The contribution of amyloid deposition in the aortic valve to calcification and aortic stenosis.

Calcific aortic valve disease (CAVD) and stenosis have a complex pathogenesis, and no therapies are available that can halt or slow their progression. Several studies have shown the presence of apolipoprotein-related amyloid deposits in close proximity to calcified areas in diseased aortic valves. In this Perspective, we explore a possible relationship between amyloid deposits, calcification and the development of aortic valve stenosis. These amyloid deposits might contribute to the amplification of the inflammatory cycle in the aortic valve, including extracellular matrix remodelling and myofibroblast and osteoblast-like cell proliferation. Further investigation in this area is needed to characterize the amyloid deposits associated with CAVD, which could allow the use of antisense oligonucleotides and/or isotype gene therapies for the prevention and/or treatment of CAVD.

Association between right ventricular dysfunction and in-hospital mortality in surges of SARS-CoV-2 infection attributed to the Alpha, Delta, and Omicron variants.

Background: Right ventricular (RV) dysfunction in acute COVID-19 was reported to be associated with poor prognosis. We studied the association between parameters of RV dysfunction and in-hospital mortality during the surges caused by different SARS-CoV-2 variants. Methods: In a retrospective single-center study, we enrolled 648 consecutive patients hospitalized with COVID-19 [66 (10 %) hospitalized during the alpha variant surge, 433 (67 %) during the delta variant surge, and 149 (23 %), during the omicron variant surge]. Patients were reported from a hospital with an underreported population of mostly African American and Hispanic patients. Patients were followed for a median of 11 days during which in-hospital death occurred in 155 (24 %) patients [Alpha wave: 25 (38 %), Delta Wave: 112 (26 %), Omicron wave: 18 (12 %), p < 0.001]. Results: RV dysfunction occurred in 210 patients (alpha: 32 %, 26 %, delta: 29 %, and omicron: 49 %, p < 0.001) and was associated with higher mortality across waves, however, independently predicted in-hospital mortality in the Alpha (HR = 5.1, 95 % CI: 2.06-12.5) and Delta surges (HR = 1.6, 95 % CI: 1.11-2.44), but not in the Omicron surge. When only patients with RV dysfunction were compared, the mortality risk was found to decrease significantly from the Alpha (HR = 13.6, 95 % CI: 3.31-56.3) to the delta (HR = 1.93, 95 % CI: 1.25-2.96) and to the Omicron waves (HR = 11, 95 % CI: 0.6-20.8). Conclusions: RV dysfunction continues to occur in all strains of the SARS-CoV-2 virus, however, the mortality risk decreased from wave to wave likely due to evolution of better therapeutics, increase rate of vaccination, or viral mutations resulting in decrease virulence.Registration number of clinical studies: BronxCare Hospital center institutional review board under the number 05 13 21 04.

Assessment of early morning serum cortisol levels in adult male patients with alcohol-related disorders.

BACKGROUND: Alcohol-related disorders are a major health problem among Indian male professionals because of the unique nature of socioeconomic and demographic conditions. Various studies have highlighted the association between alcohol-related disorders and hypothalamic-pituitary-adrenal (HPA) axis dysfunction, but the evidence accrued so far is inconclusive. In our study, we have assessed early morning serum total cortisol concentration among Indian adult male population affected with alcohol-related disorder. METHODS: A case-based cross-sectional study in which all consecutive patients admitted in the psychiatry ward of a tertiary care hospital with diagnosis of 'alcohol-related disorders', who were meeting all the inclusion criteria, and who had none of the exclusion criteria were part of the study. Diseased controls and healthy controls were chosen by applying strict inclusion and exclusion criteria. Serum early morning (0400 h) total cortisol levels were estimated using automated quantitative enzyme-linked fluorescent assay technique. RESULTS: 98 psychiatric patients and 50 healthy controls were evaluated. Out of these 98 patients 66 patients were diagnosed cases of alcohol-related disorder. Morning serum total cortisol levels in patients with alcohol-related disorders was found to be significantly different from healthy controls. CONCLUSION: Our study suggests that alcohol-related disorders are associated with chronic changes in HPA axis and significant alteration of early morning serum total cortisol levels were demonstrated in this group of patients.

Functional Effects of Cardiomyocyte Injury in COVID-19.

