Significant Left Ventricular Ejection Fraction Research Articles

Prognostic Impact of Left Ventricular Ejection Fraction Improvement after Transcatheter Aortic Valve Replacement.

Introduction: Transcatheter aortic valve replacement (TAVR) has become an efficient and safe alternative to surgical aortic valve replacement (SAVR). While severe aortic stenosis as well as severe aortic regurgitation (AR) are known to negatively impact left ventricular ejection fraction (LVEF), prior studies have shown that TAVR can lead to an improvement in LVEF. Thus far, little is known about the prognostic implication of LVEF improvement as a sole predictor of outcomes. Therefore, the aim of this study was to assess the prognostic impact of LVEF impairment before TAVR, as well as early LVEF improvement in patients undergoing TAVR. Materials and Methods: Patients undergoing TAVR in a large tertiary university hospital were consecutively included in a prospective registry. Transthoracic echocardiography (TTE) was performed at baseline, after 1 month and annually thereafter. Significant LVEF improvement was defined as a relative increase of ≥10% in LVEF at 30 days compared to baseline LVEF. The primary outcome was all-cause mortality at 1 year. Secondary outcomes were major adverse cardiovascular events (MACEs) including cardiovascular death, non-fatal myocardial infarction, stroke, bleeding and unplanned re-interventions of the aortic valve at 5 years. Results: Among 1655 patients who underwent TAVR between September 2011 and April 2024, the LVEF at baseline was available for 1556 patients. Of these, 1031 patients (66.2%) had preserved LVEF at baseline (LVEF ≥ 53%), whereas 303 patients (19.5%) had moderately reduced LVEF (40-52%) and 222 patients (14.3%) had severely reduced LVEF (<40%). Out of the patients with impaired LVEF, 155 (40.4%) patients showed a significant improvement in LVEF ≥10% after 30 days, while 229 (60.6%) patients showed no significant LVEF improvement (<10%). Patients with preserved LVEF at baseline had significantly better mortality outcomes than those with severely reduced LVEF (p < 0.001). LVEF improvement was associated with a survival benefit after 1 year (p = 0.009, HR 2.68, 0.95 CI 1.23-5.85) which diminished after 5 years (p = 0.058), but patients with LVEF improvement showed lower MACE rates at 5 years (p < 0.001). Conclusions: Preserved LVEF before TAVR is an independent predictor for improved outcomes. Additionally, early improvement in LVEF is associated with beneficial outcomes in patients undergoing TAVR.

Abstract PO5-26-03: Evaluation of cardiotoxicity in Mexican patients with Breast Cancer under neoadjuvant treatment by two-dimension speckle echocardiography

Abstract Background Cardiotoxicity is a major concern in breast cancer patients treated with anthracyclines or anti-HER-2 therapy. The assessment of left ventricular ejection fraction (LVEF) by transthoracic echocardiogram (TTE) has been the most common method to evaluate cardiotoxicity. Different TTE parameters have been studied to assess cardiotoxicity, we aimed to evaluate left atrial strain (LAS) as a parameter of diastolic cardiotoxicity in Mexican patients under neoadjuvant treatment. Methods We prospectively recruited patients with breast cancer under neoadjuvant treatment with anthracyclines and/or anti-HER-2 from March 2022 to present. The evaluation includes TTE, and troponin measurements before chemotherapy, and respective follow-ups at 3 and 6 months from the baseline. We enrolled 187 patients, 172 and 131 had completed the three and six-month follow-ups, respectively. We limited the analysis to patients we could assess cardiotoxicity status, defined according to the ESC 2022 guidelines. Clinical and echocardiographic parameters were compared according to cardiotoxicity status using Chi-squared, two-tailed t-tests or Wilcoxon tests, as appropriate. Results The mean time of follow-up at second assessment was 213 days. The patients are divided into cardiotoxicity and no cardiotoxicity group. We reported 81 events of cardiotoxicity if we include troponin measurement or 36 events if we only evaluate TTE measurements. The incidence of cardiotoxicity in this study was not related with common risk factors as high BMI, presence of hypertension/diabetes or smoking status, but it was statistically associated with the presence of elevated LDL cholesterol (p 0.026). Fourteen percent (14%) were HR-/HER-2 (+), 44% HR+/HER-2 (-), 25% HR+/HER-2 (+), and 17% triple negative subtype. Eightyfive percent (85%) of patients received anthracyclines, 28% in combination with anti-HER-2 treatment, 12% received double anti-HER-2 blockade anthracycline free. The accumulated dose of anthracycline didn’t differ between groups. The use of anthracyclines and double anti/HER blockade was statically associated with development of CTRCD (p &amp;lt; 0.01 and p &amp;lt; 0.01), respectively, but not with a single anti-HER-2 treatment. In troponin-based cardiotoxicity definition, at the three-month follow-up, those who developed cancer therapy-related cardiac dysfunction (CTRCD) had only statically significant lower LVEF (Table 1) with respect to basal assessment. LASr baseline, three months and six months was similar between groups. In the cardiotoxicity group without troponin measurement, we observed statically significant decreased LVEF and LV GLS at 3 months and six months, and tendency to decreased LASr with respect to basal evaluation. Conclusions In our cohort the only modifiable risk factor with impact in the development of CTRCD was dyslipidemia, specifically high LDL. The traditional chemotherapy schemas as anthracyclines and doble anti HER-2 blockade correlate with the development of cardiotoxicity, but not the use of anti-HER-2 as single agent. The addition of troponin measurement to cardiotoxicity definition detected a greater number of events in this study, but doesn’t reflect changes in ETT parameters as LV- GLS and LVEF at this time of follow up, which means structural changes induced by treatment take time and serological measurement of troponin can enhance sensitivity and allows early detection. Further follow up and ETT assessment are needed. Table 1. Cardiotoxicity events including or not troponin levels and TTE parameters. Citation Format: Haydee Williams-Sanchez, Jose Rodrigo Espinosa-Fernandez, Sandy Ruiz-Cruz, Areli Velazquez-Martinez, Nilda Espinola-Zavaleta, Enrique C. Guerra, Alexis D Aparicio-Ortiz, Aldo Cabello-Ganem, Santiago Luna-Alcalá, Leonardo Proaño-Bernal, Neftali Eduardo Antonio-Villa. Evaluation of cardiotoxicity in Mexican patients with Breast Cancer under neoadjuvant treatment by two-dimension speckle echocardiography [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 PO5-26-03.

