Percutaneous coronary intervention outcomes in patients with rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis.

OBJECTIVE: Patients with autoimmune rheumatic disease (AIRD) are at an increased risk of coronary artery disease. The present study sought to examine the prevalence and outcomes of AIRD patients undergoing percutaneous coronary intervention (PCI) from a national perspective. METHODS: All PCI-related hospitalizations recorded in the US National Inpatient Sample (2004-2014) were included, stratified into four groups: no AIRD, RA, SLE and SSc. We examined the prevalence of AIRD subtypes and assessed their association with in-hospital adverse events using multivariable logistic regression [odds ratios (OR) (95% CI)]. RESULTS: Patients with AIRD represented 1.4% (n = 90 469) of PCI hospitalizations. The prevalence of RA increased from 0.8% in 2004 to 1.4% in 2014, but other AIRD subtypes remained stable. In multivariable analysis, the adjusted odds ratio (aOR) of in-hospital complications [aOR any complication 1.13 (95% CI 1.01, 1.26), all-cause mortality 1.32 (1.03, 1.71), bleeding 1.50 (1.30, 1.74), stroke 1.36 (1.14, 1.62)] were significantly higher in patients with SSc compared with those without AIRD. There was no difference in complications between the SLE and RA groups and those without AIRD, except higher odds of bleeding in SLE patients [aOR 1.19 (95% CI 1.09, 1.29)] and reduced odds of all-cause mortality in RA patients [aOR 0.79 (95% CI 0.70, 0.88)]. CONCLUSION: In a nationwide cohort of US hospitalizations, we demonstrate increased rates of all adverse clinical outcomes following PCI in people with SSc and increased bleeding in SLE. Management of such patients should involve a multiteam approach with rheumatologists.

Mechanical Circulatory Support: a Comprehensive Review With a Focus on Women.

PURPOSE OF THE REVIEW: The purpose of this review is to analyze the evidence for use of mechanical circulatory support (MCS) with a focus on women, namely, intra-aortic balloon pump (IABP), Impella, ventricular assist devices (VAD), and extracorporeal membrane oxygenation (ECMO). RECENT FINDINGS: There is paucity of data examining management options for cardiogenic shock (CS) in women specifically. In published data, although only a minority of MCS recipients (33%) were women, there is a trend toward even lower use in women relative to men over time. Women presenting with CS tend to have a higher risk profile including older age, greater comorbidities, higher Society of Cardiothoracic Surgery (STS) mortality scores, more hypotension and index vasopressor requirements, and longer duration of CS. Overall, women receiving mechanical support suffer increased bleeding and vascular complications and have higher 30-day readmission rates. The incidence of cardiogenic shock (CS) has been rising at a higher rate in women compared to men. Women in CS tend to present with an overall higher risk profile including older age, greater burden of medical comorbidities, more hypotension and index vasopressor requirements, higher STS mortality scores, and more out-of-hospital cardiac arrest. After adjusting for comorbidities and traditional cardiovascular risk factors, mortality remained higher in younger women compared to men of similar age. In spite of these facts, evidence points to the underutilization of support devices in eligible female patients. Higher complication rates, such as vascular complications requiring surgery and bleeding requiring transfusion, may be deterring factors that limit the use of MCS and hinderoperator confidence and experience with devices in women. This suggests that future research should address the sex disparities in outcomes of contemporary MCS practices.

Percutaneous coronary intervention in cancer patients: a report of the prevalence and outcomes in the United States.

AIMS: This study aims to examine the temporal trends and outcomes in patients who undergo percutaneous coronary intervention (PCI) with a previous or current diagnosis of cancer, according to cancer type and the presence of metastases. METHODS AND RESULTS: Individuals undergoing PCI between 2004 and 2014 in the Nationwide Inpatient Sample were included in the study. Multivariable analyses were used to determine the association between cancer diagnosis and in-hospital mortality and complications. 6 571 034 PCI procedures were included and current and previous cancer rates were 1.8% and 5.8%, respectively. Both rates increased over time and the four most common cancers were prostate, breast, colon, and lung cancer. Patients with a current lung cancer had greater in-hospital mortality (odds ratio (OR) 2.81, 95% confidence interval (95% CI) 2.37-3.34) and any in-hospital complication (OR 1.21, 95% CI 1.10-1.36), while current colon cancer was associated with any complication (OR 2.17, 95% CI 1.90-2.48) and bleeding (OR 3.65, 95% CI 3.07-4.35) but not mortality (OR 1.39, 95% CI 0.99-1.95). A current diagnosis of breast was not significantly associated with either in-hospital mortality or any of the complications studied and prostate cancer was only associated with increased risk of bleeding (OR 1.41, 95% CI 1.20-1.65). A historical diagnosis of lung cancer was independently associated with an increased OR of in-hospital mortality (OR 1.65, 95% CI 1.32-2.05). CONCLUSIONS: Cancer among patients receiving PCI is common and the prognostic impact of cancer is specific both for the type of cancer, presence of metastases and whether the diagnosis is historical or current. Treatment of patients with a cancer diagnosis should be individualized and involve a close collaboration between cardiologists and oncologists.

