Cardiac Comorbidities Research Articles

Ischemic Stroke Risk Factor Profile at Prof. Dr. W. Z. Johannes Hospital, Kupang, East Nusa Tenggara

Highlight: Ischemic stroke is a major public health issue in Indonesia. Clinical data correlated to an ischemic stroke patient's prognosis. Several clinical factors and laboratory testing describe the tendency of ischemic stroke patients. ABSTRACT Introduction: In Indonesia, ischemic stroke is a major public health issue. Clinical data correlates with an ischemic stroke patient’s prognosis. Objective: This study aimed to provide an overview of clinical data in ischemic stroke patients from October 2020 to December 2021. Methods: This was a retrospective, descriptive study using medical records. A non-probability purposive sampling strategy with a total sampling method is used in this study. Age, gender, cardiac comorbidities, diabetes, repeated strokes, blood laboratory exams, electrolyte tests, alcohol consumption, and smoking habits were all observed variables. Results: The sample consisted of 242 ischemic stroke patients. The majority of patients (32.23%) were in the 61 to 70 age group, and men (57.4%) made up the majority of the sex group. Then, cardiac comorbidities were dominated by coronary artery disease (CAD), with 33 patients (57.4%) with 4 deaths (12.1%), while 15 patients (6.19%) were found with atrial fibrillation (AF), with 7 deaths (46.67%). Hypertension was found in 81.40% of patients, diabetes in 26.03% of patients, and recurrent stroke in 31.40% of patients. Active smokers make up 52.06% of all patients, and 18.18% are heavy alcohol drinkers. The majority of patients showed blood and electrolyte levels within the normal range, except for an increased leukocyte count and a decreased potassium level. Conclusion: The main risk factors obtained sequentially are hypertension, coronary artery diseases, active smokers, diabetes, and excessive alcohol consumption.

Eliglustat substrate reduction therapy in Gaucher disease patients with cardiac comorbidities

Eliglustat substrate reduction therapy in Gaucher disease patients with cardiac comorbidities

Myocardial Infarction in Pregnancy: What Should We Do?

Acute myocard infarct during pregnancy is a rare event with high mortality and women with cardiac comorbid such as hypercholesterolemia, hypertension, and history of myocardial infarction are one of risk that should be warning. However, the main etiology myocard infarct in pregnancy is spontaneous coronary artery dissection, especially in the third semester. Women with unusual chest pain, ST-elevation in electrocardiogram, and sudden cardiac arrest should treat as soon as possible. Patient with unstable condition revascularization is recommended. However, there are several things that should be monitor during revascularization such as consideration type of stent, how much contrast that will be use, and planning after stent implantation. Thrombolysis should be the last option because of bleeding risk. Therapy during and after pregnancy should be monitor continuously because of their side effect to mother and baby, and delivery in women with acute myocard infarct should be one of main concerns. With this review, we hope that we can raise our awareness in pregnant women with their comorbid and their future pregnancy.

Identification of Electrocardiographic Patterns Related to Mortality with COVID-19

COVID-19 is an infectious disease that has greatly affected worldwide healthcare systems, due to the high number of cases and deaths. As COVID-19 patients may develop cardiac comorbidities that can be potentially fatal, electrocardiographic monitoring can be crucial. This work aims to identify electrocardiographic and vectorcardiographic patterns that may be related to mortality in COVID-19, with the application of the Advanced Repeated Structuring and Learning Procedure (AdvRS&LP). The procedure was applied to data from the “automatic computation of cardiovascular arrhythmic risk from electrocardiographic data of COVID-19 patients” (COVIDSQUARED) project to obtain neural networks (NNs) that, through 254 electrocardiographic and vectorcardiographic features, could discriminate between COVID-19 survivors and deaths. The NNs were validated by a five-fold cross-validation procedure and assessed in terms of the area under the curve (AUC) of the receiver operating characteristic. The features’ contribution to the classification was evaluated through the Local-Interpretable Model-Agnostic Explanations (LIME) algorithm. The obtained NNs properly discriminated between COVID-19 survivors and deaths (AUC = 84.31 ± 2.58% on hold-out testing datasets); the classification was mainly affected by the electrocardiographic-interval-related features, thus suggesting that changes in the duration of cardiac electrical activity might be related to mortality in COVID-19 cases.

Association of individual comorbidities with outcomes in allogeneic hematopoietic cell transplantation from unrelated adult donors versus unrelated cord blood: A study on behalf of the Donor/Source and Transplant Complications Working Groups of the Japanese Society for Transplantation and Cellular Therapy.

