Racial disparities in women with ST elevation myocardial infarction: A National Inpatient Sample review of baseline characteristics, co-morbidities, and outcomes in women with STEMI.

BACKGROUND: A third of the patients admitted with Acute coronary syndrome (ACS) have ST-elevation myocardial infarction (STEMI). Previous studies showed that females with STEMI have higher mortality than men. HYPOTHESIS: There exist significant disparities in outcomes among women of different races presenting with STEMI. METHODS: National inpatient sample (NIS) data was obtained from January 2016 to December 2018 for the hospitalization of female patients with STEMI. We compared outcomes, using an extensive multivariate regression analysis amongst women from different races. Our primary outcome was in-hospital mortality. Secondary outcomes were revascularization use, procedure complications, and healthcare utilization. RESULTS: Of 202 223 female patients with STEMI; 11.3% were African American, 7.4% Hispanic, 2.4% Asian, and 4.3% another race. In-hospital mortality was higher in non-Caucasian groups. African American (adjusted odds ratio [aOR] 1.2; 95% confidence interval [CI]: 1.07-1.30; p < .01) and another race (aOR 1.37; 95% CI: 1.15-1.63; p < .01) had higher odds of mortality when compared with white women. African American (aOR 0.69; 95% CI: 0.62-0.72; p < .01), Hispanics (aOR 0.81; 95% CI: 0.74-0.88; p < .01), and Asian (aOR 0.79; 95% CI: 0.69-0.90; p < .01) had lower odds of percutaneous intervention (PCI) when compared with whites. African Americans had fewer odds of Coronary Artery Bypass Graft (CABG) and use of Mechanical Circulatory Support (MCS) during the index admission. Non-Caucasians had more comorbidities, complications, and healthcare utilization costs. CONCLUSION: There are significant racial disparities in clinical outcomes and revascularization in female patients with STEMI. African American women have a higher likelihood of mortality among the different races. Females from minority groups are also less likely to undergo PCI.

Physician Variability in Diastology Reporting in Patients With Preserved Ejection Fraction: A Single Center Experience.

To help standardize the assessment of diastolic dysfunction in the United States, the American Society of Echocardiography (ASE) released criteria for the assessment of diastology in patients with normal and abnormal ejection fraction. As heart failure with preserved ejection fraction (HFpEF) is a leading cause of morbidity and mortality in cardiac patients, it is imperative to assess diastology appropriately. Echocardiography is the mainstay in the assessment of diastolic function; with the new ASE guidelines, diagnosis is simplified especially in patients that have preserved baseline ejection fraction. Our study aimed to determine the extent of physician variability in diastology reporting at our medical center after the release of the new ASE criteria.

Pseudoaneurysm Leading to Aortic Dissection: An Interesting Case Presentation.

This is an interesting case of ascending penetrating aortic ulcer (PAU) leading to pseudoaneurysm and eventually type A aortic dissection and peri-aortic hematoma. PAUs are common clinical manifestations, however, uncommonly lead to pseudoaneurysms that cause aortic dissection.

Rare and Fascinating Case of ST-Elevation Myocardial Infarction Diagnosis From an Underlying Ventricular Paced Rhythm.

This is a case of a patient diagnosed with anterior ST-elevation myocardial infarction (STEMI) with a ventricular paced rhythm after the patient underwent a femoral-femoral bypass surgery for severe peripheral vascular disease. The case highlights the diagnosis of STEMI in the setting of paced rhythm in the appropriate clinical setting.

A Unique Case of Mitral Valve Dehiscence Post-mitral Valve Repair Diagnosed Using 3D Transesophageal Imaging.

This is an interesting cardiovascular imaging case of a 70-year-old male who presented with heart failure symptoms after recent mitral valve repair with Carpentier-Edwards ring. Ring dehiscence was noted on transesophageal echocardiographic imaging which aided in guiding clinical and surgical courses.

Left Ventricular Ejection Fraction along with Zwolle Risk Score for Risk Stratification to Enhance Safe and Early Discharge in STEMI Patients Undergoing Primary Percutaneous Coronary Intervention: A Retrospective Observational Study.

