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Background: An obesity paradox, with better long-term survival in obese patients undergoing percutaneous coronary intervention (PCI), has been well described. The association between obesity and health status outcomes after PCI is unknown. Methods: We prospectively enrolled 3,281 PCI patients in a 10-center observational cohort study and categorized their body mass index (BMI) into normal (18.5 to <25), overweight (25 to <30), obese (30 to <35) and morbidly obese (≥ 35).Generalized linear models were used to describe the association between BMI and health status measures at 6 & 12 months, after adjusting for baseline characteristics and health status scores. Health status outcomes included; Seattle Angina Questionnaire [SAQ] Angina Frequency (AF), and Quality of Life (QL) scores, as well as the EQ-5D visual analogue scale (EQ-5D VAS). Interaction with time was not significant, so an estimate of the average benefit over time was generated. Results: The distribution of patients’ BMI revealed that 17% were normal, 35% overweight, 28% obese and 20% morbidly obese. Compared with normal weight patients, morbidly obese individuals were younger (mean 60.8 yr vs. 67.9 yr) and had a higher prevalence of diabetes, hypertension and heart failure. They underwent radial artery access (12.0% vs. 7.0%) and drug eluting stent implantation (80.4% vs. 76.0%) more frequently. Unadjusted changes in scores were lower (worse) among morbidly obese as compared with normal weight patients for SAQ AF (mean difference [MD] -1.52; 95% Confidence Interval [CI] -3.05, -0.02), SAQ QL (MD -2.51; CI -4.48, -0.54), and EQ-5D VAS (MD -5.74;CI -7.52, -3.96). After adjustment, these differences were no longer significantly different for SAQ AF and SAQ QL (figure), although EQ-5D VAS scores remained lower among obese and morbidly obese patients. Conclusion: The overall health status was mildly worse among obese and morbidly obese individuals after PCI, but the benefits of PCI on patients’ disease-specific health status were similar across weight categories. This suggests that PCI is equally effective in improving angina and disease-specific quality of life, independent of patients’ weight.

Background: Although percutaneous coronary intervention (PCI) has not been shown to reduce the risk of death and myocardial infarction (MI) for stable coronary artery disease (CAD), many patients believe that PCI is a life-saving procedure. PCI for stable CAD is known to improve patients’ quality of life more rapidly than medications alone. We conducted a randomized trial to assess the impact of a decision aid (DA) compared to usual care (UC) for the treatment of stable CAD when there is a choice between PCI and optimal medical therapy (OMT). Methods: The PCI Choice trial was a prospective, randomized trial comparing the effects of DA versus UC. The DA was designed with a user-centered approach for an in-visit consultation, involving patients and clinicians throughout the development process. The final DA included information on myocardial infarction (MI), death and quality of life outcomes for PCI with OMT vs. OMT alone in the treatment of stable angina, stratified by angina type. Risks of procedure, bleeding, stent thrombosis, and need for future procedures were also depicted. The primary outcome was patient knowledge, measured by pre- and post-visit surveys. Additional outcomes included decisional conflict, patient satisfaction, preferred decision making style, and treatment decision. Results: A total of 110 patients were enrolled; mean age was 68.3 years and 26% of patients were women. At baseline, most patients had CCS Class I/II angina and were on a mean of two anti-anginal medications (2.3, SD 1.2). Knowledge increased among patients receiving DA compared to UC (63% vs. 44% p=0.0003). Specific knowledge about the impact of PCI for stable angina on death and MI was higher in both groups compared to prior studies (54% DA, 46% UC, p=0.45; 12% prior). Patient satisfaction was significantly higher in the DA group vs. UC (72% vs 40%, p=0.004). Decisional conflict was greater than in non-procedural DA trials, and was not different between the two arms (p=.43). Following exposure to DA, patients’ preference for sharing decision making tended to change more with DA (55% to 65%) than with UC (56% to 59%). While the proportion of patients choosing PCI over OMT was nearly half in both groups, there were fewer patients that remained undecided with DA (18% vs. 4%; p=0.14 overall difference). Conclusions: Exposure to a DA for the choice of PCI vs. optimal medical therapy in stable CAD improved patient knowledge and satisfaction and decreased uncertainty, without reducing the rate of PCI. Use of the DA in a larger patient population may further delineate impact on outcomes such as treatment choice, geographic variation and cost.

