Significant Cardiac Disease Research Articles

Endometriosis, a prevalent disease, is associated with significant cardiac disease

Abstract Background Endometriosis, a chronic systemic gynecological disease affecting 10% of women in the reproductive age, shares pathophysiological characteristics with cardiovascular disease. However, data on the relationship between endometriosis and cardiac outcomes are scarce. Further research is needed to address this gap in knowledge as highlighted by recent calls from the European Heart Journal. Purpose To examine the incidence of the following outcomes both as a composite and individually: 1) ischemic events, 2) arrhythmias, and 3) heart failure among women with endometriosis compared with the background population. Methods Using Danish nationwide registries, all women with a diagnosis of endometriosis (1977-2021) were identified and matched with women from the background population in a 1:4 ratio based on year of birth. The incidence of 1) ischemic heart disease and ischemic stroke, 2) arrhythmias (including atrial flutter/fibrillation), and 3) heart failure were examined and compared between women with and without endometriosis. Results After exclusion of women with ischemic events/arrhythmias/heart failure prior to index, 59,194 women with endometriosis and 238,352 matched controls were included (median age 37.1 years [IQR 29.8-44.4 years]). The women were followed for a median of 17 years and a maximum of 45 years. Overall, women with endometriosis were more comorbid and used more medications than their matched controls. The 40-year cumulative incidences of the composite outcome were 36.2% (95%CI 35.4-37.1%) and 30.2% (95%CI 29.8-30.7%) among women with and without endometriosis, whereas it were 23.8% (95%CI 23.0%-24.5%) and 18.8% (95%CI 18.5%-19.1%) for ischemic events, 20.1% (95%CI 19.4%-20.9%) and 17.2% (95%CI 16.8%-17.5%) for arrhythmias, and 7.5% (95%CI 7.0-8.0%) and 6.6% (95%CI 6.3-6.8%) for heart failure, respectively (Figure 1). The most common arrhythmia was atrial fibrillation/flutter constituting more than half of the events in both groups. In both unadjusted and adjusted analyses, women with endometriosis compared with controls had a significantly higher associated risks of the composite outcome (unadjusted HR 1.30 [95%CI 1.27-1.34], adjusted HR 1.29 [95%CI 1.25-1.32]), ischemic events (unadjusted HR 1.32 [95%CI 1.28-1.37], adjusted HR 1.31 [95%CI 1.26-1.35]), arrhythmias (unadjusted HR 1.25 [95%CI 1.20-1.30], adjusted HR 1.24 [95%CI 1.19-1.29]), and heart failure (unadjusted HR 1.07 [95%CI 1.01-1.14]), adjusted analysis (HR 1.05 [95%CI 0.98-1.12]). Conclusions Women with endometriosis have a higher associated long-term risk of significant cardiac outcomes compared with the background population. Despite the small relative differences, the high prevalence of endometriosis underscores the importance of these findings and emphasizes the need for enhanced understanding and prevention of its long-term cardiac outcomes.

Peripartum heart failure in Finland: A population-based record linkage study.

Heart failure in late pregnancy and the postpartum period (HFPP) is a rare but potentially life-threatening condition, with peripartum cardiomyopathy (PPCM) being the most common subtype. This study aims to comprehensively investigate the prevalence of HFPP in the Finnish population and identify the underlying risk factors associated with its occurrence. We conducted a retrospective analysis using data from the Finnish Medical Birth Register and the Finnish Care Register for Health Care, covering 1996 to 2021. The dataset comprised 1387457 deliveries. HFPP cases were identified based on specific ICD-10 codes. To ensure the accuracy of our findings, we excluded cases with pre-existing cardiomyopathies and other significant cardiac diseases diagnosed before pregnancy. We employed logistic regression models to evaluate the associations between maternal factors and the incidence of HFPP. We identified 159 cases of HFPP, resulting in an incidence rate of 11.5 per 100000 deliveries. This incidence is comparable with rates reported in other Scandinavian countries and lower than those observed in Germany. Consistent with findings from European cohorts, our study confirmed that pregnancy-associated hypertensive disorders, particularly preeclampsia, as well as complications such as preterm delivery, twin pregnancy and elective caesarean section, are substantial risk factors for HFPP. These results support previous research linking angiogenic imbalance to the pathogenesis of PPCM. Significant risk factors for HFPP included maternal pre-pregnancy body mass index ≥35 [adjusted odds ratio (aOR) 2.04, 95% confidence interval (CI) 1.28-3.25, P=0.003], history of maternal hypertensive disorder (aOR 2.44, 95% CI 1.22-4.88, P=0.012), gestational hypertension without significant proteinuria (aOR 2.14, 95% CI 1.27-3.61, P=0.004), preeclampsia (aOR 2.43, 95% CI 1.39-4.23, P=0.002), type 1 or type 2 diabetes (aOR 3.27, 95% CI 1.66-6.45, P<0.001) and twin pregnancy (aOR 2.74, 95% CI 1.37-5.49, P=0.005). Additionally, extensive prepartum [odds ratio (OR) 2.86, 95% CI 1.18-6.98, P=0.018] and postpartum blood loss (OR 2.50, 95% CI 1.44-5.02, P=0.001) and maternal mental disorders (OR 7.39, 95% CI 4.10-13.31, P<0.001) were significantly more common among HFPP patients. The incidence of HFPP among women in Finland from 1996 to 2021 was low. HFPP exhibited a strong association with several risk factors, including preeclampsia, obesity, preterm delivery, twin pregnancy, elective caesarean section, multifoetal births, type 1 and type 2 diabetes, significant prepartum and postpartum blood loss and maternal mental health disorders. These findings underscore the importance of targeted interventions and careful monitoring in high-risk groups to mitigate the impact of HFPP on maternal health.