We retrospectively evaluated the effect of 17 individual comorbidities, defined by the hematopoietic cell transplantation (HCT)-specific comorbidity index, on non-relapse mortality (NRM) and overall survival (OS) in 9531 patients aged between 16 and 70 years who underwent their first allogeneic HCT from 8/8 and 7/8 allele-matched unrelated donors (8/8 and 7/8 MUDs) or single-unit unrelated cord blood (UCB) between 2011 and 2020 using data from a Japanese registry database. In the multivariate analysis, infection (adjusted hazard ratio [HR], 1.62, 95% confidence interval [CI], 1.33-1.99 for 8/8 and 7/8 MUDs; adjusted HR, 1.33, 95%CI, 1.12-1.58 for UCB) and moderate/severe hepatic comorbidity (adjusted HR, 1.57, 95%CI, 1.04-2.38 for 8/8 and 7/8 MUDs; adjusted HR, 1.53, 95%CI, 1.09-2.15 for UCB) had a significant impact on NRM in both donor groups. Cardiac comorbidity (adjusted HR, 1.40, 95%CI, 1.08-1.80), mild hepatic comorbidity (adjusted HR, 1.22, 95%CI, 1.01-1.48), rheumatologic comorbidity (adjusted HR, 1.67, 95%CI, 1.11-2.51), renal comorbidity (adjusted HR, 2.44, 95%CI, 1.46-4.09), and severe pulmonary comorbidity (adjusted HR, 1.40, 95%CI, 1.11-1.77) were significantly associated with an increased risk of NRM but only in UCB recipients. Renal comorbidity had the strongest impact on poor OS in both donor groups (adjusted HR, 1.73, 95%CI, 1.10-2.72 for 8/8 and 7/8 MUDs; adjusted HR, 2.24, 95%CI, 1.54-3.24 for UCB). Therefore, unrelated donor selection should be taken into consideration along with the presence of specific comorbidities, such as cardiac, rheumatologic, renal, mild hepatic, and severe pulmonary comorbidities.

Prevalence and clinical characterization of oral clefts in patients with chromosome trisomy 18.

To verify the prevalence and perform the clinical characterization of oral clefts in a sample of patients with trisomy of chromosome 18 in Southern Brazil. This was a retrospective cross-sectional study, performed in a reference clinical genetic service in Southern Brazil. Theinitial sample consisted of 77 patients diagnosed in the neonatal period with trisomy 18 treated at the Clinical Genetics Service of a referral hospital at Federal University of Health Sciences of Porto Alegre (UFCSPA). The patients' diagnosis was confirmed by karyotype and care was provided during their stay in the intensive care unit (ICU) of the hospital that is a reference in Southern Brazil for care for malformed patients. The period covered was from 1975 to 2020. During the study period, 77 patients diagnosed with trisomy 18 were treated, most of them in the ICU. Of these, 13 individuals were excluded due to incomplete data. The final sample consisted of 64 patients with an average age of 2.4 years of life, ranging from one day to 16 years old, the majority of whom were female. Regarding face dysmorphisms identified in the sample, three (4,68%) patients had cleft lip and two (3,11%) had cleft lip and palate. This study contributed to the recognition of the characteristics and prevalence of oral clefts in individuals with trisomy 18 in a sample of patients from Southern Brazil. Inaddition, we described the clinical alterations found in patients with oral clefts, as well as other associated comorbidities, such as cardiac, neurological and pulmonary comorbidities, as well as cranial and facial dysmorphisms.

Is Red Cell Distribution Width Correlated with Mortality in Geriatric Patients Undergoing Hip Fracture Surgery: A Prospective Observational Study

Introduction: Our study aimed to determine the impact of preoperative red blood cell distribution width on length of intensive care unit and hospital stays, and short- and long-term mortality in elderly patients undergoing hip fracture surgery. Materials and Method: This prospective cohort study included 414 patients aged 65 and older who presented with hip fractures between November 2021 and November 2022. Patients’ demographic characteristics, American Society of Anesthesiologists score, Revised Cardiac Risk Index, comorbidities, and preoperative complete blood counts (hemoglobin, red blood cell distribution width, platelet count, etc.) were recorded at the preoperative visit. Length of intensive care unit and hospital stays were documented postoperatively. Patients were followed for one year after surgery in terms of mortality. Results: Patients with high red blood cell distribution width levels (≥14.25%) were older, had more comorbidities, and had higher American Society of Anesthesiologists score and Revised Cardiac Risk Index scores (p<0.001). In the high red blood cell distribution width group, length of hospital stays was longer (p<0.001). There was no significant difference between red blood cell distribution width groups in terms of intensive care unit stay duration and readmissions (p=0.304 and p=0.664, respectively). According to the multivariate logistic regression analysis, an red blood cell distribution width of ≥14.25 was found to increase the risk of 30-day mortality by 4.7 times and 1-year mortality by 2.74 times. Conclusion: Red blood cell distribution width is a useful, practical, and cost-effective indicator of short- and long-term mortality in elderly patients undergoing hip fracture surgery. Keywords: Aged; Anemia; Hip fracture; Mortality.

Cardiovascular Disease in Total Knee Arthroplasty: An Analysis of Hospital Outcomes, Complications, and Mortality.

