Pre-existing Cardiovascular Comorbidities Research Articles

Abstract PO1-04-13: CARDIAC-STAR: Prevalence of Cardiovascular Comorbidities in Hormone Receptor Positive Human Epidermal Growth Factor Negative metaStatic breasT cAnceR

Abstract BACKGROUND: Baseline cardiovascular (CV) comorbidities can impact treatment decisions for patients (pts) with metastatic breast cancer (mBC). There is limited data on the prevalence of CV comorbidities at the time of hormone receptor positive human epidermal growth factor negative (HR+/HER2-) mBC diagnosis. The primary objective of this study is to describe the prevalence of pre-existing CV comorbidities in women and men with newly diagnosed HR+/HER2- mBC. A secondary objective is to describe the first documented cancer treatment for patients with or without CV comorbidities. METHODS: Women and men ≥18 years of age with newly diagnosed HR+/HER2- mBC from 01/2016 to 12/2021 were included in this retrospective, observational study using the Merative™ Marketscan® Commercial and Medicare Databases which is nationally representative. Evidence of mBC was defined as having two or more claims containing one or more diagnosis code for BC at least 30 days apart and at least two secondary malignancy diagnosis codes. Previously published claims-based algorithms were used to identify the HR+/HER2- molecular subtype. The index date is defined as the date of first mBC diagnosis. Patients had a 1-year pre-index period for observation of CV comorbidities and a 6-month post-index period for first documented cancer treatmen RESULTS: We identified 5,452 pts with HR+/HER2- mBC, 99% of whom were female, with a median age of 58 years (yrs) (IQR 13), and 83% having a health plan from an employer; i.e., are still employed. At mBC diagnosis, 3,335 pts (61.2%) had at least one pre-existing CV comorbidity (see Table). The most reported CV comorbidities were hypertension (50.7%), hyperlipidemia (33.7%), and diabetes (19.2%). The median age of pts with or without a CV comorbidity was 61 and 52 yrs, respectively; 16.2% with CV comorbidities were ≥75 yrs. Additional data, including first documented treatment, will be presented at the meeting. CONCLUSIONS: The prevalence of CV comorbidities in pts with HR+/HER2- mBC is often underrecognized. In this analysis, more than half of pts had at least one CV comorbidity by mBC diagnosis. CV comorbidities may impact treatment decisions in the HR+/HER2- mBC population, particularly in older pts. Table Citation Format: Susan Dent, Avirup Guha, Heather Moore, Rachael McCaleb, Irene Arias, Stella Stergiopoulos, Benjamin Li, Doris Makari, Michael Fradley. CARDIAC-STAR: Prevalence of Cardiovascular Comorbidities in Hormone Receptor Positive Human Epidermal Growth Factor Negative metaStatic breasT cAnceR [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-04-13.

Cardiovascular events among patients with prostate cancer treated with abiraterone and enzalutamide.

There is growing concern about the adverse metabolic and cardiovascular effects of abiraterone acetate (AA) and enzalutamide (ENZ), two standard hormonal therapies for prostate cancer. We analysed the risk of cardiovascular adverse events among patients treated with AA and ENZ. We used Kythera Medicare data from January 2019 to June 2023 to identify patients with at least one pharmacy claim for AA or ENZ. The index date was the first prescription claim date. Patients were required to have 1 year of data pre- and post-index date. New users excluded those with prior AA or ENZ claims and pre-existing cardiovascular comorbidities. Demographic and clinical variables, including age, socioeconomic status (SES), comorbidity score, prostate-specific comorbidities, and healthcare costs, were analysed . Propensity score matching was employed for risk adjustment. Of the 8,929 and 8,624 patients in the AA and ENZ cohorts, respectively, 7,647 were matched after adjusting for age, sociodemographic, and clinical factors. Between the matched cohorts (15.54% vs. 14.83%, p < 0.05), there were no statistically significant differences in any cardiovascular event after adjusting for these factors. The most common cardiovascular event in both cohorts was heart failure (5.20% vs. 4.49%), followed by atrial fibrillation (4.42% vs. 3.60%) and hypotension (2.93% vs. 2.48%). This study provides real-world evidence of the cardiovascular risk of AA and ENZ that may not appear in clinical trial settings. Adjusting for age, baseline comorbidities, and SES, the likelihood of a cardiovascular event did not differ between treatment groups.

Comparative Effectiveness of Ibrutinib Flexible Dosing Treatment Strategies on Time to Next Treatment in a Largely Community-Based Claims Database: A Target Trial Emulation Study