Diagnostic value of a point-of-care cardiac troponin-I assay (i-STAT®) for clinical application in canine and feline cardiology

Introduction/ObjectivesThis study was performed to evaluate the diagnostic value and net benefits, including cost-effectiveness, of a point-of-care analyser (i-STAT®) for measurement of cardiac troponin I (cTnI) in dogs and cats. Animals, Materials and Methods120 dogs and 120 cats presented with signs of cardiac disease and suspected myocardial insult on cardiac assessment. This was a validation study expressed as agreement between the i-STAT® analyser and two common commercial reference methods (IMMULITE® 2000 and ACCESS® hsTnI). ResultsThe comparison between methods showed a negative bias between the i–STAT® and the two commercial cTnI assays. The bias was more evident when the i-STAT® values were compared to the traditional cTnI assay (IMMULITE® 2000), with a calculated difference of −1.14 ng/mL (dogs) and −0.96 ng/mL (cats). However, the bias was distinctly lower when the i-STAT® measurements were compared to the high-sensitivity cTnI assay (ACCESS®), namely −0.3 ng/mL in dogs and −0.17 in cats. DiscussionThe i-STAT® method can reliably detect normal, low and elevated cTnI values, which is fundamental to differentiate pets with and without myocardial damage and, with the rapid availability of results, this confirms the clinical utility of the i-STAT® method. ConclusionscTnI concentrations measured with the i-STAT® have good comparability with those obtained with both commercial assays for low and elevated cTnI values. However, results should be cautiously interpreted for high troponin values, especially if a strict cut-off value is adopted for diagnostic or prognostic purposes in critical clinical conditions, such as myocarditis or acute myocardial ischaemia.

Electrocardiogram Abnormalities in Children With Lyme Arthritis.

Classically, Lyme disease follows a staged illness pattern with carditis occurring in early disseminated disease and arthritis in late-stage disease. A more comprehensive understanding of Lyme suggests that clinical stages may intersect. Little is known regarding the overlap of electrocardiogram (ECG) abnormalities in children with Lyme arthritis. This study aimed to estimate the prevalence of ECG changes in pediatric patients presenting with Lyme arthritis. In this retrospective, cross-sectional study was conducted at a tertiary care children's hospital in a Lyme endemic area; patients were identified based on Lyme testing performed from January 2012 to August 2022. Children diagnosed with Lyme arthritis by 2-tiered serology with ECGs obtained within 2 days of antibiotic initiation were included. A study cardiologist reviewed all ECGs for evidence of carditis defined as atrioventricular block, ST-T wave changes, QTc interval prolongation, accelerated junctional rhythm or right bundle branch block. Two hundred thirty-three patients were diagnosed with Lyme arthritis; 90 (38.6%) had ECGs completed. Five patients (5.6%) had ECG abnormalities: 3 were diagnosed with first-degree atrioventricular block, 1 with QTc prolongation, and 1 with ST-T wave changes. No clinical or laboratory features in patients with Lyme arthritis were associated with an increased likelihood of having an abnormal ECG. All patients with ECG abnormalities were treated with oral antibiotics, and none had clinically significant cardiac disease. ECG abnormalities in children with Lyme arthritis rarely occur and, when present, are not reflective of clinically significant cardiac disease. These results do not support routine screening ECGs on asymptomatic pediatric patients with Lyme arthritis.

Low-Dose Sequential Combined Spinal–Epidural: An Anesthetic Technique for Lower Body Surgery in Patients with Significant Cardiac Disease

Low-Dose Sequential Combined Spinal–Epidural: An Anesthetic Technique for Lower Body Surgery in Patients with Significant Cardiac Disease

Peak study: A phase 3, randomized, open-label multi-center clinical study of bezuclastinib (CGT9486) and sunitinib combination versus sunitinib in patients with gastrointestinal stromal tumors (GIST).

