Pre-existing Cardiac Comorbidities Research Articles

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.

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.

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.

A Pilot Study of Percutaneous Cholecystoenteric Anastomosis: A New Option for High-Risk Patients with Symptomatic Gallstones

PurposeTo evaluate the safety and effectiveness of percutaneous cholecystoenteric anastomosis (PCEA) creation in patients with indwelling cholecystostomy tubes who are high-risk surgical candidates. Materials and MethodsFourteen (male, 10; female, 4) patients with a mean age of 79 years (range, 53–92 years) with previously inserted cholecystostomy tubes underwent PCEA with the adjacent duodenum using a lumen-apposing metal stent (LAMS) between January 2015 and October 2022. Intraprocedural adverse events and postprocedural safety and effectiveness outcomes were evaluated. Nine procedures were performed under sedation and 5 under general anesthesia. ResultsTechnical success was achieved in 100% of the patients. In 12 patients (86%), the existing cholecystostomy tube was removed after the insertion of the LAMS. Three patients (21%) had a pre-existing cholecystoduodenal fistula, in which the stent was placed, and 11 (79%) underwent creation of a de novo anastomosis. The mean procedure time was 1.5 hours (range, 1–2 hours). The mean length of stay after the procedure was 2.4 days (range, 1–10 days). There were no intraprocedural adverse events. One patient with severe pre-existing cardiac comorbidities died during his postprocedural stay despite a technically successful procedure. One patient had delayed closure of the long-standing cholecystocutaneous tract. ConclusionsEarly clinical experience with PCEA using an LAMS suggests that it is a safe and effective option for the creation of internal gallbladder drainage in patients who are not candidates for surgical cholecystectomy.

Pregnancy outcomes of women with cardiac disease.

To determine and predict the maternal and neonatal outcomes of pregnancies occurring in patients with cardiac disease. This retrospective review included 147 pregnancies identified from antenatal, delivery, and nursery records. Information concerning the nature and severity of the pre-existing cardiac disease, comorbidities, risk scores, obstetric or cardiac complications, and pregnancy outcomes were collected. The data were analyzed using SPSS Windows version 22. In all, 111 (73.5%) of the cohort had acquired heart disease and 4 (2.7%) of patients belonged to WHO class IV, in which pregnancy is not recommended. Additionally, 12 (8.1%) were categorized as being at significant risk of having a cardiac complication. The proportion of patients that had maternal and perinatal mortality was 6 (4.0%) and 7 (4.8%), respectively. The WHO and CARPREG scoring systems were reliably able to predict cardiac events (P < 0.01). Mothers who received preconception counseling had significantly fewer occurrences of cardiac and obstetric events than those who did not. Cardiac disease in pregnancy in women managed at our center was most often an acquired disease. The baseline risk assessment scores accurately predicted the likelihood of adverse cardiac outcomes.

Evaluation of IL-33R and Galectin-3 as New Biomarkers of Cardiac Damage after Polytrauma-Association with Cardiac Comorbidities and Risk Factors.

Polytrauma is one of the disorders with the greatest economic impact on healthcare in society and one predictor for poor outcome is cardiac damage. Interleukin 33 receptors (IL-33R) and galectin-3 are two new potential cardiac trauma biomarkers that are the subjects of this investigation. Additionally, this study assesses pre-existing cardiac damage or risk factors as predictors of cardiac damage after polytrauma. This retrospective study includes 107 polytraumatized patients with an ISS ≥16 admitted in a Level 1 Trauma Centre. Plasma samples were taken at admission. IL-33R and galectin-3 concentrations were detected in plasma samples by ELISA. Both did not correlate with the cardiac damage measured by troponin. Next to troponin, IL-33R was increased in patients with pre-existing cardiac comorbidities. In the subgroup of patients with cardiac comorbidities, the BMI and the initial blood sugar level were significantly increased compared to patients without cardiac comorbidities. Galectin-3 and IL-33R were shown to not correlate with cardiac damage. However, our data suggests that IL-33R protein should be revised in future studies as a marker of cardiac comorbidities. Further, our data indicate that patients with cardiac comorbidities represent a separate group of polytrauma patients characterized by higher concentrations of troponin, IL-33R, BMI and initial sugar level.

