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Study Objectives: While heart failure with preserved ejection fraction (HFpEF) is associated with the presence of obstructive sleep apnea (OSA), few studies have examined the association between scoring systems used to predict HFpEF risk, such as the H 2 FPEF and HFA-PEFF scores, and OSA prevalence and severity., Methods: We performed chart review on all patients who underwent both an echocardiogram and sleep study at the University of Pennsylvania between July 1, 2020, and June 30, 2022. There were 277 patients in the final cohort after excluding patients with relevant comorbidities. Associations between echocardiographic parameters and OSA severity, as well as between H 2 FPEF score and OSA severity, were examined using linear tests of trend. The association between H 2 FPEF score and prevalent OSA was examined with logistic regression., Results: OSA severity was associated with echocardiographic markers, including left atrial volume index ( P = .03) and left ventricular relative thickness ( P = .008). Patients with high H 2 FPEF risk scores had over 17-fold higher odds of prevalent OSA compared with those with low-risk scores (17.7; 95% CI 4.3, 120.7; P < .001). Higher H 2 FPEF scores were strongly correlated with OSA severity ( P < .001). After controlling for body mass index, H 2 FPEF scores were not associated with prevalence or severity of OSA., Conclusions: In an ambulatory population referred for sleep study and echocardiogram, markers of diastolic dysfunction were associated with OSA severity. OSA prevalence and severity were associated with increased H 2 FPEF scores, although these associations were largely explained by obesity. Clinicians should have low thresholds for referring patients with OSA for cardiac workup and patients with HFpEF for sleep study., Citation: Connolly JE, Genuardi MV, Mora JI, Prenner SB. Heart failure with preserved ejection fraction risk is associated with prevalence and severity of obstructive sleep apnea. J Clin Sleep Med . 2024;20(3):381-387., (© 2024 American Academy of Sleep Medicine.)

Background: Cardiac point of care ultrasound (POCUS) is increasingly utilized by trainees across various specialties and can rapidly assess the cardiac status of unstable patients. However, the quality of trainee performed cardiac examinations has been reported only in controlled studies. In this study we aimed to assess the quality of all cardiac POCUS performed by internal medicine trainees at a major academic medical center over a three-year period., Methods: 256 studies were included and were graded by experts blinded to postgraduate year (PGY) using a previously validated scoring metric., Results: We found significant improvement in overall quality of resident performed cardiac POCUS from PGY 1 to 3 (10.8, 10.2, 13.2, p = 0.012). Assessment of left ventricular function was possible in 82% of studies and increased from PGY 1 to PGY 3 (77%, 76%, 88%, p = 0.025). Similar trends were seen in the assessment of the pericardial space (67%, 71%, 84%, p = 0.012). Images sufficient for right ventricular and volume status assessment were less commonly found (65%, 60%, 75% and 60%, 49%, 57%, respectively)., Conclusions: This study provides a real world experience of the level of diagnostic accuracy that can be expected from IM trainees with minimal hands-on supervision., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Aims: Skeletal muscle (SkM) abnormalities may impact exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF). We sought to quantify differences in SkM oxidative phosphorylation capacity (OxPhos), fibre composition, and the SkM proteome between HFpEF, hypertensive (HTN), and healthy participants., Methods and Results: Fifty-nine subjects (20 healthy, 19 HTN, and 20 HFpEF) performed a maximal-effort cardiopulmonary exercise test to define peak oxygen consumption (VO 2, peak ), ventilatory threshold (VT), and VO 2 efficiency (ratio of total work performed to O 2 consumed). SkM OxPhos was assessed using Creatine Chemical-Exchange Saturation Transfer (CrCEST, n = 51), which quantifies unphosphorylated Cr, before and after plantar flexion exercise. The half-time of Cr recovery (t 1/2, Cr ) was taken as a metric of in vivo SkM OxPhos. In a subset of subjects (healthy = 13, HTN = 9, and HFpEF = 12), percutaneous biopsy of the vastus lateralis was performed for myofibre typing, mitochondrial morphology, and proteomic and phosphoproteomic analysis. HFpEF subjects demonstrated lower VO 2,peak , VT, and VO 2 efficiency than either control