Introduction Zwolle risk score (ZRS) is a validated scoring system to determine the time of discharge in ST-segment elevation myocardial infarction (STEMI) patients. Left ventricular ejection fraction (LVEF) also provides prognostic information after ST-elevation myocardial infarction (STEMI). We studied that the addition of LVEF to ZRS variable can improve decision making in safe and early discharge in STEMI patients post-primary coronary intervention. Methods Overall, 249 STEMI patients were studied retrospectively. LVEF was considered as an independent variable. The patients having LVEF <50% were under Group A and LVEF ≥50% were under Group B. Groups were analyzed by model comparison for overall hospital length of stay (LOS) and Intensive care unit (ICU) LOS post-primary percutaneous coronary intervention (PCI). Results There were 123 patients in Group A and 126 patients in Group B. Comparison for primary outcomes showed significant difference with hospital length of stay (LOS) being 3.1 ± 2.3 days in Group A versus 2.1 ± 0.8 days in Group B (p < 0.001). Similarly, ICU stay was also significantly higher in Group A with 36.5 ± 31.4 hours versus 24.0 ± 11.8 hours for Group B, which led to prolonged hospitalization for patients with LVEF <50%. Model 1 that considers ZRS individually is nested within Model 2 where ZRS and LVEF are considered together. The profile log-likelihood ratio test favors model 2 over model 1 (p < 0.0001). Similarly for ICU LOS, R 2 = 0.12 (Model 1) < R 2 = 0.20 (Model 2). The F test favors model 2 over model 1 (p < 0.0001). Conclusion We concluded that adding LVEF to Zwolle risk score gives a better model for risk stratification in STEMI patients to decide early and safe discharge post-primary PCI.

Management of Resistant Hypertension Based on Recommendations from Different Guidelines and the Systolic Blood Pressure Intervention Trial.

The long-term management of patients with resistant hypertension has been made even more difficult by a "moving target" goal blood pressure (BP). The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines defined resistant hypertension as the failure to achieve goal BP in patients who are adhering to full doses of an appropriate three-drug regimen that includes a diuretic. The Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8) guidelines laid out more lenient target BP goals, without addressing the definition of resistant hypertension directly. The present scenario is a state of confusion, with providers selectively adopting recommendations from different guidelines. The Systolic Blood Pressure Intervention Trial (SPRINT) trial contributed to the confusion with further evidence supporting the strict control of hypertension. In addition, the failure of another trial on renal denervation in the US has essentially put an end to six long years of experimentation with catheter ablation in patients with resistant hypertension. Other therapies are still experimental. Adding a new dimension of medical management, spironolactone has made a comeback in resistant hypertension, with reports of better responsiveness when added to existing anti-hypertensive therapy. The present review discusses the current state and management options for patients with resistant hypertension considering the new evidence. Newer advances in pharmacological and device therapy are also discussed to improve understanding and quality in the management of resistant hypertension.

Adverse alterations in mitochondrial function contribute to type 2 diabetes mellitus-related endothelial dysfunction in humans.

OBJECTIVE: Mitochondrial dysfunction plays a key pathophysiological role in type 2 diabetes mellitus (T2DM). Data delineating relationships between mitochondrial and endothelial dysfunction in humans with T2DM are lacking. METHODS AND RESULTS: In 122 human subjects (60 with T2DM, 62 without T2DM), we measured endothelial function by brachial artery ultrasound (flow mediated dilation) and digital pulse amplitude tonometery. Endothelial function in arterioles isolated from gluteal subcutaneous adipose was measured by videomicroscopy. In arterioles and mononuclear cells, we measured inner mitochondrial membrane potential (Δψ(m)), mitochondrial mass, and mitochondrial superoxide production using fluorophores. Endothelial function was impaired in T2DM subjects versus control subjects. Δψ(m) magnitude was larger and mitochondrial mass was lower in arterioles and mononuclear cells in T2DM. Mononuclear mitochondrial mass correlated with flow-mediated dilation and pulse amplitude tonometery (ρ=0.38 and 0.33, P=0.001 and 0.02, respectively), and mononuclear mitochondrial superoxide production inversely correlated with flow-mediated dilation (ρ=-0.58, P=0.03). Low doses of 2 different mitochondrial uncoupling agents (carbonyl cyanide m-chlorophenyl hydrazone and 2,4-dinitrophenol) that reduce Δψ(m) magnitude and a mitochondrial-targeted antioxidant (MitoTEMPOL) improved endothelial function and reduced mitochondrial superoxide levels in T2DM arterioles. CONCLUSIONS: Mitochondrial dysfunction may play a central role in the impairment of endothelial dysfunction in T2DM.