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.

Potential for Dose Reduction in CT-Derived Left Ventricular Ejection Fraction: A Simulation Study.

Measuring left ventricular ejection fraction (LVEF) is important for detecting heart failure, e.g., in treatment with potentially cardiotoxic chemotherapy. MRI is considered the reference standard for LVEF, but availability may be limited and claustrophobia or metal implants still present challenges. CT has been shown to be accurate and would be advantageous, as LVEF could be measured in conjunction with routine chest-abdomen-pelvis oncology CT. However, the use of CT is not recommended due to the excessive radiation dose. This study aimed to explore the potential for dose reduction using simulation. Using an anthropomorphic heart phantom scanned at 13 dose levels, a noise simulation algorithm was developed to introduce controlled Poisson noise. Filtered backprojection parameters were iteratively tested to minimise differences in myocardium-to-ventricle contrast/noise ratio, as well as structural similarity index (SSIM) differences between real and simulated images at all dose levels. Fifty-one clinical CT coronary angiographies, scanned with full dose through end-systolic and -diastolic phases, were located retrospectively. Using the developed algorithm, noise was introduced corresponding to 25, 10, 5 and 2% of the original dose level. LVEF was measured using clinical software (Syngo.via VB50) with papillary muscles in and excluded from the LV volume. At each dose level, LVEF was compared to the 100% dose level, using Bland-Altman analysis. The effective dose was calculated from DLP using a conversion factor of 0.026 mSv/mGycm. In the clinical images, mean CTDIvol and DLP were 47.1 mGy and 771.9 mGycm, respectively (effective dose 20.0 mSv). Measurements with papillary muscles excluded did not exhibit statistically significant LVEF bias to full-dose images at 25, 10 and 5% simulated dose. At 2% dose, a significant bias of 4.4% was found. With papillary muscles included, small but significant biases were found at all simulated dose levels. Provided that measurements are performed with papillary muscles excluded from the LV volume, the dose can be reduced by a factor of 20 without significantly affecting LVEF measurements. This corresponds to an effective dose of 1 mSv. CT can potentially be used for LVEF measurement with minimal excessive radiation.

Abstract 15233: Stem Cell Therapy for the Treatment of Chronic Ischemic Heart Disease: A Review

Introduction: Chronic ischemic heart disease remains a major cause of morbidity and mortality. Several clinical trials have been performed to evaluate benefit of stem cells transplantation to restore cardiac function. Aim: The review reports potential benefit of stem cells therapy in chronic ischemic heart disease. Methods: Trials were selected applying as search terms “bone marrow cells”, “stem cells”, “mesenchymal cells”, and “chronic ischemic heart disease” in www.pubmed.gov and Cochrane library from 2005 to 2023. Studies were included if they were randomized blinded trials, randomized unblinded trials, non-randomized trials. Left ventricular ejection fraction (LVEF) increase and New York Heart Association (NYHA) class decrease were the outcome parameters at 6 and 12 months follow up. Results: We analyzed 20 trials including 1812 patients (939 treated, 789 males, mean age 62 years). Bone marrow (BMC), peripheral blood (PBC), cardiac (CDC) or mesenchymal (MES) stem cells were utilized in 8, 5, 7 trials, respectively. Total number of transplanted cells ranged from 5 x 10 6 to 1,300 x 10 6 (median 70 x 10 6 ) depending on cell type, cell population purification, and transplantation route. Transplant procedure was intracoronary in 9 trials and intramyocardial in 11 trials. At baseline mean LVEF was 33.5 % (range 27.1 - 46.0 %). Eleven trials reported a statistically significant percent LVEF increase between 4% to 19% (mean 9.6%) at 12 months after stem cells transplantation ( p values ranging from 0.05 to 0.001). BMC and PBC stem cells were utilized in all these studies. A significant correlation was found between number of transplanted cells and percent LVEF increase (Pearson correlation coefficient 0.74, p = 0.01). Conclusions: Results seem to favor a moderate positive effect of stem cells transplantation in chronic ischemic heart disease at 12 months follow up. The positive effect was correlated with the number of transplanted cells. However, caution should be exercised in the evaluation of clinical trials due to the different stem cells utilized, transplant protocols and endpoints.