group (all P < 0.05). The t 1/2, Cr was significantly longer in HFpEF (P = 0.005), indicative of impaired SkM OxPhos, and correlated with cycle ergometry exercise parameters. HFpEF SkM contained fewer Type I myofibres (P = 0.003). Proteomic analyses demonstrated (a) reduced levels of proteins related to OxPhos that correlated with exercise capacity and (b) reduced ERK signalling in HFpEF., Conclusions: Heart failure with preserved ejection fraction patients demonstrate impaired functional capacity and SkM OxPhos. Reductions in the proportions of Type I myofibres, proteins required for OxPhos, and altered phosphorylation signalling in the SkM may contribute to exercise intolerance in HFpEF., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Medical procedures are traditionally taught informally at patients' bedside through observation and practice using the adage "see one, do one, teach one." This lack of formalized training can cause trainees to be unprepared to perform procedures independently. Simulation based education (SBE) increases competence, reduces complications, and decreases costs. We developed, implemented, and evaluated the efficacy of a right heart catheterization (RHC) SBE curriculum., Methods: The RHC curriculum consisted of a pretest, video didactics, deliberate practice, and a posttest. Pre-and posttest skills examinations consisted of a dichotomous 43-item checklist on RHC skills and a 14-item hemodynamic waveform quiz. We enrolled two groups of fellows: 6 first-year, novice cardiology fellows at Northwestern University in their first month of training, and 11 second- and third-year fellows who had completed traditional required, level I training in RHC. We trained the first-year fellows at the beginning of the 2018-2019 year using the SBE curriculum and compared them to the traditionally-trained cardiology fellows who did not complete SBE., Results: The SBE-trained fellows significantly improved RHC skills, hemodynamic knowledge, and confidence from pre- to posttesting. SBE-trained fellows performed similarly to traditionally-trained fellows on simulated RHC skills checklists (88.4% correct vs. 89.2%, p = .84), hemodynamic quizzes (94.0% correct vs. 86.4%, p = .12), and confidence (79.4 vs. 85.9 out of 100, p = .15) despite less clinical experience., Conclusions: A SBE curriculum for RHC allowed novice cardiology fellows to achieve level I skills and knowledge at the beginning of fellowship and can train cardiology fellows before patient contact., (© 2020 Wiley Periodicals LLC.)

Diabetes mellitus (DM) is associated with a higher risk of heart failure hospitalization and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Using SomaScan assays and proteomics analysis of plasma from participants in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial and the Penn Heart Failure Study, this study identified 10 proteins with significantly different expression in patients with HFpEF and DM. Of these, apolipoprotein M was found to mediate 72% (95% CI: 36% to 100%; p < 0.001) of the association between DM and the risk of cardiovascular death, aborted cardiac arrest, and heart failure hospitalization., Competing Interests: Dr. Hanff is supported by the National Institutes of Health (grant HL-00789). Dr. Cohen is supported by K23-HL133843. Dr. Javaheri is supported by K08-HL138262. Dr. Zamani is supported by grant K23-HL-13055. Dr. Chirinos is supported by a research grant from Bristol-Myers Squibb and by grants R01-HL 121510- 01A1, R61-HL-146390, R01-AG058969, 1R01-HL104106, P01-HL094307, R03-HL146874-01, and R56-HL136730. Dr. Javaheri has been named co-inventor on the patent application for the use of fusion protein nanodiscs for the treatment of heart failure. Drs. Zhao, Walsh, Maranville, Wang, Adam, Ramirez-Valle, Schafer, Seiffert, Gordon, and Cvijic own stock in Bristol-Myers Squibb. Dr. Cappola has received research funding from Bristol-Myers Squibb. Dr. Zamani has consulted for Vyaire. Dr. Chirinos has been a consultant for Sanifit, Microsoft, Fukuda-Denshi, Bristol-Myers Squibb, OPKO Healthcare, Ironwood Pharmaceuticals, Pfizer, Akros Pharma, Merck, Bayer, JNJ, and Edwards Life Sciences; and received research grants from National Institutes of Health, American College of Radiology Network, Fukuda Denshi, Bristol-Myers Squibb, and Microsoft, and has been named as inventor in a University of Pennsylvania patent for the use of inorganic nitrates/nitrites for the treatment of heart failure and preserved ejection fraction. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2021 The Authors.)

