Hypertension Disease Research Articles

Esophageal melanosis: Two case reports and review of literature

BACKGROUND Esophageal melanosis (EM) is a rare condition characterized by melanin pigmentation in the esophageal mucosa. It is not well understood and has been documented in less than 100 cases worldwide. CASE SUMMARY We report two cases of African American patients who complained of significant weight loss (over 20 pounds in approximately six months) and abdominal pain during their first visit. The first case involves a 54-year female with a history of hepatic steatosis and polysubstance abuse, who also experiences nausea and vomiting. The second case is a 59-year-old male with hypertension and gastroesophageal reflux disease (GERD), who was diagnosed with esophageal squamous cell carcinoma. Both cases show benign melanocytes in the basal layer on the esophagus biopsy and are diagnosed as EM. CONCLUSION It is important to note that EM has been associated with malignancies such as carcinoma and melanoma. Therefore, accurate diagnosis and appropriate management are crucial. Patients with EM, especially those with concurrent risk factors (e.g. , GERD, smoking), should be carefully monitored for any signs of malignancy.

Association between triglyceride glucose index and endometriosis in adults in the United States: A comprehensive study from the National Health and Nutrition Examination Survey (NHANES)

Background The triglyceride glucose (TyG) index has been well recognized as a reliable marker of insulin resistance and substantially correlated with the pathogenesis and progression of hypertension and cardiovascular diseases. However, no study has investigated the association between the TyG index and endometriosis. Therefore, this study aimed to uncover an association between the TyG index and endometriosis. Methods This cross-sectional investigation employed the extensive dataset derived from the National Health and Nutrition Examination Survey (NHANES) (1999–2006). To explore the potential connection between the TyG and endometriosis, a multivariate weighted logistic regression model was established. The nonlinear relationship between the TyG index and the risk of endometriosis was explored using restricted cubic spline models (RCS). Furthermore, subgroup analyses were conducted. Results Ultimately, 2,508 individuals were included in this investigation. The findings unveiled a robust positive correlation between the TyG index and the susceptibility to endometriosis (OR [95% CI]: 1.52 [1.024,2.258]; P < 0.05). This positive association remained consistent across diverse subgroups. Age, birthplace, and whether one ovary was removed were identified as significant risk factors. In RCS analysis, the TyG index showed a nearly linear relationship with the risk of endometriosis (P-nonlinear > 0.05). Conclusions The findings indicate a positive association between the TyG index and the risk of endometriosis, exhibiting an approximate non-linear relationship.

An Updated Review For Hyperuricemia and Gout Management; Special Focus on the Available Drug Delivery Systems and Clinical Trials.

Hyperuricemia belongs to metabolic syndromes where increased uric acid levels are identified in the blood serum. Such a syndrome could be responsible for kidney stone formation, gout, hypertension, and chronic kidney diseases. It has been reported that cardiovascular risks have been linked with hyperuricemia. Gout is of the most frequent manifestations due to hyperuricemia; its management involves various pharmacological available options and dietary changes. Throughout the literature, various dosage forms are studied as alternative options to the present drug delivery systems. To update and summarize the current information for gout and hyperuricemia management. Authors have performed a thorough literature research from 2010-2023 using keywords such as hyperuricemia, gout, diagnosis, guidelines, drug delivery and clinical trials. The databases used were PubMed, ScienceDirect. According to our inclusion criteria, all studies which include the previous terms, as well as drugs or other molecules that can be applied for gout and/or hyperuricemia management, were added. In this article, authors have summarized the pathogenesis, diagnosis and updated guidelines for gout and hyperuricemia management. Moreover, the authors have reviewed and discussed current drug delivery systems found in the literature, including drugs targeting the above disorders. Finally, the available clinical trials assessing the efficacy of newer drugs or combinations of the past ones, are being discussed. The available drugs and dosage forms are limited, and therefore, scientific society should focus on the development of more efficient drug delivery systems for hyperuricemia and gout management.

Glucagon-like peptide-1 receptor agonists and the risk of erectile dysfunction: a drug target Mendelian randomization study

BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1RAs) have been widely used for type 2 diabetes (T2D) and weight management. However, the causal relationship of GLP-1RAs with erectile dysfunction (ED) was still unclear.MethodsMendelian randomization (MR) analysis was conducted to reveal the association of genetically proxied GLP-1RAs with ED. The proportion of potential mediators mediating GLP-1RAs to ED was also assessed by two-step MR. Finally, a series of sensitivity analyses and Two-Sep cis-MR (TSCMR) were performed to evaluate the robustness of the results.ResultsMR evidence suggested that genetically proxied GLP-1RAs reduced the risk of ED [odds ratio (OR): 0.493; 95% confidence interval (95% CI): 0.430 to 0.565; P<0.001]. Further mediation analysis via two-step MR showed that this effect was partly mediated through reduced T2D, obesity, hypertension and cardiovascular disease (CVD), with mediated proportions of 2.89% (95% CI: 1.28% to 4.49%), 6.83% (95% CI: 2.25% to 11.41%), 3.22% (95% CI: 1.21% to 5.23%), and 3.06% (95% CI: 0.51% to 5.62%), respectively.ConclusionsGLP-1RAs were associated with a reduced risk of ED, and to a lesser extent, T2D, obesity, hypertension and CVD mediated this effect. Nevertheless, the potential implications of our results for ED prevention policies required validation in further clinical randomized controlled trials.