Cardiovascular comorbidities have been identified as a significant risk factor for adverse outcomes following surgery. The purpose of this study was to investigate its prevalence and impact on postoperative outcomes, hospital metrics, and mortality in patients undergoing total knee arthroplasty (TKA). Our hypothesis was that patients with cardiovascular comorbidities would have worse outcomes, greater postoperative complication rates, and increased mortality compared to patients without cardiovascular disease. In this retrospective study, data from the National Inpatient Sample database from 2011 to 2020 were queried for patients who underwent TKA with preexisting cardiac comorbidities, including congestive heart failure (CHF), coronary artery disease (CAD), valvular dysfunction, and arrhythmia. Multivariate logistic regression analyses compared hospital metrics (length of stay, costs, and adverse discharge disposition), postoperative complications, and mortality rates while adjusting for demographic and clinical variables. All statistical analyses were performed using R studio 4.2.2 and Stata MP 17 and 18 with Python package. A total of 385,585 patients were identified. Those with preexisting CHF, CAD, valvular dysfunction, or arrhythmias were found to be older and at higher risk of adverse outcomes, including prolonged length of stay, increased hospital charges, and increased mortality (p < 0.001). Additionally, all preexisting cardiac diagnoses led to an increased risk of postoperative myocardial infarction, acute kidney injury (AKI), and need for transfusion (p < 0.001). The presence of valvular dysfunction, arrhythmia, or CHF was associated with an increased risk of thromboembolic events (p < 0.001). The presence of CAD and valvular dysfunction was associated with an increased risk of urologic infection (p < 0.001). This study demonstrated that CHF, CAD, valvular dysfunction, and arrhythmia are prevalent among TKA patients and associated with worse hospital metrics, higher risk of perioperative complications, and increased mortality. As our use of TKA rises, a lower threshold for preoperative cardiology referral in older individuals and early preoperative counseling/intervention in those with known cardiac disease may be necessary to reduce adverse outcomes.

Comparative effects of moderate-intensity interval training on sleep quality and functional capacity in atrial fibrillation patients with two types of sleep apnea

IntroductionThis study aimed to examine the effects of moderate-intensity interval training (MIIT) on the quality of sleep and functional capacity in atrial fibrillation (AF) patients with different presentations of sleep apnoea after coronary artery bypass graft (CABG) surgery.Methods18 participants with AF and sleep apnoea aged 45–65 years were assigned into two groups: AF with obstructive sleep apnoea group (group A, n1 = 9) and AF with mixed sleep apnoea group (group B, n2 = 9). Both groups received MIIT for ten weeks (3 sessions / week) and medical treatment (i.e., Continuous Positive Airway Pressure and drug therapy). Exclusion criteria were unstable cardiac comorbidities and neurological/musculoskeletal limitations to exercise intervention. Outcome measures included sleep parameters collected from the actigraphy, overall sleep quality rating domain of the Pittsburgh Sleep Quality Index (PSQI), and six-minute walk distance (6-MWD).ResultsSignificant changes were present in the means of all outcomes in group A (p &lt; 0.05) and two outcomes (i.e., cut points &amp; 6-MWD) in group B compared to baseline (p &lt; 0.05). Also, there were significant differences in the absolute mean changes from baseline (∆) between the two groups, in favour of group A, in sleep latency (p &lt; 0.001), total sleep duration (p = 0.026), sleep efficiency (p &lt; 0.001), overall sleep quality rating item of the PSQI (p = 0.001), and 6-MWD (p = 0.008).ConclusionsMIIT can be a supplementary therapeutic intervention that could contribute to greater positive changes in sleep quality and functional capacity in AF patients with obstructive sleep apnoea rather than in AF patients with mixed sleep apnoea post-CABG. MIIT could enhance the functional capacity independent of improving sleep quality in patients with AF and mixed sleep apnoea post-CABG.

Use of Barbed Sutures for Congenital Diaphragmatic Hernia Repair.

Congenital diaphragmatic hernia (CDH) repair can be challenging, particularly when a larger defect is present. Barbed sutures prevent the suture from slipping back after approximation of the tissues. Although introduced almost 2 decades ago, barbed sutures have not been widely used for CDH repair. We report our initial experience and pitfalls. All patients presenting with CDH from 2021 onward underwent repair using barbed sutures. Demographics, operative parameters, complications, and outcomes were prospectively recorded. A total of 13 patients underwent CDH repair during the study interval (median age 6 days, range 3 days to 5.75 years). Median operative time was 89 min (range 46 to 288 min). Five thoracoscopic and eight open procedures were performed. Severe pulmonary hypertension and ECMO (extracorporeal membrane oxygenation) were considered contraindications for thoracoscopic repair. The included patients were compared to a historic controlled group performed without barbed sutures. The barbed suture facilitated easy and quick closure of the defects in most cases and obviated the need for knot tying. One patient in the thoracoscopic group had a patch placed due to high tension after the barbed sutures tore the diaphragm. At a median follow-up time of 15 months (range 2 to 34 months), one patient had died, and one patient with complete diaphragmatic agenesis was home-ventilated. There were no recurrences. Median operative time trended lower (89 min) than in the historic control group repaired without barbed sutures (119 min, p < 0.06) after eliminating outliers with large, complex patch repairs. Barbed sutures simplify congenital diaphragmatic hernia repair regardless of whether a minimal-invasive or open approach is performed. Patch repair is not a contraindication for using barbed sutures. The resulting potential time savings make them particularly useful in patients with cardiac or other severe co-morbidities in which shorter operative times are essential. In cases with high tension, though, the barbs may tear through and produce a "saw" effect on the tissue with subsequent damage.

Clinical Outcomes of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in COVID-19 Patients With Pre-existing Cardiac Comorbidities: A Literature Review.