The aim of this study was to determine the arteriovenous oxygen content difference (ΔAVo 2 ) in adult subjects with and without heart failure with preserved ejection fraction (HFpEF) during systemic and forearm exercise. Subjects with HFpEF had reduced ΔAVo 2 . Forearm diffusional conductance for oxygen, a lumped conductance parameter that incorporates all impediments to the movement of oxygen from red blood cells in skeletal muscle capillaries into the mitochondria within myocytes, was estimated. Forearm diffusional conductance for oxygen was not different among adults with HFpEF, those with hypertension, and healthy control subjects; therefore, diffusional conductance cannot explain the reduced forearm ΔAVo 2 . Instead, adiposity was strongly associated with ΔAVo 2 , suggesting an active role for adipose tissue in reducing exercise capacity in patients with HFpEF., (© 2020 The Authors.)

Little data are available regarding the determinants and prognostic significance of serum albumin in Heart Failure with Preserved Ejection Fraction (HFpEF). We sought to examine the phenotypic correlates of albumin and its independent prognostic implications in HFpEF. We analyzed data from 3,254 subjects enrolled the TOPCAT trial. We stratified subjects according to tertiles of albumin and examined differences in various phenotypic traits between these strata, including 8 protein biomarkers selected ad hoc and measured from frozen samples available in a subset of participants (n = 372). We also assessed the relationship between albumin and the trial primary endpoint. Lower albumin was associated with older age, black race, and greater prevalence of NYHA class III-IV, peripheral arterial disease, atrial fibrillation and diabetes mellitus. Lower albumin was also associated with increased levels of several inflammatory biomarkers, markers of liver fibrosis, albuminuria, and greater arterial stiffness, diastolic dysfunction and pulmonary hypertension. Albumin was a strong predictor of the primary trial endpoint, even after adjustment for the MAGGIC risk score (hazard ratio [HR] 0.72, confidence interval [CI] 0.67 to 0.78; p <0.0001) and prespecified traditional risk factors (HR 0.78, CI 0.71 to 0.85; p <0.0001). Lower albumin was strongly associated with a worse prognosis even well within normal ranges (>3.5 g/dL), with a sharp increase in risk between 4.6 and 3.6 g/dL. In conclusion, albumin is an integrated marker of various adverse processes in HFpEF, including inflammation, subclinical liver disease, arterial stiffness, and renal disease. Albumin is a powerful risk predictor independent of traditional risk prediction models, even within normal ranges., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Heart failure (HF) with recovered ejection fraction (HFrecEF) is an increasingly recognized yet not well understood phenotype. Little is known about electrical parameters associated with myocardial recovery in acute systolic HF., Methods: We identified a subset of 87 patients from a non-ischemic cardiomyopathy cohort with left ventricular ejection fraction (LVEF) < 40% during index HF hospitalization. HFrecEF was defined as follow-up LVEF ≥40% and ≥ 10% improvement from baseline. We analyzed baseline and follow up electrocardiograms (ECG) in this group for several electrical parameters known to reflect repolarization heterogeneity., Results: Among 87 patients, 30 (34%) patients recovered in a median of 122 (IQR: 58-275) days after index hospitalization. Baseline demographics were similar among HFrecEF versus persistent HFrEF except for increased diabetes in the persistent HFrEF cohort. Patients with HFrecEF had baseline decreased QRST angle, decreased QT dispersion, and less negative signed JT area compared to persistent HFrEF. Patients with HFrecEF had greater decrease in QT dispersion and QTc duration, and greater increase in the signed JT and TpTe areas over time. Baseline QRST angle correlated with longitudinal and circumferential strain and myocardial systolic performance (MSP). Signed JT area correlated with increased baseline LVEF, smaller baseline LV dimensions, increased longitudinal and circumferential strain, and MSP. Signed TpTe correlated with increased longitudinal and circumferential strain, and MSP., Conclusions: Several conventional and novel ECG parameters that reflect repolarization heterogeneity may differentiate patients with acute HF who ultimately recover LVEF. These parameters are associated with baseline structural parameters and are dynamic during recovery., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background Data regarding the phenotypic correlates and prognostic value of albumin in heart failure with preserved ejection fraction (HFpEF) are scarce. The goal of the current study is to determine phenotypic correlates (myocardial hypertrophy, myocardial fibrosis, detailed pulsatile hemodynamics, and skeletal muscle mass) and prognostic implications of serum albumin in HFpEF. Methods and Results We studied 118 adults with HFpEF. All-cause death or heart-failure-related hospitalization was ascertained over a median follow-up of 57.6 months. We measured left ventricular mass, myocardial extracellular volume, and axial muscle areas using magnetic resonance imaging. Pulsatile arterial hemodynamics were assessed with a combination of arterial tonometry and phase-contrast