Burden of Non-Communicable Disease and It’s Association with Weight Status: A Cross-Sectional Study in a Rural Community of Bangladesh

Background: Non-Communicable Diseases (NCDs) are now the leading causes of morbidity and mortality worldwide. Bangladesh has also experienced a rapid epidemiological shift from communicable diseases to non-communicable diseases due to growing urbanization and lifestyle alteration over the last few decades and this transition is also prominent in rural community of the country. Among all modifiable factors, overweight or obesity is the key risk factor for NCDs. This study aimed to determine the burden of NCD and its link to the body weight status of the rural population of Bangladesh. Materials and methods: This cross-sectional study was conducted in a village of Gomostapur Upazila under Chapainawabganj district from February to April 2024 among 135 people. The data were collected with face-to-face interview and Body Mass Index was measured. The data were compiled and tabulated according to key variables and analyzed with IBM SPSS 29.0.2. Results: Majority 44.5% of the study people belonged to age group 21-40 years. Among them 47.4% were male and 52.6% were female. Maximum respondents were of low-middle socioeconomic condition. Among them around 3/4th of the population was suffering from NCDs. Most of the respondents 24.4% had bone and joint pain followed by Hypertension, Asthma, COPD, Diabetes and Heart Disease at 20.7%, 17.0%, 14.1% and 10.4% respectively. Hypertension, Diabetes, Cardiovascular Disease, Stroke and Cancers were more prevalent in the older age group. Hypertension, Diabetes, Stroke and Bone-Joint Pain were seen more in female participants whereas male respondents had more prevalence of Asthma, COPD. Most of the study population had BMI above 25 kg/m2 and the study showed maximum NCDs were prevalent considerably in overweight and obese groups. Conclusion: The study revealed that, NCDs are highly prevalent among obese older rural population of Bangladesh while management, prevention, awareness and research are low. The integrated programs must be designed and implemented through a primary health care approach and high risk-group targeted interventions should be procurable to combat the rising burden of NCDs. IAHS Medical Journal Vol 7(1), June 2024; 74-79

Mechanistic Insights Into Redox Damage of the Podocyte in Hypertension

Podocytes are specialized cells within the glomerular filtration barrier, which are crucial for maintaining glomerular structural integrity and convective ultrafiltration. Podocytes exhibit a unique arborized morphology with foot processes interfacing by slit diaphragms, ladder-like, multimolecular sieves, which provide size and charge selectivity for ultrafiltration and transmembrane signaling. Podocyte dysfunction, resulting from oxidative stress, dysregulated prosurvival signaling, or structural damage, can drive the development of proteinuria and glomerulosclerosis in hypertensive nephropathy. Functionally, podocyte injury leads to actin cytoskeleton rearrangement, foot process effacement, dysregulated slit diaphragm protein expression, and impaired ultrafiltration. Notably, the renin-angiotensin system plays a pivotal role in podocyte function, with beneficial AT2R (angiotensin receptor 2)-mediated nitric oxide (NO) signaling to counteract AT1R (angiotensin receptor 1)-driven calcium (Ca 2+ ) influx and oxidative stress. Disruption of this balance contributes significantly to podocyte dysfunction and drives albuminuria, a marker of kidney damage and overall disease progression. Oxidative stress can also lead to sustained ion channel–mediated Ca 2+ influx and precipitate cytoskeletal disorganization. The complex interplay between GPCR signaling, ion channel activation, and redox injury pathways underscores the need for additional research aimed at identifying targeted therapies to protect podocytes and preserve glomerular function. Earlier detection of albuminuria and podocyte injury through routine noninvasive diagnostics will also be critical in populations at the highest risk for the development of hypertensive kidney disease. In this review, we highlight the established mechanisms of oxidative stress–mediated podocyte damage in proteinuric kidney diseases, with an emphasis on a hypertensive renal injury. We will also consider emerging therapies that have the potential to selectively protect podocytes from redox-related injury.

Adipokines and their potential impacts on susceptibility to myocardial ischemia/reperfusion injury in diabetes

Abstract Coronary artery disease has a high mortality rate and is a striking public health concern, affecting a substantial portion of the global population. On the early onset of myocardial ischemia, thrombolytic therapy and coronary revascularization could promptly restore the bloodstream and nutrient supply to the ischemic tissue, efficiently preserving less severely injured myocardium. However, the abrupt re-establishment of blood flow triggers the significant discharge of previously accumulated oxidative substances and inflammatory cytokines, leading to further harm referred to as ischemia/reperfusion (I/R) injury. Diabetes significantly raises the vulnerability of the heart to I/R injury due to disrupted glucose and lipid processing, impaired insulin sensitivity and metabolic signaling, and increased inflammatory responses. Numerous studies have indicated that adipokines are crucial in the etiology and pathogenesis of obesity, diabetes, hyperlipidemia, hypertension, and coronary artery disease. Adipokines such as adiponectin, adipsin, visfatin, chemerin, omentin, and apelin, which possess protective properties against inflammatory activity and insulin resistance, have been shown to confer myocardial protection in conditions such as atherosclerosis, myocardial hypertrophy, myocardial I/R injury, and diabetic complications. On the other hand, adipokines such as leptin and resistin, known for their pro-inflammatory characteristics, have been linked to elevated cardiac lipid deposition, insulin resistance, and fibrosis. Meteorin-like (metrnl) exhibits opposite effects in various pathological conditions. However, the data on adipokines in myocardial I/R, especially in diabetes, is still incomplete and controversial. This review focuses on recent research regarding the categorization and function of adipokines in the heart muscle, and the identification of different signaling pathways involved in myocardial I/R injury under diabetic conditions, aiming to facilitate the exploration of therapeutic strategies against myocardial I/R injury in diabetes.

