Baseline Left Ventricular Ejection Fraction Research Articles

HER2/neu 655 polymorphism, trastuzumab-induced cardiotoxicity, and survival in HER2-positive breast cancer patients.

HER2 overexpression in breast cancer correlates with poor outcomes. The incorporation of Trastuzumab into the treatment regimen has notably improved patient prognoses. However, cardiotoxicity emerges in approximately 20% of patients treated with the drug. This study aims to investigate the association between the HER2 655 A > G polymorphism, Trastuzumab-induced cardiotoxicity, and patient survival. The study involved 88 patients treated with Trastuzumab. Cardiotoxicity, defined as a reduction in left ventricular ejection fraction (LVEF) from baseline or the emergence of clinical signs of congestive heart failure, was identified during treatment follow-up. Genotyping of HER2 655 A > G employed TaqMan SNP technology. Genotype frequencies of HER2/neu 655 (53 AA, 32 AG, and 3 GG) were consistent with Hardy-Weinberg equilibrium. No significant differences were observed in mean baseline LVEF between patients who developed cardiotoxicity and those who did not. Within these groups, neither AA nor AG genotypes showed an association with changes in mean baseline or reduced LVEF levels. Logistic regression analysis, adjusted for hormonal status and anthracycline treatment, revealed that AG genotype carriers face a significantly higher risk of cardiotoxicity compared to AA carriers (OR = 4.42; p = 0.037). No association was found between the HER2/neu 655 A > G polymorphism and disease-free or overall survival, regardless of whether the data was adjusted for stage or not. HER2 655 A > G polymorphism is significantly linked to an increased risk of Trastuzumab-induced cardiotoxicity but does not correlate with variations in disease-free survival or overall survival rates.

Longitudinal comparison of dyssynchrony correction and strain improvement by conduction system pacing: LEVEL-AT trial secondary findings.

Our purpose was to compare echocardiographic dyssynchrony correction and strain improvement by conduction system pacing (CSP) vs. biventricular pacing (BiVP) as a marker of contractility improvement during one-year follow-up. A treatment-received analysis was performed in patients included in the LEVEL-AT trial (NCT04054895), randomized to CSP or BiVP, and evaluated at baseline (ON and OFF programming) and at 6 and 12 months (n = 69, 32% women). Analysis included intraventricular (septal flash), interventricular (difference between left and right ventricular outflow times), and atrioventricular (diastolic filling time) dyssynchrony and strain parameters (septal bounce, global longitudinal strain [GLS], left bundle branch block pattern and mechanical dispersion).Baseline left ventricular ejection fraction (LVEF) was 27.5 ± 7% and left ventricular end-systolic volume (LVESV) was 138 ± 77 ml, without differences between groups. Longitudinal analysis showed LVEF and LVESV improvement (p < 0.001), without between-group differences. At 12-month follow-up, adjusted mean LVEF was 46% with CSP (95%CI 42.2%, 49.3%) vs. 43% with BiVP (95%CI 39.6%, 45.8%) (p = 0.31) and LVESV was 80 ml (95%CI 55.3 ml, 104.5 ml) vs. 100 ml (95%CI 78.7 ml, 121.6 ml), respectively (p = 0.66).Longitudinal analysis showed a significative improvement of all dyssynchrony parameters and GLS over time (p < 0.001), without differences between groups. Baseline GLS significantly correlated with LVEF and LVESV at 12-month follow-up. CSP and BiVP provided similar dyssynchrony and strain correction over time. Baseline global longitudinal strain correction predicted ventricular remodeling at 12-month follow-up.

Catheter ablation for persistent atrial fibrillation: patterns of recurrence and impact on quality of life and health care utilisation.

Patterns of atrial fibrillation (AF) recurrence post catheter ablation for persistent AF are not well described. This study aimed to describe the pattern of AF recurrence seen following catheter ablation for persistent AF (PsAF) and the implications for healthcare utilisation and quality of life. This was a post-hoc analysis of the CAPLA study, an international, multi-centre study that randomised patients with symptomatic PsAF to pulmonary vein isolation plus posterior wall isolation or pulmonary vein isolation alone. Patients underwent twice daily single lead ECG, implantable device monitoring or three monthly Holter monitoring. 154 of 333 (46.2%) patients (median age 67.3 years, 28% female) experienced AF recurrence at 12-month follow-up. Recurrence was paroxysmal in 97 (63%) patients and persistent in 57 (37%). Recurrence type did not differ between randomisation groups (p=0.508). Median AF burden was 27.4% in PsAF recurrence and 0.9% in paroxysmal AF (PAF) recurrence (p<0.001). Patients with PsAF recurrence had lower baseline left ventricular ejection fraction (PsAF 50% vs PAF 60%, p<0.001) and larger left atrial volume (PsAF 54.2±19.3 ml/m² vs PAF 44.8±11.6 ml/m², p=0.008). Healthcare utilisation was significantly higher in PsAF (45 patients [78.9%]) vs PAF recurrence (45 patients [46.4%], p<0.001) and lowest in those without recurrence (17 patients [9.5%], p<0.001). Patients without AF recurrence had greater improvements in quality of life as assessed by the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire (Δ33.3±25.2 points) compared to those with PAF (Δ24.0±25.0 points, p=0.012) or PsAF (Δ13.4±22.9 points, p<0.001) recurrence. AF recurrence is more often paroxysmal after catheter ablation for PsAF irrespective of ablation strategy. Recurrent PsAF was associated with higher AF burden, increased healthcare utilisation and antiarrhythmic drug use. The type of AF recurrence and AF burden may be considered important endpoints in clinical trials investigating ablation of PsAF.