The growing research regarding the implementation of angiotensin-converting enzyme-2 inhibitors (ACEi) and angiotensin receptor blockers (ARBs) in the treatment of COVID-19 in patients with pre-existing cardiac comorbidities has become a large topic of discussion since the onset of the pandemic. Previous research primarily associates positive outcomes to the use of these drug classes due to their mechanism of action, which involves the downregulation of angiotensin I-converting enzyme 2 (ACE2) in the renin-angiotensin-aldosterone-system (RAAS) pathway, inflammatory mediators, and cytokines. Thus, these medications can convey preventative and protective effects in patients suffering from a SARS-CoV-2 infection. While we explored the studies that supported the positive outcomes of the use of these drugs in the first half of this review, we also expanded on the limitations of these studies in the latter portion. We also further explored the contradictory studies that indicated that using these antihypertensives can paradoxically increase the severity of COVID-19 infection as well. The studies in support of the use of these medications should consider epigenetic variations, ACE2 variants and acknowledge inherent genetic variations in certain ethnic groups as some have a predisposition for a severe COVID-19 infection. Additionally, mortality rates need to be taken into consideration in these studies as they naturally differ throughout the trajectory of the COVID-19 pandemic. While some studies are in support of the use of these antihypertensives despite other studies suggesting otherwise, further research is needed to explore the long-term effects of these antihypertensives and observe whether they are truly beneficial or not in reducing the severity of COVID-19 infections.

The changing landscape of cardiac co-morbidities and in-hospital cardiac complications mediating Covid-19 mortality between 2020 and 2021

BackgroundCardiac co-morbidities and in-hospital cardiac complications significantly contribute to COVID-19 mortality. However, their influence on mortality between 2021 and 2020 may differ due to the availability of vaccines, different viral strains, and therapeutic advancements. MethodsWe performed a retrospective chart review and individual patient analysis of all COVID-19 associated in-patient deaths in 2020 (n = 346) and 2021(n = 527) in a large Minneapolis health system. Cause of death was adjudicated by at least two health care providers, including one cardiologist. ResultsPatients who died in 2021 were younger, of similar race/ethnicity, and body mass index compared to 2020. In 2021, 24 % of the cohort was full or partially vaccinated, while none were vaccinated in 2020. Patients who died in 2021 had significantly fewer cardiovascular co-morbidities and major adverse cardiovascular events prior to COVID-19 infection, resulting in significantly fewer in-hospital cardiac adverse events compared to patients who died in 2020, including myocardial infarction, stroke, and atrial fibrillation. In contrast, patients in 2021 had significantly higher rates of venous thromboembolic events. ConclusionPatients who died from COVID-19 in 2021 had significantly fewer cardiovascular co-morbidities and in-hospital cardiovascular complications compared to patients who died in 2020. Sixteen percent of patients stipulated as dying from COVID-19 actually die from other causes.

Comparison of Alloimmunization in Pregnant People with Sickle Cell Disease Receiving Chronic Versus on-Demand Transfusions: A Multinational Study

Introduction Despite exceptional maternal morbidity and mortality risk, people with sickle cell disease (SCD) lack firm indications for chronic transfusion therapy (CTT) during pregnancy. Alloimmunization may cause hemolytic transfusion reactions and can limit the safety of future blood transfusions; thus it is a rationale for restricting CTT during pregnancy. Little data quantifies this risk. The 2020 American Society of Hematology (ASH) Guidelines for SCD TransfusionSupport recommend CTT in some pregnancies, but adoption in clinical practice is unknown. This study's purpose is to use a large two-center SCD pregnancy cohort to describe alloimmunization rates in SCD pregnancies treated with CTT vs on-demand transfusion (ODT) and to determine the fraction of SCD pregnancies meeting the ASH Guideline to initiate CTT in pregnancy. Methods We reviewed SCD pregnancies delivered at Mt. Sinai Hospital, Toronto (1990-2017) and Johns Hopkins Hospital (2000-2021). We collected data on transfusions and SCD complications before and during pregnancy, delivery, and fetal outcomes. Analyses classified subjects and pregnancies as receiving CTT or ODT. We defined CTT as pregnancies treated with scheduled, prophylactic transfusions; ODT as pregnancies transfused as-needed, including no transfusions. Sinai routinely matched transfusions for Rh and K antigens while Hopkins matched Rh only. Both centers provided extended matching if an alloantibody was detected. The first analysis included singleton pregnancies to primigravida subjects. We compared new alloantibody development, SCD complications, and pregnancy outcomes in CTT vs. ODT groups and in genotype stratified groups. We used Chi-squared and Wilcoxon rank-sum tests for categorical and continuous variables; p &amp;lt; .05 was significant. The second analysis included all cohort pregnancies and identified which met criteria for CTT per ASH Transfusion Guidelines which advise CTT for (A) severe SCD complications before or during pregnancy here defined by acute chest syndrome (ACS) or pain requiring acute care in the year before or during pregnancy, any history of venous thromboembolism (VTE), stroke, or multi-organ failure or (B) features of high-risk pregnancy, defined by multiple gestation, pre-eclampsia, gestational hypertension, cardiac comorbidities, or preterm labor history. Results Among 145singleton, primigravida pregnancies, more received ODT than CTT (119 ODT vs 26 CTT). Among ODT subjects 46/119 received at least one transfusion during pregnancy. CTT subjects had more severe SCD than ODT subjects before pregnancy (Table 1). During pregnancy, SCD severity did not differ (Table 2). Before pregnancy, 18 subjects were alloimmunized and did not differ by treatment group (6/26 CTT vs 12/119 ODT, p=0.07). During pregnancy, six subjects developed an alloantibody and did not differ by treatment group (1/26 CTT vs 5/119 ODT, p=0.93). Half (3/6) had a history of alloimmunization before pregnancy (1 CTT vs 2 ODT, p=0.27) and three did not (0 CTT vs 3 ODT, p=0.27). All subjects with new antibodies during pregnancy and historic alloimmunization developed anti-K antibodies (1 CTT, 2 ODT) at both sites. Those without alloimmunization history developed anti-Jkantibodies (3 ODT) at Sinai. In the secondary analysis, we included 299 pregnancies to 203 subjects. Among them, 249 pregnancies (83%) met at least one ASH Guideline criteria for initiating CTT. This included all CTT pregnancies (61/61, 39 subjects) and 79% of ODT pregnancies (188/238, 164 subjects), 46% of which received at least one transfusion during pregnancy (86/188). Conclusions In this SCD pregnancy cohort, alloimmunization rates were low and did not differ between those treated with CTT versus ODT. As alloimmunization events were inconsistent with institutional matching practices, new antibody development may be attributable to transfusions from outside hospitals or pregnancy-associated alloimmunization. Antigen matching per ASH Transfusion Guidelines avoids C, E, K and Jk alloimmunization. Scheduled transfusions may reduce emergency transfusion which increases alloimmunization risk. Finally, all CTT and 79% of ODT pregnancies met ASH Guideline criteria for CTT in pregnancy, however the cohort predates ASH Guideline publication. Guideline adherence may lead to increased use of CTT during pregnancy. More discriminating tools are needed to inform CTT use in SCD pregnancy.

