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.

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.

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.

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.

Changing Trends of Atherosclerotic Risk Factors Among Patients With Acute Myocardial Infarction and Acute Ischemic Stroke.

We aimed to evaluate the secular trends in demographics, risk factors, and clinical characteristics of patients presenting with acute myocardial infarction (AMI) or acute ischemic stroke (AIS), using a large nationally representative data set of in-hospital admissions. We used the 2003 to 2013 Nationwide Inpatient Sample. All admissions with primary diagnosis of AMI or AIS were included. Across 2003 to 2013, a total of 1,360,660 patients with AMI and 937,425 patients with AIS were included in the study. We noted a progressive reduction in the mean age of patients presenting with AMI and AIS (p trend <0.001 for all groups), implying that the burden of young patients with these acute syndromes is progressively increasing. In addition, there was a progressive increase in the proportion of patients who are uninsured among patients presenting with AMI and AIS. Furthermore, despite a progressively younger age at presentation, there was an observed increase in the prevalence of atherosclerotic risk factors including hypertension, hyperlipidemia, diabetes, smoking, and obesity among patients presenting with AMI or AIS during 2003 to 2013. Significant disparities were noted in the prevalence of risk factors among various demographic and geographical cohorts. Low socioeconomic status as well as uninsured patients had a significantly higher prevalence of preventable risk factors like smoking and obesity as compared to the high socioeconomic status and insured patients, respectively. In conclusion, there have been significant changes in the risk factor profile of patients presenting with AMI and AIS over the last decade.

Percutaneous Intervention for Myocardial Infarction After Noncardiac Surgery: Patient Characteristics and Outcomes.

BACKGROUND: Few studies have explored percutaneous coronary intervention (PCI) in perioperative myocardial infarction (PMI), even though PMI is a major cause of mortality in patients undergoing urgent/emergent noncardiac surgery. OBJECTIVES: This study sought to describe the angiographic characteristics and outcomes in patients presenting to the cardiac catheterization laboratory for myocardial infarction sustained after undergoing noncardiac surgery, with a detailed analysis of those undergoing PCI. METHODS: We included all patients presenting to the catheterization laboratory at our institution after PMI from 2003 to 2012, who had noncardiac surgery within the previous 7 days. Data from patients who underwent PCI were analyzed using both standard regression and time-to-event survival analysis. RESULTS: From 2003 to 2012, 1,093 patients with 3,832 person-years of follow-up underwent diagnostic coronary angiography, of whom 281 (40 ST-segment elevation myocardial infarction [STEMI] and 241 non-ST-segment elevation myocardial infarction [NSTEMI] cases) underwent PCI. Using Kaplan-Meier survival analysis, we found 30-day mortality was 5.2% and 1-year mortality was 15% in the overall population. In the PCI subpopulation, we estimated 30-day mortality to be 11.3%. The 30-day death rate in the STEMI cohort was 31.2% and 8.5% in the NSTEMI cohort of the PCI subpopulation. Stepwise logistic regression revealed the following factors as strong predictors of 30-day mortality after PCI: bleeding event after PCI (odds ratio [OR]: 4.33; 95% confidence limits (CL): 1.52 to 12.30), peak troponin T level (OR: 1.20; 95% CL: 1.08 to 1.34), and underlying peripheral vascular disease (OR: 4.86; 95% CL: 1.66 to 14.22). Cox proportional hazard analysis of survival data showed that increasing age (hazard ratio [HR]: 1.03; 95% CL: 1.01 to 1.04), bleeding after PCI (HR: 2.31; 95% CL: 1.61 to 3.32), renal insufficiency (HR: 2.26; 95% CL: 1.51 to 3.39]), and vascular surgery (HR: 1.48; 95% CL: 1.02 to 2.15]) were all significant predictors of long-term mortality after PCI. CONCLUSIONS: Perioperative MI has a markedly high mortality rate, despite PCI. Bleeding event, peak troponin T level, and peripheral vascular disease predict mortality within 30 days of PCI in this patient population. Similarly, older age, vascular surgery, bleeding event, and renal dysfunction strongly predict long-term mortality after PCI in the setting of PMI.

Degenerative Mitral Stenosis: Unmet Need for Percutaneous Interventions.

Degenerative mitral stenosis (DMS) is an important cause of mitral stenosis, developing secondary to severe mitral annular calcification. With the increase in life expectancy and improved access to health care, more patients with DMS are likely to be encountered in developed nations. These patients are generally elderly with multiple comorbidities and often are high-risk candidates for surgery. The mainstay of therapy in DMS patients is medical management with heart rate control and diuretic therapy. Surgical intervention might be delayed until symptoms are severely limiting and cannot be managed by medical therapy. Mitral valve surgery is also challenging in these patients because of the presence of extensive calcification. Hence, there is a need to develop an alternative percutaneous treatment approach for patients with DMS who are otherwise inoperable or at high risk for surgery. In this review, we summarize the available data on the epidemiology of DMS and diagnostic considerations and current treatment strategies for these patients.

Trends in the Burden of Adult Congenital Heart Disease in US Emergency Departments.

