Baseline Transthoracic Echocardiogram Research Articles

Examining the risk factors for trastuzumab-related cardiotoxicity in a predominantly Hispanic South Texas population: A descriptive study.

e24000 Background: Trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2), stands as first line treatment for HER2 positive breast cancer. Despite its efficacy, trastuzumab’s association with cardiotoxicity requires monitoring via serial transthoracic echocardiograms (TTEs). We aimed to evaluate the risk factors for trastuzumab related cardiotoxicity in a South Texas population that is uniquely a majority-minority Hispanic population. Methods: A retrospective chart review study was conducted of all female patients with HER2-positive breast cancer who received trastuzumab treatment from 2015-2021. A total of 180 patients were identified. Patients without baseline TTE or a baseline left ventricle ejection fraction (LVEF) less than 53% were excluded. The final sample size included 132 patients. Cardiotoxicity was defined as a decrease in LVEF of more than 10% during the 1-year study period. Results: The mean age at the time of diagnosis in the study population was 54.2 years. The average BMI of the study participants was 30.89. The incidence of cardiotoxicity in this study population was 6%. Among those who developed cardiotoxicity, 50% had hypertension, 25% had hyperlipidemia, 12.5% had type 2 diabetes mellitus, and 12.5% had previous coronary artery bypass surgery (CABG). In terms of cancer treatment, 12.5% of patients had a history of radiation, 25% had a history of anthracycline therapy, and 12.5% had their trastuzumab treatment ended prematurely. Of the cardiotoxicity population, 37.5% patients were former smokers and 25% were former alcohol users. Hispanic/Latino patients composed 58% of the study population and represented 50% of patients who experienced cardiotoxicity. Conclusions: The incidence of trastuzumab-related cardiotoxicity in this Hispanic/Latino majority-minority population was 6%, lower than the 9% observed in a predominantly white population in our previous study. However, further studies are needed to determine the factors contributing to this reduced cardiotoxicity rate in this population.

#189 Aortic stenosis is an independent risk factor for mortality in end-stage kidney disease patients on the transplant waitlist

Abstract Background and Aims Valvular heart disease (VHD) is a risk factor for adverse outcomes in end-stage kidney disease (ESKD) patients. However, the impact of individual valvular heart lesions on outcomes in patients on the kidney transplant waitlist is unclear. This study aims to analyse the relationship between different VHD and all-cause mortality, and to determine the characteristics of patients on the transplant waitlist stratified by the different types of VHD. Method This was a single-center retrospective cohort study of ESKD patients who were referred for kidney transplant waitlist placement from May 2008 to February 2021 and had undergone baseline transthoracic echocardiogram (TTE). Significant VHD was defined as VHD of at least moderate severity based on TTE findings. Patients were followed up until death or kidney transplantation. Results Of the 512 patients included, 89 (17.4%) had significant VHD. Mean follow-up duration was 6.6 ± 3.3 years. Significant VHD included 46 (9.0%) tricuspid regurgitation (TR), 44 (8.6%) mitral regurgitation (MR), 11 (2.2%) aortic regurgitation (AR), 7 (1.4%) aortic stenosis (AS) and 2 (0.4%) mitral stenosis (MS). Of the different VHD (Table 1), only AS was associated with all-cause mortality (hazard ratio (HR) 2.41, 95% CI 1.53-3.78, p < 0.0001, Fig. 1) and remained significant after adjusting for age, diabetes mellitus (DM) and other cardiovascular diseases (CVD) (adjusted HR 1.71, 95% CI 1.07-2.73, p = 0.02). Risk factors associated with AS included older age (odds ratio (OR) 1.12, 95% CI 1.03-1.23, p = 0.01), history of CVD (OR 7.31, 95% CI 1.59-33.6, p = 0.01), longer dialysis vintage (OR 1.01, 95% CI 1.00-1.02, p = 0.02), previous parathyroidectomy (OR 15.1, 95% CI 2.68-85.4, p = 0.002) and higher corrected calcium (OR 43.9, 95% CI 1.56-1240, p = 0.03). Age (adjusted OR 1.12, 95% CI 1.02-1.24, p = 0.02), history of CVD (aOR 7.70, 95% CI 1.50-39.5, p = 0.02) and previous parathyroidectomy (aOR 11.8, 95% CI 1.83-76.7, p = 0.01) remained significant in the multivariable model. No specific risk factors were identified for the other valvular lesions. Conclusion AS appears to be an independent risk factor for all-cause mortality in ESKD patients on the transplant waitlist. Differences in mortality and risk factors associated with different types of VHD may suggest differing underlying pathophysiological mechanisms.

Diastolic dysfunction and clinical outcomes after transcatheter or surgical aortic valve replacement in patients with atypical aortic valve stenosis.