Analysis of the Risk of Infection Stratified By Absolute Neutrophil Counts during Deferiprone-Associated Severe Neutropenia or Agranulocytosis

Introduction Patients with transfusional iron overload receiving iron chelation therapy with deferiprone may experience a decrease in absolute neutrophil counts (ANC) that range from mild (ANC &amp;lt;1.5 x 10 9/L) to severe neutropenia/agranulocytosis (typically defined as ANC &amp;lt;0.5 x 10 9/L), and which put them at risk for infections. In patients taking deferiprone, the risk of infection and/or mortality associated with ANC of &amp;lt;0.2 or &amp;lt;0.1 x 10 9/L is unknown. Our objective was to analyze data from patients taking deferiprone in clinical trials and the postmarketing setting to determine the incidence and severity of infection stratified by ANC levels. s Methods The clinical trial setting involved patients with systemic iron overload who had thalassemia, sickle cell disease, or other anemias and received deferiprone across 15 clinical trials. Data associated with episodes of severe neutropenia/agranulocytosis in patients who had been treated with at least 1 dose of deferiprone were reviewed. For the postmarketing setting, all individual case safety reports since the first market approval of deferiprone on August 25, 1999 to August 31, 2021, were reviewed; cases coded to agranulocytosis were extracted; cases without any reported ANC were removed; and cases with at least 1 ANC value were analyzed. Obtaining confirmed ANC value was not always possible in the postmarketing setting. All infections occuring within ±2 weeks of agranulocytosis onset were identified, graded for severity, and classified as serious, including fatal or life-threatening. Serious events were defined as any event that resulted in death, was life-threatening, required hospitalization or prolonged existing hospitalization, caused disability or permanent damage, caused congenital anomaly, or was classified as an important medical event. Infection events associated with ANC values were categorized into 3 groups based on the nadir ANC (all x 10 9/L): Group A, ANC ≥0.2 to &amp;lt;0.5; Group B, ANC ≥0.1 to &amp;lt;0.2; or Group C: ANC &amp;lt;0.1. Results A total of 977 patients with systemic iron overload received deferiprone in sponsored clinical trials. Among those, 9 patients were in Group A, 3 in Group B, and 10 in Group C. Of the 12 patients in Groups A and B, none had serious, severe, or fatal infections ( Table 1). Three of the 10 (30.0%) patients in Group C experienced serious or severe infections that included (1) parvovirus infection accompanied by diarrhea, a maculopaular rash, and pyrexia resulting in hospitalization; (2) a severe but nonserious respiratory tract infection with esophageal candidiasis in a patient with a history of neutropenia prior to initiating deferiprone; and (3) a fatal case of Pseudomonal sepsis in a patient who had a history of multiple cardiac and pulmonary comorbidities. Deferiprone was permanently discontinued in all 3 patients. From postmarketing data, of a total of 238 adverse reactions that were coded as agranulocytosis, 176 had at least 1 ANC value. Among those, 65 reactions were in Group A, 20 in Group B, and 91 in Group C. Among the reactions in Group A, 5/65 (7.7%) had serious infections and 3 of them (4.6%) had fatal outcomes due to sepsis ( Table 2). Among the reactions in Group B, 2/20 (10.0%) had serious infections, with a fatal outcome in one of them (5.0%); the death was from sepsis and the life-threatening infection involved pneumonia with multiple pulmonary complications. Among the reactions in Group C, 12/91 (13.2%) had serious infections and 8 of them (8.8%) had fatal outcomes; the 8 deaths were associated with sepsis. The 4 serious non-fatal infections involved sepsis; pancytopenia with ANC nadir of 0 accompanied by oropharyngeal pain, fever, and diarrhea that required hospitilization; angioinvasive mucormycosis; and disseminated herpes simplex accompanied by sepsis, resulting in hospitalization. Conclusion Patients receiving deferiprone who become neutropenic are generally at a higher risk of infections or mortality with lower neutrophil levels (ie, ANC &amp;lt;0.2 or &amp;lt;0.1 x 10 9/L compared with ANC ≥0.2 to &amp;lt;0.5 x 10 9/L). Our findings are consistent with the recently published guidelines from the European Hematology Association and the European Network for Innovative Diagnosis and Treatment of Chronic Neutropenias that used agranulocytosis to describe events with ANC of ≤0.2 x 10 9/L in association with a high risk of severe and life-threatening infections.