TPS11588 Background: Imatinib is the worldwide standard for first-line therapy of advanced KIT-mutant GIST. However, secondary resistance mutations in the KIT ATP-binding domain (exons 13, 14), activation loop (exons 17, 18), or both develop and result in loss of imatinib-sensitivity. Bezuclastinib has a highly selective inhibition profile, leading to minimal off-target toxicities and allowing for combination with sunitinib. While no single tyrosine kinase inhibitor (TKI) inhibits all KIT mutations, the combination of bezuclastinib + sunitinib targets commonly occurring primary (exons 9, 11) and secondary (exons 13, 14, 17, and 18) KIT mutations and may provide more durable responses. The early signs of clinical activity, tolerability, and safety observed with the combination thus far in Peak Part 1 (Somaiah et al. [presentation] CTOS 2023. Paper 62) are consistent with the completed Phase 1/2 study (PLX121-01). Methods: Peak (NCT05208047) is a global, randomized, open-label, multi-part Phase 3 study evaluating the efficacy and safety of bezuclastinib + sunitinib versus sunitinib as second-line treatment in adult pts who were intolerant to imatinib or whose tumors had imatinib-resistance. Current Peak study sites are located in North America (3 countries), South America (3 countries), Europe (12 countries), and Asia-Pacific (4 countries). The lead-in portion to test a new formulation of bezuclastinib, (Part 1) completed enrollment in April 2023. Based upon PK and safety, a dose of bezuclastinib 600 mg QD + sunitinib 37.5 mg QD was determined for Part 2 of the Peak study. Part 2 will enroll ~388 pts to be randomized (1:1) to bezuclastinib 600 mg QD + sunitinib 37.5 mg QD or sunitinib 37.5 mg QD alone. Key inclusion: &gt;1 measurable lesion per modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1, Eastern Cooperative Oncology Group Performance Status 0-2, adequate organ function, and prior imatinib therapy (no other prior therapy). Key exclusion: known PDGFR mutations or succinate dehydrogenase deficiency, clinically significant cardiac disease, and use of strong CYP3A4 inhibitors or inducers. The primary endpoint is progression-free survival (PFS) confirmed by blinded independent central review per mRECIST v1.1. Additional efficacy (including overall survival and objective response rate) and safety endpoints will be evaluated and circulating tumor DNA (ctDNA) will be collected and assessed. Clinical trial information: NCT05208047 .

Assessment of subclinical left ventricular systolic and diastolic dysfunction in patients with type 2 diabetes mellitus under follow-up at Tikur Anbessa specialized hospital, Ethiopia: a case-control study

BackgroundIndividuals with diabetes mellitus are at increased risk of cardiovascular diseases, which in turn are the most common cause of morbidity and mortality in the diabetic population. A peculiar feature of cardiovascular diseases in this population is that they can have significant cardiac disease while remaining asymptomatic. There is a paucity of data regarding subclinical cardiac imaging features among diabetic adults in Africa, particularly in Ethiopia. This study was conducted to compare the magnitude and spectrum of left ventricular systolic and diastolic dysfunction among asymptomatic type 2 diabetic adults versus a normotensive, non-diabetic control group and to evaluate the determinants of left ventricular diastolic and systolic dysfunction.MethodsThis was a case-control study conducted at Tikur Anbessa specialized hospital, Addis Ababa, Ethiopia. A standard transthoracic echocardiography was done for all study participants with type 2 diabetes mellitus and their normotensive and non-diabetic controls. Structured questionnaires were used to collect demographic and clinical characteristics and laboratory test results. Statistical analysis was done using the SPSS 25.0 software. The data was summarized using descriptive statistics. Bivariate and multivariate analysis was performed to determine the association between variables and echocardiographic parameters. The strength of statistical association was measured by adjusted odds ratios and 95% confidence intervals, with significant differences taken at p < 0.05.ResultsWe analyzed age- and sex-matched 100 participants in the study (diabetic) group and 200 individuals in the control group. Left ventricular systolic and diastolic dysfunction were significantly more prevalent among diabetic adults than their sex and age matched controls. Among diabetic individuals, ages of 60 years and above, dyslipidemia, use of Metformin and Glibenclamide, high serum triglyceride level, presence of neuropathy and use of statins correlated significantly with the presence of left ventricular diastolic dysfunction. Chronic kidney disease and neuropathy were determinants of left ventricular systolic dysfunction.ConclusionLeft ventricular systolic and diastolic dysfunction were significantly more prevalent among diabetic patients than their sex- and age-matched controls in our study. We recommend early screening for subclinical left ventricular dysfunction, especially in the elderly and in those with chronic kidney disease, dyslipidemia, and microvascular complications such as neuropathy.

Peak study: A phase 3, randomized, open-label multicenter clinical study of bezuclastinib (CGT9486) and sunitinib in combination versus sunitinib in patients with gastrointestinal stromal tumors (GIST).