Background: In light of well-known deficiencies in the process of informed consent for percutaneous coronary intervention (PCI), we developed and tested a personalized consent form, PRISM; this was shown to improve patients' participation in the consent process, understanding of procedural risks, and engagement in shared decision-making when compared to original PCI consent forms. It is unknown whether patient factors traditionally known to impair the consent process, including socioeconomic status, literacy and numeracy, were associated with greater benefit from the PRISM consents. Methods: We interviewed 590 patients receiving original consent documents and 527 receiving PRISM consents and compared the rates of reviewing the consent form, recalling a risk of bleeding and engaging in discussions about stent type using hierarchical modified Poisson regression analysis. The interaction of patient factors (age, gender, education level, insurance status, literacy and numeracy) with PRISM on outcomes was assessed. Results: Overall, few patient characteristics were associated with outcomes, including review of consent forms, knowledge transfer, or engagement in shared decision-making (see Table), although older patients were less likely to discuss stent types with their doctors (RR=0.84/decade for original and 0.93/decade for PRISM). Those with more than a high school education were less likely to review original consents (RR=0.77; 95% CI=0.66, 0.89) compared to those with less education; this difference was eliminated with the PRISM consents (RR=1.0; 95%CI=0.82, 1.23; p-value for interaction = 0.01). Conclusions: PRISM consent forms led to improved participation in the consent process and knowledge transfer in a 9-center study; there was little variance by sociodemographic, economic, literacy or numeracy factors, both with original consents and with PRISM.

Background: Health insurance coverage has been recently expanded to millions of Americans with the goal of improving access and quality of care. We evaluated long-term outcomes for patients with ST-elevation myocardial infarction (STEMI) with different insurance types. Methods: From 2004 to 2010, 970 consecutive STEMI patients who presented to 29 hospitals in Minnesota, Iowa or Wisconsin were treated according to the Mayo STEMI protocol. Demographic, clinical, procedural, and long-term follow up data were prospectively collected. 953 patients were categorized into groups by insurance type - private insurance (PI, n=430), Medicare (MC, n=420), Medicaid (MD, n=68), and uninsured (UN, n=35). Results: Median duration of follow-up was 32 months, and mean ages (years) were 55±8 for PI, 75±10 for MC, 49±10 for MD, and 52±9 for UN (p<0.001). Compared to PI patients, MC and MD patients were more likely to have diabetes (both 21% vs 10%, p<0.001); MC patients had more renal failure (4% vs <1%, p=0.012) but UN patients did not differ significantly (DM 12% and CRF 0%). All groups had similar frequency of cardiogenic shock (PI 9%, MC 14%, MD 9%, UN 6%, p=0.08) and comparable door-to-balloon (in minutes(Q1,Q3): PI 69(54,107), MC 79(61,114), MD 83(55,124), UN 76(58,94), p=0.09) and door-to-needle times (in minutes(Q1,Q3): PI 26(19,34), MC 29 (21,39), MD 27(22,34), UN 17(13,21), p=0.06). MC patients had the highest incidence of in-hospital death (7.6%; p=0.003 vs PI 3.0%). Significant differences in all cause mortality between insurance groups were present on 5-year follow-up (Figure). After risk factor adjustment for age (HR 1.89 per decade, p<0.001), female sex (HR 1.16, p=0.40), diabetes (HR 1.89, p<0.001), peripheral artery disease (HR 2.06, p=0.004), heart failure (HR 1.40, p=0.14), cardiogenic shock (4.22, p<0.001) and renal failure (HR 1.62, p=0.20); insurance type was not an independent risk factor for death (p=0.26). When compared to PI, the hazard ratio for UN was associated with a trend for worse survival (HR 2.69, 95%CI 0.94, 7.67, p=0.06) while MC (HR 0.94, 95%CI 0.55, 1.61, p=0.83) and MD patients (HR 1.37, 95%CI 0.52, 3.59, p=0.53) had similar survival after adjustment for covariates. Conclusion: Timeliness of reperfusion was similar across all insurance groups. After adjustment for baseline clinical variables, there was no significant difference in long-term survival according to insurance type.