Introduction: Outside of a clinical trial setting, ibrutinib is the most well-characterized of the covalent Bruton's tyrosine kinase inhibitors used in the treatment of patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in the first-line (1L) setting. However, the impact of ibrutinib dose adjustment on clinical outcomes remains to be defined. In this real-world effectiveness study, we compared time to next treatment (TTNT) as a proxy for disease progression for dose adjustment and standard dose treatment strategies in patients with CLL/SLL receiving 1L single-agent IBR. Methods: This study utilized the Komodo Health payer-complete dataset, derived from U.S. health insurance claims from &amp;gt;150 private insurers covering &amp;gt;160 million individuals from 2015-2023; 53% of these patients are from community centers. Adult patients with CLL/SLL were included if they initiated 1L single-agent IBR 420 mg/day between March 2016 - April 2023 (IBR initiation date = index date; 1L single-agent IBR was defined as no other CLL/SLL treatment in the 12-month baseline period or within 28 days after index). A target trial emulation (TTE) approach was utilized to compare TTNT, defined as the time between the index date to the initiation of a next line of therapy (LOT), for two treatment strategies: 1) Dose adjustment strategy, defined as a lead-in IBR treatment at 420mg/day for 3-12 months, followed by dose adjustment to &amp;lt;420mg/day until next LOT or IBR discontinuation; 2) Standard dose strategy, defined as a continuous IBR treatment at 420mg/day without any dose adjustment for &amp;gt;12 months until next LOT or IBR discontinuation. The TTE approach minimizes immortal time bias in a naïve observational analysis as patients in the dose adjustment cohort cannot initiate next LOT before dose adjustment occurs [Hernan et al. Am J Epidemiol. 2016]. To explicitly emulate a target trial, two clones were created for each patient, with one clone contributing person-time and event to each treatment strategy of interest, respectively. A clone was artificially censored when the actual treatment path deviated from the assigned treatment strategy. Selection bias due to artificial censoring was corrected using time-varying inverse probability of censoring weights (IPCW), accounting for post-index time-varying clinical factors related to IBR dose adjustment or IBR discontinuation. TTNT hazard ratio (HR; robust 95% confidence interval [CI]) was estimated using an IPCW-weighted pooled logistic regression model. Alternative lead-in periods with IBR standard dosing (3-6 and 3-9 months) were also evaluated. A subgroup analysis was conducted among patients with high cardiovascular (CV) risk, defined as having a preexisting CV comorbidity or a high CHA 2DS 2-Vasc risk score. Results: 3,342 adults initiated 1L single-agent IBR at 420 mg/day. Mean (standard deviation [SD]) age was 67.5 (10.6) years, 62% were male, and mean (SD) Quan-Charlson Comorbidity Index score was 3.0 (1.5). The median (interquartile range) follow-up duration was 19.6 (7.5, 35.0) months. During the study period, 463 patients (14%) initiated a subsequent LOT. The high CV risk subgroup consisted of 2,640 (79%) patients. In the overall study population, 608 (18%) patients experienced a dose adjustment after the index date. Of those, the dose adjustment occurred ≤3 months, ≤6 months, and ≤12 months post-index in 159 (26%), 300 (49%), and 440 (72%) patients, respectively, with dose used at the first reduction of 70 mg, 140 mg, or 280 mg in 4 (1%), 85 (14%), and 519 (85%) patients, respectively. The dose adjustment strategy (420 mg/day for 3-12 months followed by a reduced dose) was not associated with increased risk of initiating next LOT (adjusted HR [95% CI] 0.95 [0.80, 1.14]) compared to the continuous standard dose strategy; results for the alternative lead-in periods and the high CV risk subgroup were consistent with the primary scenario. Conclusions: In this real-world comparative effectiveness study with the majority of patients from community centers, dose adjustment of 1L single-agent IBR treatment for CLL/SLL is not associated with an increased risk of initiating next LOT when compared to continuous standard dose treatment. These findings suggest that a flexible dosing approach with IBR may be an effective option to maintain an optimal balance of clinical therapeutic efficacy and safety for patients with CLL/SLL in the 1L setting.

Cardiovascular Morbidity in Erdheim-Chester Disease (ECD) Patients with and without Cardiac Involvement