Abstract 16049: Hydrogen Sulfide Attenuates Duchenne Cardiomyopathy via Suppression of Sterile Inflammation

Background: Duchenne muscular dystrophy (DMD) is a lethal, X-linked recessive disease caused by mutations in dystrophin. There is currently no cure for DMD, and the main cause of death is dilated cardiomyopathy. Hydrogen sulfide (H 2 S) is a gaseous molecule produced endogenously, and disruptions in basal H 2 S levels have been associated with various pathophysiological conditions, including heart failure. In this study, we investigated whether H 2 S could prevent cardiac dysfunction in a mouse model of DMD. Methods: Male mdx 4cv /mTR KO mice received early treatment (ET) with the H 2 S donor, SG1002 (40 mg/kg/day in chow starting at the time of weaning) or no treatment (NT), and wildtype C57BL (WT) mice were used as control. Left ventricular ejection fraction (LVEF) was assessed by transthoracic echocardiography. Skeletal and cardiac fibrosis was determined by picrosirius red staining. NLRP3 inflammasome activity was measured through apoptosis speck like protein (ASC) staining in cardiac muscle tissue. Results: NT mice exhibited significant LVEF decline by 4 months compared to ET and WT mice and declined further by 12 months (n=15-17, NT: 45.2% ± 7.9 vs ET: 57.1% ± 8.9% and WT: 56.5% ± 7.0%, P&lt;0.001). In addition, ET mice showed significantly reduced fibrosis compared to NT mice in the myocardium (n=5-8, 2.62% ± 0.87% vs 11.32% ± 4.70%, respectively, P=0.002), diaphragm (n=11-14, 15.84% ± 9.0% vs 31.14% ± 7.1%, respectively, P&lt;0.001), and gastrocnemius (n=12-17, 7.60% ± 3.14% vs 13.48% ± 5.97%, respectively, P=0.004) at 12 months. ASC aggregation score was significantly higher in cardiac tissue samples (Fig 1) from NT mice at 12 months compared with WT mice. ET attenuated the increase in cardiac ASC aggregation at 12 months compared with NT mice (P&lt;0.001). Conclusions: Our results demonstrate that early treatment with SG1002 preserves cardiac function in a mouse model of DMD and suggest a potential therapeutic role of NLRP3 inflammasome suppression as a protective strategy in DMD.

Prognostic implications of left ventricular ejection fraction trajectory changes in heart failure.

The latest guidelines recommended to assess the trajectory of left ventricular ejection fraction (LVEF) in patients with heart failure (HF). However, there is limited data on the trajectory of LVEF in real-world settings. In this study, we investigated the frequency and prognostic implications of changes in LVEF trajectory. Patients were divided into intensified LVEF, static LVEF, and worsening LVEF groups based on the transitions of HF types from baseline to follow-up. The intensified and worsening LVEF groups were further subdivided into mild (≤10% absolute changes of LVEF) and significant (>10% absolute changes of LVEF) increase or decrease groups according to the magnitude of change. The incidences and associations of changes in LVEF with patient outcomes were analyzed. Among the 2,429 patients in the study cohort, 38.3% of HF with reduced ejection fraction (HFrEF) and 37.6% of HF with mildly reduced ejection fraction (HFmrEF) showed an improvement in their LVEF. In contrast, a decline in LVEF was observed in 19.3% of HF patients with preserved ejection fraction (HFpEF) and 34.9% of those with HFmrEF. Cox regression analysis showed that the intensified LVEF group was associated with a lower risk of composite endpoints, while the worsening LVEF group yielded opposite findings. Subgroup analysis revealed that compared to those with mild changes in LVEF, baseline HFrEF patients with significant increase showed a lower risk of composite outcome, while baseline HFpEF patients were the opposite. The trajectories of LVEF changes are strongly correlated with outcomes in patients with HF who had prior history of HF admission. The most significant prognostic implications observed in patients with significant LVEF changes. Trajectory LVEF and type of HF changes are useful tools recommended for prognostication.

ACEI/ARB and beta-blocker therapies for preventing cardiotoxicity of antineoplastic agents in breast cancer: a systematic review and meta-analysis.

Anthracyclines and trastuzumab are widely used to treat breast cancer but increase the risk of cardiomyopathy and heart failure. With the use of trastuzumab and anthracycline-containing medications, this study intends to evaluate the effectiveness and security of current treatments against cardiotoxicity. We conducted a systematic review of randomized controlled trials (RCTs), which used at least one angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), or beta-blocker (BB) to prevent cardiotoxicity of antineoplastic agents for breast cancer, in 4 databases (PubMed, Cochrane Library, EMBASE, Web of Science) from inception to 11 May 2022, without language restrictions. The outcome of interest was left ventricular ejection fraction (LVEF) and adverse events. Stata 15 and R software 4.2.1 were used to perform all statistical analyses. The Cochrane version 2 of the risk of bias tool was used to assess the risk of bias, and the grading of recommendations assessment, development, and evaluation (GRADE) assessment was used to appraise the quality of the evidence. Fifteen randomized clinical studies with a total of 1977 patients were included in the analysis. The included studies demonstrated statistically significant LVEF in the ACEI/ARB and BB treatment groups (χ2 = 184.75, I2 = 88.6%, p = 0.000; SMD 0.556, 95% CI 0.299 to 0.813). In an exploratory subgroup analysis, the benefit of experimental agents on LVEF, whether anthracyclines or trastuzumab, was prominent in patients treated with ACEIs, ARBs, and BBs. Compared to placebo, ACEI/ARB and BB treatments in breast cancer patients protect against cardiotoxicity after trastuzumab and anthracycline-containing medication treatment, indicating a benefit for both.