Diastolic dysfunction is a predictor of poor outcomes in many cardiovascular conditions. At present, it is unclear whether diastolic dysfunction predicts adverse outcomes in patients with atypical aortic stenosis who undergo aortic valve replacement (AVR). Five hundred and twenty-three patients who underwent transcatheter AVR (TAVR) (n = 303) and surgical AVR (SAVR) (n = 220) at a single institution were included in our analysis. Baseline left and right heart invasive hemodynamics were assessed. Baseline transthoracic echocardiograms were reviewed to determine aortic stenosis subtype and parameters of diastolic dysfunction. Aortic stenosis subtype was categorized as typical (normal flow, high-gradient) aortic stenosis, classical, low-flow, low-gradient (cLFLG) aortic stenosis, and paradoxical, low-flow, low-gradient (pLFLG) aortic stenosis. Cox proportional hazard models were utilized to examine the relation between invasive hemodynamic or echocardiographic variables of diastolic dysfunction, aortic stenosis subtype, and all-cause mortality. Propensity-score analysis was performed to study the relation between aortic stenosis subtype and the composite outcome [death/cerebrovascular accident (CVA)]. The median STS risk was 5.3 and 2.5% for TAVR and SAVR patients, respectively. Relative to patients with typical aortic stenosis, patients with atypical (cLFLG and pLFLG) aortic stenosis displayed a significantly higher prevalence of diastolic dysfunction (LVEDP ≥ 20mmHg, PCWP ≥ 20mmHg, echo grade II or III diastolic dysfunction, and echo-PCWP ≥ 20mmHg) and, independently of AVR treatment modality, had a significantly increased risk of death. In propensity-score analysis, patients with atypical aortic stenosis had higher rates of death/CVA than typical aortic stenosis patients, independently of diastolic dysfunction and AVR treatment modality. We demonstrate the novel observation that compared with patients with typical aortic stenosis, patients with atypical aortic stenosis have a higher burden of diastolic dysfunction. We corroborate the worse outcomes previously reported in atypical versus typical aortic stenosis and demonstrate, for the first time, that this observation is independent of AVR treatment modality. Furthermore, the presence of diastolic dysfunction does not independently predict outcome in atypical aortic stenosis regardless of treatment type, suggesting that other factors are responsible for adverse clinical outcomes in this higher risk cohort.

Implications of Mitral Annular Calcification on Outcomes Following Mitral Transcatheter Edge-to-Edge Repair.

Limited data exist regarding the impact of mitral annular calcification (MAC) on outcomes of transcatheter edge-to-edge repair for mitral regurgitation (MR). We retrospectively analyzed 968 individuals (median age, 79 [interquartile range, 70-86] years; 60.0% males; 51.8% with functional MR) who underwent an isolated, first-time intervention. Stratified by MAC extent per baseline transthoracic echocardiogram, the cohort was assessed for residual MR, functional status, all-cause mortality, heart failure hospitalizations, and mitral reinterventions post-procedure. Patients with above-mild MAC (n=101; 10.4%) were older and more likely to be female, exhibited a greater burden of comorbidities, and presented more often with severe, primary MR. Procedural aspects and technical success rate were unaffected by MAC magnitude, as was the significant improvement from baseline in MR severity and functional status along the first postprocedural year. However, the persistence of above-moderate MR or functional classes III and IV at 1 year and the cumulative incidence of reinterventions at 2 years were overall more pronounced within the above-mild MAC group (significant MR or functional impairment, 44.7% versus 29.9%, P=0.060; reinterventions, 11.9% versus 6.2%, P=0.033; log-rank P=0.035). No link was demonstrated between MAC degree and the cumulative incidence or risk of mortality and mortality or heart failure hospitalizations. Differences in outcomes frequencies were mostly confined to the primary MR subgroup, in which patients with above-mild MAC also experienced earlier, more frequent 2-year heart failure hospitalizations (20.8% versus 9.6%; P=0.016; log-rank P=0.020). Mitral transcatheter edge-to-edge repair in patients with and without above-mild MAC is equally feasible and safe; however, its postprocedural course is less favorable among those with primary MR.

Regurgitant volume to LA volume ratio in patients with secondary MR: the COAPT trial.

The conceptual framework of proportionate vs. disproportionate mitral regurgitation (MR) translates poorly to individual patients with heart failure (HF) and secondary MR. A novel index, the ratio of MR severity to left atrial volume (LAV), may identify patients with 'disproportionate' MR and a higher risk of events. The objectives, therefore, were to investigate the prognostic impact of MR severity to LAV ratio on outcomes among HF patients with severe secondary MR randomized to transcatheter edge-to-edge repair (TEER) with the MitraClip™ device plus guideline-directed medical therapy (GDMT) vs. GDMT alone in the COAPT trial. The ratio of pre-procedural regurgitant volume (RVol) to LAV was calculated from baseline transthoracic echocardiograms. The primary endpoint was 2-year covariate-adjusted rate of HF hospitalization (HFH). Among 567 patients, the median RVol/LAV was 0.67 (interquartile range 0.48-0.91). In patients randomized to GDMT alone, lower RVol/LAV was independently associated with an increased 2-year risk of HFH (adjHR: 1.77; 95% CI: 1.20-2.63). RVol/LAV was a stronger predictor of adverse outcomes than RVol or LAV alone. Treatment with TEER plus GDMT compared with GDMT alone was associated with lower 2-year rates of HFH both in patients with low and high RVol/LAV (Pinteraction = 0.28). Baseline RVol/LAV ratio was unrelated to 2-year mortality, health status, or functional capacity in either treatment group. Low RVol/LAV ratio was an independent predictor of 2-year HFH in HF patients with severe MR treated with GDMT alone in the COAPT trial. TEER improved outcomes regardless of baseline RVol/LAV ratio. Trial Name: Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (The COAPT Trial) (COAPT) ClinicalTrial.gov Identifier NCT01626079URL https://clinicaltrials.gov/ct2/show/NCT01626079.