REAL–WORLD SINGLE CENTER EXPERIENCE WITH THE WEARABLE CARDIOVERTER DEFIBRILLATOR: SEX DIFFERENCES IN RISK STRATIFICATION FOR SUDDEN CARDIAC DEATH

Abstract Background Wearable cardioverter defibrillator (WCD) demonstrated an important role for prevention of sudden cardiac death in patients with advanced heart failure and reduced left ventricular ejection fraction. Although in randomized trial there are no gender difference in WCD use and defibrillator (ICD) implantation rate, real world data in female patients is lacking. Purposes: We aimed to describe the sex differences in WCD use, the rate of cardiac events detected with WCD and the rate of ICD implantation after WCD use in women in a real–world single center experience with reduced left ventricular ejection fraction or prior ventricular tachyarrhythmia. Methods and Results According with the current guidelines indications, between August 2017 and June 2023 ninety–six consecutive patients (mean age 66.0±11.1 years) received a WCD at Piacenza Hospitals and were retrospectively included in this analysis. There were no differences in clinical characteristics between female (18 patients, 18,8%) and male: in particular baseline left ventricular ejection fraction (LV EF) were similar between the two groups (29.5±5.2 vs 27.9±7.9, p=0.23) and no differences were found in the rate of ischaemic cardiopathy (66,6% vs 69,2% p=0.51). After 3–months follow up with WCD use, a similar rate of ventricular arrhythmias were found in the two groups (5.5% vs 3.8%, p=0.48) and no ventricular fibrillation was detected. The WCD usage period and median daily wear time were not different between female and male (55.2±50.6 vs 56.2±34.8 days p=0.53, 21.0±6.4 vs 23.1±1.5 hours p=0.48, respectively). However women presented a better LV EF improvement (12.2±9.7 vs 7.2±6.8, p=0.01), with a significant lower ICD implantation rate at the end of WCD use (55.5% vs 43.8%; p&amp;lt; 0.01). Conclusions In this real word analysis women presented a nice compliance using WCD. In spite of a similar burden of ventricular arrhythmic events, women presented a better LV EF improvement with a significant lower ICD implantation rate.

Significance of QRS scoring system in left ventricular function recovery after acute myocardial infarction.

The Selvester scoring system has been derived from ECG parameters for estimating infarct size. However, there is still a lack of evidence for Selvester score as an alternative to cardiac magnetic resonance (CMR) myocardial injury makers for risk stratification and prediction of left ventricular function (LVF) recovery among patients with ST-segment elevation myocardial infarction (STEMI). This multicentre observational study enrolled 328 STEMI patients (88.4% men, 57.3±10.6years of age) undergoing CMR examination 1week post-reperfusion therapy. Patients with baseline left ventricular ejection fraction (LVEF)<50% underwent a follow-up CMR 6months later, categorized into baseline normal LVF (ejection fraction [EF]≥50% at baseline, n=155); recovered LVF (EF<50% at baseline and ≥50% after 6months, n=69); and reduced LVF (EF<50% at baseline and after 6months, n=104). The median follow-up was 4 (3-4) years for all patients, with 61 patients experiencing major adverse cardiovascular event (MACEs). Patients with reduced LVF had a higher risk of MACEs than those with baseline normal LVF (P=0.01), while the recovered LVF group had no significant difference (P>0.05). A Selvester score >10 doubled the risk of MACEs in patients with systolic dysfunction (1.91 [1.02 to 3.58], P=0.04). Additionally, Selvester score, baseline LVEF, transmural infarction, and peak CK-MB were independent predictors of recovered LVF, with Selvester score providing incremental predictive value to peak CK-MB in predicting recovered LVF (∆AUC=0.07, P<0.05). The Selvester score improves risk stratification among STEMI patients beyond LVEF and provide independent and incremental information to clinical parameters in predicting recovered LVF.

Impact of heart failure hospitalizations on clinical outcomes after mitral transcatheter edge-to-edge repair: Results from the EXPAND study.

This analysis aimed to compare the clinical outcomes associated with heart failure (HF) readmissions and to identify associations with HF hospitalizations (HFH) in patients treated with the MitraClip™ NTR/XTR System in the EXPAND study. The global, real-world EXPAND study enrolled 1041 patients with primary or secondary mitral regurgitation (MR) treated with the MitraClip NTR/XTR System. Echocardiograms were analysed by an independent echocardiographic core laboratory. The study population was stratified into HFH and No-HFH groups based on the occurrence of HFH 1 year post-index procedure. Clinical outcomes including MR severity, New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, and all-cause mortality were compared (HFH: n = 181; No-HFH: n = 860). Both groups achieved consistent 1-year MR reduction to ≤1+ (HFH vs. No-HFH: 87.3% vs. 89.5%, p = 0.6) and significant 1-year improvement in KCCQ scores (+16.5 vs. +22.3, p = 0.09) and NYHA functional class. However, more patients in the No-HFH group had 1-year NYHA class ≤II (HFH vs. No-HFH: 67.9% vs. 81.9%, p < 0.01). All-cause mortality at 1 year was 36.8% in the HFH group versus 10.4% in the No-HFH group (p < 0.001). The HFH rate decreased by 63% at 1 year post-M-TEER versus 1 year pre-treatment (relative risk 0.4, p < 0.001). Independent HFH associations were MR ≥2+ at discharge, HFH 1 year prior to treatment, baseline NYHA class ≥III, baseline tricuspid regurgitation ≥2+, and baseline left ventricular ejection fraction ≤40%. This study reports the impact of HFH on clinical outcomes post-treatment in the EXPAND study. Results demonstrate that the occurrence of HFH was associated with worse 1-year survival, and treatment with the MitraClip system substantially reduced HFH and improved patient symptoms and quality of life.