Left ventricular ejection fraction and functional capacity: insights from cardiopulmonary exercise testing

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Cardiac rehabilitation program (CRP) is a multidisciplinary intervention tailored to improve functional fitness in different cardiovascular conditions. Patients with reduced left ventricular ejection fraction (LVEF) are commonly unrepresented hence the impact of LVEF on functional fitness is uncertain. Purpose To evaluate changes on functional capacity in a cohort of patients referred to a CRP, according to baseline LVEF. Methods Tertiary-center retrospective analysis of patients referred to an exercise-based phase II CRP. To be enrolled patients had to complete a 12-weeks CRP and to perform a symptom-limiting cardiopulmonary exercise test (CPET), at the beginning and at the end of the program. Patients were stratified into a reduced (LVEF &amp;lt; 45%) or preserved (LVEF ≥ 45%) group. Four CPET parameters were evaluate: peak oxygen uptake (pVO2), predicted-pVO2 (ppVO2), O2 pulse and VE/VCO2 slope. Results 127 patients (mean age 57.8 ± 11.2 years; males 79.5%) were eligible for CRP, of which 86.6% were referred following an acute coronary event. Patients included in the reduced LVEF group (38.6%; mean LVEF 31% ± 8.1) had more dyslipidemia (48.8% vs 22.8%, p = 0.013), atrial fibrillation (24.5% vs 7.7%, p = 0.008) and implanted electronic devices with defibrillator (30.6% vs 2.6%, p&amp;lt;0.001). Regarding CPET parameters, reduced LVEF patients had a lower pVO2 (mean dif 2, p = 0.048), ppVO2 (mean dif 12.1%, p&amp;lt;0.001) and O2 pulse value (mean dif 2, p = 0.049) vs higher values of VE/VCO2 slope (mean dif 2.9, p = 0.036). The Weber and ARENA classifications analysis revealed similar distribution between groups: 24.4% of reduced vs 27.5% of preserved patients entering CRP had a low Weber class (C or D). Higher ARENA class (III-IV) included 28.5% of patients with reduced and 14.1% with preserved LVEF. At the end of the rehabilitation program, changes on CPET parameters were similar between reduced and preserved groups: ppVO2 increased by 4% vs 3.2% (p = 0.808), O2 pulse increased about 0.7 vs 0.5 mL/beat (p = 0.509) and VE/VCO2 slope reduces 1.7 vs 0.3 (p = 0.232). As a continuous variable, LVEF did not predict Weber´s (p = 0.546) or ARENA (p = 0.393) class changes. Yet, those with a reduced baseline LVEF derived a greater LVEF improvement after CRP (Δ 10.2 ± 9.8 vs Δ 2.2 ± 7.9; p&amp;lt;0.001) Conclusions All patients enrolled in CRP show improvement of exercise capacity irrespective of baseline LVEF. Thus, patients with reduced LVEF should not be denied for cardiac rehabilitation and a significant LVEF improvement is expected.

Evaluation of the pharmacotherapeutic impact on contractility recovery in patients with newly diagnosed, acute onset dilated cardiomyopathy.

In patients with acute onset dilated cardiomyopathy (DCM) an improvement of left ventricular ejection fraction (LVEF) can occur as an effect of complex therapy. The aim of the study was to evaluate a pharmacotherapeutic impact on LVEF recovery in newly diagnosed DCM heart failure (HF) patients. A total of 2436 patients hospitalized due to acute decompensated HF were retrospectively analyzed. Finally, 24 patients with newly diagnosed DCM (51.4 ± 16.3 years, New York Heart Association 2.3 ± 0.7, LVEF 25 ± 10%) were observed (13.4 ± 16.0 months) in terms of the result of complex therapy. Patients were divided according to LVEF improvement on follow-up echocardiography: "recovery group" (LVEF improvement > 5%; n = 13) and "nonrecovery group" (∆LVEF ≤ 5%; n = 11). Evaluation of baseline parameters showed lower LVEF (19 ± 6 vs 31 ± 10%; P = .0048) and lower incidence of arterial hypertension (27% vs 73%; P = .043) in "recovery" group. After follow-up period LVEF was similar in both groups; however, significant LVEF improvement was demonstrated only in the "recovery group" (19 ± 6% to 34 ± 8%; P < .001). Only the "recovery group" showed significant HF symptoms reduction (New York Heart Association class: 2.5 ± 0.7 to 1.6 ± 0.6; P = .003). The "recovery group" had prescribed higher doses of loop diuretic (equivalent dose of furosemidum: 80 ± 38 mg vs 43 ± 24 mg; P = .025). Despite optimal therapy, significant LVEF improvement is observed only in the half of the patients with newly diagnosed DCM with HF with reduced EF. Prescription of higher doses of loop diuretics may have positive effect on the reduction of symptoms in newly diagnosed DCM HF patients. Lack of other risk factors such as arterial hypertension may increase the chance of LVEF recovery.