The influence of Elixhauser comorbidity index on percutaneous coronary intervention outcomes.

BACKGROUND: Clinical outcomes with respect to the evolution of comorbidity burden in national cohorts of patients undergoing PCI have not been reported. OBJECTIVES: We sought to explore the association between comorbidity burden and periprocedural outcomes in patients treated with PCI in the National Inpatient Sample. METHODS: 6,601,526 PCI procedures were identified between 2004 and 2014 and comorbidities were defined by the Elixhauser classification system (ECS) consisting of 30 comorbidity measures. Endpoints included in-hospital mortality, periprocedural complications, length of stay and cost. Patients were classified based on their ECS in five categories (ECS I < 0, ECS II = 0, ECS III = 1-5, ECS IV = 6-13, and ECS V ≥ 14). RESULTS: Patients with a score over 13 had a fivefold increase in the odds of mortality (OR: 5.13, 95% CI: 4.76-5.54), major bleeding (OR: 11.46, 95% CI: 10.66-12.33) and doubled the hospitalization costs ($31,452 vs $17.566). CONCLUSIONS: Our study of over six million PCI procedures demonstrates that patients with the greatest comorbid burden (as defined by an ECS of >13) have a fivefold increase risk of in-hospital mortality, a fourfold increase in in-hospital periprocedural complications and an 11-fold increase in major bleeding events once differences in baseline patient characteristics are adjusted for. In addition, ECS significantly impacts the length of stay and doubles the healthcare costs. Comorbid burden is an important predictor of poor outcomes after PCI and should be considered as part of the decision-making processes in patients undergoing PCI.

Peripheral Arterial Disease in Women: an Overview of Risk Factor Profile, Clinical Features, and Outcomes.

PURPOSE OF REVIEW: Peripheral arterial disease (PAD) is the third most common manifestation of cardiovascular disease (CVD), following coronary artery disease (CAD) and stroke. PAD remains underdiagnosed and under-treated in women. RECENT FINDINGS: Women with PAD experience more atypical symptoms and poorer overall health status. The prevalence of PAD in women increases with age, such that more women than men have PAD after the age of 40 years. There is under-representation of PAD patients in clinical trials in general and women in particular. In this article, we address the lack of women participants in PAD trials. We then present a comprehensive overview of the epidemiology/risk factor profile, clinical features, treatment, and outcomes. PAD is prevalent in women and its global burden is on the rise despite a decline in global age-standardized death rate from CVD. The importance of this issue has been underlined by the American Heart Association's (AHA) "Call to Action" scientific statement on PAD in women. Large-scale campaigns are needed to increase awareness among physicians and the general public. Furthermore, effective treatment strategies must be implemented.

Characteristics of the electrocardiogram in patients with continuous-flow left ventricular assist devices.

BACKGROUND: Electrocardiograms (ECGs) are routinely obtained in patients with advanced congestive heart failure (CHF) before and after surgical implantation with a left-ventricular assist device (LVAD). As the number of patients with CHF is increasing, it is necessary to characterize the changes present in the ECG of patients with LVADs. METHODS: ECGs of 43 patients pre- and postimplantation of a HeartMate II LVAD were compared to characterize the presence of an LVAD using the following six criteria (LVADS2 ): low limb-lead voltage, ventricular pacing, artifact (electrical), duration of the QRS > 120 milliseconds, ST-elevation in the lateral leads, and splintering of the QRS complex. Additionally, 50 ECGs of non-LVAD patients coded as "lateral myocardial infarction (MI)" and 50 ECGs coded as "ventricular pacing" were chosen at random and scored. Odds ratios were calculated using Fisher's exact test. Logistic regression models were built to predict the presence of an LVAD in all patients. RESULTS: Univariate analysis of the pre- and post-LVAD ECGs confirmed that all criteria except the "Duration of QRS > 120 milliseconds" characterized the ECG of a patient with an LVAD. Electrical artifact and low limb-lead voltage yielded the greatest association with an LVAD-ECG. CONCLUSIONS: The ECG of a patient with end-stage CHF significantly changes with LVAD implantation. The LVADS2 criteria provide a framework towards characterizing and establishing a new baseline of the ECG in a patient with a continuous-flow LVAD.