Abstract PO3-01-02: Real world outcomes of neoadjuvant therapy with Trastuzumab and Pertuzumab associated with carboplatin and docetaxel (TCHP) in HER2+ early breast cancer patients unfit for anthracyclines: a retrospective cohort comparative study

Abstract Backgound Neoadjuvant chemotherapy (CT) with anti-HER2 blockade using trastuzumab (H) and pertuzumab (P) is a standard of care for patients (pts) with HER2-positive early-stage Breast Cancer (eBC). Historically, taxanes (T) and anthracyclines (A) have been the mainstays of (neo)adjuvant CT in this setting, but the added benefit of A in the era of anti-HER2 therapy has been questioned. This study aimed to assess the effectiveness, cardiac safety, and cost-effectiveness of an anthracycline-free regimen (TCHP) in a real-world population of pts deemed unfit for A, compared to pts treated with the standard regimen of doxorubicin and cyclophosphamide plus dual-blockade associated with docetaxel (AC-DHP) at a single Portuguese Comprehensive Cancer Center. Methods This retrospective cohort study included a consecutive series of female eBC HER2+ pts who initiated primary treatment with TCHP between July 2018 and August 2022. The primary endpoint was pathological complete response (pCR), and secondary endpoints were cardiac safety and disease-free survival (DFS). The outcomes were compared with a historical database of eBC HER2+ pts who started primary treatment with AC-DHP between August 2015 and May 2021. Clinical data was collected from medical and administrative records. Descriptive statistics were used to describe categorical and continuous variables, and the Kaplan-Meier method was used for DFS analysis. Costs analysis employed the micro-costing technique, considering individual medical direct costs from diagnosis until surgery. Multivariate logistic regression models were used for effectiveness analysis and the gamma general model for costs analysis. The incremental cost-effectiveness ratio (ICER) was calculated using the pCR rate as a measure of effectiveness. Results A total of 233 and 23 pts were included in the TCHP and AC-DHP groups respectively. Reasons for choosing the anthracycline-free regimen in the TCHP group were primarily age-related frailty (52%), medical comorbidities (26%), and previous exposure to anthracyclines (22%). The TCHP pts were older (median age 71 years, range [45-77] vs. 47 years [24-70]) and had lower baseline Left Ventricular Ejection Fractions (LVEF) (median 65% [51-80] vs. 60% [56-73]), with a higher proportion of hormone receptor (HR) negative pts (78.3% vs. 33.0%). Clinical stages were balanced between groups, but the TCHP group had a higher nodal involvement (N+) (73.9% vs. 61.8%). The pCR rates were higher in the TCHP group (65.2% vs. 46.1%, HR 0.98 [95% CI 0.36 - 2.70]). Subgroup analysis by HR status showed comparable pCR rates: 77.1% vs. 74.1% in HR- pts and 40% vs. 39.7% in HR+ pts. Cardiac safety analysis indicated a median decrease in LVEF of 9% in both the TCHP and AC-DHP groups, with 43.5% of TCHP pts experiencing a decline of 10% or more, and 13.0% dropping below 50%. In comparison, these figures were 44.2% and 3.9%, respectively, in the AC-DHP group. At the end of the follow-up, only one patient in the TCHP group with a LVEF &amp;lt; 50% persisted with mild symptoms of chronic heart failure. The median follow-up time for DFS events, starting from surgery, was 31.1 months in the TCHP group and 45.7 months in the AC-DHP group, with 1-year DFS rates of 91.3% and 100%, respectively. The ICER analysis indicated that TCHP was cost-effective, as the incremental cost for achieving an additional pCR in similar subgroups can be outweighed by later cost savings, mainly due to further adjuvant treatment with trastuzumab instead of TDM-1. Conclusions In a real-world population of HER2+ eBC patients unfit for anthracyclines, the TCHP regimen demonstrated a higher overall pCR rate compared to a historical control treated with the AC-DHP regimen, along with an acceptable cardiac safety profile. These results support the broader use of the TCHP regimen in HER2+ eBC pts, as recommended by current NCCN guidelines. However, larger studies involving similar populations are needed to provide higher levels of evidence. Citation Format: Ricardo Pinto, Rita Calisto, Patrícia Redondo, Ana Silva, Pedro Castro, Rute Fernandes, Raquel Teixeira, Diana Mata, Ana Ferreira, Maria Bento, Cláudia Vieira. Real world outcomes of neoadjuvant therapy with Trastuzumab and Pertuzumab associated with carboplatin and docetaxel (TCHP) in HER2+ early breast cancer patients unfit for anthracyclines: a retrospective cohort comparative study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-01-02.