Abstract 4145840: Hypertensive Cardiorenal Disease with Cardiorenal Failure vs. Hypertensive Renal Disease with Renal Failure: Racial Mortality Trends from 1999 to 2020 in the United States

Introduction: High levels of blood pressure (BP) are responsible for 7.6 million deaths each year worldwide, more than any other risk factor. The diagnosis of hypertension is associated with a significant increase in the risk of kidney or cardiovascular events, with no prior history of these events. Our study aims to analyze trends in hypertensive heart disease and hypertensive heart and kidney disease-related mortality in the United States, focusing on different races. Method: We retrieved death certificate data from the CDC-WONDER database for adults aged ≥25 years. Crude mortality rates (CMRs) and age-adjusted mortality rates (AAMRs) per 100,000 persons were calculated. Temporal trends were examined using the average annual percent change (AAPC) determined by joinpoint regression. Result: From 1999 to 2020, a total of 100,705 people died from hypertensive heart and renal disease in the USA. The overall AAMR of 1.4 per 100,000 displayed a trend during this period (AAPC: 4.8, 95% CI [3.3–6.2]). Total deaths from hypertensive heart disease and renal disease associated with heart failure were 5,274, showing an increasing trend from 1999 to 2020. The AAMR for hypertensive heart and renal disease with heart failure was 0.1 (AAPC: 5.2, 95% CI [3.8–6.7]). Black or African Americans have the highest AAMR (0.1, 95% CI [0.1–0.1]). Total deaths from hypertensive heart disease and renal disease associated with renal failure were 34,519, showing an increasing trend from 1999 to 2020. The AAMR for hypertensive heart and renal disease with renal failure was 0.4 (AAPC: 3.9, 95% CI [2.6–5.1]). Black or African American has the highest AAMR (1.6, 95% CI [1.5–1.6]), followed by American Indian or Alaska Native (0.5, 95% CI [0.4–0.5]), Asians and Pacific Islanders (0.4, 95% CI [0.4–0.4]), and White (0.4, 95% CI [0.3–0.4]). Conclusion: African Americans and other identified high-risk races should get targeted therapies to reduce the burden of hypertensive-related morbidity and mortality; those with renal impairment should receive special attention. The goals of these interventions ought to be to increase access to healthcare, raise public knowledge of hypertension, and support lifestyle changes.

Abstract 4134692: In-Hospital Mortality Rate and Predictors of 30-Day Readmission in Cancer Patients with MI Undergoing PCI -A Cross Sectional Study From Nationwide Readmission Database

Background and objectives: Data regarding readmission rates and predictors of readmission in cancer patients undergoing PCI are sparce. With the increasing survival rates and prevalence of cardiovascular complications in cancer patients, understanding the patterns and predictors of readmission in this population is paramount for optimizing their outcomes. Cancer patients pose unique clinical challenges due to their combined prothrombotic state and propensity for bleeding. We attempted to identify factors associated with readmission in cancer patients. Methods: We utilized the Nationwide Readmission Database from 2016 to 2020 and included patients more than 18 years of age with primary diagnosis of myocardial infarction(MI) who underwent percutaneous coronary intervention(PCI) and have a preexisting diagnosis of cancer. We used International Classification of Disease, Tenth Revision, Clinical Modification (ICD10 CM) codes to define MI, PCI, and cancer. The primary outcome was the 30-day readmission rate, and secondary outcomes were mortality rates, predictors of readmission, and common causes of readmission. The independent predictors of readmission were analyzed using cox regression analysis. Results: Of the 52,307 cancer patients who underwent PCI, 7,767 were readmitted within a 30-day period. The readmission rate for these patients was 15.70%. The mortality rate was 6.05% for index admission and 6.80% for readmitted cases. Among the readmitted patients in the strongest independent predictor for readmission were leaving against medical advice(AMA), anemia, congestive heart failure, and discharge to a skilled nursing facility or home health. Common causes of readmission within this time included hypertensive heart disease with concomitant CKD stage I-IV and heart failure (6.21%), sepsis (6.12%), NSTEMI (5.60%), hypertensive heart disease with concomitant heart failure (4.62%) and acute kidney injury (1.98%). Conclusions: Thirty-day readmission rate was 15.70%. Independent predictors of readmission were anemia, diabetes mellitus, congestive heart failure, malnutrition, peripheral artery disease, leaving against medical advice, and discharge to facility. Most common cause of readmission was hypertensive heart and kidney disease with heart failure, which comprised 6.21%.