Early improvement of strain imaging parameters predicts long-term response to sacubitril/valsartan in patients with heart failure with reduced ejection fraction: An observational prospective study

BackgroundManagement of patients affected by heart failure with reduced ejection fraction (HFrEF) has deeply changed thanks to novel pharmacological therapies, such as Sacubitril/Valsartan, which assured morbidity and mortality advantages in this population. These effects may be mediated by both left atrial (LA) and ventricular reverse remodeling, although left ventricular ejection fraction (LVEF) recovery still represents the main parameter of treatment response. MethodsIn this prospective, observational study, 66 patients with HFrEF and naïve from Sacubitril/Valsartan were enrolled. All patients were evaluated at baseline, at 3 months and 12 months from therapy initiation. Echocardiographic parameters, including speckle tracking analysis, LA functional and structural metrics, were collected at three timepoints. The endpoints of our study were: (1) to evaluate the effects of Sacubitril/Valsartan on echo measurements; (2) to assess the predictive role of early modifications of these parameters (expressed as ∆ 3–0 months) on long-term LVEF significant recovery, defined as >15% improvement from baseline. ResultsThe majority of echocardiographic parameters evaluated progressively improved during the observation period, including LVEF, ventricular volumes and LA metrics. ∆(3–0 months) of LV Global Longitudinal Strain (LVGLS) and LA Reservoir Strain (LARS) were associated with significant LVEF improvement at 12 months (p < 0.001 and p = 0.019 respectively). A cut-off of ∆(3–0 months) LVGLS of 3% and of ∆(3–0 months) LARS of 2% could predict LVEF recovery with satisfactory sensitivity and specificity. ConclusionsLV and LA strain analysis may identify patients who adequately respond to HFrEF medical treatment and should be routinely used in the evaluation of these patients.

The feasibility and safety of his-purkinje conduction system pacing in patients with heart failure with severely reduced ejection fraction.

The purpose of this study was to evaluate the feasibility and outcomes of conduction system pacing (CSP) in patients with heart failure (HF) who had a severely reduced left ventricular ejection fraction (LVEF) of less than 30% (HFsrEF). Between January 2018 and December 2020, all consecutive HF patients with LVEF < 30% who underwent CSP at our center were evaluated. Clinical outcomes and echocardiographic data [LVEF and left ventricular end-systolic volume (LVESV)], and complications were all recorded. In addition, clinical and echocardiographic (≥5% improvement in LVEF or ≥15% decrease in LVESV) responses were assessed. The patients were classified into a complete left bundle branch block (CLBBB) morphology group and a non-CLBBB morphology group according to the baseline QRS configuration. Seventy patients (66 ± 8.84 years; 55.7% male) with a mean LVEF of 23.2 ± 3.23%, LVEDd of 67.33 ± 7.47 mm and LVESV of 212.08 ± 39.74 ml were included. QRS configuration at baseline was CLBBB in 67.1% (47/70) of patients and non-CLBBB in 32.9%. At implantation, the CSP threshold was 0.6 ± 0.3 V @ 0.4 ms and remained stable during a mean follow-up of 23.43 ± 11.44 months. CSP resulted in significant LVEF improvement from 23.2 ± 3.23% to 34.93 ± 10.34% (P < 0.001) and significant QRS narrowing from 154.99 ± 34.42 to 130.81 ± 25.18 ms (P < 0.001). Clinical and echocardiographic responses were observed in 91.4% (64/70) and 77.1% (54/70) of patients. Super-response to CSP (≥15% improvement in LVEF or ≥30% decrease in LVESV) was observed in 52.9% (37/70) of patients. One patient died due to acute HF and following severe metabolic disorders. Baseline BNP (odds ratio: 0.969; 95% confidence interval: 0.939-0.989; P = 0.045) was associated with echocardiographic response. The proportions of clinical and echocardiographic responses in the CLBBB group were higher than those in the non-CLBBB group but without significant statistical differences. CSP is feasible and safe in patients with HFsrEF. CSP is associated with a significant improvement in clinical and echocardiographic outcomes, even for patients with non-CLBBB widened QRS.

Impact of in-Hospital Left Ventricular Ejection Fraction Recovery on Long-Term Outcomes in Patients Who Underwent Impella Support for HR PCI or Cardiogenic Shock: A Sub-Analysis from the IMP-IT Registry.