Abstract PO4-18-04: An exploratory study of Trastuzumab Deruxtecan neoadjuvant therapy in HER2-positive or HER2-low early or locally advanced breast cancer after a poor response to neoadjuvant chemotherapy

Abstract Background The current standard of care for neoadjuvant treatment of HER2-positive early-stage breast cancer consists of dual HER2-blockade with trastuzumab (H) plus pertuzumab (P) and polychemotherapy with a pathological complete response (pCR) rate of 31%~50%. Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate composed of an anti-HER2 antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor. T-DXd significantly prolonged progression-free and overall survival vs trastuzumab emtansine in HER2-positive unresectable and/or metastatic breast cancer (mBC) previously treated with H and taxane in DESTINY-Breast03 study. HER2-low breast cancer is currently treated as HER2-negative (HER2-low and HER2-zero) breast cancer, with patients stratified according to hormone-receptor (HR) status. In DESTINY-Breast04 study, T-DXd resulted in significantly longer progression-free and overall survival than the physician’s choice of chemotherapy in HER2-low mBC. Given the efficacy of T-DXd monotherapy in HER2-positive or HER2-low mBC, we conduct an exploratory study to evaluate the efficacy and safety of T-DXd in HER2-positive or HER2-low early or locally advanced breast cancer after a poor response to neoadjuvant chemotherapy, and to identify sensitive biomarkers for T-DXd neoadjuvant therapy. Methods Eligible patients were women aged 18 years to 75 years with clinical stage cT2–cT4/cN0–cN3/cM0 (stage II–III) invasive breast cancer (&amp;gt;2 cm in size) confirmed as HER2-positive (immunohistochemistry [IHC] 3+) or HER2-low (IHC2+ or IHC1+/situ hybridization-negative). Patients are required to have an Eastern Cooperative Oncology Group performance status of 0 or 1, and baseline left ventricular ejection fraction of at least 55% (as measured by echocardiogram). Patients are also required to have adequate organ function and bone marrow function. Patients with HER2-positive breast cancer should receive taxane (paclitaxel or nab-paclitaxel) or docetaxel, carboplatin, and H plus P for 2 cycles. Patients with HER2-low and HR-positive breast cancer should receive taxane (paclitaxel or nab-paclitaxel) or docetaxel, and cisplatin or carboplatin for 2 cycles. Patients with HER2-low and HR-negative breast cancer should receive taxane (paclitaxel or nab-paclitaxel) or docetaxel, and anthracycline (epirubicin, pirarubicin or liposomal doxorubicin) for 2 cycles. For patients who have responses of stable disease assessed by magnetic resonance imaging will receive T-DXd neoadjuvant therapy. T-DXd will be administered intravenously every 3 weeks at a dose of 5.4 mg per kilogram of body weight for 4 cycles. Peripheral blood and biopsy tissue will be collected before neoadjuvant chemotherapy and T-DXd neoadjuvant therapy, and peripheral blood and surgical tissue will be collected after the surgery. Lipid metabolites in peripheral blood and mass spectrometry-based protein quantification in tissue will be detected to find sensitive biomarkers for T-DXd neoadjuvant therapy. The primary endpoint is pCR rate (ypT0/Tis ypN0) and identify sensitive biomarkers for T-DXd neoadjuvant therapy. Secondary endpoints include objective response rate, breast-conserving rate and invasive disease-free survival. Citation Format: Jin Zhang, Zhendong Shi, Jingjing Liu. An exploratory study of Trastuzumab Deruxtecan neoadjuvant therapy in HER2-positive or HER2-low early or locally advanced breast cancer after a poor response to neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-18-04.

Left Ventricular Function, Congestion, and Effect of Empagliflozin on Heart Failure Risk After Myocardial Infarction

BackgroundEmpagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14 days of acute myocardial infarction (AMI). ObjectivesThis study sought to evaluate the association of left ventricular ejection fraction (LVEF), congestion, or both, with outcomes and the impact of empagliflozin in reducing HF risk post-AMI. MethodsIn the EMPACT-MI (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction) trial, patients were randomized within 14 days of an AMI complicated by either newly reduced LVEF<45%, congestion, or both, to empagliflozin (10 mg daily) or placebo and were followed up for a median of 17.9 months. ResultsAmong 6,522 patients, the mean baseline LVEF was 41 ± 9%; 2,648 patients (40.6%) presented with LVEF <45% alone, 1,483 (22.7%) presented with congestion alone, and 2,181 (33.4%) presented with both. Among patients in the placebo arm of the trial, multivariable adjusted risk for each 10-point reduction in LVEF included all-cause death or HF hospitalization (HR: 1.49; 95% CI: 1.31-1.69; P < 0.0001), first HF hospitalization (HR: 1.64; 95% CI: 1.37-1.96; P < 0.0001), and total HF hospitalizations (rate ratio [RR]: 1.89; 95% CI: 1.51-2.36; P < 0.0001). The presence of congestion was also associated with a significantly higher risk for each of these outcomes (HR: 1.52, 1.94, and RR: 2.03, respectively). Empagliflozin reduced the risk for first (HR: 0.77; 95% CI: 0.60-0.98) and total (RR: 0.67; 95% CI: 0.50-0.89) HF hospitalizations, irrespective of LVEF or congestion, or both. The safety profile of empagliflozin was consistent across baseline LVEF and irrespective of congestion status. ConclusionsIn patients with AMI, the severity of left ventricular dysfunction and the presence of congestion was associated with worse outcomes. Empagliflozin reduced first and total HF hospitalizations across the range of LVEF with and without congestion. (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction [EMPACT-MI]; NCT04509674)

Correlation of extent of left ventricular endocardial unipolar low-voltage zones with ventricular tachycardia in nonischemic cardiomyopathy