Genetic deficiency of glycogen synthase kinase-3beta corrects diabetes in mouse models of insulin resistance.

Despite treatment with agents that enhance beta-cell function and insulin action, reduction in beta-cell mass is relentless in patients with insulin resistance and type 2 diabetes mellitus. Insulin resistance is characterized by impaired signaling through the insulin/insulin receptor/insulin receptor substrate/PI-3K/Akt pathway, leading to elevation of negatively regulated substrates such as glycogen synthase kinase-3beta (Gsk-3beta). When elevated, this enzyme has antiproliferative and proapoptotic properties. In these studies, we designed experiments to determine the contribution of Gsk-3beta to regulation of beta-cell mass in two mouse models of insulin resistance. Mice lacking one allele of the insulin receptor (Ir+/-) exhibit insulin resistance and a doubling of beta-cell mass. Crossing these mice with those having haploinsufficiency for Gsk-3beta (Gsk-3beta+/-) reduced insulin resistance by augmenting whole-body glucose disposal, and significantly reduced beta-cell mass. In the second model, mice missing two alleles of the insulin receptor substrate 2 (Irs2-/-), like the Ir+/- mice, are insulin resistant, but develop profound beta-cell loss, resulting in early diabetes. We found that islets from these mice had a 4-fold elevation of Gsk-3beta activity associated with a marked reduction of beta-cell proliferation and increased apoptosis. Irs2-/- mice crossed with Gsk-3beta+/- mice preserved beta-cell mass by reversing the negative effects on proliferation and apoptosis, preventing onset of diabetes. Previous studies had shown that islets of Irs2-/- mice had increased cyclin-dependent kinase inhibitor p27(kip1) that was limiting for beta-cell replication, and reduced Pdx1 levels associated with increased cell death. Preservation of beta-cell mass in Gsk-3beta+/- Irs2-/- mice was accompanied by suppressed p27(kip1) levels and increased Pdx1 levels. To separate peripheral versus beta-cell-specific effects of reduction of Gsk3beta activity on preservation of beta-cell mass, mice homozygous for a floxed Gsk-3beta allele (Gsk-3(F/F)) were then crossed with rat insulin promoter-Cre (RIP-Cre) mice to produce beta-cell-specific knockout of Gsk-3beta (betaGsk-3beta-/-). Like Gsk-3beta+/- mice, betaGsk-3beta-/- mice also prevented the diabetes of the Irs2-/- mice. The results of these studies now define a new, negatively regulated substrate of the insulin signaling pathway specifically within beta-cells that when elevated, can impair replication and increase apoptosis, resulting in loss of beta-cells and diabetes. These results thus form the rationale for developing agents to inhibit this enzyme in obese insulin-resistant individuals to preserve beta-cells and prevent diabetes onset.

Racial, Ethnic, and Sex Disparities in Patients With STEMI and Cardiogenic Shock.