Abstract 4134744: Trends and Disparities in Mortality Among Patients with Hypertensive Heart Disease and Congestive Heart Failure in the United States from 1999 to 2020

Background: Hypertensive heart disease (HHD) poses a growing public health concern. Global data reveal a concerning rise in HHD prevalence, deaths, and disability-adjusted life years (DALYs) between 1990 and 2019. The Framingham Study highlights that hypertension is linked to approximately one-quarter of heart failure cases. This association is even stronger among older adults, in whom hypertension is responsible for up to 68% of heart failure cases. Methods: This study analyzed death certificates within the CDC WONDER database for patients in the United States from 1999 to 2020. We identified deaths among individuals aged 25 years and older caused by HHD and CHF using the International Classification of Diseases, Tenth Revision (ICD-10) code I11.0. Age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and annual percent change (APC) were computed and categorized based on year, gender, race/ethnicity, and urbanization status. Results: Between 1999 and 2020, a total of 302,270 deaths were reported in patients due to HHD with CHF. Overall, AAMR increased from 37.3 to 134.9 per 1,000,000 population between 1999 and 2020, with a significant decrease from 1999 to 2004 (APC: -7.91; 95% CI: -20.16 to -1.04), followed by a significant increase from 2004 to 2007 (APC: 42.47; 95% CI: 21.27 to 55.62), a slight decrease from 2007 to 2014 (APC: -0.9; 95% CI: -9.38 to 2.39), and finally a steep increase from 2014 to 2020 (APC: 14.22; 95% CI: 10.87 to 20.84). Gender-based analysis revealed that men had slightly higher AAMRs than women (Men: 63.1; 95% CI: 62.8 to 63.5 vs. Women: 60.7; 95% CI: 60.5 to 61). Moreover, AAMRs were highest among non-Hispanic African Americans (109.6; 95% CI: 108.6 to 110.6), followed by non-Hispanic American Indian or Alaska Natives (66.6; 95% CI: 63.1 to 70.1), non-Hispanic Whites (58.5; 95% CI: 58.2 to 58.7), Hispanics (53.7; 95% CI: 52.9 to 54.5), and non-Hispanic Asian or Pacific Islanders (39; 95% CI: 38–39.9). In addition, non-metropolitan areas had higher AAMRs than metropolitan areas (non-metropolitan: 65.7; 95% CI: 65.2 to 66.3 vs. metropolitan: 62.1; 95% CI: 61.8 to 62.3) (Figure 1). Conclusions: Despite an initial decline, mortality from combined HHD and CHF has risen significantly since 1999. Notably, mortality was most pronounced among men, non-Hispanic African Americans, and individuals residing in non-metropolitan areas.

Abstract 4145842: The Incidence, Predictors and Impact of 30-day Readmission of Takotsubo Cardiomyopathy Hospitalization: A Retrospective Nationwide Analysis

Objective: This study aimed to describe the recent readmission and mortality rates of unplanned 30-day all cause readmission after takotsubo cardiomyopathy hospitalization. Methods: We conducted an analysis of the 2020 Nationwide Readmission Database. Using the ICD-10 code, we identified hospitalizations for takotsubo cardiomyopathy. We excluded hospitalizations for age<18years and planned or elective readmissions. To compare baseline characteristics between readmissions and index hospitalizations, Pearson χ2 tests were employed. We utilized multivariate Cox regression analyses to identify independent predictors of readmissions. Results: A total of 7554 patients were hospitalized for index admission for takotsubo cardiomyopathy, and 633 of them were readmitted. The 30-day all-cause readmission rate was 8.5% while specific takotsubo readmission rate was 0.4%. The mortality rate in the index admission was 1.9% and 5.5% in readmitted patients. The mean age of index admission was 67.6years vs 70.7 years in readmission, about 89.0% were female in index admission vs 85.0% in readmission cohorts. The most common reasons for readmission were hypertensive heart disease with heart failure, hypertensive heart disease and chronic kidney disease with heart failure, takotsubo syndrome, sepsis, NSTEMI, COPD exacerbation, acute kidney failure, pneumonia, atrial fibrillation. Readmissions had more acute kidney injury (20.6% vs 11.3%, p-value <0.001) and atrial fibrillation (23.0% vs 13.0%, p <0.001) compared to the index admission, however the index admission had more ventricular tachycardia (4.6% versus 1.8%, p=0.02) compared to readmission cohorts. Readmission had longer length of hospital stay (4.9 days vs 3.7 days, p< 0.001), but less mean total hospital charge of (US$51039 vs US$60617, P =0.008). Older age, acute renal failure, pulmonary disease, coronary dissection, longer length of hospital stays and transfer to rehabilitation facility after discharge were identified as statistically significant predictors of readmissions. Conclusion: About one in twelve patients hospitalized with takotsubo cardiomyopathy were readmitted within 30days. Readmissions had a higher mortality rate; acute renal failure, pulmonary disease, coronary dissection were notable reasons for readmission. Understanding the predictors for readmission highlighted in this study would enable clinicians implement preventive strategies to improve the rate of takotsubo cardiomyopathy readmission