Abstract 12534: Incidence of Cardiotoxicity After Immune Checkpoint Inhibitor Therapy

Introduction: Immune checkpoint inhibitors (ICI) have transformed care for cancer patients but can lead to immune-mediated toxicities in multiple organ systems. Cardiovascular toxicities are thought to be infrequent, but existing data likely underestimate this. We utilized Medicare claims data to define the incidence of cardiotoxicity after ICI therapy at a population level. Methods: We identified all fee-for-service beneficiaries who received an ICI, including CTLA-4 inhibitors, PD-1 inhibitors or PD-L1 inhibitors, between March 2011 through December 2018 using 100% Medicare Parts A and B. Demographic information, preexisting cardiac conditions, other comorbidities and cancer types were determined in the year prior to ICI exposure. Cardiac toxicities were identified using ICD-9/10 codes in the year after initial exposure. Results: In total, 40,676 patients were identified. Most (75%) received a PD-1 inhibitor and a significant minority (10%) received combination therapy. Across all ICI therapies, the incidence of myocarditis and related complications (ventricular arrhythmia, sudden cardiac death, heart block and cardiogenic shock) was 2.95% at one year. The incidence of acute decompensated heart failure was 10.76%, acute coronary syndrome 3.06% and death 1.92%. The highest incidence of myocarditis and associated cardiac diagnoses was seen with combination therapy (3.56%). Conclusions: Immune checkpoint inhibitors are associated with myocarditis and other serious cardiac toxicities. Results from our population level study suggest the incidence of cardiotoxicity after ICI exposure is likely higher than previously reported. The incidence of myocarditis and related complications is highest with combination therapy, as reported in prior studies.

Oculomotor nerve palsy following coronary artery bypass graft surgery: can pituitary apoplexy complicate the post-operative course of cardiac surgery?

Oculomotor nerve palsy, due to pituitary apoplexy, has been previously reported in the literature. However, the association with coronary artery bypass graft surgery (CABG) is rarely investigated. This article reports a case of pituitary apoplexy presenting with oculomotor nerve palsy following CABG. A 65-year-old male, known to have ischemic heart disease, diabetes mellitus and hypertension, presented with ptosis, diplopia and anisocoria that developed after 1 day of CABG. Radiological imaging demonstrated a pituitary adenoma with acute/subacute hemorrhage causing mild mass effect on the cavernous sinus. Considering the acute state of bypass surgery and pre-existing cardiac co-morbidities, expectant management was considered. The visual acuity and palsy gradually improved. Pituitary apoplexy, following CABG, is a rare phenomenon in the post-operative period. High index of suspicious is required to promptly identify high-risk patients to avoid further neurological sequelae.

Abstract P758: Ischemic Stroke Induced Cardiac Dysfunction in Aged Mice

Introduction: Acute ischemic stroke patients with cardiac complications have increased in-hospital mortality. Most of these cardiac complications have been attributed to pre-existing cardiac comorbidities. Aging is a known risk factor for both stroke and myocardial injury. It is being increasingly recognized that ischemic injury to the brain in itself may lead to cardiac injury. However, the post stroke brain- heart interaction is not well defined in the aged. This study was designed to fill this gap in our knowledge. Methods: C57BL6/J young (3 months) and aged (18 months) male mice were subjected to 60 minutes of middle cerebral artery occlusion (MCAO). Mice had electrocardiogram (EKG, using rodent surgical monitor) and Echocardiogram (using vevo 3100 imaging system) pre-stroke, post stroke day 3, 7, and 14. All mice were sacrificed at day 14. EKG and ECHO results were analyzed using generalized estimated equation method with post hoc group comparison test at each time point, Bonferroni correction. Results: There was a significant decrease in cardiac output after stroke in aged but not young mice at three days post stroke, as compared to baseline (young, baseline:18.5±1.6ml/min vs day 3:16.6±5.16 ml/min, n=8; aged, baseline 25.4±6.8 6 ml/min vs. day 3, 16.8±6.8 n=6, p=0.0038). The cardiac output normalized to baseline in young but remained significantly low in aged mice even at day 14. Interestingly, the Left ventricular (LV) mass decreased significantly after stroke in aged mice at day 3, 118.4±23.2 mg as compared to baseline, 160.7±22.9 mg. This remained significantly lower than baseline at post stroke day seven, 124.6±32.9 mg and fourteen, 129.5±37.2 mg, p&lt;0.05. A similar trend was seen in left ventricular anterior and posterior wall thickness. There was no significant change in LV mass in young mice, p&gt;0.05. Conclusion: Our data indicates that cardiac output decreases after stroke in aged mice. Interestingly, there is a significant decrease in left ventricular mass and ventricular wall thickness in aged mice after MCAO, indicating cardiac atrophy. We speculate this may be secondary to cardiac ischemia caused by stroke. Ongoing work in our laboratory is aimed at examining the histological changes in cardiomyocytes after MCAO.