Abstract 13305: Energetic Basis of Recovered Ejection Fraction in Human Heart Failure

Introduction: Left ventricular ejection fraction (LVEF) improvement in HFrEF patients is classified as heart failure with improved ejection fraction (HFimpEF) and is associated with better long-term outcomes than persistent HFrEF. HFimpEF is difficult to predict and underlying mechanisms remain poorly understood. Hypothesis: Better myocardial high-energy phosphate metabolism at baseline predicts future LVEF recovery and outcomes in a general HFrEF population Methods: We measured cardiac energetics, the ratio of the two main high-energy phosphates, phosphocreatine and ATP (PCr/ATP), and the rate of ATP synthesis through the primary cardiac energy reserve reaction creatine kinase (“CK flux”), in 37 nonischemic HFrEF patients (LVEF ≤40%) with 31 P cardiac magnetic resonance spectroscopy (MRS) at 3T. Baseline transthoracic echocardiogram (TTE) was obtained prior to 31 P MRS and follow-up consecutive TTEs with the two highest LVEFs meeting HFimpEF criteria (LVEF >40% and ≥10% increase over baseline LVEF) over a median follow-up of 6.9 years were averaged and used to classify HFimpEF. Results: There were no significant differences in demographics, HF etiology, baseline TTE metrics, or medications between persistent HFrEF (n=22) and eventual HFimpEF (n=15). Cardiac CK flux was significantly higher at baseline in patients who later recovered to HFimpEF than in those who remained HFrEF (p=0.031). Better baseline cardiac CK flux was associated with increases in LVEF (p=0.025) and decreases in LV end-diastolic diameter (p=0.016) over time. By both dichotomous and continuous metrics, better preserved CK flux was associated with future HFimpEF. Fourteen subjects (38%), all persistent HFrEF, experienced cardiac death, transplant, or LVAD and had significantly lower baseline CK flux than outcome-free patients (p=0.017). Cardiac PCr/ATP was not associated with eventual HFimpEF, outcomes, or changes in TTE indices. Conclusion: Better preserved cardiac CK flux is associated with future LVEF recovery and LV reverse remodeling while lower CK flux is associated with worse cardiac outcomes in HFrEF patients. Interventions restoring CK flux, and possibly other energy-generating metabolic reactions, may elicit myocardial recovery in HFrEF patients.

Natural history of echocardiographic changes in atrial fibrillation: A case-controlled study of longitudinal remodeling

BackgroundAtrial fibrillation (AF) can be a cause and consequence of cardiac remodeling. The natural history of remodeling associated with AF is incompletely described. ObjectiveThe purpose of this study was to describe the frequency and timing of AF-associated echocardiographic changes. MethodsPatients within the Duke University Health System with ≥2 transthoracic echocardiograms (TTEs) performed between 2005 and 2018 were evaluated. Patients with AF and normal baseline TTEs were matched to patients without AF on year of TTE, age, and CHA2DS2-VASc score. Frequency and timing of changes in chamber size, ventricular function, mitral regurgitation, and all-cause mortality were compared over 5 years of follow-up. ResultsThe cohort included 3299 patients with AF at baseline and 7613 controls without AF. Normal baseline TTEs were acquired from 730 of patients with AF; 727 of these patients were matched to controls without AF. Patients with AF had higher rates of left atrial enlargement (hazard ratio [HR] 1.53; 95% confidence interval 1.27–1.85; P < .001), left ventricular (LV) systolic dysfunction (HR 1.80; 95% confidence interval 1.00–3.26; P = .045), LV diastolic dysfunction (HR 1.51; 95% confidence interval 1.08–2.10; P = .01), and moderate or greater mitral regurgitation (HR 2.09; 95% confidence interval 1.27–3.43; P = .003) than did controls. Atrial enlargement, systolic dysfunction, and mitral regurgitation surpassed the rates seen in controls within 6–12 months, whereas differences in diastolic dysfunction emerged at 24 months. There were no differences in ventricular sizes or mortality. ConclusionAF is associated with higher rates of left atrial enlargement, LV systolic and diastolic dysfunction, and mitral regurgitation that typically manifest within 6–24 months of diagnosis. The natural history of cardiac remodeling in patients with AF may inform treatment decisions and facilitate patient-tailored care.

Successful aspiration of an iatrogenic clot in transit secondary to a failed mechanical thrombectomy in pulmonary embolism.