Abstract 4128457: Trends in Hypertension-Related Mortality Among Younger Adults in the United States From 1999-2021

Background: The U.S. population has seen a dramatic increase in the burden of hypertension (HTN) among younger adults. However, HTN-related mortality trends among younger adults have not been investigated. Aim: We examined the trends and demographic differences in HTN-related mortality among younger adults in the U.S. Methods: Data from the CDC WONDER database was examined from 1999 to 2021 for HTN-related mortality in adults between 15 to 45 years of age. The International Statistical Classification of Diseases and Related Health Problems-10th Revision (ICD-10) codes employed were as follows: I10-I15 (hypertensive diseases). Age-adjusted mortality rates (AAMRs) per 100,000 persons and annual percent changes (APCs) with 95% confidence intervals (CIs) were calculated and stratified by year, sex, race/ethnicity, urbanization status and census region. Results: Between 1999 and 2021, 201,860 HTN-related mortalities occurred among younger adults in the U.S. The AAMR increased from 2.8 in 1999 to 5.0 in 2001 (APC, 35.3 [20.6 to 44.5]), after which it steadily increased to 9.4 in 2019 (APC 3.1, [2.7 to 3.5]), and sharply increased to 13.9 in 2021 (APC 22.3; 95% CI 15.1 to 26.4). Men had consistently higher AAMRs than women from 1999 (AAMR men: 3.6 vs women: 1.9) to 2021 (AAMR men: 18.9 vs women: 8.8). Non-Hispanic (NH) Black or African American young adults had the highest AAMR in 2020 (30.2), followed by NH American Indian/Alaska Natives (29.6), NH White (9.9), Hispanics or Latino (9.3) and NH Asian or Pacific Islanders (5.0). AAMR also varied substantially by region (overall AAMR: South 9.3; Midwest 6.4; West 5.8; Northeast 5.4), and rural areas had higher HTN-related mortality (8.5) than their urban counterparts (7.0). Figure 1. Conclusion: Following a steady increase until 2019, HTN-related mortality increased among young adults between 2020 and 2021. The highest AAMRs were observed among men and Black or African American young adults, and people residing in the Southern and non-metropolitan areas. This emphasizes the necessity of tailored interventions to mitigate the burden and reduce the current disparities in HTN-related mortality among young adults in the U.S.

Abstract 4138220: Traditional and HIV-specific Risk Factors Are Associated with Incident Non-valvular Atrial Fibrillation and Atrial Flutter among Underrepresented Racial and Ethnic Minority Groups Living with HIV

Introduction: With effective antiretroviral therapy (ART), HIV can now be managed as a chronic disease. Chronic disease and cardiovascular risk factor management is especially important for underrepresented racial and ethnic minority groups (UREG). Non-valvular atrial fibrillation and atrial flutter (NVAF) have not been adequately studied in UREG with HIV. Research Questions: Among UREG with HIV, what is the incidence of NVAF? What factors are associated with incident NVAF? Aims: To narrow an evidence gap among UREG with HIV by 1) describing the incidence of NVAF and 2) identifying factors associated with incident NVAF. Methods: This is an ancillary study of the Pathways to Cardiovascular Disease Prevention and Impact of Specialty Referral in Underrepresented Racial and Ethnic Minorities with HIV (PATHWAYS) study, a retrospective population-based study of HIV care patterns among UREG with HIV. Patients without a known history of NVAF entered our study cohort at the date of their first documented HIV diagnosis. We computed the cumulative incidence of NVAF over five years of follow-up (mean 3.4, SD 1.6), handling death as a competing risk. Cox regression analysis was used to examine the univariate associations between characteristics at HIV diagnosis and incident NVAF, adjusting for site and date of HIV diagnosis. Results: From 2015-2019, 10,945 UREG meeting entry criteria were identified. On average, patients were 67.1% male, 94.4% Black, and 8.5% Hispanic. Average CHA2DS2VASc score was 0.92 (SD 1.1) and 63.4% were on ART. Cumulative incidence of NVAF at one and five years after HIV diagnosis were 0.48% (95% CI 0.36-0.63) and 2.16% (95% CI 1.85-2.51), respectively. HIV-related factors associated with incident NVAF included baseline CD4 count <200 (HR 1.84, 95% CI 1.20-2.80) and initial ART including protease inhibitors (HR 1.56, 95% CI 1.14-2.13) and/or integrase strand transfer inhibitors (HR 1.47, 95% CI 1.08-1.99). Additional associated factors included older age, Medicare, cardiology visit(s) in prior year, and co-morbid diseases including hypertension, hyperlipidemia, coronary and peripheral artery disease, prior stroke/transient ischemic attack, heart failure, and chronic kidney disease. Conclusions: In a large cohort of UREG living with HIV, both traditional and HIV-specific risk factors are associated with increased risk of incident NVAF. Interventions to mitigate NVAF risk in this population will require interdisciplinary, team-based approaches.

Abstract 4135127: Traveling more than a 20-mile radius to a Heart Failure Center can affect the quality of Heart Failure Care.