Impact of the Mexican Healthcare Reform on Optimal Treatment Delivery, Survival, and Response Rates Among a Cohort of Patients with Diffuse Large B Cell Lymphoma in a Single National Reference Institution

Introduction: The creation of Seguro Popular (SP) in Mexico, back in 2003, was the first step towards creating a universal healthcare system. After it was implemented, there was a 4-times boost in health spend and the creation of the Protection Fund Against Catastrophic Expenses, a fund meant for covering the costs of illnesses with a high financial burden, such as most cancers. As of January 2020, the Health Institute for Wellbeing (INSABI, Spanish acronym) has taken its place with promises to provide free health coverage for everyone. This scheme has been accompanied by multiple shortages of cancer medications due to its lack of planning and budget allocation. As a consequence, a proportion of lymphoma patients haven't been able to receive full treatment regimens. Our study aims to identify differences in survival and response rates among patients with diffuse large B cell lymphoma (DLBCL) receiving R-CHOP as first line treatment under SP and INSABI, in the National Cancer Institute (INCan) in Mexico City. Methods: This is a retrospective study where two groups with histologically documented DLBCL were compared. Group A consisted of a cohort of adult patients treated at INCan from 2011 to 2018 under the SP scheme, receiving full funding for diagnostic approach and treatment with R-CHOP as first line therapy. Group B consisted of a cohort of adult patients treated at INCan from 2020 to 2021 under INSABI's gratuity policy, receiving R-CHOP as first line therapy. Variables collected included sex, age at diagnosis, comorbidities, B-symptoms, molecular subtype, stage, bulky disease, and IPI, among others. Optimal treatment was evaluated and defined as the proportion of patients who received full drugs' dosage according to the recommendation of the attending physician. Response was assessed with 18F-FDG PET-CT according to the Lugano classification, and was defined as the proportion of patients with complete remission (CR) for all patients evaluable for response. Event free survival (EFS) was defined as time to relapse or progression during treatment. Overall survival (OS) was defined as time to death in years from the date of primary diagnosis. The significance of variation in the distribution of outcomes with healthcare regime (SP, INSABI) was assessed with Pearson's Chi-square tests or Fisher's Exact test as appropriate. Survival distributions were done with Kaplan-Meier methodology. Cox regression analysis was used to evaluate factors influencing on relapse rate and survival. All statistical testing was two sided and differences between groups were regarded as significant for p values &amp;lt;0.05. Results: Group A consisted of 505 patients, 258 were female (51%), with a mean age of 55.5 ± 13.6 years. Group B consisted of 169 patients, 94 were female (55%), with a mean age of 55.9 ± 12.7 years. Other demographic and clinical prognostic factors were similar in both groups, as shown in table 1. While both groups received treatment in 100%, 14.2% patients in group A received diminished doses of chemotherapy due to attending physicians' criteria, no other causes of dose modifications were found. In group B, 11.2% of patients received diminished doses of chemotherapy due to medical reasons as indicated by attending physicians, while 33.7% of patients received diminished doses of chemotherapy due to drug shortages. Overall response rate (ORR) for group A was 82.7%, while for group B was 73% (p = 0.05). CR for group A was 75.2%, and for group B was 60.4% (p = 0.00). Progression rate for group A was 14.8%, while for group B was 13%; relapse rate for group A was 14.6%, while for group B was 12.4%, not statistically significant (p = 0.5). EFS for group A was 85.3% and for group B was 87.6%, while OS for group A was 75.8% and for group B was 78.1%. Conclusion: Our study shows important differences in optimal treatment delivery for first-line R-CHOP in DLBCL during the INSABI era, compared to the SP era. Under the SP regime, the only reason for diminishing chemotherapy doses were medical reasons, usually in relation to cardiac comorbidities or patient's performance status. During the INSABI era, drug shortages account for incomplete treatment delivery in 33.7% of the cases. After Cox regression analysis, the administration of an optimal treatment was a factor that tends to influence EFS (p = 0.34). However, a longer follow-up time and further research is needed to assess the long term effects of the incomplete chemotherapy administration in group B.