magnetic resonance imaging. Subjects with lower serum albumin exhibited a higher body mass index, and a greater proportion of black ethnicity and diabetes mellitus. A low serum albumin was associated with higher myocardial extracellular volume (52.3 versus 57.4 versus 39.3 mL in lowest to highest albumin tertile, respectively; P =0.0023) and greater N-terminal pro B-type natriuretic peptide levels, but not with a higher myocardial cellular volume (123 versus 114 versus 102 mL; P =0.13). Lower serum albumin was also associated with an increased forward wave amplitude and markedly increased pulsatile power in the aorta. Serum albumin was a strong predictor of death or heart failure hospitalization even after adjustment for N-terminal pro B-type natriuretic peptide levels and the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score (adjusted standardized hazard ratio=0.56; 95% CI=0.37-0.83; P <0.0001). Conclusions Serum albumin is associated with myocardial fibrosis, adverse pulsatile aortic hemodynamics, and prognosis in HFpEF. This readily available clinical biomarker can enhance risk stratification in HFpEF and identifies a subgroup with specific pathophysiological abnormalities.

Background: Rehospitalization for heart failure (HF) is common, and subclinical congestion may be present at discharge. Larger inferior vena cava (IVC) size and lower collapsibility at discharge assessed via bedside ultrasound are predictive of rehospitalization; however, the utility of IVC assessment with the use of pocket-carried ultrasound (PCUS) during the transition from discharge to the posthospitalization follow-up visit (FU) has not been investigated., Methods and Results: IVC max and IVC min were measured with the use of PCUS, and the collapsibility index (IVCCI = [IVC max  - IVC min ]/IVC max ) was determined. The primary outcome was 90-day rehospitalization or death. We prospectively enrolled 49 adults (71 ± 13 years of age, 51% male, 47% black, 43% preserved ejection fraction) hospitalized for HF. Nineteen patients (39%) experienced the outcome. Within the rehospitalized group, discharge and FU mean IVC max were both >2.1 cm (2.2 ± 0.5 and 2.2 ± 0.7) and IVCCIs <50% (44 ± 20% and 45 ± 24%). Within those not rehospitalized, FU IVC max was ≤2.1 cm (2.1 ± 0.6 and 1.9 ± 0.6; P = .038) and IVCCI >50% at both time points (55 ± 25% and 62 ± 19%; P = NS). FU IVCCI below an optimal cutoff of 42% had modest discrimination alone (c-statistic = 0.73). FU IVCCI <42% was associated with a greater hazard of the outcome independent of admission log B-type natriuretic peptide (adjusted hazard ratio = 6.8; 95% confidence interval 2.4-19.0; P < .001)., Conclusions: Posthospitalization IVCCI assessment with PCUS predicts HF rehospitalization and may identify patients in need of intervention., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Heart Failure with Preserved Ejection Fraction (HFpEF) is increasing in prevalence due to the aging of the United States population as well as the current obesity epidemic. While obesity is very common in patients with HFpEF, obesity may represent a specific phenotype of HFpEF characterized by unique hemodynamics and structural abnormalities. Obesity induces a systemic inflammatory response that may contribute to myocardial fibrosis and endothelial dysfunction. The most obese patients continue to be excluded from HFpEF clinical trials, and thus ongoing research is needed to determine the role of pharmacologic and interventional approaches in this growing population., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Mastery learning in health professions education requires learners to learn and undergo assessment until they demonstrate a high level of competence. Setting defensible standards is key to accurately assessing educational outcomes in mastery learning. The Mastery Angoff method was proposed recently to set a minimum passing standard (MPS) for mastery learning curricula. However, it is unknown whether prior knowledge of trainee performance affects judges' decisions about setting an MPS using the Mastery Angoff method., Objective: We sought to determine the effect of introducing baseline data about trainee performance on faculty judges' decisions about the Mastery Angoff MPS for a written examination., Methods: We developed a mastery learning curriculum to train internal medicine residents and cardiology fellows about the correct interpretation of inpatient telemetry monitoring. All learners were required to meet or exceed an MPS on a 35-item written examination at the end of training. The MPS was set in 2017 by judges who used the item-based Mastery Angoff method without prior examinee performance information. The judges subsequently reevaluated the test items after receiving baseline data about trainee performance collected during pilot testing. Mastery Angoff MPSs with and without baseline performance data were compared., Results: Twelve judges participated in the standard-setting exercise. The initial MPS was similar to the repeat MPS set after judges received trainee performance data (86.2% versus 86.9%, P  = .23)., Conclusions: Prior knowledge about medical trainee performance data did not affect MPS as determined by the Mastery Angoff procedure., Competing Interests: Conflict of interest: The authors declare they have no competing interests.