Introduction: We recognized the profound importance of access to care among patients with heart failure (HF). The geographical location of HF centers may significantly impact health outcomes, especially for those with limited transportation. This social determinant of health (SDOH) aspect is critical in bridging the gap in achieving HF care. Hypothesis/Methods: This was a single-center observational study conducted at a tertiary heart failure center in central Pennsylvania. We assessed the impact of travel distance by comparing patients who travel within a 20-mile radius to those who travel beyond a 20-mile radius. A total of 322 patients were referred to the HF clinic and enrolled in a guideline-directed medical therapy (GDMT) optimization program. Data collected included distance to Hershey Medical Center (HMC), health insurance coverage, HF etiology, onset, and echocardiogram. The distance was calculated based on the patient’s zip code. Results: Among patients enrolled in the HF-GDMT program, 194 travel within 20 miles, and 128 travel beyond a 20-mile radius to HMC. The mean travel distance to HMC was 9.1 miles (within) and 40.9 miles beyond 20 miles. The majority of patients were 81.3% white, 67% male, and the average age was 64. Most patients had heart failure with reduced ejection fraction (HFrEF) at 92.9%, 63% nonischemic, and 57.5% new onset. The comorbidities in both groups were similar, including hypertension, hyperlipidemia, and coronary artery disease (CAD). When comparing both groups, those who traveled beyond the 20-mile radius to HMC had more chronic HF at 55.5% vs. 34% in patients who traveled within the 20-mile radius. Upon enrollment, most patients were on suboptimal doses of either 1 or 2 of the four pillars of GDMT for HFrEF. Conclusions: The findings of this study revealed that patients with HF who travel beyond a 20-mile radius to HMC are more likely to have chronic HF, suggesting a delay in seeking care. A delay in referral may affect the timely initiation of appropriate GDMT and will likely lead to worse health outcomes. This underscores the urgent need for interventions to address barriers like transportation to improve HF care, offering a potential avenue for better patient outcomes.

Abstract 4144530: IL-37 promotes resolution of Right Heart Disease-induced inflammation and atrial fibrillation.

INTRODUCTION: Atrial Fibrillation (AF) is the most common cardiac arrhythmia. Hypertension, obesity, diabetes or right heart disease (RHD) are important risk factors for AF. Inflammation stands as a common denominator among most AF risk factors. Studies have shown that patients with AF present high levels of circulating IL-18. Our group recently described that inflammation-resolution may prevent AF in RHD, however, the mechanism remains unclear. To inhibit IL-18-induced inflammation, IL37, a specific antagonist of IL-18-receptor was shown to attenuate cardiac fibrosis in a mice model of myocardial infarction, but little is known about its efficacy to prevent AF. HYPOTHESIS: IL-37 curbs RHD-induced atrial inflammation and AF vulnerability. METHODS: To induce right-sided cardiac hypertrophy and dilation, pulmonary artery banding (PAB) was performed in male and female Wistar rats (250-300g). Sham animals did not receive the ligation. Animals were randomized into four groups: Sham and PAB treated or not with IL37 (100 ng/ml/kg). Electrophysiological studies and echocardiography were performed in vivo before sacrifices at day (D)0, D7, D14 and D21. To analyze the atrial conduction, right atrial (RA) optical mapping was performed on Langendorff-perfused hearts. Histology, western blot, and qPCR were performed to study the expression of proteins and genes involved in atrial inflammation, fibrosis, and electrical remodeling. RESULTS: Twenty-one days after surgery, PAB rats were more vulnerable to AF and developed severe right-sided hypertrophy and dilation compared to Sham. Reliable to clinical evidence, female rats might be more resistant to AF than males. AF was associated with increased RA levels of inflammatory biomarkers including IL18, IL1β, and IL6. IL37 treatment was associated with decreased atrial expression of inflammatory markers. CONCLUSION: IL37 is a potential new therapeutic strategy to reduce atrial inflammation and prevent AF vulnerability in RHD.

Abstract 4119169: Navigating Complexity: The Carlino Technique in Multivessel Percutaneous Coronary Intervention for Chronic Total Occlusion

Introduction: Since the advent of percutaneous coronary intervention (PCI), the scope of this therapeutic intervention has broadened to include cases of life-threatening multivessel coronary artery disease that previously may have only been corrected surgically. PCI has become a common treatment of chronic total occlusion, and techniques continue to be developed to tackle more challenging cases. We present a complex case of NSTEMI with multi-vessel coronary artery disease treated with PCI via the Carlino technique. Case Description: A 60-year-old female with a history of hypertension, diabetes mellitus, and ischemic heart disease presented with severe chest pain that radiated to the neck and was associated with nausea and vomiting. Her EKG showed marked left-axis deviation, ST depressions in V2-V4, and RBBB. She was diagnosed with NSTEMI with a thrombolysis in myocardial infarction (TIMI) score of 5. She was loaded with aspirin and clopidogrel and was taken for left heart catheterization (LHC), which demonstrated three-vessel coronary artery disease with chronic 100% occlusion of the proximal left anterior descending artery, ostial 60-70% stenosis, and proximal 90-95% diseased left circumflex artery, while her right coronary artery had proximal 20-30% obstruction and mid 50-60% with right to left filling. The patient was advised CABG by the heart team, but the patient refused, and PCI was attempted on a shared decision basis. PCI was successful with the use of the Carlino technique: 0.5 ml of contrast dye was injected through a microcatheter to hydraulically recanalise the occlusion. The patient showed dramatic improvement and was discharged home on oral medications. Discussion: Treating multi-vessel coronary artery disease and CTO is challenging. PCI, particularly with the Carlino technique, offers a reliable approach. This technique, a modification of contrast-guided STAR, involves gentle contrast injection via microcatheter to modify plaque compliance and provide topographic information with regards to equipment location within vasculature, enhancing procedural success, especially in cases with impenetrable caps or calcified areas. Conclusion: This case is an example of how adaptive PCI techniques, such as the Carlino technique, can be employed to tackle complex instances of MvCAD that previously may have only been surgically corrected.