A 68-year-old female presented with an intermediate-high-risk bilateral pulmonary embolism (PE) (Panel A) with a severely dilated right ventricle (Panel B). Ultrasound of both femoral veins was normal. Thrombolysis was not performed owing to recent history of gastrointestinal bleeding. The PE team decided to perform a percutaneous mechanical thrombectomy (MT) using the FlowTriever (FT) system (Inari Medical, Irvine, CA, USA). After the first procedure, a large thrombus was obtained from the right pulmonary artery (Panels C–E and Supplementary Video 1); however, we failed to extract any thrombus from the left pulmonary artery (LPA) with both the 24 and 16 Fr catheters, due to tortuosity and poor wire support, with non-sustained ventricular tachycardia. A transthoracic echocardiogram (TTE) and a subsequent transoesophageal echocardiography revealed the presence of a massive clot attached to the tricuspid valve, with severe tricuspid regurgitation (Panels F and G and Supplementary Video 2) that was not present in baseline TTE. Considering it was an iatrogenic event due to a ‘lollipop thrombus’, and the risk of re-embolization, a further MT procedure was performed, with TTE guidance, with the successful retrieval of the clot in transit (Panels H and I), and the remaining LPA thrombi (Panels J–L, Supplementary Video 3).

Abstract P5-08-17: Monitoring for cardiotoxicity in early breast cancer: an Australian experience

Abstract Background Breast cancer is the most commonly diagnosed cancer in Australia. Patient outcomes continue to improve with current 10 year survival of 86%. Given this, greater focus is needed to minimise potential long term toxicities of prescribed therapies. Anthracyclines and HER2 targeted therapies are commonly prescribed agents for high risk early breast cancers and are associated with acute and long term cardiotoxicity. Despite this, screening of cardiotoxicity in Australian patients receiving these therapies remains variable due to a lack of endorsed national screening guidelines. We conducted a retrospective review of screening procedures for cardiotoxicity in 2 major oncology centres in metropolitan Sydney and compared the findings to current international recommendations from ASCO/ESMO guidelines. Methods Patients were included if they received doxorubicin, epirubicin or trastuzumab with neoadjuvant or adjuvant intent during 2021. Baseline patient and tumour characteristics including cardiovascular risk factors were reviewed. Baseline ECG, transthoracic echocardiogram (TTE) or cardiac biomarkers (cardiac troponin or brain natriuretic peptide) were recorded, as well as frequency of serial monitoring and incidence of cardiotoxicity and cardiology referrals. Results 111 patients receiving initial curative therapy were included of which 45 received anthracycline therapy without trastuzumab. 66 received trastuzumab of which 34 also received anthracycline. 38 patients were aged greater than 60 and 31 had 2 or more cardiovascular risk factors. Of the patients receiving anthracycline only, 96% had a baseline TTE. All patients receiving trastuzumab only had a baseline TTE and of the 34 patients who received anthracycline and trastuzumab 3 did not undergo baseline TTE but underwent one prior to commencing trastuzumab. 3 patients total had a baseline ECG. No patients had baseline biomarkers measured. Only 5 patients had biomarkers measured at 1 year and all 5 had developed grade 1 heart failure on treatment. These 5 patients were referred for cardiology review and 2 required an interruption of trastuzumab. All patients receiving trastuzumab underwent 3 monthly TTEs on treatment. Of the 35 patients now more than 1 year post treatment completion, only 3 patients had a TTE at 12 months. No patients referred to cardiology have reached 12 months post treatment. Discussion International guidelines recommend screening to identify and treat early cardiotoxicity and prevent long term morbidity. ASCO and ESMO guidelines both recommend patients receiving anthracycline undertake a TTE at baseline and at 6-12 months after completing therapy. Both recommend 3 monthly TTEs for patients receiving trastuzumab. The ESMO guidelines recommend a baseline ECG and consideration of further TTE at 2 years post therapy. For high risk patients the ASCO guidelines discuss offering routine TTEs during treatment. The ESMO guidelines recommend measurement of cardiac biomarkers for patients receiving anthracycline prior to each cycle and routine monitoring can be considered for patients receiving anti HER2 therapy. The ASCO guidelines reserve use of cardiac biomarkers for patients who develop signs or symptoms of cardiac dysfunction. Our study demonstrates that while baseline cardiac assessment is well performed a personalised approach to cardiac monitoring during curative therapy is not. These were unexpected findings given both treatment units are located in well resourced areas of Sydney. An outcome of this study has been the development of a cardio-oncology group within our oncology and cardiology departments. This has led to the development of new clinical guidelines to screen and manage high risk breast cancer patients receiving cardiotoxic therapies. This has empowered patients, care coordinators and physicians to proactively manage cardiac risks from therapy and we hope these institutional guidelines will be adopted nationally. Citation Format: Brendan Kirwin, Lina Pugliano, Sally Baron Hay. Monitoring for cardiotoxicity in early breast cancer: an Australian experience [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-08-17.