Does preoperative dipyridamole-thallium scanning reduce 90-day cardiac complications and 1-year mortality in patients with femoral neck fractures undergoing hemiarthroplasty?

BackgroundThis study aimed to evaluate the effect of dipyridamole-thallium scanning (DTS) on the rates of 90-day cardiac complications and 1-year mortality in patients with a femoral neck fracture treated with hemiarthroplasty.MethodsBetween 2008 and 2015, 844 consecutive patients who underwent cemented or cementless hemiarthroplasty were identified from the database of a single level-one medical center. One-hundred and thirteen patients (13%) underwent DTS prior to surgery, and 731 patients (87%) did not. Patient characteristics, comorbidities, surgical variables, and length of the delay until surgery were recorded. A propensity score-matched cohort was utilized to reduce recruitment bias in a 1:3 ratio of DTS group to control group, and multivariate logistic regression was performed to control confounding variables.ResultsThe incidence of 90-day cardiac complications was 19.5% in the DTS group and 15.6% in the control group (p = 0.343) among 452 patients after propensity score-matching. The 1-year mortality rate (10.6% vs 13.3%, p = 0.462) was similar in the two groups. In the propensity score-matched patients, utilization of DTS was not associated with a reduction in the rate of 90-day cardiac complications (matched cohort, adjusted odds ratio [aOR] = 1.32; 95% confidence interval [CI] 0.75–2.33, p = 0.332) or the 1-year mortality rate (aOR = 0.62; 95% CI 0.27–1.42, p = 0.259). Risk factors for cardiac complications included an American Society of Anesthesiologists grade ≥ 3 (OR 3.19, 95% CI 1.44–7.08, p = 0.004) and pre-existing cardiac comorbidities (OR 5.56, 95% CI 3.35–9.25, p < 0.001). Risk factors for 1-year mortality were a long time to surgery (aOR 1.15, 95% CI 1.06–1.25, p = 0.001), a greater age (aOR 1.05, 95% CI 1.00 to 1.10, p = 0.040), a low body mass index (BMI; aOR 0.89, 95% CI 0.81–0.98, p = 0.015), and the presence of renal disease (aOR 4.43, 95% CI 1.71–11.46, p = 0.002).DiscussionPreoperative DTS was not associated with reductions in the rates of 90-day cardiac complications or 1-year mortality in patients with a femoral neck fracture undergoing hemiarthroplasty. The necessity for DTS should be re-evaluated in elderly patients with femoral neck fractures, given that this increases the length of the delay until surgery.Level of evidencePrognostic level III

Pulmonary hypertension and right ventricular involvement in hospitalised patients with COVID-19

ObjectiveTo assess the prevalence, characteristics and prognostic value of pulmonary hypertension (PH) and right ventricular dysfunction (RVD) in hospitalised, non-intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19).MethodsThis single-centre,...

Frontline Treatment with Ibrutinib with Rituximab (IR) Combination Is Highly Effective in Elderly (≥65 years) Patients with Mantle Cell Lymphoma (MCL) - Results from a Phase II Trial

Frontline Treatment with Ibrutinib with Rituximab (IR) Combination Is Highly Effective in Elderly (≥65 years) Patients with Mantle Cell Lymphoma (MCL) - Results from a Phase II Trial

Confidence level of pediatric trainees in management of shock states.

AIMTo assess overall confidence level of trainees in assessing and treating shock, we sought to improve awareness of recurrent biases in clinical decision-making to help address appropriate educational interventions.METHODSPediatric trainees on a national listserv were offered the opportunity to complete an electronic survey anonymously. Four commonly occurring clinical scenarios were presented, and respondents were asked to choose whether or not they would give fluid, rank factors utilized in decision-making, and comment on confidence level in their decision.RESULTSPediatric trainees have a very low confidence level for assessment and treatment of shock. Highest confidence level is for initial assessment and treatment of shock involving American College of Critical Care Medicine/Pediatric Advanced Life Support recommendations. Children with preexisting cardiac comorbidities are at high risk of under-resuscitation.CONCLUSIONPediatric trainees nationwide have low confidence in managing various shock states, and would benefit from guidance and teaching around certain common clinical situations.

Heart failure following oncological treatment.