OBJECTIVES: The aim of this study was to evaluate the combined impact of race, ethnicity, and sex on in-hospital outcomes using data from the National Inpatient Sample. BACKGROUND: Cardiogenic shock (CS) is a major cause of mortality following ST-segment elevation myocardial infarction (STEMI). Early revascularization reduces mortality in such patients. Mechanical circulatory support (MCS) devices are increasingly used to hemodynamically support patients during revascularization. Little is known about racial, ethnic, and sex disparities in patients with STEMI and CS. METHODS: The National Inpatient Sample was queried from January 2006 to September 2015 for hospitalizations with STEMI and CS. The associations between sex, race, ethnicity, and outcomes were examined using complex-samples multivariate logistic or generalized linear model regressions. RESULTS: Of 159,339 patients with STEMI and CS, 57,839 (36.3%) were women. In-hospital mortality was higher for all women (range 40% to 45.4%) compared with men (range 30.4% to 34.7%). Women (adjusted odds ratio [aOR]: 1.11; 95% confidence interval [CI]: 1.06 to 1.16; p < 0.001) as well as Black (aOR: 1.18; 95% CI: 1.04 to 1.34; p = 0.011) and Hispanic (aOR: 1.19; 95% CI: 1.06 to 1.33; p = 0.003) men had higher odds of in-hospital mortality compared with White men, with Hispanic women having the highest odds of in-hospital mortality (aOR: 1.46; 95% CI: 1.26 to 1.70; p < 0.001). Women were older (age: 69.8 years vs. 63.2 years), had more comorbidities, and underwent fewer invasive cardiac procedures, including revascularization, right heart catheterization, and MCS. CONCLUSIONS: There are significant racial, ethnic, and sex differences in procedural utilization and clinical outcomes in patients with STEMI and CS. Women are less likely to undergo invasive cardiac procedures, including revascularization and MCS. Women as well as Black and Hispanic patients have a higher likelihood of death compared with White men.

High-sensitivity cardiac troponin T increases after stress echocardiography.

INTRODUCTION: Exercise (ESE) and dobutamine stress echocardiography (DSE) have high sensitivity and specificity to detect inducible myocardial ischemia in patients with significant coronary artery disease (CAD). High-sensitivity cardiac troponin (hs-cTn) assays detect troponin concentrations in the ng/L range. The aim of this study was to determine the kinetics of hs-cTnT in patients undergoing ESE and DSE and possible association of hs-cTnT with inducible myocardial ischemia. METHODS: In this prospective study adult patients undergoing ESE/DSE were enrolled. Peripheral blood samples were obtained before, and 30 min, 1, 2, and 4-6 h after completion of ESE/DSE. Hs-cTnT was measured on a Roche Diagnostics Elecsys 2010 analyzer. RESULTS: We enrolled 48 patients (33 ESE and 15 DSE); 11 patients (23%) had elevated baseline hs-cTnT concentrations >14 ng/L (99th percentile URL); 31/48 (65%) developed an hs-cTnT increase after ESE/DSE (peak 4-6 h post stress test), but only three patients (all in ESE group) had a positive stress test. Absolute and relative hs-cTnT increases were higher after DSE (median Δhs-cTnT +9.7 ng/L [IQR 4.5, 27.2]; +123% [IQR 49, 271]) compared to ESE (median Δhs-cTnT +2.3 ng/L [IQR 1, 4.9]; +37% [IQR 9.1, 221]). CONCLUSIONS: One in four patients undergoing ESE/DSE had increased hs-cTnT values prior to stress testing. Hs-cTnT increased above the upper limit of normal occurred commonly after ESE/DSE but was more pronounced after DSE. Increases in hs-cTn did not appear to be associated with inducible myocardial ischemia. These findings may have important implications for the clinical use of hs-cTnT within 6 h after ESE/DSE.

"Treat-to-close": Non-repairable ASD-PAH in the adult: Results from the North American ASD-PAH (NAAP) Multicenter Registry.

BACKGROUND: Adults presenting with an unrepaired atrial septal defect and pulmonary arterial hypertension (ASD-PAH) are typically classified as "correctable" or "non-correctable". The use of directed PAH medical therapy in non-correctable ASD-PAH leading to favorable closure candidacy, repair status and long-term follow-up is not well studied. We therefore sought to characterize response to PAH targeted therapy in 'non-correctable' ASD-PAH. METHODS AND RESULTS: Nine North American tertiary care centers submitted retrospective data from adults with unrepaired ASD-PAH that did not meet recommendations for repair at initial presentation (1996-2017). Sixty-nine patients (women 51(74%), 40 ±â€¯15 years, mean pulmonary artery pressure (mPA) 51 ±â€¯13 mm Hg, pulmonary vascular resistance (PVR) 8.7 ±â€¯4.9 Wood units, Qp:Qs 1.6 ±â€¯0.4) were enrolled. All patients were prescribed PAH targeted therapy and late shunt repair occurred in 19(28%) (Women 15(29%) vs. Men 4(22%), p = 0.6). At late follow-up (4.4 ±â€¯2.9 years) 6-minute walk test distance (6MWTD) was significantly better in the group that underwent repair (486 ±â€¯89 m vs. 375 ±â€¯139 m, p < 0.05). Transthoracic echo showed significant improvement in right ventricular (RV) function (severe dysfunction in repaired 8(40%) vs. unrepaired groups 35(69%), p < 0.05). Divergent survival curves suggest that with larger studies and more follow-up, differences in survival between repaired and unrepaired groups may be important. (repaired: 17(94%) vs. unrepaired: 32(81%), p = 0.18). CONCLUSIONS: This is the first and largest multicenter study evaluating the "treat-to-close" approach in non-correctable ASD-PAH. Our new data supports further study of this strategy in patients who have reversibility of PAH in response to targeted therapy. We demonstrate that in the carefully selected patient with non-correctable ASD-PAH, successful shunt repair is possible if post-therapy PVR is ≤6.5 Wood units. Patients who underwent repair had improved RV function following PAH targeted therapy. Divergent survival curves suggest that with further study, defect repair may affect medium-term to late survival.