TPS766 Background: Imatinib is the worldwide standard for first-line therapy of advanced KIT-mutant GIST. However, secondary resistance mutations in the KIT ATP-binding domain (exons 13, 14), activation loop (exons 17, 18), or both develop and result in loss of imatinib-sensitivity. While no single tyrosine kinase inhibitor (TKI) inhibits all KIT mutations, the combination of bezuclastinib + sunitinib targets commonly occurring primary (exons 9, 11) and secondary (exons 13, 14, 17, and 18) KIT mutations. In a Phase 1/2 clinical study, pts with relapsed and/or refractory GIST and a median of 3 prior lines of therapy treated with bezuclastinib + sunitinib (n=15) experienced clinical benefit and an acceptable safety profile, warranting further evaluation in a randomized trial. Methods: Peak (NCT05208047) is a global, randomized, open-label, multi-part Phase 3 study evaluating the efficacy and safety of bezuclastinib + sunitinib versus sunitinib as second-line treatment in adult pts who were intolerant to imatinib or whose tumors had imatinib-resistance. The lead-in portion, to test a new formulation of bezuclastinib, (Part 1) has completed enrollment. Based upon PK and safety, a dose of bezuclastinib 600 mg QD + sunitinib 37.5 mg QD has been determined for Part 2 of the Peak study. Part 2 will enroll ~388 pts to be randomized (1:1) to bezuclastinib 600 mg QD + sunitinib 37.5 mg QD or sunitinib 37.5 mg QD alone. Key inclusion: &gt;1 measurable lesion per modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1, Eastern Cooperative Oncology Group Performance Status 0-2, adequate organ function, and prior imatinib therapy (no other prior therapy). Key exclusion: PDGFR mutations or succinate dehydrogenase deficiency, clinically significant cardiac disease, and use of strong CYP3A4 inhibitors or inducers. The primary endpoint is progression-free survival (PFS) confirmed by blinded independent central review per mRECIST v1.1. Additional efficacy (including overall survival and objective response rate) and safety endpoints will be evaluated. Clinical trial information: NCT05208047 .

Modern methods of magnetic resonance imaging in cardiology

The article is devoted to a review of the most promising MRI techniques in cardiac imaging, as part of personalized medicine.A brief historical and terminological outline is provided, as well as a description of the current state of the problem. The results of promising methods of MR studies are considered. Issues of clinical importance and recommendations for use of the data are discussed.Various approaches to the diagnosis and treatment of the most significant cardiac diseases are summarized.In conclusion, the views and innovativeness of best practices in modern healthcare are summarized.

Prognostic value of left ventricular structure and strain in chronic kidney disease patients by cardiovascular magnetic resonance imaging: a retrospective study.

Individuals suffering from chronic kidney disease (CKD) frequently face a heightened likelihood of experiencing cardiovascular complications, including heart failure and cardiac mortality. Cardiovascular magnetic resonance feature tracking (CMR-FT) is utilized to assess the micro-contraction function of the myocardium. The objective of this research is to explore the relationship between the left ventricular anatomy, myocardial strain, and the clinical outcomes in patients with CKD. A total of 77 patients with late-stage CKD were enrolled in this retrospective study. They underwent cardiac magnetic resonance imaging and were followed up, with no history of significant cardiac diseases. The patients were divided into two groups: those with a left ventricular global longitudinal strain (LVGLS) ≥ -15.2% (n=49) and those with LVGLS < -15.2% (n=28). The clinical endpoints were defined as hospitalization for heart failure or all-cause mortality. Over an average observation period of 22 ±9 months, 11 (14%) patients passed away and 30 (39%) were admitted to the hospital for heart failure, with eight encountering both incidents. Those with LVGLS ≥ -15.2% had markedly lower rates of event-free survival concerning heart failure admissions and overall mortality than their counterparts (log-rank P=0.014). Cox multivariable analysis indicated that reduced LVGLS consistently predicted a higher likelihood of combined outcomes of heart failure admissions and total mortality (HR: 3.40, 95% CI [1.35-8.56], P=0.009), even when factoring in age, diabetes, left atrial diameter, and left ventricular mass index (LVMI). However, the LVMI showed no significant correlation with the risk of heart failure admissions or overall mortality. Compared to patients with LVGLS < -15.2%, CKD patients with LVGLS ≥ -15.2% have an increased risk of heart failure hospitalization and all-cause mortality. The prognostic role of LVMI in assessing CKD patients among the Asian population requires further investigation.

Daratumumab, Pomalidomide and Dexamethasone (DPd) in Relapsed/ Refractory Light Chain Amyloidosis Previously Exposed to Daratumumab

Daratumumab, Pomalidomide and Dexamethasone (DPd) in Relapsed/ Refractory Light Chain Amyloidosis Previously Exposed to Daratumumab

A Phase 1/2, open label dose-escalation and expansion trial of NKT2152, an orally administered HIF2α inhibitor, to investigate safety, PK, PD and clinical activity in patients with advanced ccRCC