Abstract 159: Time-course Of Left Ventricular Systolic Dysfunction Recovery After Cardiac Arrest

Introduction: Myocardial dysfunction is a well-documented feature of post-cardiac arrest syndrome. The natural history of left ventricular systolic dysfunction (LVSD) remains largely unknown. We sought to characterize the change in left ventricular systolic function after return of spontaneous circulation (ROSC). Methods: This is a retrospective review of cardiac arrest patients at a single tertiary center between 2015 and 2020. We included patients with a transthoracic echocardiogram (TTE) documenting left ventricular ejection fraction (EF) within 1 day of ROSC and at least one follow-up TTE within 6 months after cardiac arrest. LVSD was defined as EF &lt;40% on TTE. Patients with known LVSD preceding cardiac arrest were excluded. Using paired t-test, we compared initial (within 1 day of ROSC) and follow up TTEs, stratified by shockable rhythm status. Recovery of LVSD was defined as improvement in EF to &gt;50%. Results: Of 477 cardiac arrest patients, 89 (18.7%) patients met the inclusion criterion. 28 (31.5%) had a baseline TTE on file; 5 patients had LVSD prior to arrest and were excluded, leaving a cohort of 84 patients. Thirty-one (36.9%) patients had LVSD on TTE after ROSC, of which 16 (51.6%) had recovery of EF on follow up TTE. The figure shows the timeline of EF recovery for the whole cohort. In-hospital follow up TTE (n=84) was done at a median (IQR) of 7 (4,16) days and post-discharge follow up (n=26) at 63 (29, 115) days. In patients with shockable rhythm arrest, EF improved from ROSC to inpatient follow up TTE [mean (SD) 36% (2.6) to 50% (2.5), P &lt;0.001]. Patients with non-shockable rhythm arrest had a higher baseline EF with a non-significant change at follow up [50% (2.6) to 56% (2.5), p=0.072]. Conclusion: Among survivors of cardiac arrest, significant recovery of LVSD was common. Further work is necessary to elucidate predictors of myocardial recovery and to determine optimal timing for repeat echocardiography.

Abstract 12566: Use Of Aortic Valve Area Index By Actual Body Weight Overestimates Aortic Stenosis Severity In Obese Patients

Introduction: Guidelines recommend indexing aortic valve area (AVA) to body surface area in grading the severity of aortic stenosis (AS), which overestimates severity in obese patients. The indexing of AVA to ideal or adjusted body weight has not been explored. Hypothesis: We hypothesized that using actual body weight compared to ideal or adjusted body weight in obese patients would result in overestimation of the severity of AS using AVAi. Methods: We conducted retrospective chart review on 305 individuals who received a transthoracic echocardiogram (TTE) at Tufts Medical Center from June 2021 to Sept. 2021 with AVA &lt;1.5cm 2 . We selected 73 subjects with moderate AS (AVA 1-1.5cm 2 ). These subjects were divided into an overweight and obese group (BMI &gt; 25; n = 56) and a normal weight group (BMI 18-24.9; n = 17). We recorded baseline characteristics and TTE data. AVAi was calculated with actual, ideal, and adjusted body weight. The primary outcome was reclassification, defined as a change in severity from severe AS to mild or moderate AS after recalculating AVAi using adjusted or ideal body weight. Results: The overweight and obese group was significantly younger (age 74.4±11.2 versus 80.7±5.7 years, P=0.018) with higher BSA (2.0±0.2 versus 1.7±0.2, P=0.010) compared to the normal weight group. The recorded median AVAi was 0.61 with interquartile range(IQR) of 0.17. There was no significant difference in blood pressure, ejection fraction, AVA, peak aortic velocity, peak gradient, and mean gradient. After calculating AVAi with adjusted and ideal body weight, 18 patients in the overweight and obese group were reclassified to a lower grade of AS based on AVAi (median AVAi 0.58, IQR 0.17), compared with 0 reclassifications in the normal weight group (0.67, 0.18). Patients who were reclassified had a significantly smaller AVA compared to patients who were not reclassified (1.09±0.11 versus 1.23±0.19 cm 2 , P&lt;0.001), while no differences were observed in peak gradient, mean gradient, and peak velocity. Conclusions: Using actual body weight to calculate AVAi in overweight and obese patients can lead to overestimation of AS severity. Further research is needed to investigate the optimal indexing strategy for AVAi and the effects of classification on cardiovascular outcomes.

Abstract 12085: Cardiac Structural and Functional Differences Between the Types of Sleep Apnea in Patients With Heart Failure With Reduced Ejection Fraction

Introduction: In patients with heart failure with reduced ejection fraction (HFrEF), sleep-disordered breathing (SDB) may affect, or be affected by cardiac structure and function. We hypothesized that patients with OSA would demonstrate left ventricular (LV) remodeling and impaired LV function intermediate between that of patients with CSA and patients with no SDB. Methods: ADVENT-HF is a multinational randomized trial investigating the effect of adaptive servo ventilation in patients with HFrEF and SDB. Inclusion required LV ejection fraction (LVEF) ≤45%, and a polysomnographic (PSG) apnea-hypopnea index (AHI) ≥15. Subjects with an AHI &lt;15 were excluded from randomization but comprised a no-SDB (NSDB) group. All transthoracic echocardiograms (TTE) and PSGs were analyzed in core laboratories at University Health Network in Toronto. Patients with SDB were subdivided into those with OSA and those with CSA. We then compared baseline demographic and TTE characteristics of the NSDB, OSA and CSA cohorts. Results: Among them, 665 with acceptable TTE were analyzed. As shown in the table, the CSA group was older, more predominantly male, and had a higher AHI than the other groups, and a higher prevalence of atrial fibrillation and a lower minimum arterial oxyhemoglobin saturation level than the NSDB group. The CSA group also had greater LV mass index than the other groups, greater LV volume indices and lower LVEF than the OSA group, and lower cardiac index than the NSDB group. Although the OSA group had no significant differences in TTE findings compared to the NSDB group, the OSA group was older, more predominantly male, and had a greater AHI than the NSDB group and a higher BMI than the CSA group and lower minSaO 2 than the other groups. Conclusion: In patients with HFrEF, the degree of LV remodeling and dysfunction did not differ between the OSA and NSDB groups, but those with CSA had more advanced LV remodeling and dysfunction than the other groups signaling more advanced HF.