Transcatheter aortic valve replacement outcomes in bicuspid compared to trileaflet aortic valves.

AIM: TAVR in patients with bicuspid aortic valves (BAV) is more challenging compared to individuals with trileaflet aortic valves (TAV). BAV have been excluded from the large randomized clinical trials assessing transcatheter aortic valve replacements (TAVR) and has been considered as a relative contraindication to TAVR. To report the outcomes of TAVR in BAV and compare them to TAV in the National Inpatient Sample (NIS). METHODS AND RESULTS: TAVR procedures were identified between 2011 and 2014 in the NIS dataset. Endpoints assessed included in-hospital mortality, periprocedural complications, length of stay and cost. Of 40,604 identified TAVR procedures, 407 (1%) were BAV and the 40,197 (99%) were TAV. Patients with BAV were younger and had a lower comorbidity burden. In hospital mortality (4.89% vs 4.17%, OR: 1.71, 95%CI: 0.57-5.12, P = 0.21), AMI (3.49% vs 3.58%, OR: 1.12, 95%CI: 0.36-3.54, P = 0.85), stroke and TIA (2.49% vs 3.55%, OR: 0.75, 95%CI: 0.18-3.16, P = 0.70), vascular complications (2.39% vs 5.58%, OR:0.47, 95%CI: 0.11-1.93, P = 0.29), major bleeding (16.96% vs 23.50%, OR: 0.63, 95%CI: 0.34-1.17, P = 0.15) and rates of permanent pacemaker (PPM) (9.88% vs 10.88%, OR: 1.19, 95%CI: 0.57-2.51, P = 0.64) were similar in both cohorts. CONCLUSIONS: With multimodality imaging and further improvement in technology, our study demonstrates off-label TAVR should not be considered prohibitive and can be successfully performed for BAV with similar peri-procedural outcomes compared to those with TAV. However, there is a need for robust large prospective studies.

Temporal trends and predictors of time to coronary angiography following non-ST-elevation acute coronary syndrome in the USA.

OBJECTIVE: This study aims to investigate the temporal trends in utilization of invasive coronary angiography (CA) at different time points and changing profiles of patients undergoing CA following non-ST-elevation acute coronary syndrome (NSTEACS). We also describe the association between time to CA and in-hospital clinical outcomes. PATIENTS AND METHODS: We queried the National Inpatient Sample to identify all admissions with a primary diagnosis of NSTEACS from 2004 to 2014. Patients were stratified into early (day 0, 1), intermediate (day 2) and late strategy (day≥3) according to time to CA. Multivariable logistic regression was used to investigate the association between time to CA and in-hospital mortality, major bleeding, stroke and Major Adverse Cardiac and Cerebrovascular Events. RESULTS: A total of 4 380 827 records were identified with a diagnosis of NSTEACS, out of which 57.5% received CA. The proportion of patients undergoing early CA increased from 65.6 to 72.6%, whereas late CA commensurately declined from 19.6 to 13.5%. Patients receiving early CA were younger (age: 64 vs. 70 years), more likely to be male (63.7 vs. 55.3%) and of Caucasian ethnic background (68.7 vs. 64.7%) compared with late CA group. Similarly, Women, weekend admissions and African Americans remain less likely to receive early CA. In-hospital mortality was lowest in the intermediate group (odds ratio=0.30, 95% confidence interval: 0.28-0.33). CONCLUSION: Use of early CA has increased in the management of NSTEACS; however, there remain significant disparities in utilization of an early invasive approach in women, African Americans, admission day and older patients in the USA.