The aim of this review is to give the reader an up-to-date overview of the progress made in the burgeoning field of cardio-oncology, encompassing oncological treatments conferring risk, prediction strategies to identify patients at risk, imaging and biomarker monitoring for emergent or subclinical toxicity and prevention in primary and secondary settings with a focus on heart failure. The rapid recent advances in cancer management, particularly with the expansion of targeted and immunotherapies, have led to substantial improvements in outcome, but have also added to the potential causes of cardiac toxicity, which can lead to heart failure. Against this, there has been progression in the field of imaging for cardiac toxicity, identification of at-risk individuals and the clarification of the role of therapy for prevention and treatment of cardiac toxicity. The findings described in this review provide guidance to clinicians in order to direct monitoring strategy and therapy choice, both in the individual with preexisting cardiac comorbidities and in those predicted to be at the highest risk of cardiac toxicity wherever therapy elements carrying cardiac risk are considered oncologically appropriate.

THE INCIDENCE OF SWIMMING-INDUCED PULMONARY OEDEMA DURING MASS-PARTICIPATION TRIATHLON RACES: OPTIMISING ATHLETE SAFETY

BackgroundSwimming Induced Pulmonary Edema (SIPE) is life-threatening condition that can affect healthy triathletes. There have been several reported cases amongst triathletes, however the current estimation of incidence is derived from...

Cardiac Radiation Dose Distribution and Cardiotoxicity in Early-Stage Non–small Cell Lung Cancer Treated with Stereotactic Body Radiation Therapy

Cardiac dose has been associated with overall survival in locally advanced lung cancer. The impact of radiation dose to the heart in early-stage NSCLC patients treated with definitive SBRT is not known. We therefore conducted a study to determine whether greater radiation doses to cardiac substructures, tumor location near the heart, pre-existing cardiac disease and medical comorbidities would lead to an increase in cardiac toxicity. 44 patients with 46 tumors treated definitively with SBRT for early-stage NSCLC were retrospectively analyzed. Patients were selected for tumor locations within 6 cm of the heart. The whole heart and cardiac substructures including atria, ventricles, heart valves, AV node and four major coronary artery branches were contoured using commercial treatment planning software. For each structure multiple dose-volume parameters were recorded including mean and max dose (Gy). The relation between radiation doses to cardiac substructures, tumor location, and preexisting medical conditions (e.g. cardiovascular diseases, diabetes (DM) and hypercholesterolemia (HCL)) with the development of cardiac events following SBRT was assessed. The average follow-up was 3.2 years (range 2 mo-10.8 yrs). The median prescribed dose was 48 Gy in 4 fractions (range 40-60 Gy in 3-8 fractions). Overall, there was considerable variability in dose to different cardiac substructures: mean heart dose (MHD) averaged 2.62 Gy (range 0.1-10.7) and average max dose to the left anterior descending artery was 5.92 Gy (range 0.1-21.1). As expected lower lobe tumors and tumors with central tumor location had significantly higher heart doses compared to upper lobe tumors (p=0.0006) and peripheral location (p=0.022). Distance between heart and tumor was correlated with the mean heart dose (R2=0.39). No patient with a distance of > 5 cm between PTV edge and heart in this cohort had a MHD > 5 Gy. 10 patients developed cardiac complications on average at 2 years (range 3 mo-4.1 yrs). Complications included defibrillator placement, arrhythmia development and worsening heart failure. 7/19 patients with a history of cardiac disease developed cardiac events compared to 3/25 of the patients with no history of cardiac events (p=0.051). While radiation dose to the cardiac substructures was not different between patients with and without post SBRT cardiac events, patients with cardiac complications more frequently had DM (5/10 vs 5/34, p=0.019) and HCL (7/17 vs 3/27, p=0.02). Conclusion: Doses to the heart and its substructures show large variability and depend on the tumor location. Cardiac events occurred more frequently in patients with a history of heart problems, diabetes and hypercholesterolemia and do not depend on the radiation dose to the cardiac substructures. Longer follow up is needed to determine the impact of radiation dose on cardiac toxicity after SBRT.

Risk of arterial (ATE) and venous thromboembolism (VTE) in a population-based cohort of bevacizumab-treated metastatic colorectal cancer (mCRC) patients.