BackgroundEndocardial electrogram (EGM) characteristics in nonischemic cardiomyopathy (NICM) have not been explored adequately for prognostication. ObjectiveWe aimed to study correlation of bipolar and unipolar EGM characteristics with left ventricular ejection fraction (LVEF) and ventricular tachycardia (VT) in NICM. MethodsElectroanatomic mapping of the left ventricle was performed. EGM characteristics were correlated with LVEF. Differences between groups with and without VT and predictors of VT were studied. ResultsIn 43 patients, unipolar EGM variables had better correlation with baseline LVEF than bipolar EGM variables: unipolar voltage (r = +0.36), peak negative unipolar voltage (r = −0.42), peak positive unipolar voltage (r = +0.38), and percentage area of unipolar low-voltage zone (LVZ; r = −0.41). Global mean unipolar voltage (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.2–0.8), extent of unipolar LVZ (HR, 1.6; 95% CI, 1.1–2.3), and percentage area of unipolar LVZ (HR, 1.6; 95% CI, 1.1–2.3) were significant predictors of VT. For classification of patients with VT, extent of unipolar LVZ had an area under the curve of 0.82 (95% CI, 0.69–0.95; P < .001), and percentage area of unipolar LVZ had an area under the curve of 0.83 (95% CI, 0.71–0.96; P = .01). Cutoff of >3 segments for extent of unipolar LVZ had the best diagnostic accuracy (sensitivity, 90%; specificity, 67%) and cutoff of 33% for percentage area of unipolar LVZ had the best diagnostic accuracy (sensitivity, 95%; specificity, 60%) for VT. ConclusionIn NICM, extent and percentage area of unipolar LVZs are significant predictors of VT. Cutoffs of >3 segments of unipolar LVZ and >33% area of unipolar LVZ have good diagnostic accuracies for association with VT.

Myocardial extracellular volume derived from contrast-enhanced chest computed tomography in longitudinal evaluation of cardiac toxicity in patients treated with immune checkpoint inhibitors.

The immune-related adverse effects after immune checkpoint inhibitors (ICIs) treatment have always been a hot topic. Although the incidence of myocarditis is not high among the related adverse effects, the mortality rate is extremely high once it occurs. In the past, the risk of cancer therapy-related cardiac dysfunction (CTRCD) after drug treatment was evaluated based on imaging examinations, but this evaluation still had certain limitations. Currently, the extracellular volume (ECV) score measurement calculated using cardiac magnetic resonance T1 mapping has become a reliable method for evaluating myocardial toxicity and computed tomography (CT) examination may become an alternative. This study aimed to longitudinally evaluate the cardiac toxicity of patients treated with ICIs using myocardial ECV derived from contrast-enhanced chest CT. A total of 500 patients with III-IV lung cancer and esophageal cancer treated with ICIs were evaluated. Participants underwent baseline examination and at least 1 follow-up examination after treatment. Contrast-enhanced chest CT-ECV, left ventricular ejection fraction (LVEF), and measurement of cardiac troponin T (cTnT) were conducted before the first treatment, 3-6 months after the first treatment, and about 12 months after the first treatment, respectively. The ECV value of the middle part of the left ventricular septum was evaluated on CT venography and plain scan, the LVEF value was evaluated by color Doppler ultrasound, and the quantity of cTnT was detected by chemiluminescence. Cancer therapy-related cardiac dysfunction was recorded. The mean baseline LVEF value was 68.51%±4.81% (N0=500), and those of LVEF1, LVEF2, and LVEF3 were 68.77%±4.30%, 68.16%±3.59%, and 66.23%±4.20%, respectively (N1=500, N2=467, and N3=361, respectively). There was no significant difference between LVEF1, LVEF2, and LVEF0 (P1=0.095, P2=0.062), whereas LVEF3 was significantly lower than LVEF0 (P<0.001). The average baseline cTnT0 value was 7.42±3.95 (N0=500). The values of cTnT1, cTnT2, and cTnT3 were 10.05±11.40, 12.24±13.59, and 14.54±14.49, respectively (N1=500, N2=467, N3=361). The values of cTnT1, cTnT2, and cTnT3 were significantly higher than cTnT0 (P1<0.001, P2<0.001, P3<0.001). The average ECV0 was 47.14%±7.48% (N0=500). ECV1, ECV2, and ECV3 were 50.85%±6.79%, 53.44%±6.96% and 52.64%±7.58% respectively (N1=500, N2=467 and N3=361). ECV1, ECV2, and ECV3 were significantly higher than ECV0 (P1<0.001, P2<0.001, P3<0.001). CTRCD occurred in 49 patients. There were significant differences between the CTRCD (+) group and the CTRCD (-) group in cTnT1, cTnT2, and cTnT3 (P1<0.001, P2<0.001, and P3<0.001, respectively) and in ECV1, ECV2, and ECV3 (P1=0.039, P2=0.041, and P3=0.013, respectively). CT-ECV began to increase at the early stage after the treatment of ICIs. CT-ECV is a potential biomarker for dynamically monitoring the cardiac toxicity of tumor patients after receiving ICIs. ECV may be used to speculate the CTRCD caused by the treatment of ICIs.

Abstract 6298: The value of routine trastuzumab-related cardiac toxicity monitoring in gastrointestinal cancers