A Patient-Centric Registry Dataset Generates Real-World Insights about Cause, Timing, Type, and Impact of Cardiotoxic Adverse Events in Chronic Lymphocytic Leukemia

INTRODUCTION Chronic Lymphocytic Leukemia (CLL) is a hematological malignancy characterized by a progressive accumulation of abnormal monoclonal B lymphocytes. The treatment landscape for CLL has undergone significant changes with the introduction of novel targeted agents, notably BTK inhibitors (BTKis). While BTKis have contributed to advancements in CLL management, the class effect of cardiac-related toxicity has emerged in several clinical trials, particularly associated with the first generation BTKi ibrutinib. Our study utilizes a real-world registry dataset to quantify cardiotoxic adverse events (CT AEs) across treatment classes, and explores resulting changes in the treatment journey and disease course for CT AEs associated with ibrutinib. METHODS 766 participants with CLL from the Leukemia and Lymphoma Society (LLS) registry had data extracted from collected medical records via the Invitae CiitizenⓇ platform, a patient-centric platform that leverages the HIPAA right-of-access to organize clinical data into a standardized, research-ready format using machine learning and human clinician review. Lines of therapy (LOTs) were generated using a proprietary logic-based algorithm, and defined as “ibrutinib” if they contained ibrutinib, “2nd-generation” if they contained a 2nd-generation BTKi (e.g. acalabrutinib), or “CD20” if they contained a CD20-targeting monoclonal antibody (e.g. rituximab). Categories were not mutually exclusive (e.g. LOT containing ibrutinib and rituximab counted as both “ibrutinib” and “CD20”). If the medical record stated that AEs resulted from only one medication in the LOT, the AE was assigned to that medication; if it was unclear which medication in a LOT caused the AE, that LOT and AE were excluded from analysis. A proprietary logic-based algorithm was used to calculate endpoints. Statistical significance was assessed using chi-square, with Bonferroni correction applied for multiple comparisons. RESULTS Out of 766 patients in the cohort, 411 received a total of 703 LOTs, of which 228 contained ibrutinib, 91 contained 2nd-generation BTKis, 358 contained CD20s, and 71 contained neither BTKis nor CD20s (“Other”). Ibrutinib-containing LOTs had a statistically significantly higher rate of at least one CT AE (21.5%; 49/228) as compared to LOTs containing 2nd-generation BTKis (5.5%; 5/91; p=0.002), CD20s (2.8%; 10/358; p&amp;lt;0.00001), or Other (8.5%; 6/71; p=0.005). The 49 individuals with an ibrutinib-associated cardiac AE experienced a total of 57 events, which were then characterized for timing, pre-existing cardiac comorbidities, treatment setting, and treatment impact ( Table 1). Ibrutinib CT AEs were not significantly concentrated in any numerical LOT, with a 22.5% (34/151) frequency in 1L, 28.6% (16/56) in 2L, and 22.6% (7/31) in 3+L settings. Individuals with a pre-existing cardiac comorbidity were neither more likely to experience an ibrutinib-associated CT AE, nor more likely to have a treatment impact if they did have a CT AE. Atrial fibrillation was more likely to result in a dose reduction, treatment hold, or discontinuation than hypertension (60% (12/20) vs. 18.2% (4/22), p=0.008); other differences were not statistically significant. We next explored outcomes and subsequent treatments for ibrutinib-containing LOTs that did or did not have any associated CT AE ( Table 2). Outcomes for LOTs associated with a CT AE were not statistically significantly different for ToT, TtNT, CRR, or ORR (see table 2). While the overall distribution of subsequent classes of therapy was similar for those who did or did not experience a CT AE, we note that for those who had treatment discontinued as a result of the CT AE, only 2/11 switched to a 2nd gen BTKi (the remainder switched to a BCL2i-containing regimen), suggesting a potential trend towards out-of-class switching. CONCLUSION Our data support the established higher rate of CT AEs associated with ibrutinib compared to 2nd-generation BTKis or non-BTKi LOTs. However, in this dataset the presence of an ibrutinib-associated CT AE did not significantly alter either the patient's treatment journey or disease course overall. Future analyses will characterize the real-world incidence and impact of other types of AEs at the level of individual medications, LOTs, and medication classes.

Effects of beta-blocker withdrawal in patients with heart failure with preserved ejection fraction: A protocol for systematic review and meta-analysis.

The primary chronic symptom of patients with heart failure with preserved ejection fraction (HFpEF) is severe exercise intolerance. The inability to adequately increase heart rate during exercise (chronotropic incompetence) is commonly present in HFpEF patients and contributes importantly to exercise intolerance in these patients. Since HFpEF patients often have cardiac comorbidities such as hypertension, coronary artery disease, and atrial fibrillation, beta-blockers are frequently prescribed for the treatment of these comorbidities. However, there is a concern that beta-blockers may worsen chronotropic incompetence by slowing heart rate in HFpEF patients and may further exacerbate their symptoms. There are several studies on the effects of beta-blocker withdrawal in HFpEF patients. We aim to perform the systematic review and meta-analysis of studies on the effects of beta-blocker withdrawal in HFpEF patients. This meta-analysis will include randomized controlled trials and prospective cohort studies on the effect of beta-blocker withdrawal in HFpEF patients. Information of studies will be collected from PubMed, Web of Science, and Scopus. The primary outcome will be peak oxygen uptake (peak VO2). The secondary outcome will be 6-minute walk distance. Other outcomes of interest will be health-related quality of life, plasma BNP levels, and cardiac structure and function. This systematic review and meta-analysis will evaluate whether beta-blocker withdrawal is beneficial for HFpEF patients, providing evidence regarding beta-blocker withdrawal in these patients. Systematic review registration: INPLASY202370066.