Uptake of echocardiography amongst different risk groups for patients treated with cardiotoxic chemotherapy

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiovascular complications of cancer therapy are increasingly becoming a significant medical issue. Hence, the role of cardiovascular imaging in the assessment of baseline cardiovascular risk is becoming increasingly important. Current guidelines recommend a baseline transthoracic echocardiogram (TTE) prior to commencement of cardiotoxic chemotherapy (CC) but the uptake is presently inconsistent. Purpose Our study aimed to determine the uptake of a baseline TTE in a cohort of patients with solid organ malignancies (SOM) prior to commencing their treatment and to examine the patterns of uptake based on the risk of development of cardiotoxicity. Methods Patients with a SOM admitted to our institution between 2014-18 were examined. Demographic data, clinical comorbidities, cancer type, and chemotherapeutic regimens used were obtained from the patient’s electronic medical record. Included patients were divided into those receiving one of the 8 CC classes identified in the Cardio-Oncology Study Group and International Cardio-Oncology Society (COSG/ICOS) 2020 position statement1, and those who did not (control group). Those receiving CC were further stratified into risk groups according to the proformas proposed by the COSG/ICOS, while patients receiving immunotherapy for whom a proforma was not available, were considered a separate group. The uptake patterns of TTE in each group determined. Results Of 800 patients reviewed, 712 patients were included, and categorised into groups as shown in figure 1. Patients treated with CC had low uptake of a baseline TTE, and there was no difference compared to controls (14.4% vs 13.9%, p = 0.9). They were however more likely to have received a TTE during the course of treatment (32.3% vs 23.2%, p = 0.009). Figure 2 shows the rates of baseline TTE stratified by risk group. Compared to patients not on CC, only very high risk patients had a higher rate of baseline TTE (p &amp;lt; 0.001), while low risk patients had lower rates (p = 0.005). Compared to those not on CC, there was no difference in the rate of baseline TTE amongst immunotherapy patients, medium risk and high risk patients. Conclusion The uptake of baseline TTE in accordance with guidelines amongst patients receiving CC was very low. Based on the risk stratification proformas proposed by the COSG/ICOS, only very high risk patients were having a baseline TTE more frequently than those not treated with CC. The risk of future cardiotoxicity amongst low, medium and high risk patients, and those receiving immunotherapy, appears to be underappreciated, as these patients were not screened by TTE prior to commencing therapy. Increasing awareness of the agents that cause cardiotoxicity, and the establishment of formal protocols for these patients, may increase compliance with recommendations for TTE prior to commencing CC. Abstract Figure. Distribution of patients by risk group Abstract Figure. Percentage of patients with baseline TTE

Abstract 11158: Clinical Impact of Concomitant MR Among Patients Undergoing Transcatheter Aortic Valve Replacement

Background: Mitral regurgitation (MR) is seen in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). However, clinical outcomes in these patients have varied. The purpose of this study is to assess outcomes and changes in EF after TAVR in patients with concomitant MR. Methods: Retrospective chart review from March 2018-June 2020 identified all TAVR patients from the University of Illinois, Chicago. MR was assessed as none, mild, moderate, or severe regurgitation on baseline transthoracic echocardiogram. Patients were included if they demonstrated 6 or 12-month follow-up after valve replacement. Outcomes included all-cause mortality, major adverse cardiovascular events (MACE), clinically significant bleeding, and improvement in EF category, which included normal (50-70%), mildly (40-49%), moderately (30-39%), or severely (&lt;30%) reduced. Results: 118 patients (age 76±10 years, 79% male, 46% white) followed up at 6-months and 112 at 12-months. Of these, 33% had baseline MR with 79% being mild and 21% moderate. Patients with AS+MR were more likely to have atrial fibrillation (41.0 vs. 19.0%, p=0.01) and an EF&lt;50% (33.3 vs. 8.9%, p=0.001) compared to those with AS only. After TAVR, patients with MR were more likely to show improvements in EF category at 6 months (19.4 vs. 5.5%, p=0.039, Fig. 1). In those with AS+MR vs. AS only, there were no differences in all-cause mortality (12.8 vs. 5.1%, p=0.14), MACE (17.9 vs. 8.9%, p=0.15), or bleeding (10.3 vs. 6.3%, p=0.45) at 6 months. There were also no differences in all-cause mortality (16.2 vs. 14.7%, p=0.83), MACE (24.3 vs. 20.0%, p=0.60), or bleeding (13.5 vs. 10.7%, p=0.66) at 12 months. Conclusion: At 6 and 12 months after TAVR, patients with AS+MR experienced similar clinical outcomes as compared to those with only AS. Patients with AS+MR were more likely to show increases in EF 6 months after valve replacement. Our results suggest that patients with AS+MR stand to benefit after TAVR.

