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Background: Prior research has demonstrated that individuals with peripheral artery disease (PAD) often have comorbid opioid use disorder (OUD) and major depressive disorder (MDD), with limited data regarding their impact on readmission outcomes, length of stay, and cost. This study aimed to investigate these healthcare utilization outcomes in patients with PAD who have comorbid OUD and MDD., Methods: Data were obtained from the National Readmission Database from 2011 through 2018. The study population included all hospitalizations with PAD as the primary or secondary diagnosis, from which hospitalizations with OUD and MDD were extracted using appropriate ICD-9/10 diagnosis codes. Primary outcomes were 30-day and 90-day readmission, total cost, and total length of stay within the calendar year. We created hierarchical multivariable logistic regression models examining OUD with and without MDD, with a random effect for healthcare facility location., Results: From 2011 to 2018, 13,265,817 weighted admissions with PAD were identified. These admissions were segmented into four categories: No OUD/No MDD (12,056,466), OUD/No MDD (323,762), No OUD/MDD (867,641), and OUD/MDD (17,948). The group with No OUD/No MDD was used as the reference group for all subsequent comparisons. Regarding 30-day and 90-day readmissions, patients with OUD/MDD had odds of 1.14 (95% CI 1.10, 1.18) and 1.09 (95% CI 1.06, 1.13), respectively. Patients with OUD/No MDD bore the highest median cost of $64,354 (IQR $30,797-137,074), and patients with OUD/MDD marked the lengthiest median stay of 6.01 days (IQR 2.01-13.30)., Conclusion: This study found a significant association between these comorbidities and outcomes and therefore calls for targeted interventions and pain management strategies., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Mena-Hurtado receives unrestricted grant funding from Janssen, Philips, Abbott, Shockwave, and Merck and serves as a consultant for Abbott, Cook Medical, Terumo, and Penumbra. Dr. Smolderen receives unrestricted grant funding from Janssen, Philips, Abbott, Shockwave, and Merck and serves as a consultant for Happify, Cook Medical, and Terumo.

Background: National quality reporting efforts after revascularization for peripheral artery disease (PAD) are ongoing. Validation of endpoints are necessary in national quality registries., Objectives: This study sought to examine the interrater reliability for the endpoint of major amputation at 1 year in the Vascular Quality Initiative (VQI) registry and the Medicare-linked Vascular Quality Initiative registry (VQI-VISION) against electronic health record (EHR) review., Methods: Surgical or endovascular revascularization procedures between January 1, 2010, and December 31, 2017, in the VQI registry and VQI-VISION for 2 academic health systems were queried. Major amputation data were abstracted by trained data collectors for the VQI and derived from Current Procedural Terminology codes for VQI-VISION. Cases underwent protocolized adjudication for the endpoint of major amputation by EHR review. Paired tests were used to evaluate the sensitivity and specificity. Spearman's ρ and Cohen's κ were used to evaluate interrater reliability., Results: Amputation endpoints for 1,936 revascularizations were examined. Compared with major amputation data in EHR review, the sensitivity for the VQI registry was 35.9% and the specificity was 99.4% (ρ = 0.53; κ = 0.48). For VQI-VISION, sensitivity was 67.7% and specificity was 98.9% (ρ = 0.75; κ = 0.74). For any amputation in VQI data, sensitivity was 35.3% and specificity was 99.3% (ρ = 0.53; κ = 0.46), and for VQI-VISION, they were 71.6% and 97.7%, respectively (ρ = 0.75; κ = 0.74)., Conclusions: Almost two-thirds of the amputations in the VQI registry and one-third of amputations in VQI-VISION were missing at 1 year compared against adjudicated EHR review. In preparing for national reporting systems for major amputation tracking, data collection system reform is needed., Competing Interests: Funding Support and Author Disclosures The VISION registry was supported by a Food and Drug Administration grant (U01FD006936 [to Dr Goodney]). Drs Smolderen and Mena are supported by National Institutes of Health grants 1R21AT012430-01 and 1R01HL163640-01A1. Dr Goodney is supported by a research grant from the American Heart Association (SRFN #18SFRN33900147). Dr Smolderen has received unrestricted research grants from Philips, Abbott, Merck, and Johnson & Johnson; and has served as a consultant for Optum Labs and Abbott, Happify, and Haemonetics. Dr Mena-Hurtado has served as a consultant for Abbott Vascular, Cook, Medtronic, Cardinal Health, and Optum Labs. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Peripheral artery disease (PAD) and microvascular disease (MVD) are highly prevalent conditions that share common risk factors. This observational study aimed to characterize patients with both conditions and determine the impact of comorbid PAD/MVD on outcomes., Methods and Results: Patients admitted across 31 states January 2011 through December 2018 with a primary or secondary diagnosis of PAD or MVD were included from the National Readmissions Database and weighted to approximate a national sample. Those age <18 years or with nonatherosclerotic leg injuries were excluded. Patients were divided into 3 groups: PAD-only, MVD-only, or comorbid PAD/MVD. Multiple logistic regression was used to evaluate associations with major and minor amputations, major adverse cardiac events, and in-hospital mortality. Cox regression was used to evaluate associations with readmission within 1 year. The PAD group was used as reference. The final cohort included 33 972 772 admissions: 9.1 million with PAD, 21.3 million with MVD, and 3.6 million with both. Annual admissions for PAD/MVD increased to >500 000 in 2018. Major and minor amputations increased ≈50% for PAD/MVD between 2011 and 2018. Compared with PAD-only, PAD/MVD was associated with a higher risk for major amputation (odds ratio [OR], 1.30 [95% CI, 1.28-1.32]), minor amputation (OR, 2.15 [95% CI, 2.12-2.18]), major adverse cardiac events (OR, 1.04 [95% CI, 1.03-1.04]), in-hospital mortality (OR, 1.07 [95% CI, 1.05-1.09]), and readmission (hazard ratio, 1.02 [95% CI, 1.02-1.02]) after adjustment for baseline factors., Conclusions: Comorbid MVD is present in a large and growing number of patients with PAD and is associated with augmented risk for adverse outcomes. Further prospective research is merited to understand this vulnerable population.