9624 Background: Bevacizumab potentiates the risk of ATE and VTE in cancer patients who are in a prothrombotic state. Whether there are specific factors that add to this risk and how bevacizumab-related thromboembolisms are best managed remain unclear. Our objectives were to 1) characterize the incidence of ATE and VTE in a population-based cohort of mCRC patients, 2) describe patient and treatment factors associated with thromboembolisms, and 3) examine how ATE and VTE are managed in routine practice. Methods: All patients diagnosed with mCRC from 2006 to 2008, evaluated at 1 of 5 regional cancer centers in British Columbia, and offered bevacizumab were included. Multivariate regression models were constructed to explore the associations between clinical factors and thromboembolisms. Results: A total of 541 mCRC patients were identified: 27 never started bevacizumab and 14 were lost to follow-up. Of the 500 remaining patients: median age was 61 years (IQR 53-67), 297 (59%) were men, 309 (62%) had ECOG 0/1, and 39 (8%) reported prior ATE or VTE. Median number of bevacizumab cycles was 11 (IQR 7-15). After receiving bevacizumab, 91 (18%) patients developed 12 ATE and 88 VTE, with 8 patients experiencing &gt;1 event. Baseline characteristics, such as median age (61 vs 61 years), gender distribution (61 vs 58% men), and ECOG 0/1 (66 vs 58%) were similar between patients with and without thromboembolisms, respectively (all p&gt;0.05). In regression models, individuals who experienced ATE or VTE were more likely to have a prior history (14 vs 6%, p=0.02), reported greater pre-existing cardiac comorbidities (42 vs 32%, p=0.05), and received a higher median number of bevacizumab cycles (13 vs 9, p&lt;0.01), suggesting a potential dose-related effect. Following the development of ATE or VTE, management varied: bevacizumab was discontinued in 46%, held temporarily in 14%, and continued in 40% of patients. Conclusions: In this population-based cohort, the thromboembolism risk is high, especially in patients with pre-existing risk factors and those heavily treated with bevacizumab. Management of bevacizumab-related ATE and VTE appears variable, underscoring the need for guidelines.

The ineligible patient: how to treat patients not included in clinical studies

Targeted therapies are currently the standard of care for metastatic renal cell carcinoma (mRCC). Five VEGF pathway inhibitors (sorafenib, sunitinib, bevacizumab in combination with interferon-alpha, pazopanib, and axitinib) and two mTOR inhibitors (everolimus and temsirolimus) are now FDA approved for mRCC based on results from phase III randomized clinical trials (RCTs). However, several subgroups of patients are excluded from enrollment due to strict eligibility criteria. The toxicity and efficacy of targeted therapies in these populations are unknown. PubMed was searched for citations of the pivotal phase III RCTs leading to FDA approval. These publications were cross-referenced with their associated entries on www.ClinicalTrials.gov, and both were abstracted for eligibility criteria for patient enrollment. Based on this data, PubMed was searched for both prospective and retrospective studies evaluating toxicity and efficacy of targeted therapies for mRCC in these ineligible patient subgroups. We reviewed published toxicity and efficacy data in several ineligible patient subgroups, including patients with non-clear cell renal cell carcinoma, poor performance status, poor renal function, CNS metastases, significant cardiac comorbidities, and prior systemic therapy. Targeted therapies appear to be safe in most ineligible patient populations, including patients with poor renal function. However, patients with preexisting cardiac comorbidities are at greater risk of developing cardiac toxicity on sunitinib. Targeted therapies appear to have some efficacy in maintaining stable disease in these subgroups, but are limited to rare partial responses. Prospective cohort studies are needed to accurately assess the safety and efficacy of targeted therapies in ineligible patient subgroups.

Acute myocardial infarction in the obstetric patient.

Acute myocardial infraction (AMI) in the obstetric patient is a rare event, although the incidence is rising due to advancing maternal age and pre-existing cardiac risk factors and medical co-morbidities. While atherosclerotic disease is the leading cause of AMI, coronary artery dissection is an important consideration in pregnancy and in the postpartum period. The physiological changes of pregnancy as well as pregnancy-specific risk factors can predispose the obstetric patient to AMI. Diagnosis of AMI can be challenging as symptoms may be atypical. Furthermore, diagnostic tests must be interpreted in the context of pregnancy. While the overall management of the obstetric patient with AMI is similar to that outside of pregnancy, drug therapy requires modification as some medications may be contraindicated in pregnancy and breastfeeding. There is limited information about prognosis and risk stratification but it is anticipated that future studies will address this issue.

Mohammad Ripon Mustafa

<h3>Objective</h3> To assess the prevalence, characteristics and prognostic value of pulmonary hypertension (PH) and right ventricular dysfunction (RVD) in hospitalised, non-intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19)....