Management of cardiovascular complications of bruton tyrosine kinase inhibitors.

Management of cardiovascular complications of bruton tyrosine kinase inhibitors.

Novel staging classification of primary mitral regurgitation based on the presence of cardiac damage

Abstract Background The indication for surgery in patients with severe primary mitral regurgitation (MR) is currently based on the presence of symptoms, left ventricular (LV) dilatation and dysfunction, atrial fibrillation and pulmonary hypertension. The aim of this study was to evaluate the prognostic impact of a new staging classification based on cardiac damage including the known risk factors but also including global longitudinal strain (GLS), severe left atrial (LA) dilatation and right ventricular (RV) dysfunction. Methods In total 614 patients who underwent surgery for severe primary MR with available baseline transthoracic echocardiograms were included. Patients were classified according to the extent of cardiac damage (Figure): Stage 0-no cardiac damage, Stage 1-LV damage, Stage 2-LA damage, Stage 3-pulmonary vasculature or tricuspid valve damage and Stage 4-RV damage. Patients were followed for all-cause mortality. Results Based on the proposed classification, 172 (28%) patients were classified as Stage 0, 102 (17%) as Stage 1, 134 (21%) as Stage 2, 135 (22%) as Stage 3 and 71 (11%) as Stage 4. The more advanced the stage, the older the patients were with worse kidney function, more symptoms and higher EuroScore. Kaplan-Meier curve analysis revealed that patients with more advanced stages of cardiac damage had a significantly worse survival (log-rank chi-square 35.2; p&amp;lt;0.001) (Figure). On multivariable analysis, age, male, chronic obstructive pulmonary disease, kidney function, and stage of cardiac damage were independently associated with all-cause mortality. For each stage increase, a 22% higher risk for all-cause mortality was observed (95% CI: 1.064–1.395; p=0.004). Conclusion In patients with severe primary MR, a novel staging classification based on the extent of cardiac damage, may help refining risk stratification, particularly including also GLS, LA dilatation and RV dysfunction in the assessment. Funding Acknowledgement Type of funding source: None

Relationship between coronary microvascular dysfunction and left ventricular diastolic function in patients with chest pain and unobstructed coronary arteries.

Diastolic dysfunction (DD) is reported to affect up to 35% of the adult general population. The consequence of progressive DD is heart failure with preserved ejection fraction (HFpEF). Coronary microvascular dysfunction (CMD) has been suggested as one of the pathologic mechanisms leading to HFpEF. We investigated whether there was an association between coronary microvascular function and echocardiographic indices of left ventricular diastolic function at rest in patients with chest pain and unobstructed coronary arteries (CPUCA). This retrospective observational study recruited patients referred to cardiology clinics assessment of chest pain who subsequently underwent assessment via CT coronary angiogram (CTA). Coronary microvascular dysfunction was determined by myocardial blood flow reserve (MBFR; <2.0) using myocardial contrast echocardiography. Echocardiographic indices of diastolic function (septal mitral annular e'; septal mitral annular E/e', E/A ratio) were measured from baseline transthoracic echocardiogram. 149 patients (52% men) with a mean age 59.7(9.5) years were recruited. Mean (standard deviation) MBFR was 2.2 (0.51). 37% (55/149) had MBFR<2.0. Median [interquartile range] septal mitral annular e' velocity and septal mitral annular E/e' were 7.6cm/s [6.2, 8.9] and 9.5 [7.5, 10.8], respectively. Univariate regression analysis showed only age was a significant predictor of increasing septal mitral annular E/e' (β=+0.20 95% CI 0.13, +0.28, P<.001) but not MBFR. Multivariable analysis also showed no association between these septal mitral annular E/e' and MBFR after adjustment for cardiovascular risk factors. There was no relationship found between echocardiographic indices of left ventricular diastolic function and coronary microvascular function at rest.

4-2TAXANES-INDUCED CARDIOTOXICITY: A CASE REPORT IN BREAST CANCER PATIENT WITH PRE-EXISTING HYPERTENSION

Background: Hypertension is one of the most common comorbidities reported in patients with malignancy. This population had a higher risk of developing cardiotoxicity. Taxanes is an important therapeutic agent for several malignancies, including breast cancers. Their applicability, however, is limited by cardiotoxicity. The optimal strategy to prevent and manage chemotherapy-related cardiotoxicity (CTRCT) has not yet implemented in clinical practices. Case: A 63 years old breast cancer female patient was planned to be treated with Taxanes for six cycles. On admission, there were no cardiovascular symptoms. The patient had a history of hypertension and no history of myocardial infarction or congestive heart failure (CHF). Baseline transthoracic echocardiogram demonstrated normal left ventricular ejection fraction (LVEF) 66%. She received calcium channel blocker for her hypertension during chemotherapy. After the second cycle, the patient experienced palpitation, and there were no other cardiovascular symptoms. Electrocardiogram showed Left Bundle Branch Block. Echocardiogram revealed LVEF 46% with anteroseptal and inferoseptal hypokinetic. She was suspected as CHF chemotherapy-induced. Taxane was stopped, and she was treated with angiotensin receptor blocker, beta-blocker, and loop diuretic. Two months after therapy, her LVEF revealed partial recovery with LVEF 60% and no reported symptoms. Conclusion: Prophylactic agents targeting pre-existing cardiac risk factor has not been implemented in clinical practice but may soon change. Early detection and prompt management appear crucial to reverse left ventricular dysfunction in cancer patients receiving taxanes, especially in patients with pre-existing hypertension.