Effect of Comorbidity On Unplanned Readmissions After Percutaneous Coronary Intervention (From The Nationwide Readmission Database).

It is unclear how comorbidity influences rates and causes of unplanned readmissions following percutaneous coronary intervention (PCI). We analyzed patients in the Nationwide Readmission Database who were admitted to hospital between 2010 and 2014. The comorbidity burden as defined by the Charlson Comorbidity Index (CCI). Primary outcomes were 30-day readmission rates and causes of readmission according to comorbidity burden. A total of 2,294,346 PCI procedures were included the analysis. The patients in CCI = 0, 1, 2 and ≥3 were 842,272(36.7%), 701,476(30.6%), 347,537(15.1%) and 403,061(17.6%), respectively. 219,227(9.6%) had an unplanned readmission within 30 days and rates by CCI group were 6.6%, 8.6%, 11.4% and 15.9% for CCI groups 0, 1, 2 and ≥3, respectively. The CCI score was also associated with greater cost (cost of index PCI for not readmitted vs readmitted was CCI = 0 $21,257 vs $19,764 and CCI ≥ 3 $26,736 vs $27,723). Compared to patients with CCI = 0, greater CCI score was associated with greater independent odds of readmission (CCI = 1 OR 1.25(1.22-1.28), p < 0.001, CCI ≥ 3 OR 2.08(2.03-2.14), p < 0.001). Rates of non-cardiac causes for readmissions increased with increasing CCI group from 49.4% in CCI = 0 to 57.1% in CCI ≥ 3. Rates of early unplanned readmission increase with greater comorbidity burden and non-cardiac readmissions are higher among more comorbid patients.

Persistent sex disparities in clinical outcomes with percutaneous coronary intervention: Insights from 6.6 million PCI procedures in the United States.

BACKGROUND: Prior studies have reported inconsistencies in the baseline risk profile, comorbidity burden and their association with clinical outcomes in women compared to men. More importantly, there is limited data around the sex differences and how these have changed over time in contemporary percutaneous coronary intervention (PCI) practice. METHODS AND RESULTS: We used the Nationwide Inpatient Sample to identify all PCI procedures based on ICD-9 procedure codes in the United States between 2004-2014 in adult patients. Descriptive statistics were used to describe sex-based differences in baseline characteristics and comorbidity burden of patients. Multivariable logistic regressions were used to investigate the association between these differences and in-hospital mortality, complications, length of stay and total hospital charges. Among 6,601,526 patients, 66% were men and 33% were women. Women were more likely to be admitted with diagnosis of NSTEMI (non-ST elevation acute myocardial infarction), were on average 5 years older (median age 68 compared to 63) and had higher burden of comorbidity defined by Charlson score ≥3. Women also had higher in-hospital crude mortality (2.0% vs 1.4%) and any complications compared to men (11.1% vs 7.0%). These trends persisted in our adjusted analyses where women had a significant increase in the odds of in-hospital mortality men (OR 1.20 (95% CI 1.16,1.23) and major bleeding (OR 1.81 (95% CI 1.77,1.86). CONCLUSION: In this national unselected contemporary PCI cohort, there are significant sex-based differences in presentation, baseline characteristics and comorbidity burden. These differences do not fully account for the higher in-hospital mortality and procedural complications observed in women.

Relation Between Age and Unplanned Readmissions After Percutaneous Coronary Intervention (Findings from the Nationwide Readmission Database).

It is unclear how age affects rates and causes of unplanned early readmissions after percutaneous coronary intervention (PCI). We analyzed patients in the Nationwide Readmission Database in the United States from 2010 to 2014 and examined the impact of age on readmissions after PCI. The primary outcomes were age-specific 30-day rates and causes of unplanned readmissions. A total of 2,294,345 procedures were analyzed with a 9.6% unplanned readmission rate within 30 days. Unplanned readmissions were 8.1%, 8.1%, 9.5%, and 12.6% for age groups <55, 55.0 to 64.9, 65.0-74.9, and ≥75 years, respectively. With increasing age, there was an increase in the rate of noncardiac causes for readmissions (for ages <55, 55.0 to 64.9, and ≥75 years, the rates were 54.1%, 54.8%, 56.6%, and 57.1%, respectively; p <0.001). Older age was associated with an increased prevalence of infections (13.9% ≥75 years vs 7.7% <55 years), gastrointestinal disease (11.5% ≥75 years vs 9.5% <55 years), and bleeding (7.4% ≥75 years vs 2.9% <55 years) as causes for noncardiac readmissions and a reduced prevalence of nonspecific chest pain (9.9% ≥75 years vs 31.4% <55 years). For cardiac causes, older age was associated with increased prevalence for readmissions due to heart failure (34.6% ≥75 years vs 11.9% <55 years) but a reduced prevalence of coronary artery disease, including angina (25.7% ≥75 years vs 51.3% <55 years). In conclusion, older patients have the highest rates of unplanned 30-day readmissions after PCI, with different causes for readmission compared with younger patients. Interventions designed to reduce readmissions after PCI should be age specific.