Abstract 4117414: Risk Factors Associated with Cardiac Hospital Admissions in Cancer Patients Treated with Immune Checkpoint Inhibitors

Background: Immune checkpoint inhibitors (ICIs) are highly effective anti-cancer treatments for several cancers. However, treatment with ICIs is associated with metabolic perturbations, accelerated atherosclerosis, and increased risks of adverse cardiovascular events. In this study, we aimed to determine risk factors associated with cardiac hospital admissions in patients treated with ICIs for their cancer. Methods: Retrospective data was collected for all patients treated with ICIs between 1 January 2010 and 1 January 2020 through the Hunter New England Local Health District (HNELHD), Australia. Patient medical history and demographics were collected through electronic medical records. Outcome data was obtained from the HNELHD Institutional Cardiac and Stroke Outcomes Unit database. Cardiac admission was defined as cardiac disease based on hospital administration ICD-10 codes. Binary logistic regression was used for multivariate analysis and performed through SPSS version 28. Results: A total of 1,080 patients were included in the final analysis. Mean age of patients was 66.9 ± 11.7 years, with the majority male sex ( n =685; 63.4%). Primary cancer diagnosis of patients treated with ICIs included melanoma ( n =417; 38.7%), and cancer of the lung ( n =327; 30.3%). Nivolumab monotherapy was the most used first-line ICI treatment ( n =475; 44.0%) followed by pembrolizumab monotherapy ( n =428; 39.6%). A total of 266 (24.6%) patients had at least one cardiac hospital admission. On univariate analysis, pre-existing cardiovascular disease (CVD) ( p <0.001), diabetes mellitus ( p <0.001), chronic kidney disease ( p <0.001), and prior CVD medications ( p <0.001) were associated with cardiac hospitalisation. On multivariate analysis, prior history of heart failure ( p <0.001), hypertension ( p =0.003), ischaemia, and peripheral vascular disease ( p =0.049) were independently associated with an increased risk of cardiac hospital admission. Conclusions: In cancer patients treated with ICIs, pre-existing CVD risk factors increases the risk of cardiac-associated hospitalisations. Adequate CVD risk modification and monitoring during treatment with ICIs may be necessary to reduce cardiac hospitalisations.

Abstract 4144552: Difference in Characteristics and Outcomes of Atrial Fibrillation patients based on type of Heart Failure: An NRD Propensity Matched Analysis

Background: Heart Failure(HF) significantly deteriorates outcomes in patients with Atrial Fibrillation. Heart Failure with Preserved Ejection Fraction(HFpEF) and Atrial Fibrillation(AFib) share common disease progression pathways and are gradually increasing in prevalence. Aim: We aim to study the variation in characteristics and outcomes based on type of heart failure in patients with AFib using the National Readmission Database(2016-2020). Methods: NRD database was used to identify patients with Atrial Fibrillation using ICD-10 codes. Patients were stratified into two groups based on the presence of systolic dysfunction and diastolic dysfunction. Patients with combined systolic and diastolic dysfunction were excluded. Information was collected on patient demographics, comorbidities, and outcomes. Propensity score matching was performed to compare outcomes among AFib patients with HFrEF and HFpEF. Results: A total of 6,673,080 patients with AFib and isolated systolic or isolated diastolic dysfunction were included in the analysis. 3,914,695(58.66%) had HFpEF and 2,758,385 (41.34%%) had HFrEF. In the HFpEF group 57.8% were females in comparison with 33.12% females in the HFrEF group. HFpEF group had a higher rate of hypertension (84.9% vs 82%, p<0.001), OSA(19.35 vs 14.9, p<0.001), immunocompromised status (0.06 vs 0.04%, p<0.001), hypothyroidism(23.7% vs 18.47%,P<0.001), Anemia(10.1% vs 7.95%, p<0.001), Pneumonia (13.51%) and Pulmonary disease(37.34% vs 30.98%) as compared to the HFrEF group. In the propensity matched analysis, HFpEF group had lower in-hospital death (5.26% vs 6.59%, p<0.001), acute kidney injury (33.19% vs 38.92%; p<0.001), stroke (0.99% vs 1.71%), cardiogenic shock (1.02% vs 3.29%; p<0.001), Myocardial infarction (3.60% vs 7.65%; p<0.001), sudden cardiac arrest (1.95% vs 2.62%;p<0.001), mechanical circulatory device use(0.16% vs 0.77%;p<0.001) and major adverse cardiovascular event(9.79% vs 16.06%;p<0.001). Discussion: In Afib patients with HFpEF, yearly admissions were higher in comparison to the HFrEF group. Furthermore, we found a higher prevalence of hypertension, obesity, OSA, pulmonary disease, pneumonia, immunocompromised status, hypothyroidism, and anemia in comparison with the HFrEF group. However, mortality rate in HFpEF group and MACE were lower. At present, there are no definite therapies for patients with HFpEF that have displayed a clear mortality benefit highlighting the need for further inquiry.