Abstract Background: It is a common practice to monitor trastuzumab-related cardiac toxicity (TRCT) using left ventricular ejection fraction (LVEF) in patients who receive trastuzumab-containing therapy for human epidermal growth factor receptor 2 (HER2)-positive cancers. However, this monitoring approach does not appear cost effective in patients with HER2-positive gastrointestinal (GI) cancers given poor overall survival (OS). Here, we aim to examine the incidence of clinically significant TRCT in this target population. Methods: This is a retrospective cohort study of patients with advanced HER2-positive GI cancers who received trastuzumab-containing therapies (trastuzumab +/- pertuzumab, chemotherapy +/- immunotherapy + trastuzumab, trastuzumab deruxtecan) between 2011 and 2023. HER2 status was determined by immunohistochemistry, fluorescent in situ hybridization, and/or next generation sequencing. LVEF was estimated by serial transthoracic echocardiograms (TTE). Continuous variables were summarized as median and interquartile range (IQR). Paired Wilcoxon signed rank test was used to compare serial LVEF. OS was estimated using Kaplan-Meier method. Results: A total of 243 patients were included in this study with a median age of 64 (IQR: 55-70) years. 139 (57%) patients had esophageal or GEJ adenocarcinoma; 45 (19%) patients had gastric cancer; 37 (15%) patients had colorectal cancer; and the rest had other GI cancers. Median follow-up time was 18.6 (IQR: 9.2-36) months. Median OS from cancer diagnosis and the first dose of trastuzumab-containing therapy were 24.1 (95%CI: 20.2-30.2) and 11.7 (95%CI: 10.4-15.6) months, respectively. Patients received a median of 13 cycles of trastuzumab-containing therapy for a median duration of 4.1 (IQR: 1.4-10.1) months. The median number of TTE each patient had throughout therapy was 2 (IQR: 1-4). Median baseline LVEF was 61% (IQR: 56-65%) which was significantly higher (p&amp;lt;0.001) than the median lowest LVEF of 58% (IQR: 53-62%) during therapy, but not different (p=0.14) from the most recent median LVEF of 60% (IQR: 56-64%) after discontinuation of trastuzumab. Among 176 patients with serial LVEF data, 16 (9%) had &amp;gt; 10% LVEF drop; 7 (44%) of these 16 patients had LVEF recovery. None of the cardiovascular risk factors prior to trastuzumab treatment including hypertension, diabetes, hyperlipidemia, peripheral arterial disease, coronary artery disease, and stroke were significantly associated with the development of TRCT. Conclusion: The incidence of clinically significant LVEF drop appears low in patients with advanced GI cancers as post-treatment LVEF recovery to baseline was observed at the population level. The value of using TTE to monitor TRCT in these patients with short OS should be further assessed in the perspective of cost effectiveness. Citation Format: Samual R. Kosydar, Matteo Castrichini, Mojun Zhu, Hao Xie. The value of routine trastuzumab-related cardiac toxicity monitoring in gastrointestinal cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6298.

Predicting factors for omitting beta-blockers in patients with tachycardia-induced cardiomyopathy after successful catheter ablation for atrial fibrillation.

Tachycardia induces a reduction in the left ventricular ejection fraction (LVEF), which is defined as tachycardia-induced cardiomyopathy (TIC). Conversion to and maintenance of sinus rhythm by catheter ablation can improve LVEF in patients with TIC due to atrial fibrillation (AF). Beta-blockers are mandatory for the treatment of heart failure with reduced LVEF(HFrEF), but the necessity of beta-blockers in TIC patients even after catheter ablation remains unclear. We examined the effect of beta-blockers on cardiac function in TIC patients after catheter ablation. We retrospectively analyzed 124 patients with a history of heart failure and an LVEF of ≤ 50% who underwent catheter ablation for AF. TIC was defined as a ≥ 10% improvement in the baseline LVEF and an improvement to an LVEF of ≥ 50% at 6months after ablation. Patients with other cardiomyopathy diagnosed before the ablation were excluded. LVEF was significantly increased with the reductions of the left ventricular and left atrial volumes at the 6-month follow-up in all 80 patients with TIC. No beta-blockers were prescribed during the post-ablation follow-up in 21 patients with TIC. The absolute values of and changes in the echocardiographic parameters between before and after ablation were not significantly different between patients with and without beta-blockers after the ablation. A simple score using the history of hospitalization for heart failure and use of beta-blockers or diuretics prior to ablation was useful in identifying TIC patients who did not need prescription of beta-blockers after catheter ablation. LVEF similarly improved in both patients with and without prescription of beta-blockers after the ablation. Beta-blockers may not need to be prescribed after successful catheter ablation for AF in LVEF of ≤ 50% patients without other cause of cardiomyopathy diagnosed before the ablation, a history of hospitalization for heart failure and prescription of beta-blockers and diuretics before the ablation.

Paced QRS morphology mimicking complete left bundle branch block induced by right ventricular pacing is associated with pacing-induced cardiomyopathy.

Right ventricular (RV) pacing sometimes causes left ventricular (LV) systolic dysfunction, also known as pacing-induced cardiomyopathy (PICM). However, the association between specifically paced QRS morphology and PICM development has not been elucidated. This study aimed to investigate the association between paced QRS mimicking a complete left bundle branch block (CLBBB) and PICM development. We retrospectively screened 2009 patients who underwent pacemaker implantation from 2010 to 2020 in seven institutions. Patients who received pacemakers for an advanced atrioventricular block or bradycardia with atrial fibrillation, baseline LV ejection fraction (LVEF) ≥ 50%, and echocardiogram recorded at least 6 months postimplantation were included. The paced QRS recorded immediately after implantation was analyzed. A CLBBB-like paced QRS was defined as meeting the CLBBB criteria of the American Heart Association/American College of Cardiology Foundation/Heart Rhythm Society in 2009. PICM was defined as a ≥10% LVEF decrease, resulting in an LVEF of <50%. Among the 270 patients analyzed, PICM was observed in 38. Baseline LVEF was lower in patients with PICM, and CLBBB-like paced QRS was frequently observed in PICM. Multivariate analysis revealed that low baseline LVEF (odds ratio [OR]: 0.93 per 1% increase, 95% confidence interval [CI]: 0.89-0.98, p = 0.006) and CLBBB-like paced QRS (OR: 2.69, 95% CI: 1.25-5.76, p = 0.011) were significantly associated with PICM development. CLBBB-like paced QRS may be a novel risk factor for PICM. RV pacing, which causes CLBBB-like QRS morphology, may need to be avoided, and patients with CLBBB-like paced QRS should be followed-up carefully.