Purpose: The understanding of cardiac-involved ECD (ECD-CV) and how this affects outcomes and pre-existing diseases remains limited. We aimed to determine the association, burden, and severity of pre-existing and de novo cardiovascular (CV) comorbidities with ECD-CV compared to patients (pts) without cardiac-involved ECD (ECD-noCV). Methods: Records of pts with ECD diagnosed from Jan-1990 to Dec-2021, consecutively seen at Mayo Clinic, AZ, FL, and MN were reviewed. Cardiac involvement was diagnosed by imaging. CV comorbidities were captured before and after ECD diagnosis. CTCAE v3.0 based grading system was used to assess CV comorbidities which graded the conditions as mild (grade 1), moderate (grade 2), severe (grade 3), and life-threatening or disabling (grade 4). Chi-square test was used to determine if having ECD-CV worsens pre-existing CV comorbidities in pts with ECD. As per the established methods, the cumulative CV disease burden was defined after considering 8 CV morbidities that are known to have direct structural and functional implications on the heart, including hypertension (HTN), coronary artery disease (CAD), myocardial infarction (MI), congestive heart failure (CHF), atrial fibrillation (afib), pericardial effusion, valvular disease, and conduction disorders. A composite CV morbidity grade was assigned based on the highest grade in one of the 8 CV comorbidities (Oeffinger, NEJM, 2006). Lastly, a multivariant analysis was conducted using the presence of BRAFV600E mutation, smoking, age ≥ 60 years (yr), conventional vs targeted therapy, and ECD-CV in pts with a composite grade of 4. Results: Among 106 ECD pts, 38% (n=40) had cardiac involvement. The median age at diagnosis of ECD was 57 yr (range: 49-67); 61% were males. The median follow-up was 5 yr (95% CI: 3.5-6.1), and 4.1 yr (95% CI: 3.2-6.5) for ECD-CV and ECD-noCV pts, respectively p=0.92. The median time of CV diagnoses for the entire cohort before and after ECD diagnosis was 4.8 yr (range: 0.06-42.5) and 3.4 yr (range: 0.05-18.7), respectively. BRAFV600E mutation was present in 65% (n=26) of ECD-CV vs 42% (n=28) of ECD-noCV, p=0.02. Eight pts with ECD-CV died; one from sudden cardiac death, while 9 ECD-noCV pts died, p=0.39. Smoking was present in 43% (n=18) of ECD-CV pts compared to 24% with ECD-noCV (n=16), p=0.05. In comparison to ECD-noCV pts, increased prevalence of pre-existing HTN [59% (n=23) vs 35% (n=23), p=0.016] and MI [10% (n=4) vs 2% (n=1), p=0.046] was seen in ECD-CV. There was no difference in hyperlipidemia, diabetes mellitus, CAD, CHF, valvular disease, afib, and conduction disorders among the two cohorts. After ECD diagnosis, de novo diagnosis of hyperlipidemia [67% (n=26) vs 38% (n=25); p=0.004] and CHF [35% (n=14) vs 7% (n=5); p=&amp;lt;0.001] was seen more frequently in ECD-CV pts compared to ECD-noCV. Following the diagnosis of ECD, the severity of pre-existing conditions did not change in pts with or without ECD-CV. ECD-CV pts had a greater cumulative CV disease burden as the total number of CV morbidities was greater in ECD-CV pts both before and after ECD diagnosis (Table 1). Additionally, pts with ECD-CV had greater severity of CV morbidity (composite grade ≥4) than ECD-noCV before (35% v 3%; p=&amp;lt;0.001) and after (42.5% vs 7.6%; p=&amp;lt;0.001) ECD diagnosis. The composite grade of 4 before ECD diagnosis was most attributable to pericardial effusion (42% in pts with ECD-CV vs 0% in pts with ECD-noCV) and CAD (50% in pts with ECD-CV vs 100% in pts with ECD-noCV); after ECD diagnosis pericardial effusion (42% in pts with ECD-CV vs 0% in pts with ECD-noCV) and CAD (41% in pts with ECD-CV vs 100% in pts with ECD-noCV). After considering BRAFV600E mutation, age ≥60, smoking, ECD-CV, and first-line therapy (conventional vs targeted therapy), ECD-CV was the only factor independently associated with a composite grade of ≥4, before (OR 25.6, 95% CI: 4.8-137) and after (OR 9.7, 95% CI: 3.0-30.8) ECD diagnosis. Nonetheless, smoking, age &amp;gt;60, and ECD-CV were independent factors associated when considered a composite grade of ≥3, before and after ECD diagnosis. Conclusion: ECD-CV did not prognosticate pts and did not worsen the pre-existing CV conditions compared to pts with ECD-noCV. However, ECD-CV pts had a higher cumulative CV disease burden and a higher grade of pre-existing and de novo CV morbidities compared to ECD-noCV. The presence of cardiac involvement in ECD was independently associated with a severe cumulative CV disease burden grade.

Mortality in Patients With Primary Aldosteronism: A Swedish Nationwide Study.

Primary aldosteronism (PA) is associated with increased mortality. The extent to which this phenomenon is affected by gender, age, comorbidities at diagnosis, and different treatment modalities is largely unknown. The objective was to determine all-cause and cause-specific mortality in a population-based cohort of patients with PA and the impact of age at diagnosis, sex, comorbidities, and treatment modalities. We used national registers to identify patients diagnosed with PA between 1997 and 2019 (n=2419) and controls (n=24 187) from the general population, matched for sex, age, and county of residence. We obtained mortality data from the Cause-of-Death Register. We used Cox regression models, adjusted for socioeconomic factors and diabetes, to estimate adjusted hazard ratios (HRs [95% CI]). Overall, 346 (14.3%) patients with PA and 2736 (11.3%) controls died during a median follow-up time of 8.1 years. PA was associated with increased risk from all-cause mortality (HR, 1.23 [95% CI, 1.10-1.38]), death from cardiovascular disease (HR, 1.57 [95% CI, 1.30-1.89]), and stroke (HR, 1.85 [95% CI, 1.16-2.93]). Patients with cardiovascular disease at diagnosis (HR, 1.53 [1.26-1.85]), age >56 years (HR, 1.28 [95% CI, 1.13-1.45]), patients treated with a low dose of a mineralocorticoid receptor antagonist (HR, 1.30 [95% CI, 1.02-1.66]), and untreated patients (HR, 2.51 [95% CI, 1.72-3.67]) had excess mortality. Mortality, mainly due to cardiovascular disease, is increased in patients with PA compared with controls from the general population, particularly in patients aged >56 years, patients with preexisting cardiovascular comorbidities, and patients receiving low dose of a mineralocorticoid receptor antagonist.