(1) Background: Percutaneous left ventricle assist devices (pLVADs) demonstrated an improvement in mid-term clinical outcomes in selected patients with severely depressed left ventricular ejection fraction (LVEF) undergoing percutaneous coronary interventions. However, the prognostic impact of in-hospital LVEF recovery is unclear. Accordingly, the present sub-analysis aims to evaluate the impact of LVEF recovery in both cardiogenic shock (CS) and high-risk percutaneous coronary intervention (HR PCI) supported with pLVADs in the IMP-IT registry. (2) Methods: A total of 279 patients (116 patients in CS and 163 patients in HR PCI) treated with Impella 2.5 or CP in the IMP-IT registry were included in this analysis, after excluding those who died while in the hospital or with missing data on LVEF recovery. The primary study objective was a composite of all-cause death, rehospitalisation for heart failure, left ventricle assist device (LVAD) implantation, or heart transplantation (HT), overall referred to as the major adverse cardiac events (MACE) at 1 year. The study aimed to evaluate the impact of in-hospital LVEF recovery on the primary study objective in patients treated with Impella for HR PCI and CS, respectively. (3) Results: The mean in-hospital change in LVEF was 10 ± 1% (p < 0.001) in the CS cohort and 3 ± 7% (p < 0.001) in the HR PCI group, achieved by 44% and 40% of patients, respectively. In the CS group, patients with less than 10% in-hospital LVEF recovery experienced higher rates of MACE at 1 year of follow-up (FU) (51% vs. 21%, HR 3.8, CI 1.7-8.4, p < 0.01). After multivariate analysis, LVEF recovery was the main independent protective factor for MACE at FU (HR 0.23, CI 0.08-0.64, p = 0.02). In the HR PCI group, LVEF recovery (>3%) was not associated with lower MACE at multivariable analysis (HR 0.73, CI 0.31-1.72, p = 0.17). Conversely, the completeness of revascularisation was found to be a protective factor for MACE (HR 0.11, CI 0.02-0.62, p = 0.02) (4) Conclusions: Significant LVEF recovery was associated with improved outcomes in CS patients treated with PCI during mechanical circulatory support with Impella, whereas complete revascularisation showed a significant clinical relevance in HR PCI.

PO-455617-16 EFFECTS OF ADDING POSTERIOR WALL ISOLATION TO PULMONARY VEIN ISOLATION IN PERSISTENT ATRIAL FIBRILLATION AND HEART FAILURE WITH REDUCED EJECTION FRACTION (HFREF)

Catheter ablation in AF and heart failure with reduced ejection fraction (HFrEF) is associated with improved left ventricular ejection fraction(LVEF) and survival compared with medical therapy. Previous non-randomized studies have shown high success rates with adjunctive ablation strategies beyond pulmonary vein isolation (PVI), including posterior wall isolation (PWI). To examine differences in arrhythmia outcomes between PVI alone versus PVI with PWI in patients with concomitant persistent AF (PsAF) and HFrEF CAPLA was a multi-centre, prospective, randomized trial involving PsAF patients assigned to PVI alone or PVI with PWI. This substudy included patients with HFrEF(LVEF<50% on echocardiography). The primary endpoint was freedom from any documented atrial arrhythmia of>30 seconds, after a single ablation procedure, off anti-arrhythmic therapy(AAD) at 12 months. 98 patients with PsAF and HFrEF(mean age 62.1+/-9.8 years, 79.5% males, median LVEF 35+/-13%). 46.9% underwent PVI with PWI. After 12 months, 58.7% with PVI and PWI were free from recurrent atrial arrhythmia off AAD vs 61.5% of patients with PVI alone (HR1.02, 95% CI 0.54-1.91, p=0.96). There were no significant differences in freedom from any atrial arrhythmia on/off AAD after multiple procedures (PVI with PWI 60.9% vs PVI 65.4%; HR1.12, 95%CI 0.58-2.16; p=0.73), freedom from symptomatic atrial arrhythmia on/off AAD after multiple procedures (PVI with PWI 69.5% vs PVI 75%; HR 1.23, 95%CI 0.58-2.62; p=0.59), or median AF burden at 12 months (PVI with PWI 0% [IQR 0-2.63] vs PVI 0% [IQR0-2.59]; p=0.78). Median LVEF improved in PVI with PWI(LVEF increased by19.3+/-12.9%,p<0.01), and PVI alone (LVEF increased by 18.2+/-14%, p<0.01), with no difference between groups(p=0.71). Normalisation of LV function(≥50%) occurred in 71.4% in PVI with PWI compared with 59.1% with PVI alone(p=0.26). Catheter ablation is associated with significant LVEF improvements in PsAF and HFrEF. However adding PWI to PVI did not improve freedom from arrhythmia recurrence nor recovery of LVEF.

AB-452643-4 EFFECTS OF ADDING POSTERIOR WALL ISOLATION TO PULMONARY VEIN ISOLATION IN PERSISTENT ATRIAL FIBRILLATION AND HEART FAILURE WITH REDUCED EJECTION FRACTION (HFREF)

Catheter ablation in AF and heart failure with reduced ejection fraction (HFrEF) is associated with improved left ventricular ejection fraction(LVEF) and survival compared with medical therapy. Previous non-randomized studies have shown high success rates with adjunctive ablation strategies beyond pulmonary vein isolation (PVI), including posterior wall isolation (PWI). To examine differences in arrhythmia outcomes between PVI alone versus PVI with PWI in patients with concomitant persistent AF (PsAF) and HFrEF CAPLA was a multi-centre, prospective, randomized trial involving PsAF patients assigned to PVI alone or PVI with PWI. This substudy included patients with HFrEF(LVEF<50% on echocardiography). The primary endpoint was freedom from any documented atrial arrhythmia of>30 seconds, after a single ablation procedure, off anti-arrhythmic therapy(AAD) at 12 months. 98 patients with PsAF and HFrEF(mean age 62.1+/-9.8 years, 79.5% males, median LVEF 35+/-13%). 46.9% underwent PVI with PWI. After 12 months, 58.7% with PVI and PWI were free from recurrent atrial arrhythmia off AAD vs 61.5% of patients with PVI alone (HR1.02, 95% CI 0.54-1.91, p=0.96). There were no significant differences in freedom from any atrial arrhythmia on/off AAD after multiple procedures (PVI with PWI 60.9% vs PVI 65.4%; HR1.12, 95%CI 0.58-2.16; p=0.73), freedom from symptomatic atrial arrhythmia on/off AAD after multiple procedures (PVI with PWI 69.5% vs PVI 75%; HR 1.23, 95%CI 0.58-2.62; p=0.59), or median AF burden at 12 months (PVI with PWI 0% [IQR 0-2.63] vs PVI 0% [IQR0-2.59]; p=0.78). Median LVEF improved in PVI with PWI(LVEF increased by19.3+/-12.9%,p<0.01), and PVI alone (LVEF increased by 18.2+/-14%, p<0.01), with no difference between groups(p=0.71). Normalisation of LV function(≥50%) occurred in 71.4% in PVI with PWI compared with 59.1% with PVI alone(p=0.26). Catheter ablation is associated with significant LVEF improvements in PsAF and HFrEF. However adding PWI to PVI did not improve freedom from arrhythmia recurrence nor recovery of LVEF.