Competing Interests: Conflict of interest: None declared.

Competing Interests: Conflicts of interest: None declared.

Background: Plant-based diets (PBDs) are typically recommended to those at risk of type 2 diabetes mellitus (T2DM)., Objectives: We examined how including eggs, compared with excluding them from PBDs, affected cardiometabolic risk factors in adults at risk of T2DM., Methods: This was a randomized, controlled, single-blind, crossover trial of 35 adults (mean age: 60.7 y; 25 women, 10 men) at risk of T2DM assigned to 1 of 2 sequence permutations of 2 dietary treatments (plant-based plus eggs, and exclusively plant-based), with a 4-wk washout period. A dietitian counseled participants to exclude or include 2 eggs daily in the context of PBDs for a 6-wk interval. Our primary outcome measure was endothelial function (EF) measured as flow-mediated dilatation. Secondary outcome measures included lipid profile, blood pressure, insulin sensitivity, anthropometry, and dietary intake. Data were analyzed using generalized linear models., Results: Compared with egg exclusion, egg inclusion in the context of PBDs did not adversely affect EF (-1.7% ± 6.5% compared with -1.8% ± 7.5%; P = 0.9805). Likewise, egg inclusion, compared with egg exclusion, did not adversely affect (P = 0.1096-0.9781) lipid profile, blood pressure, insulin sensitivity, or anthropometry. Egg inclusion, compared with egg exclusion, improved reported intakes of selenium (23.1 ± 30.3 μg/d compared with 2.3 ± 34.9 μg/d; P = 0.0124) and choline (172.0 ± 96.0 mg/d compared with -3.4 ± 68.1 mg/d; P < 0.0001)., Conclusions: Consuming 2 eggs daily in the context of PBDs does not adversely affect cardiometabolic risk factors among adults at risk of T2DM. Eggs could be used as an adjuvant to enhance PBDs that are typically recommended for those at risk of T2DM.This trial was registered at clinicaltrials.gov as NCT04316429., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Normal pregnancy is associated with adaptive hemodynamic, hormonal, and vascular changes, and estrogen (E2) may promote vasodilation during pregnancy; however, the specific E2 receptor (ER) subtype, post-ER signaling mechanism, and vascular bed involved are unclear. We tested whether pregnancy-associated vascular adaptations involve changes in the expression/distribution/activity of distinct ER subtypes in a blood vessel-specific manner. Blood pressure (BP) and plasma E2 were measured in virgin and pregnant (day 19) rats, and the thoracic aorta, carotid artery, mesenteric artery, and renal artery were isolated for measurements of ERα, ERβ, and G protein-coupled receptor 30 [G protein-coupled ER (GPER)] expression and tissue distribution in parallel with relaxation responses to E2 (all ERs) and the specific ER agonist 4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)-tris-phenol (PPT; ERα), diarylpropionitrile (DPN; ERβ), and G1 (GPER). BP was slightly lower and plasma E2 was higher in pregnant versus virgin rats. Western blots revealed increased ERα and ERβ in the aorta and mesenteric artery and GPER in the aorta of pregnant versus virgin rats. Immunohistochemistry revealed that the increases in ERs were mainly in the intima and media. In phenylephrine-precontracted vessels, E2 and PPT caused relaxation that was greater in the aorta and mesenteric artery but similar in the carotid and renal artery of pregnant versus virgin rats. DPN- and G1-induced relaxation was greater in the mesenteric and renal artery than in the aorta and carotid artery, and aortic relaxation to G1 was greater in pregnant versus virgin rats. The nitric oxide synthase inhibitor N(ω)-nitro-l-arginine methyl ester with or without the cyclooxygenase inhibitor indomethacin with or without the EDHF blocker tetraethylammonium or endothelium removal reduced E2, PPT, and G1-induced relaxation in the aorta of pregnant rats, suggesting an endothelium-dependent mechanism, but did not affect E2-, PPT-, DPN-, or G1-induced relaxation in other vessels, suggesting endothelium-independent mechanisms. E2, PPT, DPN, and G1 caused relaxation of Ca(2+) entry-dependent KCl contraction, and the effect of PPT was greater in the mesenteric artery of pregnant versus virgin rats. Thus, during pregnancy, an increase in ERα expression in endothelial and vascular smooth muscle layers of the aorta and mesenteric artery is associated with increased ERα-mediated relaxation via endothelium-derived vasodilators and inhibition of Ca(2+) entry into vascular smooth muscle, supporting a role of aortic and mesenteric arterial ERα in pregnancy-associated vasodilation. GPER may contribute to aortic relaxation while enhanced ERβ expression could mediate other genomic vascular effects during pregnancy., (Copyright © 2015 the American Physiological Society.)