Cardiovascular Events After Hematopoietic Stem Cell Transplant: Incidence and Risk Factors

BackgroundHematopoietic stem cell transplantation (HSCT) is associated with various cardiovascular (CV) complications. ObjectivesWe sought to characterize the incidence and risk factors for short-term and long-term CV events in a contemporary cohort of adult HSCT recipients. MethodsWe conducted a multicenter observational study of adult patients who underwent autologous or allogeneic HSCT between 2008 and 2019. Data on demographics, clinical characteristics, conditioning regimen, and CV outcomes were collected through chart review. CV outcomes were a composite of CV death, myocardial infarction, heart failure, atrial fibrillation/flutter, stroke, and sustained ventricular tachycardia and were classified as short-term (≤100 days post-HSCT) or long-term (>100 days post-HSCT). ResultsIn 3,354 patients (mean age 55 years; 40.9% female; 30.1% Black) followed for a median time of 2.3 years (Q1-Q3: 1.0-5.4 years), the 100-day and 5-year cumulative incidences of CV events were 4.1% and 13.9%, respectively. Atrial fibrillation/flutter was the most common short- and long-term CV event, with a 100-day incidence of 2.6% and a 5-year incidence of 6.8% followed by heart failure (1.1% at 100 days and 5.4% at 5 years). Allogeneic recipients had a higher incidence of long-term CV events compared to autologous recipients (5-year incidence 16.4% vs 12.1%; P = 0.002). Baseline CV comorbidities were associated with a higher risk of long-term CV events. ConclusionsThe incidence of short-term CV events in HSCT recipients is relatively low. Long-term events were more common among allogeneic recipients and those with pre-existing CV comorbidities.

Anti-SARS-Cov-2 IgG Antibody Response in COVID- 19 Ischemic Heart Disease Patients

Background: Coronavirus disease-2019 (COVID-19), a contagious disease caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has reached pandemic status, overwhelmed health care systems, strangled the global economy, and led to a devastating loss of life. The presence of cardiovascular comorbidities in COVID-19 patients acts as risk factor for disease severity and is associated with higher rates of cardiac injury, cardiac attack, intensive care unit admission and high mortality. Without pre-existing cardiovascular comorbidities, COVID-19 itself can cause serious heart damage. Serum Anti-SARS-CoV-2 IgG estimation is an important tool for monitoring of COVID-19 patients. Objectives: To assess post COVID-19 Anti-SARS-CoV-2 IgG antibody response in Ischemic heart disease patients. Method: This cross-sectional analytical study was conducted in the Department of Biochemistry, Dhaka Medical College, Dhaka during the period of January 2021 to December 2021. For this study, a total number of 70 diagnosed COVID-19 patients with or without IHD, were selected according to inclusion and exclusion criteria from Cardiology Department (OPD and Indoor) and Post COVID-19 Follow-up Clinic of Dhaka Medical College Hospital, Dhaka. Among 70 subjects, 35 were post COVID-19 with IHD patients (Cases in group-A) and 35 were post COVID-19 without IHD patients (Comparison group in Group-B). By using safety measures, informed written consent was taken from each patient and venous blood sample was collected for estimation of serum Anti-SARS-CoV-2 IgG level. The results were compared statistically between two groups and the significance was defined as p&lt;0.05. Results: Mean ± SD years of age of the subjects in group-A and Group-B were 57.62 ± 11.32 years and 54.14 ± 11.29 years respectively. Majority of patients were in &gt;60 year’s age group followed by 51-60 years. The serum Anti-SARS-CoV-2 IgG level was significantly higher in group-A than Group-B (Median [IQR]: 10786.5 ......

#5507 ANTIHYPERTENSIVE PRESCRIBING PATTERNS IN CKD: FINDINGS FROM THE SALFORD KIDNEY STUDY

Abstract Background and Aims Hypertension is the second leading cause of chronic kidney disease (CKD) following diabetes and occurs in most patients with CKD. Finding an optimal treatment regime for hypertension remains challenging due to the complex bidirectional cause-and-effect relationship between hypertension and CKD, and hypertensive CKD patients may require treatment with multiple antihypertensive drugs. Database studies and practice guidelines have continued to demonstrate international variability in antihypertensive treatment practices. We analysed data from the Salford Kidney Study (SKS) database in relation to antihypertensive prescribing patterns amongst study patients. Method The SKS is an ongoing prospective study recruiting patients with CKD since the year 2002. Data including patient demographics, comorbidities, physical parameters, concurrent medications, and biochemical results are collected at baseline (study enrolment). All patients are followed up annually until they reach their endpoints [reaching end-stage kidney disease (ESKD), death, or discharge from follow-up] individually, with updates in their medical records including a list of medications. We have used Cox regression analysis and Kaplan Meier charts to investigate the associations between Renin-Angiotensin-Aldosterone System inhibitor (RAASi) use and the number of antihypertensive agents (binary groups of ≤3 or &amp;gt;3), and clinical outcomes (ESKD and all-cause mortality). Results A total of 3230 patients recruited between October 2002 and December 2019 were included in this analysis. At baseline, the median age of the cohort was 67 years with a predominance of males (62%) and those of white ethnicity (96%). 90% had a history of hypertension and 32% were diabetic. The median blood pressure was 138/75 mmHg. Previous myocardial infarction was recorded in 15%, congestive cardiac failure in 17% and cerebrovascular disease in 7.7% of the patients. The median estimated glomerular filtration rate (eGFR) was 30 ml/min/1.73 m2 and the median urine protein creatinine ratio (uPCR) was 33 mg/mmol. RAASi agents (ACEi &amp; ARB) (56%) were the most common antihypertensive medications to be prescribed, followed by diuretics (50%), calcium channel blockers (45%), and beta blockers (34%). The proportion of patients prescribed RAASi was associated with greater proteinuria (43 vs 33%, p&amp;lt;0.001). CKD patients with preexisting cardiovascular comorbidities were more likely to be prescribed beta blockers (44 vs 27%, p&amp;lt;0.001), diuretics (58 vs 39%, p&amp;lt;0.001) and mineralocorticoid antagonists (6.4 vs 1.85%, p&amp;lt;0.001). An increasing number of CKD patients were being prescribed ARBs over 24-month follow-up (34 vs 28%, p = 0.02). In a multivariable Cox-regression analysis, RAASi intake was not associated with reaching ESKD (HR 0.91; p = 0.49) but was associated with a significant survival benefit (HR 0.84; p = 0.001) (Figure 1). Use of a higher number of antihypertensive agents (i.e. &amp;gt;3) was associated with both greater mortality (HR 1.28; p = 0.02) and worse dialysis-free survival (HR 1.46; p = 0.007) (Figure 2). Conclusion Antihypertensive prescribing patterns in the SKS were consistent with current guidelines in the U.K. (e.g. NICE guidance 2022), with RAASi being predominantly prescribed as the first-line antihypertensive agent. An overall survival benefit was noted with RAASi use, although there was no signal for reducing progression towards ESRD. Outcomes were poor in patients with resistant hypertension needing multiple antihypertensive agents. Considering existing variations between the U.K. and other international guidelines regarding antihypertensive treatment in CKD, continued research is indicated to bridge the gaps between these recommendations and optimise patient outcomes.