Abstract Background: Inactivation of the VHL gene leading to aberrant HIF2α activity is nearly universal in clear cell renal cell carcinoma (ccRCC). NKT2152 is a novel, potent, selective orally available HIF2α inhibitor optimized for enhanced PK exposure and sustained target inhibition which has demonstrated robust activity in both ccRCC cell line-derived and patient-derived xenograft RCC and other solid tumor models. This is a Phase 1/2 open label, multicenter, first in human study of NKT2152 in adults with advanced clear cell renal cell carcinoma (ccRCC) (NCT05119335). In Phase 1, up to ~60 patients will be enrolled according to a 3 + 3 design with backfill as permitted by the Safety Review Committee. The primary objective of phase 1 is to determine the recommended dose for expansion (RDE) based on the totality of clinical data. Phase 2 will enroll ~50 additional patients with the primary objective of determining investigator-assessed by RECIST v1.1. Key secondary objectives include safety, tolerability, PD effects, progression free survival, duration of response, and disease control rate. Exploratory objectives include evaluation of biomarkers predictive of tumor response. Adults who have advanced ccRCC without available standard therapy), ECOG PS 0-2, with measurable disease per RECIST 1.1 are eligible. Patients who have had prior HIF2a inhibitors, require supplemental oxygen, and with significant cardiac disease are excluded. Tumor assessments by CT or MRI are conducted every 8 weeks until 48 weeks, then every 12 weeks thereafter. Adverse events will be monitored and graded in severity using CTCAE v5.0. The Phase 1 study is currently actively accruing in the United States with Phase 2 dose expansion anticipated to start in Q3, 2023.

Use of furosemide in preterm neonates with acute kidney injury is associated with increased mortality: results from the TINKER registry.

Diuretics are commonly used in neonatal AKI with the rationale to decrease positive fluid balance in critically sick neonates. The patterns of furosemide use vary among hospitals, which necessitates the need for a well-designed study. The TINKER (The Indian Iconic Neonatal Kidney Educational Registry) study provides a database, spanning 14 centres across India since August 2018. Admitted neonates (≤ 28days) receiving intravenous fluids for at least 48h were included. Neonatal KDIGO criteria were used for the AKI diagnosis. Detailed clinical and laboratory parameters were collected, including the indications of furosemide use, detailed dosing, and the duration of furosemide use (in days). A total of 600 neonates with AKI were included. Furosemide was used in 8.8% of the neonates (53/600). Common indications of furosemide use were significant cardiac disease, fluid overload, oliguria, BPD, RDS, hypertension, and hyperkalemia. The odds of mortality was higher in neonates < 37 weeks gestational agewith AKIwho received furosemide compared to those who did not receive furosemide 3.78 [(1.60-8.94); p = 0.003; univariate analysis] and [3.30 (1.11-9.82); p = 0.03]; multivariate logistic regression]. In preterm neonates with AKI, mortality was independently associated with furosemide treatment. The furosemide usage rates were higher in neonates with associated co-morbidities, i.e. significant cardiac diseases or surgical interventions. Sicker babies needed more resuscitation at birth, and died early, and hence needed shorter furosemide courses. Thus, survival probability was higher in neonates treated with long furosemide courses vs. short courses.

Significance of electrocardiogram abnormalities in children presenting to the emergency department with acute COVID-19 infection

ObjectivesAcute COVID-19 infection may be associated with electrocardiogram (EKG) abnormalities in pediatric patients. We have anecdotally observed EKG abnormalities in patients without MIS-C or significant cardiac disease requiring intervention or further follow-up. Our aim was to determine the incidence of abnormal EKG findings and correlate with evidence of significant cardiac pathology in pediatric patients who present to the emergency department during an acute COVID-19 infection. MethodsWe conducted a retrospective chart review of 209 pediatric patients diagnosed in the emergency department with acute COVID-19 infection and had an EKG during the same encounter; patients with MIS-C were excluded. Primary objectives included determination of the incidence of EKG abnormalities in patients presenting to the emergency department (ED) with acute COVID-19 infection who did not require hospitalization. Secondary objectives included correlation of these findings with other concomitant testing of possible cardiac pathology (echocardiograms, biomarkers), and clinical outcomes. ResultsEKG abnormalities were identified in 84 (40%) patients. Echo was performed in 28 (13.4%) patients; only 1 was abnormal, and considered an incidental finding. The most common EKG abnormality involved nonspecific ST-T wave patterns, suggestive of but not diagnostic for underlying pericardial or myocardial disease. Serum troponin and BNP values were normal in all patients tested, either with a normal or abnormal EKG. A normal EKG had a 100% sensitivity and negative predictive value in predicting a normal echocardiogram. No patients were hospitalized and there was normalization of EKG abnormalities during short-term follow up. ConclusionsDespite a high incidence of abnormal EKG repolarization patterns in pediatric patients presenting with acute (non-MIS-C) COVID-19 infections, these patients generally do not have abnormal cardiac biomarkers or echocardiograms, and the risk for adverse cardiac events is low.