Nitric oxide synthase-dependent vasodilation of human subcutaneous arterioles correlates with noninvasive measurements of endothelial function.

BACKGROUND: Noninvasive measurements of endothelial function predict future adverse cardiovascular events, but offer limited opportunities for mechanistic insights into phenotypic observations. Subcutaneous adipose arterioles, accessible through minimally invasive methods, provide an opportunity for complimentary mechanistic studies. Limited data relating subcutaneous arteriolar endothelial function, cardiovascular risk factors, and noninvasive measurements of endothelial function currently exist. METHODS: Forty-four subjects underwent noninvasive studies of endothelial function (brachial reactivity (flow-mediated dilation (FMD) and digital pulse arterial tonometry (PAT)) and measurements of endothelial-dependent vasodilation of gluteal subcutaneous arterioles to acetylcholine. Arteriolar endothelial function was measured (i) percent vasodilation to maximal acetylcholine dose (10(-5) mol/l) and (ii) total area under the curve (AUC) for the entire acetylcholine dose-response curve (total AUC-acetylcholine (Ach), doses 10(-10)-10(-5) mol/l). RESULTS: Acetylcholine responses were almost completely nitric oxide (NO) dependent. Total AUC-Ach predicted FMD and PAT, but maximal acetylcholine vasodilation was not associated with these measures. A history of hypertension, diabetes, smoking, and low-density lipoprotein cholesterol levels were independent predictors of total AUC-Ach. In regression models, total AUC-Ach independently predicted FMD. CONCLUSIONS: Acetylcholine vasodilator responses in human gluteal subcutaneous arterioles are NO synthase dependent and correlate with cardiac risk factors and in vivo measures of endothelial function. These data suggest subcutaneous arterioles offer an opportunity for translational studies of mechanisms of modulating NO bioavailability relevant to in vivo endothelial function measures.

Acute exposure to low glucose rapidly induces endothelial dysfunction and mitochondrial oxidative stress: role for AMP kinase.

OBJECTIVE: Hypoglycemia is associated with increased mortality. The reasons for this remain unclear, and the effects of low glucose exposure on vascular endothelial function remain largely unknown. We endeavored to determine the effects of low glucose on endothelial cells and intact human arterioles. METHODS AND RESULTS: We exposed human umbilical vein endothelial cells to low glucose conditions in a clinically relevant range (40-70 mg/dL) and found rapid and marked reductions in nitric oxide (NO) bioavailability (P<0.001). This was associated with concomitantly increased mitochondrial superoxide production (P<0.001) and NO-dependent mitochondrial hyperpolarization (P<0.001). Reduced NO bioavailability was rapid and attributable to reduced endothelial nitric oxide synthase activity and destruction of NO. Low glucose rapidly activated AMP kinase, but physiological activation failed to restore NO bioavailability. Pharmacological AMP kinase activation led to phosphorylation of endothelial nitric oxide synthase's Ser633 activation site, reversing the adverse effects of low glucose. This protective effect was prevented by L-NG-Nitroarginine methyl ester. Intact human arterioles exposed to low glucose demonstrated marked endothelial dysfunction, which was prevented by either metformin or TEMPOL. CONCLUSION: Our data suggest that moderate low glucose exposure rapidly impairs NO bioavailability and endothelial function in the human endothelium and that pharmacological AMP kinase activation inhibit this effect in an NO-dependent manner.

Measuring FMD in the brachial artery: how important is QRS gating?