Real-world (RW) dosing patterns and outcomes among chronic lymphocytic leukemia (CLL) patients (pts) with or without an ibrutinib (IBR) dose adjustment (DA) in first-line (1L).

7537 Background: Pts treated for CLL with IBR, a once-daily Bruton’s tyrosine kinase inhibitor with dosing flexibility options, may adjust their daily dose to help prevent recurrence or worsening of adverse events, while preserving efficacy. This RW study describes outcomes for CLL pts treated with 1L IBR who did or did not have a DA. Methods: Electronic medical records from the Acentrus database (1/1/2016-4/30/2022) were used to identify CLL pts initiated on 1L IBR (index date). The first 6 months post-index were used to identify pts who remained on a starting dose of 420mg/day or with a DA (reducing to a dose lower than 420mg/day; reasons for DA not available). Treatment adherence (measured by proportion of days covered [PDC] and medication possession ratio [MPR]) and time to next treatment (TTNT) were described for patients with and without a DA. Descriptive analyses are reported for all pts and among a subgroup of pts with high cardiovascular (CV) risk, defined as having a pre-existing CV comorbidity or a high CV risk score (CV subgroup). Results: 1,171 CLL patients were initiated on 1L IBR at the recommended dose of 420mg/day (Table). Of those, 1,038 (88.6%) remained on 420 mg for ≥6 months (mean age=70.2 years, 33.6% female, median follow-up: 30.5 months); 229 (19.6%) had a DA at any time post-index (median time to DA: 5.5 months) and 126 had the DA during the first 6 months (mean age=72.2 years, 42.9% female, median follow-up: 35.1 months). Mean PDC and MPR were descriptively higher in pts with a DA (overall: PDC=0.81, MPR=0.84; CV subgroup: PDC=0.78, MPR=0.81) relative to pts with no DA (overall: PDC=0.70, MPR=0.73; CV subgroup: PDC=0.69, MPR=0.72). Median TTNT was not reached for pts with or without a DA; 12-month Kaplan-Meier (KM) rates were similar for pts with a DA (overall: 89.1%; CV subgroup: 92.7%) and with no DA (overall: 92.5%; CV subgroup: 92.0%). Conclusions: Among CLL pts initiating 1L with standard-of-care IBR, 19.6% had a DA. Those with a DA had descriptively higher treatment adherence with no detriment to TTNT, relative to those who maintained 420mg/day starting dose, regardless of baseline CV risk. These findings are consistent with other RW studies and suggest that IBR DA can be an effective treatment strategy that does not negatively affect efficacy while being well-tolerated outside of clinical trials. [Table: see text]

PO-04-156 INSIGHTS REGARDING OUTCOMES FOR COVID-19 HOSPITALIZATIONS WITH ADULT CONGENITAL HEART DISEASE (ACHD)