Objectives: The aim of this study is to determine whether simulation-based education (SBE) translates into reduced procedure time, radiation, and contrast use in actual clinical care., Background: As a high volume procedure often performed by novice cardiology fellows, diagnostic coronary angiography represents an excellent target for SBE. Reports of SBE in interventional cardiology are limited and there is little understanding of the potential downstream clinical impact of these interventions., Methods: All diagnostic coronary angiograms performed at a single center between January 1, 2011 and June 30, 2015 were analyzed. Random effects linear regression models were used to compare outcomes between procedures performed by 12 cardiology fellows who underwent simulation-based training and those performed by 20 traditionally trained fellows., Results: Thirty-two cardiology fellows performed 2,783 diagnostic coronary angiograms. Procedures performed by fellows trained with SBE were shorter (mean of 23.98 min vs. 24.94 min, P = 0.034) and were performed with decreased radiation (mean of 56,348 mGycm 2 vs. 66,120 mGycm 2 , P < 0.001). After controlling for year in training, procedure year, access site, and supervising attending physician, training on the simulator was independently associated with 117 fewer seconds of fluoroscopy time per procedure (P = 0.04)., Conclusions: Diagnostic coronary angiography SBE is associated with decreased use of fluoroscopy in downstream clinical care. SBE may be a useful tool to reduce radiation exposure in the cardiac catheterization laboratory., (© 2017 Wiley Periodicals, Inc.)

Purpose of Review: To highlight the current data for treatment of hepatitis C virus (HCV) in patients with hepatocellular carcinoma (HCC) awaiting orthotopic liver transplant and incorporation of various factors to decide the optimal time to initiate HCV therapy., Recent Findings: Viral eradication on the waiting list has been found to lead to significant clinical improvement in approximately 20% of HCV-positive patients. However, there have been concerns raised for direct-acting antiviral (DAA) therapy in patients listed with HCC. DAA therapy leading to rapid HCV clearance has been reported to be associated with an increased risk of HCC recurrence, especially when DAA therapy is initiated in close proximity to HCC therapy. Additionally, the presence of viable HCC may significantly lower the chances of achieving sustained virologic response. Lastly, sustained virologic response can decrease the organ pool in HCV-positive waitlisted patients., Summary: The decision to treat HCV in patients listed for HCC pre vs. postliver transplant will require additional research.