Glucose regulates Foxo1 through insulin receptor signaling in the pancreatic islet beta-cell.

Glucose controls islet beta-cell mass and function at least in part through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway downstream of insulin signaling. The Foxo proteins, transcription factors known in other tissues to be negatively regulated by Akt activation, affect proliferation and metabolism. In this study, we tested the hypothesis that glucose regulates Foxo1 activity in the beta-cell via an autocrine/paracrine effect of released insulin on its receptor. Mouse insulinoma cells (MIN6) were starved overnight for glucose (5 mmol/l) then refed with glucose (25 mmol/l), resulting in rapid Foxo1 phosphorylation (30 min, P < 0.05 vs. untreated). This glucose response was demonstrated to be time (0.5-2 h) and dose (5-30 mmol/l) dependent. The use of inhibitors demonstrated that glucose-induced Foxo1 phosphorylation was dependent upon depolarization, calcium influx, and PI3K signaling. Additionally, increases in glucose concentration over a physiological range (2.5-20 mmol/l) resulted in nuclear to cytoplasmic translocation of Foxo1. Phosphorylation and translocation of Foxo1 following glucose refeeding were eliminated in an insulin receptor knockdown cell line, indicating that the glucose effects are mediated primarily through the insulin receptor. Activity of Foxo1 was observed to increase with decreased glucose concentrations, assessed by an IGF binding protein-1 promoter luciferase assay. Starvation of MIN6 cells identified a putative Foxo1 target, Chop, and a Chop-promoter luciferase assay in the presence of cotransfected Foxo1 supported this hypothesis. The importance of these observations was that nutritional alterations in the beta-cell are associated with changes in Foxo1 transcriptional activity and that these changes are predominantly mediated through glucose-stimulated insulin secretion acting through its own receptor.

Prospective Assessment of Frailty Using the Fried Criteria in Patients Undergoing Left Ventricular Assist Device Therapy.

Frail patients are more prone to adverse events after cardiac surgery, particularly after implantation of left ventricular assist devices. Thus, frailty assessment may help identify patients unlikely to benefit from left ventricular assist device therapy. The purpose was to establish a suitable measure of frailty in adults with end-stage heart failure. In a prospective cohort of 75 patients (age 58 ± 12 years) with end-stage heart failure, we assessed the association between frailty (5-component Fried criteria) and the composite primary outcome of inpatient mortality or prolonged length of stay, as well as extubation status, time on ventilator, discharge status, and long-term mortality. Fried frailty criteria were met in 44 (59%) patients, but there was no association with the primary outcome (p = 0.10). However, an abridged set of 3 criteria (exhaustion, inactivity, and grip strength) was predictive of the primary outcome (odds ratio 2.9, 95% confidence interval 1.1 to 7.4), and of time to extubation and time to discharge. In patients with advanced heart failure, the 5-component Fried criteria may not be optimally sensitive to clinical differences. In conclusion, an abridged set of 3 frailty criteria was predictive of the primary outcome and several secondary outcomes, and may therefore be a clinically useful tool in this population.

Controversies surrounding percutaneous coronary intervention in the diabetic patient.

Diabetic patients with coronary artery disease are common and complex, with an aggressive progression of atherosclerosis, increased rate of stent complications, and increased rates of incomplete revascularization in multivessel disease compared to non-diabetic patients. In this review, we first discuss the pathophysiologic elements of insulin resistance and presentations of coronary artery disease in diabetic patients. Next, we outline the evolution and present the data on revascularization strategies on diabetic patient outcomes. The overall conclusion of our review is that a strategy of complete and durable revascularization and guideline-directed medical therapy currently provides the best possible chance at closing the gap between outcomes in patients with and without diabetes.