As of December 2022, SARS-CoV-2 coronavirus resulted in over 6 million deaths worldwide.[1] It was realized early into the pandemic, that COVID-19 significantly impacts the Cardiovascular system. [2] Patients with pre-existing cardiovascular comorbidities were particularly at higher risk of adverse outcomes during their hospitalizations. [3] Similarly, it can be safe to assume patients with adult congenital heart disease (ACHD) should considered a high-risk population for the development of severe COVID infection with increased rates of significant cardiovascular complications. Based on this reasoning and the paucity of data available on this topic using a large database, we sought to investigate the outcomes of patients with ACHD who were admitted to the hospital with COVID-19. The National Inpatient Sample database for 2020 was queried to identify adult hospitalizations with a primary diagnosis of COVID-19 and a secondary diagnosis of ACHD using International Classification of Diseases – 10 Clinical Modification (ICD-10-CM) codes. The primary outcome studied was inpatient mortality, while secondary outcomes included inpatient complications, mean length of stay (LOS), and total hospital charge (THC). Multivariate logistic and linear regression analyses were used to adjust for possible confounders and analyze the variables. Out of 1,050,045 COVID-19 hospitalizations registered, 2,425 (0.23%) had ACHD as a secondary diagnosis. Encounters with ACHD who were hospitalized with COVID-19 had significantly higher adjusted odds of inpatient mortality (Adjusted Odds Ratio [aOR]: 1.4, [95% CI: 1.05-1.88], p=0.022), Longer LOS (Mean 2.4 days, [95% CI: 1.35-3.40], p <0.001), and higher Total Hospital Charges (Mean $53,000, [95% CI: 20811-85190], p <0.001). A Forrest plot (Figure 1) demonstrates a graphical representation of the multivariate analysis of the significant in-hospital complications when adjusted for patient demographics, comorbidities, and hospital characteristics. Among COVID-19 hospitalizations, those with a history of congenital heart diseases had significantly worse outcomes in terms of in-hospital mortality, sepsis; the need for endotracheal intubation, mechanical ventilation, and vasopressors; developing acute kidney injury and pulmonary embolism, in addition to the longer length of stay, and higher total hospital charges.

Abstract 265: Coronavirus Infection Induced Interferon Signaling Promotes Atherosclerotic Plaque Vulnerability

Atherosclerosis is a chronic inflammatory vascular disease characterized by the formation of lipid-rich plaques inside arteries. The rupture of vulnerable plaques and consequent acute complications, such as myocardial infarction and stroke, are the leading causes of morbidity and mortality worldwide. It is known that pre-existing cardiovascular comorbidities pose a risk for severe outcomes in COVID-19, though the underlying pathophysiology is not fully understood. To investigate the role of coronavirus infection in established atherosclerotic plaques, we developed an atherosclerotic model of natural murine beta coronavirus infection with mouse hepatitis virus strain-A59 (MHV-A59). We fed Ldlr-/- mice a Western diet for three months prior to MHV-A59 intranasal inoculation and assessed plaque morphology at day post infection (dpi) 7 and dpi 30. Respiratory infection in mice recapitulated many aspects of COVID-19 pathophysiology. More strikingly, virus was detected in atherosclerotic aorta and induced multiple features of vulnerable plaques, a prerequisite for plaque rupture, characterized by thinner fibrous caps, less collagen content, and larger necrotic cores. The phenotype was persistent at dpi 30 when the mice were fully recovered. To further explore the underlying mechanism, we performed single-cell RNA sequencing (scRNA-seq) on infected aortas isolated at dpi 7. Our data revealed that interferon &amp;#947; was exclusively upregulated in activated T cells and elicited various responses across multiple cell populations within infected aortas. The drastic responses that potentially contribute to plaque instability include activation of a more proinflammatory endothelial cell phenotype, downregulation of TGF- &amp;#946; mediated fibroblast to myofibroblast transition, and enhanced degradation of extracellular matrix and smooth muscle cell senescence. Moreover, macrophages in infected plaques activate inflammasomes, release IL-18, and undergo pyroptosis, thereby further contributing to the hyperinflammatory state of the atherosclerotic plaques. Taken together, our data shed light on a molecular mechanism for coronavirus infection induced plaque instability and provide a small animal model to explore future therapeutics.

Relugolix in the management of prostate cancer

ABSTRACT Introduction Relugolix is the first oral gonadotrophin-releasing hormone (GnRH) receptor antagonist. Based on the phase III HERO trial results, relugolix received Food and Drug Administration approval for adult patients with advanced prostate cancer (PCa). Areas covered We provide an overview of the preclinical and clinical development of relugolix and its role in the current treatment landscape of PCa. Expert opinion Relugolix leads to rapid inhibition of testicular production of testosterone and its rapid recovery upon discontinuation. In the HERO trial, relugolix was associated with a superior cardiovascular safety profile compared to GnRH agonists. These attributes make relugolix a promising therapy for patients with preexisting cardiovascular comorbidities, those pursuing intermittent androgen deprivation therapy, and those who desire rapid testosterone recovery during ‘off-treatment’ periods. In the HERO trial, very few patients received concomitant enzalutamide (n = 17, 2.7%) or docetaxel (n < 10, 1.3%). Safety of relugolix has not been established in combination with many androgen-receptor-axis targeted therapies (e.g. abiraterone, apalutamide), cabazitaxel, or lutetium Lu 177 vipivotide tetraxetan, which precludes its use in combination with these agents. In addition, being an oral drug, relugolix may also be associated with challenges of affordability, adherence, and compliance in this predominantly elderly population.

Cardiac Complications of COVID-19 in Low-Risk Patients.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in over 6 million deaths and significant morbidity across the globe. Alongside common respiratory symptoms, COVID-19 is associated with a variety of cardiovascular complications in the acute and post-acute phases of infection. The suggested pathophysiological mechanisms that underlie these complications include direct viral infection of the myocardium via the angiotensin-converting enzyme 2 (ACE2) protein and a cytokine release syndrome that results in indirect inflammatory damage to the heart. Patients with pre-existing cardiovascular disease and co-morbidities are generally more susceptible to the cardiac manifestations of COVID-19. However, studies have identified a variety of complications in low-risk individuals, including young adults and children. Myocarditis and paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS) are among the adverse events reported in the acute phase of infection. Furthermore, patients have reported cardiac symptoms persisting beyond the acute phase in post-COVID syndrome. This review summarises the acute and chronic cardiac consequences of COVID-19 in low-risk patients, explores the pathophysiology behind them, and discusses new predictive factors for poor outcomes.

