMI system from March 2003 to November 2006, 199 (15.0%) were ≥80 years old. In-hospital mortality in elderly patients was 11.6%, with a 1-year mortality rate of 25.6%. Of the 166 patients with age ≥80 who lived independently or in assisted living before hospital admission and survived, 150 (90.4%) were discharged to a similar living situation or projected to such a living situation after temporary nursing home care. The median length of hospital stay was 4 days for these patients. In conclusion, elderly patients with age ≥80 receiving PCI for STEMI in a regional STEMI program have short hospital stays and excellent functional recovery on the basis of a very high rate of return to a similar previous living situation.

Age-related functional effects linked to phosphatase activity in ventricular myocytes.

Conflicting reports exist regarding the influence of beta-adrenergic stimulation on the maximum velocity of shortening (Vmax) in ventricular myocytes. This may be due to an unrecognized effect of maturation. In the present study, the effects of beta-adrenergic receptor stimulation on myocytes from hearts of juvenile nonbred and young adult retired breeder female rats were compared. Ventricular myocytes from young adults had a beta-adrenergic-dependent increase in Vmax and Ca2+-dependent actomyosin ATPase that was not observed in myocytes from juveniles. Myocytes from young adults had both an increase in beta-myosin heavy chain (MHC) and higher basal serine/threonine phosphatase activity compared with juvenile rats. Additional studies established moderate increases in beta-MHC induced by hypothyroidism do not confer myocardial beta-adrenergic responsiveness, whereas inhibition of the higher phosphatase activity in myocytes from young adults blocks the age-dependent, beta-adrenergic-induced increase in cross-bridge cycling rates. We propose that the higher phosphatase activity of myocytes from young adults compared with juveniles allows for a greater functional response of the myocardium to beta-adrenergic stimulation.