Abstract 4141486: Site-Specific Transcriptomic Patterns and Cell Types Associated with Hypertension

Introduction: The biology of early human hypertensive heart disease (HHD) is largely unexplored due to limited cardiac tissue access. Site-specific transcriptomics of human cardiac tissue before development of overt HHD offers a unique vantage to understand the biology of HHD in human cardiac tissue. Hypothesis: We hypothesize that transcriptomic signatures and cell subtype proportions differ in human heart tissue from HTN donors compared to normotensive (NTN) donors in a site-specific manner. Methods: We performed bulk RNA-seq on rRNA-depleted libraries from left (LV) and right (RV) mid-ventricular-wall tissue (average depth 114 million reads/sample) collected postmortem from HTN (n=3, 67% Black/Latinx) and NTN (n=2, 50% Black/Latinx) donors. We performed single-nucleus RNA-seq (snRNA-Seq) on cardiac tissue from the same donors (average of 4,062 LV nuclei). Differential gene expression, lineage identification, and Gene Set Enrichment Analysis (GSEA) were performed with publicly available software. Results: All donors were female with matched postmortem intervals (time from death to tissue preservation; HTN 19±9 hours, NTN 18±6 hours). HTN donors were older (65±7 years) than NTN donors (36±16 years). A total of 416 genes were associated with HTN (Wald test, FDR q <0.05) across both ventricles (correcting for site). When tested separately, 72 (LV) or 83 (RV) genes were associated with HTN (FDR q <0.05), with 13 common genes, indicating site-specific differences. GSEA of genes ranked by Wald statistic computed across both ventricles showed that transcripts involved in single-stranded DNA helicase activity, branched-chain amino acid catabolism, and NAD-dependent deacetylase activity were coordinately associated with HTN (FDR q <0.05). snRNA-seq revealed 9 cell types in these samples, including immune cells and chamber-specific cardiomyocytes (CMs) with higher proportions of LV CMs and lymphocytes associated with HTN compared to NTN. MYH6 and MYL7 expression was unchanged with respect to HTN by RNA-seq but lower in LV HTN CMs compared to NTN by snRNA-seq, suggesting dysregulation of contractile programming in HTN LV CMs. Conclusion: HTN is associated with altered cardiomyocyte/lymphocyte ratios, and site-specific differential expression of cardiac contractile elements. Further study is required to validate these findings with additional samples and elucidate mechanisms driving transcriptional program differences in the hypertensive human heart.

Abstract 4137484: Clinical implications of combined midodrine and pulmonary vasodilator therapy in Portopulmonary Hypertension

Introduction: Portopulmonary hypertension (POPH) and associated pulmonary vascular resistance (PVR) elevation is seen in the context of underlying portal hypertension and liver disease. In the systemic circulation, liver cirrhosis can cause inappropriate splanchnic and systemic vasodilation with decreased systemic vascular resistance (SVR). Midodrine is used to maintain blood pressure in the setting of low SVR. Pulmonary vasodilators have systemic vasodilatory effects; the implications of combined midodrine and pulmonary vasodilator use in POPH are unanswered questions. Hypothesis: We hypothesized that SVR would decrease over time in patients with POPH started on pulmonary vasodilators, and that use of midodrine (as a surrogate for depressed SVR), may be associated with increased risk of mortality in patients with POPH starting pulmonary vasodilator therapy. Methods: Patients from the 3 Mayo Clinic sites (Rochester, MN; Jacksonville, FL; Scottsdale, AZ) diagnosed with POPH from 1988-2020 were included in the database. Patients met hemodynamic criteria for POPH via right heart catheterization (RHC). Hemodynamics were obtained from echocardiography and RHC at initial and subsequent visits. The hazard ratio for risk of death was estimated using Cox proportional hazards method. SVR was calculated using mean arterial pressure and cardiac output. Results: Analysis included 147 POPH patients, 34 (23%) on midodrine and 113 (77%) not requiring midodrine. There were 116 patients with longitudinal SVR data. The mean initial SVR was 1224 Dyne sec cm-5 and decreased 251 Dyne sec cm-5 [95% CI -337 to -165 251 Dyne sec cm-5, p<0.0001] with no difference between midodrine groups (p=0.57). Patients in the midodrine POPH group had an increased risk of mortality compared to those without midodrine use (HR 1.51, 95% CI: 1.02-2.21, p=0.0371). Conclusions: Patients with POPH starting pulmonary vasodilator have a reduction in SVR related to vasodilator therapy. Midodrine use with pulmonary vasodilator therapy is associated with increased mortality in the POPH population. Further study of the safety of combined midodrine and pulmonary vasodilator use in POPH is needed along with exploration of more selective pulmonary vasodilators.