History, ECG, Risk Factors (HER) Scoring for Cardiac Risk Stratification in Patients

Background Chest pain is a common chief complaint of patients presenting to the emergency department. Acute coronary syndrome (ACS) is found to be the etiology of this symptom in a minority of these patient encounters. This study aimed to determine the utility of using the History, ECG, Risk Factors (HER) components of theHistory, ECG, Age, Risk Factors, Troponin (HEART) score in ruling out 30-day Major Adverse Cardiac Event (MACE), ACS, ventricular tachycardia, and ventricular fibrillation in patients aged less than 45. Additionally, the utility of this score in ruling out a positive troponin was investigated as well. Methodology This is a retrospective chart review study that examined a consecutive cohort of 7,724 patients presenting with chest pain to the 11 emergency departments of a single healthcare system over a two-year period (January 2019 to December 2020). HER scores of 0 to 1 were categorized as negative (-) and scores of two or greater were categorized as positive (+). Sensitivity, specificity, and predictive values were calculated for the relationship between HER score positivity and primary cardiac disease and troponin results. Results Test characteristics of HER scoring for significant primary cardiac disease in patients between 18 and 45 years of age presenting with undifferentiated chest pain were sensitivity of 88.0 (CI = 80.0-94.0), specificity of 72.6 (CI = 71.8-73.8), positive predictive value of 3.1 (CI = 2.4-3.9), and negative predictive value of 99.8 (CI = 99.7-99.9). Furthermore, an HER score >1 was neither sensitive nor specific in predicting a positive troponin (sensitivity = 80, CI = 71.9-86; specificity = 71.3, CI = 70.3-72.3). However, the negative predictive value of an HER score of 0-1 was 99.5 (CI = 99.3-99.7) and the positive predictive value was 4.7 (CI = 3.9-5.7). Conclusions According to this study, when evaluating young patients who are deemed to have a subjectively non-highly suspicious history, who have minimal risk factors, and who have an ECG without significant ST deviation, troponin testing is low yield in the risk stratification of patients under the age of 45 for serious primary cardiac disease.

Randomised open-label phase II study of induction standard of care fulvestrant and CDK4/6 inhibition with addition of ipatasertib in metastatic ER+/HER2- breast cancer patients without circulating tumour (ct) DNA suppression (FAIM).

TPS1111 Background: The combination of fulvestrant and one of the three approved CDK4/6 inhibitors (i) is the standard of care for patients with ER+/HER2 metastatic breast cancer progressing on first-line endocrine therapy, or relapsing on or within a year of completing adjuvant endocrine therapy. AKT inhibition combined with fulvestrant has recently demonstrated clinically important activity in patients with advanced ER+/HER2- breast cancer progressing on first-line CDK4/6i plus an AI. Monitoring ctDNA dynamics has potential utility as an early response evaluation tool: Lack of suppression of ctDNA at day 15 in patients treated with palbociclib and fulvestrant in the PALOMA-3 trial was predictive for shorter PFS. We designed FAIM to establish whether the addition of the AKT inhibitor, ipatasertib, improves PFS in patients with poor ctDNA suppression during cycle 1 of fulvestrant and CDK4/6i. Methods: FAIM is a phase 2 multi-centre, randomised, open-label superiority trial in patients with ER+/HER2- advanced breast cancer, recruiting at centres in the UK. Patients will undergo ctDNA testing at days 1 and 15 of cycle 1 fulvestrant and CDK4/6 inhibitor. Eligible patients must be aged ≥18, have ER+ (≥1% or Allred score 3/8 or greater) and HER2- advanced breast cancer, measurable disease or assessable bone disease (RECIST 1.1), adequate organ function, fasting glucose ≤150mg/dL and HbA1c ≤7.5% and be eligible for NHS treatment with fulvestrant and CDK4/6i. Patients with diabetes requiring insulin, significant cardiac disease, a history of pneumonitis, or prior exposure to CDK4/6i are excluded. The FoundationOne Liquid CDx assay will be used for ctDNA analysis, a pan-cancer, tumour-agnostic liquid biopsy test that uses error-corrected next-generation sequencing. Patients with poor ctDNA suppression at day 15 will be eligible for the randomised (minimisation) study. Up to 483 patients starting fulvestrant andCDK4/6i will enroll for ctDNA screening to allow 174 patients to enter the randomised study. The primary endpoint of the study is to compare PFS in patients randomised to palbociclib/fulvestrant +/- ipatasertib. Secondary endpoints include safety, overall survival and overall response rate in all randomised patients and PFS in the sub-group of patients with alterations in the PIK3CA/AKT1/PTEN pathway. One hundred patients with ctDNA suppression at day 15, and up to 50 patients with no detectable ctDNA at day 1, will form additional control groups for exploratory outcome comparison to patients with poor ctDNA suppression. Enrolment began in December 2022 and is anticipated to continue for 2 years (NCT04920708). Clinical trial information: NCT04920708 .