Heart failure with preserved ejection fraction (HFpEF) is a highly heterogeneous syndrome associated with multiple medical comorbidities and pathophysiologic pathways or phenotypes. We recently developed a phenomapping method combining deep phenotyping with machine learning analysis to classify HFpEF patients into 3 clinically distinct phenotypic subgroups (phenogroups) with different clinical outcomes. Phenogroup #1 was younger with lower B-type natriuretic peptide levels, phenogroup #2 had the highest prevalence of obesity and diabetes mellitus, and phenogroup #3 was the oldest with the most factors for chronic kidney disease, the most dysfunctional myocardial mechanics, and the highest adverse outcomes. The pathophysiological differences between these phenogroups, however, remain incompletely described. We sought to evaluate whether these 3 groups differ on the basis of repolarization heterogeneity, which has previously been linked to adverse outcomes in HFpEF. The T-peak to T-end (TpTe) interval, a well-validated index of repolarization heterogeneity, was measured by 2 readers blinded to each other and all other clinical data on the electrocardiograms of 201 HFpEF patients enrolled in a systematic observational study. TpTe duration was associated with higher B-type natriuretic peptide level (p = 0.006), increased QRS-T angle (p = 0.008), and lower septal e' velocity (p = 0.007). TpTe duration was greatest in phenogroup #3 (100.4 ± 24.5 ms) compared with phenogroups #1 (91.2 ± 17.3 ms) and #2 (90.2 ± 17.0 ms) (p = 0.0098). On multivariable analyses, increased TpTe was independently associated with the high-risk phenogroup #3 classification. In conclusion, repolarization heterogeneity is a marker of a specific subset of HFpEF patients identified using unsupervised machine learning analysis and therefore may be a key pathophysiologic marker in this subset of HFpEF patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background & Aims: The approval of all-oral direct-acting antiviral (DAA) regimens for the treatment of hepatitis C virus (HCV) has led to the expansion of therapy to include patients with cirrhosis who have hepatocellular carcinoma (HCC). Data on the use of DAAs in HCV+ patients with HCC is limited. The aim of this study was to assess the efficacy of all-oral-DAA regimens in HCV+ cirrhotic patients who have or had HCC compared to those without HCC., Methods: A retrospective cohort study was conducted on all cirrhotic patients who were treated for HCV with DAAs at our institution between January 2014 and November 2015., Results: A total of 421 HCV+ patients with cirrhosis were identified, of whom 33% had active or a history of HCC. Failure to achieve sustained virologic response (SVR) occurred in 21% of patients with HCC compared to 12% of patients without HCC (p=0.009). Of the 29 patients with HCC who did not achieve SVR, 27 (93%) occurred when an active tumor was present. DAA therapy in the presence of an inactive tumor or after removal of tumor (resection/transplant) resulted in excellent SVR rates, similar to those without HCC (p<0.0001). In multivariable analysis, the primary predictor of DAA treatment failure was the presence of active HCC at the time of HCV treatment initiation (adjusted odds ratio=8.5, 95% confidence interval=3.90-18.49)., Conclusions: The presence of active HCC tumor at the initiation of HCV therapy is significantly associated with all-oral DAA treatment failure. HCV treatment after curative therapies for HCC resulted in excellent SVR., Lay Summary: The new medications for hepatitis C have excellent cure rates. However, our study shows that in patients with both liver cancer and hepatitis C, they do not achieve these cure rates. Patients with liver cancer are almost 8 times more likely to fail hepatitis C treatment than patients without liver cancer., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: We investigated the association of electrocardiographic (ECG) abnormalities with markers of insulin resistance and pancreatic beta-cell dysfunction in a cross-sectional study of type 2 diabetes patients., Methods: Electrocardiographic criteria were evaluated in the Penn Diabetes Heart Study participants (n = 1671; 64% male; 61% Caucasian), including a sub-sample (n = 710) that underwent oral glucose tolerance testing. The Matsuda Insulin Sensitivity Index and homeostasis model assessment of insulin resistance (HOMA-IR) estimated insulin sensitivity; Insulinogenic Index and homeostasis model assessment of beta-cell function assessed beta-cell function. Multivariable regression modelling was used to analyse associations of ECG changes with these indices., Results: In unadjusted analyses, subjects in the highest quartile of Matsuda index had the lowest prevalence of Q-waves (6.3% versus 15.3%, p = 0.005). In adjusted models, an inverse association was seen between Q-waves and log Matsuda index [one standard deviation increase; OR = 0.59 (95% CI 0.43-0.87 p = 0.001)]. In the full Penn Diabetes Heart Study, there was a direct association between Q-waves and HOMA-IR [one standard deviation increase; OR = 1.43 (95% CI 1.13-1.81, p = 0.003)]. In adjusted models, left ventricular hypertrophy also was inversely associated with Matsuda index and directly with HOMA-IR. Higher Insulinogenic Index scores were associated with a lower prevalence of nonspecific ST changes [OR = 0.78 (95% CI 0.62-0.98, p = 0.032)]., Conclusions: In type 2 diabetic patients, both oral glucose tolerance testing-derived and HOMA-derived measures of insulin resistance were associated with pathologic Q-waves and left ventricular hypertrophy on ECGs. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Purpose of Review: Numerous evidence-based medical and device therapies proven to reduce morbidity and mortality have advanced care for heart failure with reduced ejection fraction (HFrEF). The primacy of this approach has now been superseded by striking new data resulting in the approval of the combination of valsartan and sacubitril, a neprilysin inhibitor (also known as LCZ696), in 2015 for the treatment of HFrEF. LCZ696 is a novel heart failure drug that simultaneously inhibits the renin-angiotensin system and potentiates the natriuretic peptide system., Recent Findings: In the Prospective Comparison of ARNI with ACE-I to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, LCZ696 significantly improved cardiovascular outcomes compared to current guideline-directed medical therapy. Compared to an angiotensin-converting enzyme (ACE) inhibitor, LCZ696 was associated with a 20 % reduction in cardiovascular mortality (number needed to treat [NNT] 32) and a similar reduction in total mortality (NNT 36). Morbidity benefits of the drug were seen within 1 month of initiation. However, hypotension due to enalapril or the LCZ696 regimen during a run-in phase eliminated 20 % of patients. Safety concerns included the risk of angioedema and the theoretical concern of neurocognitive dysfunction due to the protean effects of neprilysin inhibition. The role of LCZ696 in patients with asymptomatic left ventricular systolic dysfunction is uncertain. LCZ696 is currently being evaluated in patients with heart failure with preserved ejection fraction, with promising initial results. LCZ696 represents a novel mechanistic approach to targeting heart failure with reduced ejection fraction, and ongoing studies will address its use in other cardiovascular populations.

Arterial stiffness is an age-related process that is a shared consequence of numerous diseases including diabetes mellitus (DM), and is an independent predictor of mortality both in this population and in the general population. While much has been published about arterial stiffness in patients with DM, a thorough review of the current literature is lacking. Using a systematic literature search strategy, we aimed to summarize our current understanding related to arterial stiffness in DM. We review key studies demonstrating that, among patients with established DM, arterial stiffness is closely related to the progression of complications of DM, including nephropathy, retinopathy, and neuropathy. It is also becoming clear that arterial stiffness can be increased even in pre-diabetic populations with impaired glucose tolerance, and in those with the metabolic syndrome (METS), well before the onset of overt DM. Some data suggests that arterial stiffness can predict the onset of DM. However, future work is needed to further clarify whether large artery stiffness and the pulsatile hemodynamic changes that accompany it are involved in the pathogenesis of DM, and whether interventions targeting arterial stiffness are associated with improved clinical outcomes in DM. We also review of the potential mechanisms of arterial stiffness in DM, with particular emphasis on the role of advanced glycation endproducts (AGEs) and nitric oxide dysregulation, and address potential future directions for research., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: While recent genomic studies have focused attention on triglyceride (TG) rich lipoproteins in cardiovascular disease (CVD), little is known of very low-density lipoprotein cholesterol (VLDL-C) relationship with atherosclerosis and CVD. We examined, in a high-risk type-2 diabetic population, the association of plasma VLDL-C with coronary artery calcification (CAC)., Methods: The Penn Diabetes Heart Study (PDHS) is a cross-sectional study of CVD risk factors in type-2 diabetics (n = 2118, mean age 59.1 years, 36.5% female, 34.1% Black). Plasma lipids including VLDL-C were calculated (n = 1879) after ultracentrifugation., Results: In Tobit regression, VLDL-C levels were positively associated with increasing CAC after adjusting for age, race, gender, Framingham risk score, body mass index, C-reactive protein, exercise, medication and alcohol use, hemoglobin A1c, and