COVID-19 affects multiple organs. Clinical data from the Mount Sinai Health System show that substantial numbers of COVID-19 patients without prior heart disease develop cardiac dysfunction. How COVID-19 patients develop cardiac disease is not known. We integrated cell biological and physiological analyses of human cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the presence of interleukins (ILs) with clinical findings related to laboratory values in COVID-19 patients to identify plausible mechanisms of cardiac disease in COVID-19 patients. We infected hiPSC-derived cardiomyocytes from healthy human subjects with SARS-CoV-2 in the absence and presence of IL-6 and IL-1ß. Infection resulted in increased numbers of multinucleated cells. Interleukin treatment and infection resulted in disorganization of myofibrils, extracellular release of troponin I, and reduced and erratic beating. Infection resulted in decreased expression of mRNA encoding key proteins of the cardiomyocyte contractile apparatus. Although interleukins did not increase the extent of infection, they increased the contractile dysfunction associated with viral infection of cardiomyocytes, resulting in cessation of beating. Clinical data from hospitalized patients from the Mount Sinai Health System show that a significant portion of COVID-19 patients without history of heart disease have elevated troponin and interleukin levels. A substantial subset of these patients showed reduced left ventricular function by echocardiography. Our laboratory observations, combined with the clinical data, indicate that direct effects on cardiomyocytes by interleukins and SARS-CoV-2 infection might underlie heart disease in COVID-19 patients. IMPORTANCE SARS-CoV-2 infects multiple organs, including the heart. Analyses of hospitalized patients show that a substantial number without prior indication of heart disease or comorbidities show significant injury to heart tissue, assessed by increased levels of troponin in blood. We studied the cell biological and physiological effects of virus infection of healthy human iPSC-derived cardiomyocytes in culture. Virus infection with interleukins disorganizes myofibrils, increases cell size and the numbers of multinucleated cells, and suppresses the expression of proteins of the contractile apparatus. Viral infection of cardiomyocytes in culture triggers release of troponin similar to elevation in levels of COVID-19 patients with heart disease. Viral infection in the presence of interleukins slows down and desynchronizes the beating of cardiomyocytes in culture. The cell-level physiological changes are similar to decreases in left ventricular ejection seen in imaging of patients' hearts. These observations suggest that direct injury to heart tissue by virus can be one underlying cause of heart disease in COVID-19.

Physiology of cardiomyocyte injury in COVID-19.

COVID-19 affects multiple organs. Clinical data from the Mount Sinai Health System shows that substantial numbers of COVID-19 patients without prior heart disease develop cardiac dysfunction. How COVID-19 patients develop cardiac disease is not known. We integrate cell biological and physiological analyses of human cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs) infected with SARS-CoV-2 in the presence of interleukins, with clinical findings, to investigate plausible mechanisms of cardiac disease in COVID-19 patients. We infected hiPSC-derived cardiomyocytes, from healthy human subjects, with SARS-CoV-2 in the absence and presence of interleukins. We find that interleukin treatment and infection results in disorganization of myofibrils, extracellular release of troponin-I, and reduced and erratic beating. Although interleukins do not increase the extent, they increase the severity of viral infection of cardiomyocytes resulting in cessation of beating. Clinical data from hospitalized patients from the Mount Sinai Health system show that a significant portion of COVID-19 patients without prior history of heart disease, have elevated troponin and interleukin levels. A substantial subset of these patients showed reduced left ventricular function by echocardiography. Our laboratory observations, combined with the clinical data, indicate that direct effects on cardiomyocytes by interleukins and SARS-CoV-2 infection can underlie the heart disease in COVID-19 patients.

Prognostic significance of exercise-induced diastolic dysfunction: A systematic review.

BACKGROUND: Recent guidelines recommend diastolic stress testing among patients with unexplained dyspnea. Previous studies have reported exercise related change in diastolic parameters as a prognostic marker for worse outcomes. However, the role of exercise-induced diastolic dysfunction (DD) in predicting adverse outcomes has not been fully established. METHOD: We conducted a meta-analysis to explore the prognostic significance of exercise-induced DD. PUBMED/EMBASE/SCOPUS databases were searched for studies reporting adverse outcomes in patients undergoing exercise echocardiography based on diastolic response during exercise. Exercise-induced DD was defined as an increase in E/e' or E/A ratio with stress. Outcomes of interest were cardiovascular mortality or hospitalizations. RESULTS: A total of 8 studies were identified, including 4,462 patients who underwent exercise stress echocardiography. The follow-up ranged from 13 months to 5 years. The major indication for stress testing was exertional dyspnea. All studies reported cardiac mortality and hospitalization in the composite outcome. Meta-analysis conducted using random-effects model showed that exercise-induced DD was associated with a higher likelihood of cardiovascular mortality or hospitalization (HR = 1.32, P < .05). Significant heterogeneity was noted among the studies. CONCLUSIONS: Exercise-induced DD is associated with worse cardiovascular outcomes. Changes in echocardiographic parameters such as e' with exercise might be useful for risk stratification and identification of high-risk patients.