PO-689-05 PREDICTORS OF ARRHYTHMIA OCCURRENCE IN HOSPITALIZED COVID-19 PATIENTS

Studies have shown that the Coronavirus Disease 2019 (COVID-19) is associated with cardiovascular (CV) complications. Though, risk factors for the development of CV complications, specifically arrhythmias, amongst COVID-19 patients with pre-existing CV comorbidities warrant further investigation.

Associations of pre-existing cardiovascular morbidity with severity and the fatality rate in COVID-19 patients: a systematic review and meta-analysis.

ObjectivesThe aim of this study was to evaluate the association of pre-existing cardiovascular comorbidities, including hypertension and coronary heart disease, with coronavirus disease 2019 (COVID-19) severity and mortality.MethodsPubMed, ScienceDirect, and Scopus were searched between January 1, 2020, and July 18, 2020, to identify eligible studies. Random-effect models were used to estimate the pooled event rates of pre-existing cardiovascular disease comorbidities and odds ratio (OR) with 95% confidence intervals (95% CIs) of disease severity and mortality associated with the exposures of interest.ResultsA total of 34 studies involving 19,156 patients with COVID-19 infection met the inclusion criteria. The prevalence of pre-existing cardiovascular disease in the included studies was 14.0%. Pre-existing cardiovascular disease in COVID-19 patients was associated with severe outcomes (OR, 4.1; 95% CI, 2.9 to 5.7) and mortality (OR, 6.1; 95% CI, 2.9 to 12.7). Hypertension and coronary heart disease increased the risk of severe outcomes by 3 times (OR, 3.2; 95% CI, 2.0 to 3.6) and 2.5 times (OR, 2.5; 95% CI, 1.7 to 3.8), respectively. No significant publication bias was indicated.ConclusionCOVID-19 patients with pre-existing cardiovascular comorbidities have a higher risk of severe outcomes and mortality. Awareness of pre-existing cardiovascular comorbidity is important for the early management of COVID-19.

The association between transthoracic echocardiographic parameters and severity of COVID-19 in hospitalised adults - a retrospective analysis

Funding AcknowledgementsType of funding sources: None.BackgroundThe coronavirus disease 2019 (COVID-19) is an ongoing global pandemic with more than 220 million cases and 4.5 million deaths reported worldwide. Its clinical spectrum varies widely, and non-invasive prognostic markers are valuable as they can guide efficient resource allocation. Cardiovascular complications of COVID-19 include myocardial injury, acute heart failure, and arrhythmias. Both de novo cardiovascular complications and pre-existing cardiovascular co-morbidities are associated with a poor prognosis. Transthoracic echocardiography (TTE) can be used to assess cardiovascular structure and function non-invasively.PurposeTo investigate the association between TTE parameters and severity of disease in hospitalised adults with confirmed COVID-19MethodsThis single-centre retrospective analysis was conducted at a COVID-19 referral hospital in Indonesia. All consecutive adults hospitalised with confirmed COVID-19 who underwent TTE assessment between 3 April 2020 to 6 April 2021 were included. Comprehensive data including demographics, peak COVID-19 severity, pre-existing co-morbidities, and TTE findings were extracted from electronic medical records. Patients with mild-moderate and severe-critical disease were compared using the chi-square test and odds ratios (OR), with a confidence level of 95%.ResultsA total of 488 patients were included in this study; 202 with mild-moderate disease and 286 with severe-critical disease. Frequency of old age (>60 years), obesity, diabetes, chronic kidney disease, and congestive heart failure were higher in the severe-critical group (P < 0.05). On TTE assessment, Patients with severe-critical disease had higher odds of left ventricular hypertrophy (LVH) (OR: 2.20; CI: 1.49 – 3.24), LV wall motion abnormality (OR: 3.33; CI: 1.68 – 6.60), diastolic dysfunction (OR: 1.46; CI: 1.02 – 2.11), valve abnormality (OR: 1.93; CI: 1.27 – 2.92), and right ventricular (RV) dysfunction (OR: 5.53; CI: 1.63 – 18.73). After matching for age, obesity, and diabetes, patients with severe-critical COVID-19 continued to have higher odds of LVH (OR: 1.91; CI: 1.21 – 3.02), LV wall motion abnormality (OR: 2.76; CI: 1.28 – 5.96), diastolic dysfunction (OR: 1.55; CI: 1.00 – 2.38), and RV dysfunction (OR: 3.86; CI: 1.06 – 14.08).ConclusionsThe presence of LVH, LV wall motion abnormality, diastolic dysfunction, and RV dysfunction on TTE assessment were associated with severe-critical disease in hospitalised adults with COVID-19. These findings must be validated in a larger prospective study. Figure. Odds Ratios for the Entire Cohort Figure. Odds Ratios for the Matched Cohort