Background. Measurement of PCI quality has previously focused on post-procedure outcomes and processes of care. PCI appropriateness provides an assessment of quality as it relates to patient selection and anticipated procedural benefit relative to potential harm. The relationship, if any, between case selection and in-hospital procedural outcomes is unknown. Methods. We identified 203,531 consecutive patients from 779 hospitals undergoing non-acute (elective) PCI within the CathPCI Registry ® between July, 2009 and April, 2011. We examined the association between a hospital’s proportion of inappropriate PCI in non-acute settings (as assessed by the Appropriate Use Criteria (AUC) for Coronary Revascularization) and (1) risk-adjusted in-hospital mortality; (2) risk-adjusted bleeding complications; and (3) use of optimal guideline directed discharge medications (i.e. aspirin, thienopyridine, and statin on discharge). Results. Of the 24,532 patients who received PCI for non-acute indications, 453 (0.2%) died in-hospital and 3699 (1.8%) suffered bleeding events. The hospital proportion of inappropriate PCI in non-acute settings ranged from 0.0% to 58.6%. Categorized as hospital tertiles, the median proportion of inappropriate PCI was 5.3% in hospitals of the lowest-tertile, 10.9% in the middle-tertile, and 20.0% in the highest-tertile. The hospital proportion of inappropriate PCI was not associated with mortality for PCI in non-acute settings (Risk-adjusted mortality ratio; 0.7 vs. 0.7 vs. 0.8 from lowest to highest-tertile, P=0.75 for trend), risk-adjusted bleeding complications (Risk-adjusted bleeding ratio; 0.6 vs. 0.6 vs. 0.6, P=0.81), or use of optimal PCI discharge medications (85.3% vs. 85.7% vs. 85.2%, P=0.58). Conclusions. In a national cohort of non-acute PCIs from 779 hospitals, hospital proportion of inappropriate PCI indications was not associated with in-hospital mortality, bleeding, or process of care measures of PCI quality. These findings suggest PCI appropriateness and post-procedural outcomes measure different aspects of hospital PCI quality.

Background: While lack of insurance is known to be associated with worse outcomes after myocardial infarction (MI), it is unknown whether health insurance status is associated with rates of non-elective hospitalizations after MI. Methods: Using data on 3571 U.S. MI patients enrolled between April 2005 to December 2008 in the 24-center, prospective TRIUMPH registry, we examined the association between being insured (reference), underinsured, and uninsured on rates of non-elective readmissions (all-cause) in the 1 st year following MI. Insurance status was obtained from medical records, and underinsurance was defined as those patients with insurance but with financial concerns about accessing care from patient interviews. Multivariable modified Poisson regression models were used to adjust for site, demographics, MI severity, risk factors, socio-economic, and psychological factors. Results: A total of 2269 (63.5%) patients were insured; 650 (18.2%) were underinsured; and 652 (18.3%) were uninsured. Emergency readmissions were highest for uninsured patients (25.0%), followed by the underinsured (21.8%), and lowest in insured patients (19.5%) (P<.001). After multivariable adjustment, uninsured patients had significantly higher rates of emergency readmission (adjusted RR, 1.52 [95% CI: 1.22-1.90] while underinsured patients did not (adjusted RR, 0.99 [95% CI: 0.81-1.21]) (Figure). Conclusions: Uninsured patients had a significantly higher adjusted risk of non-elective readmissions after MI, while underinsured patients did not. Future studies are needed to determine if providing even modest insurance coverage to the uninsured can minimize readmission rates.

Abstract Foxp3⁺ regulatory T cells (Tregs) maintain immune homeostasis, yet the process that preserves their stability during aging remain unclear. Mechanistic progress has been hindered by models that ablate Tregs or delete Foxp3 , which induce acute autoimmunity and prevent longitudinal study of physiological regulatory drift. Here, we establish a dose-dependent mitochondrial framework that preserves Treg lineage survival while permitting gradual metabolic attenuation. Using Treg-restricted TFAM modulation, a complementary haploinsufficient model, and whole-spleen single-cell profiling. We identify lineage-selective immune remodeling characterized by contraction of naïve CD8⁺ and follicular B-cell pools, alteration of CD4⁺ states, expansion of activated Tregs, and emergence of neuroimmune stress linked transcriptional modules that parallel physiological aging. Mechanistically, mitochondrial insufficiency is associated with functional loss of FOXP3- centered chromatin coordination and enrichment of NF-κB/NFAT/AP-1 inflammatory and senescence programs while lineage identity remains detectable. Partial mitochondrial attenuation within Tregs alone is sufficient to drive chronic low-grade systemic inflammation, neuromuscular decline, gut microbial restructuring, and elevated microglial responsiveness without Treg depletion. Pharmacologic and microbiota-directed interventions partially reduce inflammatory tone and improve functional metrics. Together, our findings identify TFAM as a key regulator of immune aging and reveal that healthy mitochondrial function in Tregs is essential for protecting against inflammaging and age-associated functional decline.