Echocardiography in Patients with HIV Infection.

PURPOSE OF REVIEW: This review aims to outline the important echocardiographic findings observed in patients with human immunodeficiency virus (HIV) infection in the current era of treatment. RECENT FINDINGS: HIV infection has a wide spectrum of cardiac manifestations. Myocardial and pericardial involvement were the primary cardiac manifestations in HIV patients early during the epidemic in the developed countries. In the current era of effective antiretroviral therapy, the spectrum has shifted to metabolic abnormalities (hyperlipidemia, hypertension, etc.), accelerated atherosclerotic disease, and cardiac sequelae related to these abnormalities. Dramatic improvement in life expectancy of patients with HIV infection has resulted in a shift in the developed nations in the spectrum of cardiac manifestations, currently dominated by diastolic dysfunction and coronary artery disease. Echocardiography and advanced echocardiographic techniques play a major role in diagnosis and screening of HIV patients with underlying cardiovascular abnormalities.

Acute myocardial infarction in the young - National Trend Analysis with gender-based difference in outcomes.

INTRODUCTION: Although acute myocardial infarction (AMI) is a disease predominantly affecting adults >60 years of age, a significant proportion of the young population who have different risk profiles, are also affected. We undertook a retrospective analysis using National Inpatient Sample (NIS) 2010 to 2014 to evaluate gender differences in characteristics, treatments, and outcomes in the younger AMI population. METHODS: The NIS 2010-2014 was used to identify all patient hospitalizations with AMI between 18 to <45 years using ICD-9-CM codes. We demonstrated a gender-based difference of in-hospital all-cause mortality, other complications, and revascularization strategies in the overall AMI population and other subgroups of AMI [anterior wall ST-segment elevation MI (STEMI), and non-anterior wall STEMI and non-STEMI (NSTEMI)]. RESULTS: A total of 156,018 weighted records of AMI hospitalizations were identified, of which 111,894 were men and 44,124 were women. Young women had a higher prevalence of anemia, chronic lung disease, obesity, peripheral vascular disease, and diabetes. Conversely, young men had a higher prevalence of dyslipidemia, smoking, and alcohol. Among non-traditional risk factors, women had a higher prevalence of depression and rheumatologic/collagen vascular disease. There was no difference in all-cause in-hospital mortality in women compared to men [2.03% vs 1.48%; OR 1.04, CI (0.84-1.29); P = .68], including in subgroup analysis of NSTEMI, anterior wall STEMI, and non-anterior wall STEMI. Women with AMI were less likely to undergo percutaneous coronary intervention [47.13% vs 61.17%; OR 0.66, 95% CI (0.62-0.70; P < .001] and coronary artery bypass grafting [5.6% vs 6.0%; OR 0.73, 95% CI 0.64-0.83; P < .001] compared to men. Women were also less likely to undergo percutaneous coronary intervention within 24 h of presentation (38.47% vs 51.42%, P < .001). CONCLUSION: Despite higher baseline comorbidities in young women with AMI, there was no difference in in-hospital mortality in women compared to men. Additional studies are needed to evaluate the impact of gender on clinical presentation, treatment patterns, and outcomes of AMI in young patients.

Readmissions in ST-Elevation Myocardial Infarction and Cardiogenic Shock (from Nationwide Readmission Database).