BACKGROUND: We assessed trends in incidence, in-hospital mortality, and admission among patients with adult congenital heart disease (ACHD) presenting to the emergency department (ED) from 2006 to 2012. HYPOTHESIS: There is a considerable burden of ACHD in the US EDs. METHODS: We used the 2006-2012 US Nationwide Emergency Department Sample. All ED visits with ACHD were identified using standard International Classification of Diseases, Ninth Edition, Clinical Modification codes. RESULTS: The number of patients presenting to the ED with simple (40.6%) as well as complex (37.6%) ACHD across 2006-2012 increased significantly. Also, there was a considerable increase in prevalence of traditional cardiovascular risk factors among ACHD patients, including hypertension, diabetes, smoking, obesity, and chronic kidney disease. Besides miscellaneous noncardiovascular conditions, nonspecific chest pain (15.9%) and respiratory disorders (15.0%) were the most common reasons for ED visits among patients with simple and complex ACHD, respectively. Although there was a trend toward decrease in admissions across 2006-2012 (Ptrend < 0.001), the proportion of patients with ACHD presenting to ED requiring admission remained substantial (63.4%). Finally, there was significant variation in admission trends across different geographic locations, hospital types, insurance status, and ED volume among ACHD patients presenting to the ED. CONCLUSIONS: There has been a progressive increase in number of ED visits among ACHD patients across 2006-2012 in the United States. Moreover, the cardiovascular risk-factor profile of ACHD patients has changed, adding to complexity in management. Current health care delivery to ACHD patients also shows significant geographical, hospital-based, and insurance status-based disparities.

Nationwide Trends of Hospital Admission and Outcomes Among Critical Limb Ischemia Patients: From 2003-2011.

BACKGROUND: Critical limb ischemia (CLI) continues to be a major cause of vascular-related morbidity and mortality in the United States. OBJECTIVES: The study sought to characterize the trends in hospitalization of U.S. patients with CLI from 2003 to 2011, using the Nationwide Inpatient Sample. We compared the cost utilization and in-hospital outcomes of endovascular and surgical revascularization procedures for CLI. METHODS: CLI and revascularization procedures were identified using International Classification of Diseases-Ninth Edition-Clinical Modification codes. In-hospital mortality and amputation were coprimary outcomes. Length of stay (LOS) and cost of hospitalization were secondary outcomes. RESULTS: We included a total of 642,433 admissions with CLI across 2003 to 2011. The annual rate of CLI admissions has been relatively constant across 2003 to 2011 (∼150 per 100,000 people in the United States). There has been a significant reduction in the proportion of patients undergoing surgical revascularization from 13.9% in 2003 to 8.8% in 2011, while endovascular revascularization has increased from 5.1% to 11.0% during the same time period. This was accompanied by a steady reduction in the incidence of in-hospital mortality and major amputation. Compared to surgical revascularization, endovascular revascularization was associated with reduced in-hospital mortality (2.34% vs. 2.73%, p < 0.001), mean LOS (8.7 days vs. 10.7 days, p < 0.001), and mean cost of hospitalization ($31,679 vs. $32,485, p < 0.001) despite similar rates of major amputation (6.5% vs. 5.7%, p = 0.75). CONCLUSIONS: While CLI admission rates have remained constant from 2003 to 2011, rates of surgical revascularization have significantly declined and endovascular revascularization procedures have increased. This has been associated with decreasing rates of in-hospital death and major amputation rates in the United States. Despite multiple adjustments, endovascular revascularization was associated with reduced in-hospital mortality compared to surgical revascularization during 2003 to 2011.

Nationwide Hospitalization Trends in Adult Congenital Heart Disease Across 2003-2012.

BACKGROUND: We aimed to assess trends in hospitalization, outcomes, and resource utilization among patients admitted with adult congenital heart disease (ACHD). METHODS AND RESULTS: We used the 2003-2012 US Nationwide Inpatient Sample for this study. All admissions with an ACHD were identified using standard ICD codes. Resource utilization was assessed using length of stay, invasive procedure utilization, and cost of hospitalization. There was a significant increase in the number of both simple (101%) as well as complex congenital heart disease (53%)-related admissions across 2003-2012. In addition, there was a considerable increase in the prevalence of traditional cardiovascular risk factors including older age, along with a higher prevalence of hypertension, diabetes, smoking, obesity, chronic kidney disease, and peripheral arterial disease. Besides miscellaneous causes, congestive heart failure (11.8%), valve disease (15.5%), and cerebrovascular accident (26.1%) were the top causes of admission to the hospital among patients with complex ACHD, simple ACHD without atrial septal defects/patent foramen ovale and simple atrial septal defects/patent foramen ovale patients, respectively. In-hospital mortality has been relatively constant among patients with complex ACHD as well as simple ACHD without atrial septal defects/patent foramen ovale. However, there has been considerable increase in the average length of stay and cost of hospitalization among the ACHD patients during 2003-2012. CONCLUSIONS: There has been a progressive increase in ACHD admissions across 2003-2012 in the United States, with increasing healthcare resource utilization among these patients. Moreover, there has been a change in the cardiovascular comorbidities of these patients, adding a layer of complexity in management of ACHD patients.