Abstract 12182: Importance of Comorbidities in 24-month AF-Free Survival After Catheter Ablation

Background: Presence of cardiac and non-cardiac comorbidities is reported to affect success of catheter ablation (CA) of atrial fibrillation (AF), however their predictive value in 1 and 2 year AF free survival is not reported. Research Questions: Which cardiac and non-cardiac comorbidities are most useful in predicting AF free survival after a single CA for paroxysmal and persistent AF. Goals: Create a model to identify potential risk factors that may reduce the long term success of catheter ablation for patients with AF to allow for risk modification Methods: We included 1435 patients with symptomatic AF undergoing first time CA in 1 of 8 Hospitals of Northwell Health and follow ups for at least 24 months ablation. Baseline echocardiographic and laboratory data were extracted from our common EMR, and clinical outcomes were determined after manual review of the 6, 12 and 24 month visit. Baseline patient characteristics included age, gender, BMI, diagnoses, laboratory and echocardiographic measures used in a stepwise estimation logistic regression model using STATA /IC 16.1. Results: From our patient cohort (age 67.1±10.4, 565 female, 645 persistent), 28% of patients had AF recurrence within the 1st year, and 32.5% within 2 years. Multivariate analysis identified persistent AF as the only independent risk factor for AF recurrence within 12 months (P=.001). For 24-month recurrence the independent predictors were LVEF (p=.014), Diabetes Mellitus (p=.045), cardioversions prior to ablation (DCCV) (p=.001), and pulmonary disease (p=.001). Energy modality was not a significant predictor of AF recurrence. Hypertension (p=.008) was found to be negatively associated with AF recurrence. Our prediction model (Figure 1) for AF recurrence 24 months post-CA produced an ROC curve of 0.8048 and was 77% accurate. Conclusion: The presence of baseline comorbidities implies that such comorbidities, rather than procedural failure, are mostly related with AF recurrence after 1 year.

Abstract 17614: “Watchful Waiting” - Successful Medical Management of an Infected Watchman Device

Description of Case: A 68-year-old male with a past medical history of alcoholic cirrhosis, ischemic cardiomyopathy, atrial fibrillation, ventricular tachycardia, and sick sinus syndrome presented with exertional dyspnea and lower extremity edema consistent with acutely decompensated systolic heart failure. He had multiple implantable cardiac devices including a watchman device. He was subsequently found to have methicillin-sensitive staphylococcus aureus (MSSA) bacteremia and developed sepsis. A transesophageal echocardiogram (TEE) was done to evaluate for infective endocarditis and a 1 cm mobile echodensity attached to the anterior aspect of the watchman device was found. Given active bacteremia, the echocardiographic appearance was felt to be most likely consistent with a vegetation. Due to significant medical and cardiac comorbidities, device extraction was deemed very high risk and deferred in favor of antibiotic therapy by a multi-disciplinary team. The patient was treated with intravenous cefazolin and oral rifampin. Clinical defervescence and clearance of bacteremia were achieved. A follow-up TEE in 6 weeks showed complete resolution of the watchman device vegetation. Discussion: Cardiac implantable devices provide significant morbidity and mortality benefits to patients but incur the potential risk of infection. Watchman device infection, though rare, has been reported. The current guidelines recommend the removal of all hardware in patients with established device infection. However, percutaneous, or surgical extraction of the watchman device bears significant risk and may not be feasible in all patients. Our case demonstrates the potential role of antimicrobial therapy alone with close surveillance in treating high-risk patients with watchman device infection.

Cardiac healthcare disparities and electrocardiography (ECG) differences in schizophrenia at end of life

Schizophrenia is associated with early mortality of 15 to 20 years, and 80 % of deaths are due to cardiovascular disease with a three-times greater risk of sudden-cardiac-death. While lifestyle, medications, genetics, and healthcare disparities are contributing factors, the etiology of this complex process is not fully understood. The aim of this study is to examine cardiac-related healthcare utilization and electrocardiogram (ECG) outcomes in schizophrenia at the end of life (EOL). A cohort of individuals with schizophrenia (SG) (n = 610, ≥50 years) were identified retrospectively from a unified clinical data platform and measures of cardiovascular healthcare utilization were evaluated within a 12-month period prior to death. Similarly, a control group (n = 610) was randomly identified and matched by gender (53 % females) and age of death (72.8 ± 12.4 years). Statistical methods included Cochran-Mantel-Haenszel and mixed-effects logistic & linear regression tests with adjustments for match strata and marital status, race, age, and gender as covariates. Results indicate that SG was more likely to be unmarried, unemployed, or from minority groups (all p < 0.001), and more likely to have diabetes and/or cardiovascular disease (p < 0.001). SG was less likely to receive an ECG (p = 0.001) or cardiac catheterization procedure (p < 0.001). SG had a greater mean QTc (447.2 ms vs. 434.6 ms; p = 0.001) and were twice as likely to have “prolonged QT” on ECG report (p = 0.006). In conclusion, SG had reduced likelihood of cardiac-related healthcare interventions, and despite greater likelihood of prolonged QTc, a recognized biomarker of cardiac risk, ECG was less likely at EOL. Given greater cardiac comorbidity and risk of sudden cardiac death in schizophrenia, improved practice guidelines are needed.