Aldosterone interacts with mineralocorticoid receptor (MR) to stimulate sodium reabsorption in renal tubules and may also affect the vasculature. Caveolin-1 (cav-1), an anchoring protein in plasmalemmal caveolae, binds steroid receptors and also endothelial nitric oxide synthase, thus limiting its translocation and activation. To test for potential MR/cav-1 interaction in the vasculature, we investigated if MR blockade in cav-1-replete or -deficient states would alter vascular function in a mouse model of low nitric oxide (NO)-high angiotensin II (AngII)-induced cardiovascular injury. Wild-type (WT) and cav-1 knockout mice (cav-1(-/-)) consuming a high salt diet (4% NaCl) received Nω-nitro-l-arginine methyl ester (L-NAME) (0.1-0.2 mg/ml in drinking water at days 1-11) plus AngII (0.7-2.8 mg/kg per day via an osmotic minipump at days 8-11) ± MR antagonist eplerenone (EPL) 100 mg/kg per day in food. In both genotypes, blood pressure increased with L-NAME + AngII. EPL minimally changed blood pressure, although its dose was sufficient to block MR and reverse cardiac expression of the injury markers cluster of differentiation 68 and plasminogen activator inhibitor-1 in L-NAME+AngII treated mice. In aortic rings, phenylephrine and KCl contraction was enhanced with EPL in L-NAME+AngII treated WT mice, but not cav-1(-/-) mice. AngII-induced contraction was not different, and angiotensin type 1 receptor expression was reduced in L-NAME + AngII treated WT and cav-1(-/-) mice. In WT mice, acetylcholine-induced relaxation was enhanced with L-NAME + AngII treatment and reversed with EPL. Acetylcholine relaxation in cav-1(-/-) mice was greater than in WT mice, not modified by L-NAME + AngII or EPL, and blocked by ex vivo L-NAME, 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), or endothelium removal, suggesting the role of NO-cGMP. Cardiac endothelial NO synthase was increased in cav-1(-/-) versus WT mice, further increased with L-NAME + AngII, and not affected by EPL. Vascular relaxation to the NO donor sodium nitroprusside was increased with L-NAME + AngII in WT mice but not in cav-1(-/-) mice. Plasma aldosterone levels increased and cardiac MR expression decreased in L-NAME + AngII treated WT and cav-1(-/-) mice and did not change with EPL. Thus, during L-NAME + AngII induced hypertension, MR blockade increases contraction and alters vascular relaxation via NO-cGMP, and these changes are absent in cav-1 deficiency states. The data suggest a cooperative role of MR and cav-1 in regulating vascular contraction and NO-cGMP-mediated relaxation during low NO-high AngII-dependent cardiovascular injury., (Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.)