Abstract 9877: Burden and Predictors of Hypertensive Crisis-Related Hospitalizations and Outcomes in Young Cannabis Users: A Nationwide Multi-Center Analysis

Introduction: With the increasing use of recreational cannabis in the youth and earlier reports suggesting its potential association with systolic hypertension, we planned to assess the burden with disparities, predictors and outcomes of hypertensive (HTN) crisis in young cannabis users vs. non-users. Methods: We queried the National Inpatient Sample (October2015-2017) to identify admissions among young (18-44 years) cannabis users with HTN crisis. Rates of HTN crisis admissions with racial/sex disparities were assessed in cannabis users vs. non-users. Multivariable analysis was performed adjusting for covariates to assess the predictors of HTN crisis in cannabis users and odds of inpatient mortality. Results: Of 623,715 admissions among young cannabis users, 4675 (0.7%) had HTN crisis. Among cannabis users, non-whites and females were more often admitted for HTN crisis cohort compared to non-users (Figure 1). Among young cannabis users, males (OR 1.12, CI 1.04-1.19), blacks (OR 3.28, CI 3.02-3.56), patients admitted non-electively (OR 3.09, CI 2.53-3.76) with comorbidities like chronic kidney disease (OR 8.83, CI 8.14-9.59), congestive heart failure (OR 3.35, CI 2.13-3.08), obesity (OR 2.83, CI 2.62-3.05), valvular diseases (OR 2.56, CI 2.13-3.08), fluid and electrolytes disorders (OR 2.25, CI 2.11-2.40), diabetes mellitus (OR 1.82, CI 1.67-1.97) and hyperlipidemia (OR 1.71, CI 1.56-1.87) predicted higher odds of HTN crisis (p&lt;0.001). Interestingly, cannabis users admitted for HTN crisis had lower odds of in-hospital mortality (OR 0.67, CI 0.45-0.99, p&lt;0.05) compared to non-users when adjusted for confounders. Conclusions: Non-white and male cannabis users had higher odds of HTN-crisis admissions. Cannabis users with preexisting cardiovascular and metabolic comorbidities had higher odds of developing HTN crisis. Lower risk of inpatient mortality following HTN-crisis in cannabis users warrants future prospective studies.

The Role of Endothelium in COVID-19.

The 2019 novel coronavirus, known as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), is causing a global pandemic. The virus primarily affects the upper and lower respiratory tracts and raises the risk of a variety of non-pulmonary consequences, the most severe and possibly fatal of which are cardiovascular problems. Data show that almost one-third of the patients with a moderate or severe form of COVID-19 had preexisting cardiovascular comorbidities such as diabetes mellitus, obesity, hypertension, heart failure, or coronary artery disease. SARS-CoV2 causes hyper inflammation, hypoxia, apoptosis, and a renin–angiotensin system imbalance in a variety of cell types, primarily endothelial cells. Profound endothelial dysfunction associated with COVID-19 can be the cause of impaired organ perfusion that may generate acute myocardial injury, renal failure, and a procoagulant state resulting in thromboembolic events. We discuss the most recent results on the involvement of endothelial dysfunction in the pathogenesis of COVID-19 in patients with cardiometabolic diseases in this review. We also provide insights on treatments that may reduce the severity of this viral infection.

Comprehensive Review of Cardiovascular Complications of Coronavirus Disease 2019 and Beneficial Treatments.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 and was first reported in December 2019 in Wuhan, China. Since then, it caused a global pandemic with 212,324,054 confirmed cases and 4,440,840 deaths worldwide as of August 22, 2021. The disease spectrum of COVID-19 ranges from asymptomatic subclinical infection to clinical manifestations predominantly affecting the respiratory system. However, it is now evident that COVID-19 is a multiorgan disease with a broad spectrum of manifestations leading to multiple organ injuries including the cardiovascular system. We review studies that have shown that the relationship between cardiovascular diseases and COVID-19 is indeed bidirectional, implicating that preexisting cardiovascular comorbidities increase the morbidity and mortality of COVID-19, and newly emerging cardiac injuries occur in the settings of acute COVID-19 in patients with no preexisting cardiovascular disease. We present the most up-to-date literature summary to explore the incidence of new-onset cardiac complications of coronavirus and their role in predicting the severity of COVID-19. We review the association of elevated troponin with the severity of COVID-19 disease, which includes mild compared to severe disease, in nonintensive care unit compared to intensive care unit patients and in those discharged from the hospital compared to those who die. The role of serum troponin levels in predicting prognosis are compared in survivors and non-survivors. The association between COVID-19 disease and myocarditis, heart failure and coagulopathy are reviewed. Finally, an update on beneficial treatments is discussed.

Adverse Cardiovascular Effects of Anti-COVID-19 Drugs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 infection is the cause of the ongoing global pandemic. Mortality from COVID-19 infection is particularly high in patients with cardiovascular diseases. In addition, COVID-19 patients with preexisting cardiovascular comorbidities have a higher risk of death. Main cardiovascular complications of COVID-19 are myocardial infarction, myocarditis, acute myocardial injury, arrhythmias, heart failure, stroke, and venous thromboembolism. Therapeutic interventions in terms of drugs for COVID-19 have many cardiac adverse effects. Here, we review the relative therapeutic efficacy and adverse effects of anti-COVID-19 drugs.