AbstractPurposeRural populations are disproportionately affected by the COVID‐19 pandemic. We characterized urban‐rural disparities in patient portal messaging utilization for COVID‐19, and, of those who used the portal during its early stage in the Midwest.MethodsWe collected over 1 million portal messages generated by midwestern Mayo Clinic patients from February to August 2020. We analyzed patient‐generated messages (PGMs) on COVID‐19 by urban‐rural locality and incorporated patients’ sociodemographic factors into the analysis.FindingsThe urban‐rural ratio of portal users, message senders, and COVID‐19 message senders was 1.18, 1.31, and 1.79, indicating greater use among urban patients. The urban‐rural ratio (1.69) of PGMs on COVID‐19 was higher than that (1.43) of general PGMs. The urban‐rural ratios of messaging were 1.72‐1.85 for COVID‐19‐related care and 1.43‐1.66 for other health care issues on COVID‐19. Compared with urban patients, rural patients sent fewer messages for COVID‐19 diagnosis and treatment but more messages for other reasons related to COVID‐19‐related health care (eg, isolation and anxiety). The frequent senders of COVID‐19‐related messages among rural patients were 40+ years old, women, married, and White.ConclusionsIn this Midwest health system, rural patients were less likely to use patient online services during a pandemic and their reasons for its use differ from urban patients. Results suggest opportunities for increasing equity in rural patient engagement in patient portals (in particular, minority populations) for COVID‐19. Public health intervention strategies could target reasons why rural patients might seek health care in a pandemic, such as social isolation and anxiety.

277 Background: The prognostic importance of local failure (LF) after definitive radiotherapy (RT) in patients with NCCN intermediate- (IRPCa) and high-risk prostate cancer (HRPCa) remains unclear, particularly given the likelihood that occult distant metastases (DMs) at presentation may be the true driver of natural history. Here, we leverage individual patient data (IPD) from 18 randomized control trials (RCTs) to evaluate the prognostic impact of LF and the kinetics of DM after RT. Methods: IPD for 18 RCTs were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium, comprising a total of 12533 patients (6288 HRPCa & 6245 IRPCa). Multivariable Cox proportional hazards (PH) models were developed to evaluate the relationship between overall survival (OS), PCa-specific survival (PCSS), DM-free survival (DMFS) & LF as a time-dependent covariate, adjusted for clinicodemographic parameters. Markov PH models, defined via transitions between 4 states, were developed to evaluate the aforementioned relationship. Proportional hazards assumption was imposed and examined for both models. Time is from randomization. Results: Median follow-up was 9.1 years. There were 795 (13%) LF & 1288 (21%) DM events for patients with HRPCa; these numbers were 449 (7%) & 451 (7%) for IRPCa. For HRPCa & IRPCa, 81% and 81% of DMs developed from a clinically relapse-free state (cRFS), with a median time of 46 and 60 months, respectively (p < 0.0001). 39% & 13% of DM events occurred within 2 years after RT for HRPCa & IRPCa, respectively. At later time points, DM events were more likely to emerge after an LF event for both HRPCa (9% vs. 34% between 0-2 vs. 8-10 years post-RT, p = 0.001) and IRPCa (10% vs. 34% between 0-2 vs. 8-10 years post-RT, p = 0.008). LF was significantly associated with OS (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.06–1.30), PCSS (HR 2.02, 95% CI 1.75-2.33) & DMFS (HR 1.94, 95% CI 1.75–2.15) (p < 0.01 for all) in patients with HRPCa. LF was also significantly associated with DMFS (HR 1.57, 95% CI 1.36–1.81) but not OS in patients with IRPCa. Patients who had not transitioned to the LF state had a significantly lower HR of transitioning to a PCa-specific death state than those who transitioned to the LF state (HR 0.32, 95% CI 0.21–0.50, p < 0.001). Conclusions: LF is an independent prognosticator of OS, PCSS & DMFS in HRPCa and of DMFS in IRPCa. The predominant mode of DM development is from the cRFS state, underscoring the importance of accurate upfront staging & systemic therapy. However, particularly at late time points, an increasing proportion of DM events originated after diagnosis of a LF, constituting a “second wave” of DM events. This suggests that optimizing local control is also important, though the majority of DM events appear prior to a clinically-detected LF.