Impact of left ventricular ejection fraction and aortic valve gradient on mortality following transcatheter aortic valve intervention

BackgroundData regarding the impact of reduced left ventricular ejection fraction (LVEF) and/or reduced mean aortic valve gradient (AVG) on outcomes following transcatheter aortic valve intervention (TAVI) have been conflicting. We sought to assess the relationship between LVEF, AVG, and 1-year mortality in patients undergoing TAVI. MethodsWe prospectively evaluated 298 consecutive adults undergoing TAVI from 2015 to 2018 at an academic tertiary medical center. Patients were categorized according to LVEF and mean AVG. The primary outcome of interest was all-cause mortality at 1 year. ResultsOf 298 adults undergoing TAVI, 66 (22.1%) had baseline LVEF ≤45% while 232 (77.9%) had baseline LVEF >45%; 173 (58.1%) had baseline AVG < 40mmHg while 125 (41.9%) had baseline AVG ≥ 40mmHg. Rates of 1-year all-cause mortality were significantly higher in patients with LVEF ≤45% (28.8% vs 12.1%, p = 0.001) and those with AVG < 40mmHg (19.7% vs 10.4%, p = 0.031) compared to those with LVEF >45% and AVG ≥ 40mmHg respectively. In multivariable analysis, higher AVG (per mmHg) (OR 0.97, 95% CI 0.94–0.99, p = 0.026) was noted to be independently associated with lower rates of 1-year mortality, while LVEF was not (OR 0.98, 95% CI 0.96–1.01). ConclusionsIn this prospective, contemporary registry of adults undergoing TAVI, while 1-year unadjusted mortality rates are significantly higher in patients with reduced LVEF and reduced AVG, risk-adjusted mortality at 1 year is only higher in those with reduced AVG – not in those with reduced LVEF.

Clinical characteristics and long-term outcomes of patients with heart failure with improved ejection fraction. First Polish experience from LECRA-HF registry

PurposeHeart failure (HF) with improved ejection fraction (HFimpEF) is a new category of HF introduced in the newest European Society of Cardiology guidelines. However, clinical characteristics and long-term outcomes of HFimpEF patients remain insufficiently elucidated. We sought to characterize Polish HFimpEF patients and determine their long-term mortality. Material and methodsOf 1186 patients enrolled in the single-center Lesser Poland Cracovian Heart Failure (LECRA-HF) registry between 2009 and 2019 and hospitalized due to HF decompensation, 340 (28.7%) were those with HF with reduced ejection fraction (HFrEF). Based on follow-up echocardiography, 61 (17.9%) of them were classified as HFimpEF and the remaining as HFnon-impEF. ResultsHFimpEF patients were more frequently females (P ​< ​0.001), had higher baseline left ventricular ejection fraction (LVEF, P ​< ​0.001), had less often a history of diabetes (P ​= ​0.024), severe chronic kidney disease (P ​= ​0.026) or prior myocardial infarction (P ​= ​0.008) than HFnon-impEF patients. By multivariable analysis the HFimpEF diagnosis was independently predicted by baseline NYHA I/II (odds ratio [OR] 2.347, 95% confidence interval [95%CI] 1.020–5.405), non-ischemic etiology (OR 3.096, 95%CI 1.587–6.024), lack of diabetes mellitus (OR 2.016, 95%CI 1.059–3.846) and higher baseline LVEF (OR 1.084, 95%CI 1.042–1.126, per 1%). Within the median 49 (25–77) months all-cause mortality was lower in HFimpEF than in HFnon-impEF (10.8 vs 16.4%/year, P ​= ​0.004). ConclusionsOur findings indicate that every sixth Polish patient with HFrEF has a chance to improve LVEF during follow-up and to become a HFimpEF patient. Baseline characteristics of HFimpEF patients are different from HFnon-impEF. Simultaneously, the HFimpEF diagnosis is associated with higher long-term survival.

Ventricular Arrhythmias and Hemodynamic Collapse During Acute Coronary Syndrome- Increased Risk for Sudden Cardiac Death?

In acute phase of acute coronary syndrome (ACS), ventricular tachycardia (VT) and/or ventricular fibrillation (VF) leading to resuscitation are not considered to be associated with increased long-term sudden cardiac death (SCD) because the cause - acute ischemia - is believed to be reversible.Aim of this study was to investigate whether ventricular arrhythmias leading to sudden cardiac arrest during ACS associate with the risk of incident SCD in patients with normal or mildly impaired left ventricular ejection fraction (LVEF). This study is based on a retrospective analysis of all 8,062 consecutive ACS patients undergoing coronary angiography with baseline LVEF ≥40% between 2007-2018 (follow-up until December 31st, 2021). The primary outcome was SCD equivalent life-threatening ventricular arrhythmias (LTVA) composing of true SCDs, aborted SCDs by successful resuscitation or appropriate ICD therapy. The risk of sudden LTVA was estimated with multivariate subdistribution hazard model using other deaths as competing events. Two-hundred and thirteen (n=211, 2.6%) patients suffered acute phase VF/VT leading to resuscitation and survived to discharge and most happened before angiography (80.6%, N=170) and were VF (92.9%, N=196). During a median follow-up of 7.6 years, 3.9% (N=316) of all the patients had LTVA (10.0% in VF/VT group vs 3.8% in other patients). VF/VTs during ACS associated with an increased risk for future SCD (HR 3.07; 95% CI 1.94-4.85, p<0.001). Most LTVAs occurred in patients without ICDs. VF/VT in ACS associates with remarkably high long-term risk for SCD in patients with LVEF ≥40%.