Prospective, Comprehensive Cardiac Assessment in Patients Receiving BTK Inhibitor Therapy

The development of Bruton Kinase Inhibitors (BTKi) has been a major advance in the treatment of chronic lymphocytic leukaemia and related B cell malignancies, but atrial fibrillation (AF) and sudden cardiac deaths are emerging as unique side effects of BTKi. The pathophysiology of cardiac side effects in BTKi treated patients is not known, and an excess of cardiac diseases is not exhibited in the congenital BTK deficiency population. Our group has previously shown in cell models that ibrutinib inhibits the phosphoinositide 3-kinase (PI3K)-AKT pathway in the heart, providing a potential explanation for cardiotoxicity. The PI3K pathway is the major cardioprotective mechanism in the heart under stress conditions, and mice with cardiomyopathy and reduced PI3K can display AF, ventricular arrhythmias and develop severe cardiomyopathy. Concerningly, given the above information, cardiac surveillance has not been routinely incorporated in BTKi trials. We therefore sought to prospectively and systemically assess cardiac function and rhythm in patients commencing BTKi therapy. Method: This is a prospective, multicentre study with the aim of conducting comprehensive cardiac assessment of patients commencing BTKi. This assessment involved 2 domains: 1) detection of subclinical arrhythmias by performing baseline and 3 month follow-up Holter Monitor testing, 2) quantification of subclinical structural changes including dynamic atrial and ventricular contractile function using transthoracic echocardiogram (TTE) and exercise cardiac magnetic resonance imaging (MRI) at baseline and 3 months. The primary outcome assessed was significant reduction in left atrial(LA) volume as a measure of ibrutinib-induced myocardial dysfunction. A 12.5% difference in LA volume is clinically meaningful given that it has been associated with greater AF risk in predisposed individuals. A sample size of 40 provides adequate power of 0.8, α = 0.05 for detecting a 12.5% increase in LA volume from an expected baseline of -18±3. Secondary outcomes measured were: 1) Reduction in ventricular ejection fraction during exercise cardiac MRI, 2) reduction in VO2 max on cardiopulmonary exercise testing. Results: A total number of 40 patients with median age of 68 years were recruited over median follow-up of 12 months (Table 1). 6/40 patients demonstrated significant reduction in left atrial volume at 3 month follow-up. They were not clinically symptomatic and did not have co-existing history of AF. Functional testing with VO2 max on cardiopulmonary exercise testing showed significant reduction in VO2 max in 8/40 patients. There were no significant reduction in ventricular ejection fraction during exercise cardiac MRI. 1/40 patients developed symptomatic AF 257 days after commencing ibrutinib and symptoms were controlled with a beta blocker. He had normal baseline TTE but was found to have enlargement of LA volume during follow-up. One patient with Waldenstrom Macroglobulinameia with normal baseline cardiac testing died from presumed ventricular tachycardia 3 months after commencing trial drug, before reassessment could be conducted. Overall, our data indicated that despite thorough cardiac surveillance, no significant cardiac abnormalities were detected at 3 month follow-up. Conclusion: This prospective and comprehensive cardiac study demonstrated no significant evidence of functional, structural or rhythm abnormalities at 3 month follow-up of patients commencing BTKiinhibitor, as assessed by Holter monitor, exercise cardiac MRI, cardiopulmonary testing and transthoracic echocardiography. Longer follow-up and additional electrophysiological studies may be required to further delineate the cause of BTKi induced cardiotoxicity. Disclosures McMullen: CLL Global Research Funding: Research Funding. Handunnetti:Gilead: Honoraria; Abbvie: Other: Travel Grant. Tam:Abbvie, Janssen: Research Funding; Abbvie, Janssen, Beigene, Roche, Novartis: Honoraria.

Sex Differences in Takotsubo Syndrome: A Narrative Review.

Takotsubo syndrome (TTS), or apical ballooning syndrome, is a transient and usually reversible form of cardiac dysfunction. It has classically been described in women with cardiac susceptibility when exposed to emotional or physical stress. Various hypotheses on the pathophysiology of TTS have been suggested, but the underlying mechanism remains unknown. There is increasing recognition of the sex differences in the presentation, triggers, severity, and complications of TTS. A literature review was conducted and found 75 relevant articles on PubMed Cochrane Library, and Google Scholar from 2001 to 2019 regarding TTS. We found remarkable sex differences existed in the underlying triggers, pathophysiology, illness severity, complications, and mortality. However, no sex differences were identified for baseline transthoracic echocardiogram findings, age at presentation, presenting symptoms, recurrence, and treatment approach. Much information regarding TTS remain lacking, but collaboration of national and international registries will be beneficial in addressing these gaps.