0454 A Specific STOP-BANG Score Cutoff is Not Predictive of Severe Obstructive Sleep Apnea in Bariatric Patients

Abstract Introduction Obstructive sleep apnea (OSA) is a common sleep disorder with obesity being a significant risk factor. Undiagnosed OSA increases the risk of complications at the time of surgery and those with severe OSA at increased risk of post-operative MI, stroke, arrhythmias, and death as well as readmission and acuity of post-operative care. Because of this, our Bariatric program screens all patients pre-operatively with a STOP-BANG questionnaire. Those with severe OSA (AHI or REI &amp;gt; 29) require pre-treatment with PAP therapy until compliance is reached before the patient is eligible for surgery. This study examines those that screened at high risk for OSA with a STOP-BANG score &amp;gt; 2 to see if there was a specific cutoff that predicts those having severe OSA in order to better expedite sleep testing as recent supply chain issues have greatly impacted the timeliness of care for these patients. Methods During the months of January to June 2022, demographic, clinical and sleep data was collected on all new patients being evaluated by the Bariatric Sleep clinic for use in quality assessment. Bariatric patients with BMI &amp;lt; 50 and no significant cardiac or pulmonary disease were tested using HSAT, whereas those who met one or more of the above comorbidities underwent PSG. Results There were 143 bariatrics patients who screened as “high risk” for OSA with a STOP-BANG score &amp;gt; 2 during these 6 months and 112 (78%) of them completed sleep testing. There were 25 patients (22%) with severe OSA. The average STOP-BANG score for those with severe OSA was 4.3. Women averaged 4.0 (range 3-6), while men averaged higher at 4.8 (range 4-6) likely reflecting that male gender garners an extra point with the STOP-BANG. STOP-BANG scores increased with age: 20s x=3, 30s x=4.1, 40s x=4.4, 50s x=4.6, 60s x=6. Conclusion There was no specific cutoff for the STOP-BANG score that predicted severe OSA in our bariatric patients to help our program triage those most at surgical risk in order to place them in an expedited sleep testing and PAP therapy pathway. Overall, STOP-BANG scores were impacted by gender and age. Support (if any)

Serum Hemoglobin and Potassium Levels in Sudden Cardiac Death at Hemodialysis Center of Aziz Bhatti Hospital Gujrat

Background: Sudden cardiac arrest has become a serious pandemic and a substantial public health burden. Significant morbidity and death are linked to it. Hemodialysis is considerably a heavy burden on cardiac patients. A sudden cardiac arrest is sometimes a disastrous event that happens without warning and is regrettably a significant cardiac disease manifestation in individuals surviving on kidney dialysis. Aim: To determine Serum Hemoglobin and potassium levels in sudden cardiac death patients admitted in hemodialysis center of Aziz Bhatti Shaheed Teaching Hospital Gujrat. Study Design: Cross-Sectional Study Methodology: This research study was conducted at the hemodialysis center of Aziz Bhatti Shaheed Teaching Hospital Gujrat. The Ethics Committee approved to conduct of this descriptive cross-sectional study on 40 (20 males and 20 females) sudden cardiac patients. All information and the goal of the research project were explained to patients or their relatives before the collection of blood serum. Prescription drug lists, smoking histories, and medication or dialysis report data were randomly evaluated. Laboratory results from recent month were collected, together with dialysis run sheets and cardiac arrest data forms. Results: Results of this result study showed that the mean value of age was 50 years with a mean standard deviation of 15.1 (p= &lt;0.001). The mean BMI (kg/m2) was estimated as 26.8 with a mean standard deviation value of 2.6 (p= 0.01). Almost 21.6% of male patients were smokers and overall 36.1% were associated with cardiac arrest due to coronary artery disease. Systolic blood pressure (mmHg) was 165 (95% CI of 117-140) (p= &lt;0.001), diastolic blood pressure (mm Hg) was 89 ( 95% CI of 64-72) (p= &lt;0.001), hemoglobin level was 0.73 (95% CI of 0.70-0.76) (p= &lt;0.001), Hemoglobin A1 c was 6.4% (95% CI of 5.8-7.6) (p= &lt;0.001), Urea was 56 (95% CI of 41-79) (p= &lt;0.001), and estimated glomerulus filtration rate (mL/min per 1.73mm2 ) was 1.16 (1.10-1.22) in sudden cardiac patients with low K (serum &lt;4.0mmole/L). For the sudden cardiac patients with higher K level (serum &gt;4.0mmole/L) showed that there was a significant change in the estimated values i.e. estimated glomerular filtration rate (mL/min per 1.73 mm2) was 0.67 (95% CI of 0.54-0.58) (p=&lt;0.01). The practical implication of this research study suggests that the higher proportion of cardiac patients were reported higher concentration of K level serum. For diagnosis purposes K-level was directly associated with the cardiac disease progression. Conclusion: Hemodialysis patients with sudden cardiac arrest had reported very low concentrations of potassium levels. Dialysate prescriptions should be continuously reviewed and changed, especially after hospitalization in high-risk patients, to lower the risk of adverse cardiac events during hemodialysis. It was suggested that in the high-normal range of serum potassium seems to be safe and is linked to better outcomes. Keywords: Sudden cardiac arrest, Hemodialysis, serum potassium level, Hemoglobin

Role of Coxsackievirus B3-Induced Immune Responses in the Transition from Myocarditis to Dilated Cardiomyopathy and Heart Failure.