Striatin is a protein regulator of vesicular trafficking in neurons that also binds caveolin-1 and Ca(2+)-calmodulin and could activate endothelial nitric oxide synthase. We have shown that striatin colocalizes with the mineralocorticoid receptor and that mineralocorticoid receptor activation increases striatin levels in vascular cells. To test whether striatin is a regulator of vascular function, wild-type and heterozygous striatin-deficient mice (Strn(+/-)) were randomized in crossover intervention to restricted (0.03%) and liberal sodium (1.6%) diets for 7 days on each diet, and blood pressure and aortic vascular function were measured. Compared with wild-type, sodium restriction significantly reduced blood pressure in Strn(+/-). On liberal salt intake, phenylephrine and high KCl caused a greater vascular contraction in Strn(+/-) than wild-type, and endothelium removal, nitric oxide synthase inhibitor L-NAME, and guanylate cyclase inhibitor ODQ enhanced phenylephrine contraction to a smaller extent in Strn(+/-) than wild-type. On liberal salt, acetylcholine relaxation was less in Strn(+/-) than in wild-type, and endothelium removal, L-NAME, and ODQ blocked acetylcholine relaxation, suggesting changes in endothelial NO-cGMP. On liberal salt, endothelial nitric oxide synthase mRNA expression and the ratio of endothelial nitric oxide synthase activator pAkt/total Akt were decreased in Strn(+/-) versus wild-type. Vascular relaxation to NO donor sodium nitroprusside was not different among groups. Thus, striatin deficiency is associated with salt sensitivity of blood pressure, enhanced vasoconstriction, and decreased vascular relaxation, suggesting a critical role for striatin, through modulation of endothelial NO-cGMP, in regulation of vascular function and BP during changes in sodium intake., (© 2015 American Heart Association, Inc.)

Introduction: This study compares the effectiveness and cost of trans-catheter verses surgical closure of secundum atrial septum defect (ASD). ASD accounts for 10% of congenital cardiac defects. Trans-catheter closure of secundum ASD is increasingly used as the primary intervention. Surgical repair is advised in a proportion of secundum type defects which are unsuitable for device closure., Methods: We reviewed the clinical course of 176 patients who underwent closure of isolated secundum ASD. The patients were assigned to either the device or surgical group depending upon the treatment they received. Successful closure was assessed immediately after the procedure. The following outcomes were studied: mortality, morbidity, hospital stay, and costs., Results: Ninety five patients were in the surgical group and 81 patients were in the group undergoing device closure. The median age was 14.0 years (range 1.1-61.0) for surgical group and 24.0 years (range 0.5-68.0) for the device group. The mortality in both groups was 0. The procedure success rate was 100% for the surgical group and 96.3% for the device group. The complication rate was 13.7% for surgical group and 7.4% for the device group. The mean length of hospital stay was 5.0 ± 2.7 days for surgical group and 3.0 ± 0.4 days for device group. The procedure cost for surgery was found to be 12.3% lower than that of trans-catheter closure., Conclusion: Successful closure is achieved by both methods. Trans-catheter closure results in lower rate of complication and hospital stay but the cost of the procedure tends to be higher than surgery.

Objective: To examine the outcomes of surgical repair of atrial septal defects in paediatric and adult patients., Methods: The retrospective study comprised data of 84 patients who had undergone surgical correction of atrial septal defect at the Aga Khan University Hospital, Karachi, between June 2006 and December 2011. All patients with isolated atrial septal defect (ostium secundum, ostium primum and sinus venosus with or without partial anomalous pulmonary venous connection) were included. Clinical and transthoracic echocardiographic data was reviewed. SPSS 17 was used for statistical analysis., Results: There were no deaths in the study population. The mean time for follow-up was 6.5 +/- 9.9 months. Most of the patients (n = 80; 95.2%) were in NewYork Heart Association class I at follow-up, while the remaining 4 (4.8%) were in New York Heart Association class II. Post-operatively, 8 (9.5%) patients developed brief episodes of arrhythmias. There were 3 (3.57%) patients who were re-admitted within 30 days; 2 (66.7%) had superficial wound infection, while 1 (33.3%) had to be re-opened because of cardiac tamponade., Conclusion: Surgical repair of atrial septal defects is a safe procedure which is associated with excellent results and low morbidity.