Recommendations for the measurement of brachial flow-mediated dilation (FMD) typically suggest images be obtained at identical times in the cardiac cycle, usually end diastole (QRS complex onset). This recommendation presumes that inter-individual differences in arterial compliance are minimized. However, published evidence is conflicting. Furthermore, ECG gating is not available on many ultrasound systems; it requires an expensive software upgrade or increased image processing time. We tested whether analysis of images acquired with QRS gating or with the more simplified method of image averaging would yield similar results. We analyzed FMD and nitroglycerin-mediated dilation (NMD) in 29 adults with type 2 diabetes mellitus and in 31 older adults and 12 young adults without diabetes, yielding a range of brachial artery distensibility. FMD and NMD were measured using recommended QRS-gated brachial artery diameter measurements and, alternatively, the average brachial diameters over the entire R-R interval. We found strong agreement between both methods for FMD and NMD (intraclass correlation coefficients = 0.88-0.99). Measuring FMD and NMD using average diameter measurements significantly reduced post-image-processing time (658.9 ± 71.6 vs. 1,024.1 ± 167.6 s for QRS-gated analysis, P < 0.001). FMD and NMD measurements based on average diameter measurements can be performed without reducing accuracy. This finding may allow for simplification of FMD measurement and aid in the development of FMD as a potentially useful clinical tool.

Altered mitochondrial membrane potential, mass, and morphology in the mononuclear cells of humans with type 2 diabetes.

Mitochondrial membrane hyperpolarization and morphologic changes are important in inflammatory cell activation. Despite the pathophysiologic relevance, no valid and reproducible method for measuring mitochondrial homeostasis in human inflammatory cells is available currently. The purpose of this study was to define and validate reproducible methods for measuring relevant mitochondrial perturbations and to determine whether these methods could discern mitochondrial perturbations in type 2 diabetes mellitus (T2DM), which is a condition associated with altered mitochondrial homeostasis. We employed 5,5',6,6'-tetrachloro-1,1'3,3'-tetraethylbenzamidazol-carboncyanine (JC-1) to estimate mitochondrial membrane potential (Psi(m)) and acridine orange 10-nonyl bromide (NAO) to assess mitochondrial mass in human mononuclear cells isolated from blood. Both assays were reproducible. We validated our findings by electron microscopy and pharmacologic manipulation of Psi(m). We measured JC-1 and NAO fluorescence in the mononuclear cells of 27 T2DM patients and 32 controls. Mitochondria were more polarized (P = 0.02) and mitochondrial mass was lower in T2DM (P = 0.008). Electron microscopy demonstrated diabetic mitochondria were smaller, were more spherical, and occupied less cellular area in T2DM. Mitochondrial superoxide production was higher in T2DM (P = 0.01). Valid and reproducible measurements of mitochondrial homeostasis can be made in human mononuclear cells using these fluorophores. Furthermore, potentially clinically relevant perturbations in mitochondrial homeostasis in T2DM human mononuclear cells can be detected.

Natural antioxidants and hypertension: promise and challenges.

Hypertension reigns as a leading cause of cardiovascular morbidity and mortality worldwide. Excessive reactive oxygen species (ROS) have emerged as a central common pathway by which disparate influences may induce and exacerbate hypertension. Potential sources of excessive ROS in hypertension include nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, mitochondria, xanthine oxidase, endothelium-derived NO synthase, cyclooxygenase 1 and 2, cytochrome P450 epoxygenase, and transition metals. While a significant body of epidemiological and clinical data suggests that antioxidant-rich diets reduce blood pressure and cardiovascular risk, randomized trials and population studies using natural antioxidants have yielded disappointing results. The reasons behind this lack of efficacy are not completely clear, but likely include a combination of (1) ineffective dosing regimens, (2) the potential pro-oxidant capacity of some of these agents, (3) selection of subjects less likely to benefit from antioxidant therapy (too healthy or too sick), and (4) inefficiency of nonspecific quenching of prevalent ROS versus prevention of excessive ROS production. Commonly used antioxidants include Vitamins A, C and E, L-arginine, flavanoids, and mitochondria-targeted agents (Coenzyme Q10, acetyl-L-carnitine, and alpha-lipoic acid). Various reasons, including incomplete knowledge of the mechanisms of action of these agents, lack of target specificity, and potential interindividual differences in therapeutic efficacy preclude us from recommending any specific natural antioxidant for antihypertensive therapy at this time. This review focuses on recent literature evaluating naturally occurring antioxidants with respect to their impact on hypertension.