Clinical, hemodynamic and biochemical improvement related to left bundle branch area pacing.

Right ventricular pacing is associated with risk of heart failure and left ventricular dysfunction. Left bundle branch area pacing (LBBP) has emerged as an alternative method for delivering physiological pacing. The effect of LBBP on N-terminal pro-brain natriuretic peptide (NT-proBNP) has not been investigated. Finally, 50 patients referred for pacemaker implantation were included. LBBP was performed as described previously by Huang et al. Transthoracic echocardiogram and NT-proBNP were performed before and four weeks after the procedure. 50 patients were analyzed. There were not differences between ventricular thresholds during the procedure and 3 months later, LBBP significantly reduced QRS complex duration (148 ± 21 vs. 107 ± 11 ms; p = 0.029). LBBP significantly improved NYHA functional class and reduced NT-proBNP concentration (2888.2 ± 510 vs. 1181 ± 130 pg/ml; p = 0.04). In patients showing left ventricular ejection fraction (LVEF) < 50% and ventricular desynchrony LBBP showed a significant LVEF increase (40.2 ± 7 vs. 55.2 ± 7%; p < 0.001). LBBP was feasible and safe in most of patients. LBBP was associated with reduction in QRS width and with increase in LVEF in patients with ventricular desynchrony, while in patients with normal LVEF it remained unchanged during follow-up.

Cardiac Safety and Efficacy of SB3 Trastuzumab Biosimilar for ERBB2-Positive Early Breast Cancer

Trastuzumab has been the standard of care for the treatment of patients with ERBB2-positive breast cancer; however, cardiac events have been reported. This long-term follow-up study provides clinical evidence supporting the similarity of a trastuzumab biosimilar (SB3) to reference trastuzumab (TRZ). To compare cardiac safety and efficacy between SB3 and TRZ for patients with ERBB2-positive early or locally advanced breast cancer after up to 6 years of follow-up. This prespecified secondary analysis of a randomized clinical trial, conducted from April 2016 to January 2021, included patients with ERBB2-positive early or locally advanced breast cancer from a multicenter double-blind, parallel-group, equivalence phase 3 randomized clinical trial of SB3 vs TRZ with concomitant neoadjuvant chemotherapy who completed neoadjuvant and adjuvant treatment. In the original trial, patients were randomized to either SB3 or TRZ with concomitant neoadjuvant chemotherapy for 8 cycles (4 cycles of docetaxel followed by 4 cycles of fluorouracil, epirubicin, and cyclophosphamide). After surgery, patients continued SB3 or TRZ monotherapy for 10 cycles of adjuvant treatment per previous treatment allocation. Following neoadjuvant and adjuvant treatment, patients were monitored for up to 5 years. The primary outcomes were the incidence of symptomatic congestive heart failure and asymptomatic, significant decrease in left ventricular ejection fraction (LVEF). The secondary outcomes were event-free survival (EFS) and overall survival (OS). A total of 538 female patients were included (median age, 51 years [range, 22-65 years]). Baseline characteristics were comparable between the SB3 and TRZ groups. Cardiac safety was monitored for 367 patients (SB3, n = 186; TRZ, n = 181). Median follow-up was 68 months (range, 8.5-78.1 months). Asymptomatic, clinically significant LVEF decreases were rarely reported (SB3, 1 patient [0.4%]; TRZ, 2 [0.7%]). No patient experienced symptomatic cardiac failure or death due to a cardiovascular event. Survival was evaluated for the 367 patients in the cardiac safety cohort and an additional 171 patients enrolled after a protocol amendment (538 patients [SB3, n = 267; TRZ, n = 271]). No difference was observed in EFS or OS between treatment groups (EFS: hazard ratio [HR], 0.84; 95% CI, 0.58-1.20; P = .34; OS: HR, 0.61; 95% CI, 0.36-1.05; P = .07). Five-year EFS rates were 79.8% (95% CI, 74.8%-84.9%) in the SB3 group and 75.0% (95% CI, 69.7%-80.3%) in the TRZ group, and OS rates were 92.5% (95% CI, 89.2%-95.7%) in the SB3 group and 85.4% (95% CI, 81.0%-89.7%) in the TRZ group. In this secondary analysis of a randomized clinical trial, SB3 demonstrated cardiac safety and survival comparable to those of TRZ after up to 6 years of follow-up in patients with ERBB2-positive early or locally advanced breast cancer. ClinicalTrials.gov Identifier: NCT02771795.