diabetes duration [Tobit ratio (TR) and 95% confidence interval (CI) 0.38 (0.12-0.65), P = 0.005] and even after inclusion of apolipoprotein B data [TR 0.31 (0.03-0.58), P = 0.030]. Approximately 3-fold stronger effect was observed in women [TR 0.75 (0.16-1.34), P = 0.013] than men [TR 0.20 (-0.10-0.50), P = 0.189; gender interaction P = 0.034]. Plasma VLDL-C was related more strongly to CAC scores than TG levels (e.g., Akaike information criteria of 7263.65 vs. 7263.94) and had stronger CAC association in individuals with TGs >150 mg/dl (TR 0.80, P = 0.010) vs. those with TGs <150 mg/dl (TR 0.27, P = 0.185)., Conclusions: In PDHS, VLDL-C is associated with CAC independent of established CVD risk factors, particularly in women, and may have value even beyond apolipoprotein B levels and in patients with elevated TGs., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: Compared with open repair of abdominal aortic aneurysms (AAA), endovascular repair (EVAR) is associated with decreased perioperative morbidity and mortality in a standard patient population. This study sought to determine if the advantage of EVAR extends to patients aged ≥90 years., Methods: This was a retrospective review from a prospectively maintained computerized database. Of the 322 patients aged ≥80 treated with EVAR from January 1997 to November 2007, 24 (1.9%) were aged ≥90. Mean age was 91.5 ± 1.5 years (range, 90-95 years), and 83.3% were men. Mean aneurysm size was 6.8 cm (range, 5.2-8.7 cm)., Results: Mean procedural blood loss was 490 mL (range, 100-4150 mL), and 20.8% required an intraoperative transfusion. Mean postoperative length of stay was 6.0 days, (median, 4 days; mode, 1 day; range, 1-42 days), with 33.3% of patients discharged on the first postoperative day. Amongst the 24 patients, there were 6 (25.0%) perioperative major adverse events, and 2 patients died, for a perioperative mortality rate of 8.3%. Mean follow-up was 20.5 months (range, 1-49 months). Overall, three patients (12.5%) required a secondary intervention, comprising thrombectomy, angioplasty, and proximal cuff extension. No patients required conversion to open repair. Two patients (8.3%) died of AAA rupture at 507 and 1254 days. Freedom from all-cause mortality was 83.3% at 1 year and 19.3% at 5 years. Freedom from aneurysm-related mortality was 87.5% at 1 year and 73.2% at 5 years. Endoleak occurred in five patients (20.8%), with three type I and two of indeterminate type; of these, two patients with type I endoleak underwent secondary intervention at 153 and 489 days after EVAR, of which one case was successful., Conclusion: Our study supports that EVAR in nonagenarians is associated with acceptable procedural success and perioperative morbidity and mortality. The medium-term results suggest that EVAR may be of limited benefit in very carefully selected patients who are aged ≥90 years., (Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Compared to open repair of abdominal aortic aneurysms (AAA), endovascular aneurysm repair (EVAR) is associated with decreased perioperative morbidity and mortality. This study sought to examine the outcomes of EVAR in patients >or=80 years of age., Methods: This was a retrospective review from a prospectively maintained computerized database. A total of 322 patients aged >or=80 underwent elective EVAR from January 1997 to November 2007. Mean age was 84 years +/- 3.4 years (range, 80-95 years), and 78.5% were male. Mean aneurysm size was 62 mm +/- 12 mm (range, 39-110 mm)., Results: Mean procedural blood loss was 350 mL (range, 50-2700 mL), and 13.9% required intraoperative transfusion. Mean length of postoperative stay was 2.46 days (median, 1 day; range, 1-42 days), with 54.3% of patients discharged on the first postoperative day. There were 25 (7.8%) perioperative major adverse events. The most common were categorized as device-related (6), cardiac (4), gastrointestinal (4), and bleeding/hematoma (3). The perioperative 30-day mortality rate was 3.1% (10 of 322). Mean follow-up was 25.7 months (range, 1-110 months). Overall, 47 patients (14.6%) required secondary intervention, 7 patients (2.2%) underwent conversion to open repair, and 4 patients (1.2%) died from AAA rupture. Endoleaks occurred in 95 patients (29.4%), with 20 type I, 48 type II, and 27 of indeterminate type; of these, 10 patients with type I endoleaks underwent secondary intervention. Freedom from all-cause mortality at 1 year was 84.3% and at 5 years was 27.4%. Freedom from aneurysm-related mortality at 5 years was 92.9%., Conclusion: EVAR in octogenarians is associated with high procedural success and low perioperative morbidity and mortality. The midterm results of this study support the use of EVAR in this patient population. Further studies are needed to predict short-term and long-term mortality risk, and treatment for other causes of death., (Copyright (c) 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)