Management of ST-elevation myocardial infarction complicated by cardiogenic shock (STEMI-CS) has evolved in the last decade. There is paucity of data on readmissions in this study population. We aimed to assess the burden, major etiologies, and resource utilization for 30-day readmissions among patients with STEMI and CS. The Nationwide Readmission Database was queried from 2010 to 2014. All adult patients with an index admission for STEMI-CS were identified using International Classification of Diseases, ninth edition codes. Patient with mortality on index admission and transfers to other hospitals were excluded. A total of 18,659 admissions were identified with primary diagnosis of STEMI-CS for the study duration. Percutaneous coronary interventions was performed in 78.1% and mechanical circulatory devices were utilized in 53.9% with a mean length of stay of 10.6 (±0.2) days and mean cost of hospitalization of $47,744 (±327). Among these, 2,404 (12.9%) patients were readmitted within 30 days. Major etiologies for readmission include congestive heart failure (25.7%), acute myocardial infarction (9.4%), arrhythmias (4.5%), and sepsis (4.2%). The mean length of stay and cost of hospitalization for 30-day readmission were 5.9 (±0.3) days and $17,043 (±590), respectively. Older age, female gender, lower socioeconomic status, and discharge to home health care were significant predictors for readmission. In conclusion, there is a significant burden of 30-day readmission among patients with STEMI-CS. Percutaneous coronary interventions and mechanical circulatory devices were utilized in a majority of index admissions. Congestive heart failure was the single most common reason for 30-day readmission. Patients discharged to skilled nursing facility, patients with private insurance and higher socioeconomic status were less likely to be readmitted. Moreover, readmissions among STEMI-CS patients contribute to significant resource utilization.

The prevalence and predictors of resistant hypertension in high-risk overweight and obese patients: A cross-sectional study based on the 2017 ACC/AHA guidelines.

Obesity is significantly associated with uncontrolled blood pressure and resistant hypertension (RH). There are limited studies on the prevalence and determinants of RH in patients with higher body mass index (BMI) values. Since the hypertension guidelines changed in 2017, the prevalence of RH has become unknown and now is subject to be estimated by further studies. We conducted a cross-sectional study in an urban Federally Qualified Health Center in New York City aiming to estimate the prevalence of RH in high-risk overweight and obese patients based on the new hypertension definition, BP threshold ≥130/80 mm Hg, and also to describe the associated comorbid conditions in these patients. We identified 761 eligible high-risk overweight and obese subjects with hypertension between October 2017 and October 2018. Apparent treatment-RH was found in 13.6% among the entire study population. This represented 15.4% of those treated with BP-lowering agents. True RH confirmed with out-of-office elevated BP was found in 6.7% of the study population and 7.4% among patients treated with BP-lowering agents. Prevalence was higher with higher BMI values. Those with true RH were more likely to be black, to have diabetes mellitus requiring insulin, chronic kidney disease stage 3 or above and diastolic heart failure. In conclusion, obesity is significantly associated with RH and other significant metabolic comorbid conditions.

Predictors and etiologies of 30-day readmissions in patients with non-ST-elevation acute coronary syndrome.

BACKGROUND: Despite improvements in acute care and survival after non-ST-elevation acute coronary syndrome (NSTE-ACS) hospitalization, early readmissions remain common, and have significant clinical and financial impact. OBJECTIVES: Determine the predictors and etiologies of 30-day readmissions in NSTE-ACS. METHOD: The study cohort was derived from the National Readmission Database 2014 identifying patients with a primary diagnosis of NSTE-ACS using ICD9 code. RESULTS: We identified a total of 300,269 patients admitted with NSTE-ACS; 13.4% were readmitted within 30-day. The most common cause of readmission was heart failure (HF) (15.6%), followed by a recurrent myocardial infarction (MI) (10%). Predictors of increased readmissions were age ≥ 75 years (OR: 1.34, 95% CI: 1.30-1.39), female gender (OR 1.12, 95% CI 1.09-1.16), a Charlson Comorbidity Index (CCI) >3 (OR 2.11, 95% CI: 2.04-2.18), ESRD (OR 2.01, 95% CI 1.89-2.14), CKD (OR: 1.58, 95% CI: 1.51-1.64), length of stay ≥5 days (OR: 1.51, 95% CI 1.46-1.56) and adverse events during the index admission such as AKI (OR:1.31, 95% CI: 1.25-1.36), major bleeding (OR:1.20, 95% CI: 1.12-1.24); whereas admission to a teaching hospital (OR 0.92, 95% CI 0.89-0.95) and PCI (OR 0.70, 95% CI 0.67-0.72) were associated with less likelihood of 30-day readmission. CONCLUSION: Readmission rate at 30-days is high among NSTE-ACS patients and the most common readmission etiologies are HF and recurrent MI. A CCI more than 3 and ESRD were the most significant predictors for readmission; patients undergoing PCI had less odds of readmission.