High platelet adrenergic activity and concomitant activation of the pituitary/medullar axis as alarming laboratory parameters in ACS survivors-the STRESS-AMI study.

Kinetics of stress-related biological parameters were determined in acute coronary syndrome (ACS) patients undergoing complex cardiovascular rehabilitation. We determined platelet functionality in the absence/presence of a selective alpha-2 adrenergic receptor inhibitor, atipemazole parallel with salivary cortisol levels at enrolment, and at 3- and 12-months follow-up in 75 ACS patients with percutaneous coronary intervention. Pharmacological/non-pharmacological secondary prevention methods have been efficiently applied. Baseline aggregometry indicated platelet hyperactivity, decreasing gradually and being significantly reduced late, at 12 months (p < 0.05). Cortisol levels followed similar kinetics (p < 0.05). Baseline epinephrine-induced aggregations (EIA) significantly correlated with most of the other platelet agonists, even at subsequent time-points. Patients with upper-quartile EIA at enrolment (EIA-UQ) had significantly higher ADP- and collagen-induced aggregations at enrolment, at 3- and 12-months follow-up as well, indicating that high adrenergic response in the acute phase is accompanied by general platelet hyperactivity and predicts sustained platelet activation. In the EIA-UQ group higher cardiac biomarker release, elevated C-reactive protein and cortisol levels, and lower baseline left ventricular ejection fraction were detected.Atipemazole significantly reduced platelet aggregation induced by several platelet agonists, being most potent and comparable to full in vitro P2Y12 inhibition on collagen-induced aggregations (p < 0.05), indicating that catecholamines might serve as promt/long-term modulators of platelet function. Despite effective CCR programme and dual antiplatelet therapy, prolonged activation of sympathetic neuroendocrine system and general platelet hyperactivity can be detected up to one year in ACS patients with high adrenergic platelet activity. Moreover, initial high adrenergic activity is accompanied by clinical parameters associated to increased cardiovascular risk, therefore early identification of these patients might support complex optimal long-term therapy.

Mitral Valve Surgery for Mitral Regurgitation Results in Reduced Left Ventricular Ejection Fraction in Barlow's Disease as Compared with Fibro-Elastic Deficiency.

Surgical correction of severe mitral regurgitation (MR) can reverse left ventricular (LV) remodeling in patients with mitral valve prolapse (MVP). However, whether this process is similar to the case in Barlow's Disease (BD) and Fibro-elastic Deficiency (FED) is currently unknown. The aim of this study is to evaluate post-operative LV reverse remodeling and function in patients with BD versus FED. In this study, 100 MVP patients (BD = 37 and FED = 63) with severe MR who underwent mitral valve surgery at three Belgian centers were retrospectively included. Transthoracic echocardiography was used to assess MR severity, LV volumes and function before surgery and 6 months thereafter. Baseline MR severity, LV ejection fraction (LVEF), indexed LV end-diastolic (LVEDVi) and end-systolic volumes (LVESVi) were not different between the groups. After a median follow-up of 278 days, there was a similar decrease in LVEDVi, but a trend towards a smaller decrease in LVESVi in BD compared to FED (-3.0 ± 11.2 mL/m2 vs. -5.3 ± 9.0 mL/m2; p = 0.154). This resulted in a significantly larger decrease in LVEF in BD (-8.3 ± 9.6%) versus FED (-3.9 ± 6.9%) after adjusting for baseline LVEF (p < 0.001) and type of surgical intervention (p = 0.01). These findings suggest that LV (reverse) remodeling in BD could be affected by other mechanisms beyond volume overload, potentially involving concomitant cardiomyopathy.

Catheter Ablation for Atrial Fibrillation in Patients with Left Ventricular Ejection Fraction ≤ 45%: A Meta-Analysis of Randomized Controlled Trials.

Atrial fibrillation (AF) and heart failure (HF) frequently coexist, resulting in adverse outcomes. However, controversies remain regarding the efficacy of catheter ablation (CA) in AF patients with severe left ventricular dysfunction. The purpose of this study was to perform a meta-analysis of prospective randomized controlled trials to evaluate the efficacy of CA versus medical therapy (MT) in AF patients with left ventricular ejection fraction (LVEF) ≤45%. We searched the literature for studies that compared CA to MT in AF patients with LVEF ≤45%. A meta-analysis of 7 clinical trials was performed, including 1163 patients with AF and HF. Subgroup analysis was performed based on baseline LVEF. All tests were 2-sided; only the p-value <0.05 was considered statistically significant. We found that CA was associated with lower all-cause mortality (risk ratio: 0.52, 95% CI: 0.37 to 0.72; p<0.01) and greater improvements in LVEF (mean difference: 4.80%, 95% CI: 2.29% to 7.31%; p<0.01) compared to MT. Patients in the CA group had a lower risk of HF hospitalization and AF recurrence and a significantly better quality of life than those in the MT group. The results of subgroup analysis indicated that patients with milder left ventricular dysfunction improved LVEF after AF ablation (mean difference: 6.53%, 95% CI: 6.18% to 6.88%; p<0.01) compared to patients with more severe disease (mean difference: 2.02%, 95% CI: 0.87% to 3.16%; p<0.01). Our meta-analysis demonstrated that CA was associated with significant improvements in outcomes of AF patients with LVEF ≤45%. Additionally, AF patients with milder left ventricular dysfunction could benefit more from CA.