Dilated cardiomyopathy (DCM) is a cardiac disease marked by the stretching and thinning of the heart muscle and impaired left ventricular contractile function. While most patients do not develop significant cardiac diseases from myocarditis, disparate immune responses can affect pathological outcomes, including DCM progression. These altered immune responses, which may be caused by genetic variance, can prolong cytotoxicity, induce direct cleavage of host protein, or encourage atypical wound healing responses that result in tissue scarring and impaired mechanical and electrical heart function. However, it is unclear which alterations within host immune profiles are crucial to dictating the outcomes of myocarditis. Coxsackievirus B3 (CVB3) is a well-studied virus that has been identified as a causal agent of myocarditis in various models, along with other viruses such as adenovirus, parvovirus B19, and SARS-CoV-2. This paper takes CVB3 as a pathogenic example to review the recent advances in understanding virus-induced immune responses and differential gene expression that regulates iron, lipid, and glucose metabolic remodeling, the severity of cardiac tissue damage, and the development of DCM and heart failure.

Abstract CT172: A phase 1, open-label, dose-escalation study of PRT1419, a selective induced myeloid leukemia cell differentiation protein (MCL-1) inhibitor, in patients (pts) with advanced/metastatic solid tumors

Abstract Introduction: PRT1419, a selective inhibitor of MCL-1, has demonstrated preclinical activity in solid tumors and hematologic malignancies. We report the results of a phase 1, open-label, multicenter, dose-escalation study of PRT1419 in pts with advanced/metastatic solid tumors (NCT04837677). Methods: Adults with select advanced/metastatic solid tumors were enrolled. Key inclusion criteria were absolute neutrophil count &amp;gt;1.0, platelets &amp;gt;75, hemoglobin &amp;gt;9, and left ventricular ejection fraction ≥50%. Key exclusion criteria were active central nervous system malignancy, significant cardiac disease, and concurrent strong CYP2C8 inhibitors. The study employed a 3+3 dose escalation design. PRT1419 was administered as a once-weekly (QW) infusion. Primary outcome measures were to evaluate dose-limiting toxicities (DLT) and establish the maximum tolerated dose and recommended phase 2 dose (RP2D). Secondary outcome measures included safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity. Results: Pts with melanoma (n=8), sarcoma (n=5), esophageal (n=4), cervical (n=3), head and neck (n=3), non-small cell lung, small cell lung, and triple-negative breast cancer (all n=1) were enrolled. Median age was 59.5 (range, 32-78) years, 61.5% pts were female, and median prior lines of systemic therapy was 3 (range, 1-8). Overall, 26 pts received ≥1 dose of PRT1419 (20 mg/m2 [n=4], 40 mg/m2 [n=4], 80 mg/m2 [n=15], and 120 mg/m2 [n=3]). Most pts (84.6%) discontinued treatment (primary reason: progressive disease, 72.7%). No DLTs, adverse events (AEs) of increased troponin or heart failure, or grade 5 (fatal) AEs were observed. Any grade treatment-related AEs (TRAE) occurred in 80.8% pts; the most common were nausea (50.0%), diarrhea (46.2%), and vomiting (46.2%). Grade 3/4 TRAEs occurred in 11.5% pts; the most common was neutropenia (11.5%), which was dose related. Due to neutropenia observed at doses &amp;gt;80 mg/m2, further dose escalation was not investigated. BAX and caspase 3 activation in peripheral blood monocytes was observed at 80 mg/m2 and 120 mg/m2. Stable disease was the best response observed. Tumor shrinkage was seen in 1 pt with melanoma (10% reduction) and 1 pt with lung cancer (4% reduction) but did not meet the criteria for partial response. At Week 3, mean clearance was 12.6 L/hr and mean half-life was 2.5 hrs; no PRT1419 accumulation was seen with QW dosing. Conclusions: PRT1419 demonstrated acceptable safety and tolerability in pts with advanced/metastatic solid tumors, with primary TRAEs of neutropenia, nausea, diarrhea, and vomiting. No cardiac toxicity was observed. BAX and caspase 3 activation was observed, suggesting potentially successful MCL-1 inhibition. Investigation of PRT1419 in pts with hematologic malignancy in a separate study is ongoing (NCT05107856). Citation Format: Gerald Falchook, Manish Patel, Meredith McKean, Alexander Philipovskiy, Rachel Chiaverelli, William Sun, Michael Fossler, William Novotny, Michael Kurman, Sarah Rowe, Deborah Hunter, Mohammed Milhem. A phase 1, open-label, dose-escalation study of PRT1419, a selective induced myeloid leukemia cell differentiation protein (MCL-1) inhibitor, in patients (pts) with advanced/metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT172.