The therapeutic benefit of upgrade to cardiac resynchronization therapy in patients with pacing-induced cardiomyopathy

Pacing-induced cardiomyopathy (PICM) is an important cause of heart failure in patients with a right ventricular pacing burden. Recent evidence suggests that an upgrade to cardiac resynchronization therapy (CRT) may confer benefit in PICM. To assess the extent and identify predictors of improvement following upgrade to CRT in patients with PICM. We retrospectively analyzed 43 patients undergoing CRT upgrade for PICM over the 10-year period of 2011 to 2021 at our center. All patients with PICM who underwent device upgrade from a dual- or single-chamber ventricular pacemaker to CRT were included. PICM was defined as a decrease of ≥10% in left ventricular ejection fraction (LVEF), resulting in an LVEF <50% among patients with ≥20% Right ventricular pacing burden without an alternative cause for cardiomyopathy. LVEF significantly improved from 28.7% preupgrade to 44.3% post-CRT upgrade (P < .01). Of 37 patients with severe LV dysfunction, 34 (91.9%) improved to an LVEF >35% and 13 (35.1%) improved to an LVEF >50%. The LV end-diastolic diameter decreased from 5.9 cm preupgrade to 5.4 cm postupgrade (P < .01). Using linear regression, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use was associated with significant LVEF improvement (+7.21%, P = .05). We observed a low rate of complications, and 1 in 4 CRT upgrades required venoplasty (n = 10 of 43, 23.3%). We provide further evidence for the benefit of CRT upgrade in the management of patients with PICM.

Effects of trastuzumab and trastuzumab emtansine on corrected QT interval and left ventricular ejection fraction in patients with metastatic (HER2+) breast cancer

BackgroundTrastuzumab and trastuzumab emtansine are specific antibody and antibody–drug conjugates used in the treatment of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer. The aim of this study was to test their effect on the QTc interval duration and left ventricular ejection fraction (LVEF) in our patients, two parameters used in evaluation of cardiotoxicity. From May 2015 to October 2017, 26 patients with preserved LVEF were included in the study. All of them were previously treated with standard paclitaxel and cisplatin-based chemotherapy regimens. Electrocardiogram (ECG) was recorded just before each trastuzumab dose application and six months after the last dose. Echocardiography with LVEF measurement was performed several days before the application of the initial dose, and six months after the last cycle. Later, 24 patients with metastatic disease received additional treatment with trastuzumab emtansine after six months and the same ECG and echocardiography protocol was performed again. Due to reduction in LVEF, two patients were discontinued from additional treatment.ResultsA statistically significant QTc prolongation was found after each drug dose application, with an increase in mean QTc duration with every successive application, reaching the peak QTc values just before the fifth cycle of treatment. The QTc interval returned to its initial value six months after the last cycle (p < 0.001). These results were similar for both drugs. Mean LVEF before both treatment protocols was significantly higher compared to LVEF value after the treatment. LVEF before trastuzumab emtansine treatment was non-significantly higher than LVEF after trastuzumab treatment.ConclusionTrastuzumab and trastuzumab emtansine cardiotoxicity manifested as a significant and progressive QTc prolongation after successive drug applications, reaching the peak value just before the fifth cycle of both drugs. Both medications also caused statistically significant but asymptomatic LVEF reduction. Complete reversibility of cardiotoxic effects of both drugs was confirmed by QTc interval and LVEF normalisation after the treatment discontinuation.

Cardioprotective medication in Duchenne muscular dystrophy: a single-centre cohort study.

Duchenne muscular dystrophy (DMD) is a neuromuscular disorder characterised by progressive muscle wasting impacting mobility, ventilation and cardiac function. Associated neuromuscular cardiomyopathy remains a major cause of morbidity and mortality. We investigated the effects of cardioprotective medications [angiotensin-converting enzyme inhibitors (ACE-I), beta-blockers] on clinical outcomes in DMD patients. This was a retrospective cohort study (reference: 2021/12469) of DMD patients at a tertiary centre between 1993-2021 screening the electronic records for demographics, comorbidities, medication, disease specific features, echocardiography, hospitalisations, and ventilator use. A total of 68 patients were identified aged 27.4 (6.6) years, of which 52 were still alive. There was a difference in body mass index (BMI) between survivors and deceased patients [23.8 (5.9) vs. 19.9 (3.8) kg/m2, P=0.03]. Home mechanical ventilation (HMV) was required in 90% of patients, 85% had DMD associated cardiomyopathy. About 2/3 of all hospitalisations during the observation period were secondary to cardiopulmonary causes. The left ventricular ejection fraction (LVEF) at initial presentation was 44.8% (10.6%) and declined by 3.3% [95% confidence interval (CI): 0.4% to -7.0%] over the follow up period (P=0.002). A total of 61 patients were established on ACE-I for 75.9% (35.1%), and 62 were on beta-blockers for 73.6% (33.5%) of the follow up period. There was a significant LVEF decline in those taking ACE-I for limited periods compared to those permanently on ACE-I (P=0.002); a similar effect was recorded with beta-blockers (P=0.02). Long-term use of ACE-I and beta-blockers is associated with a reduced decline in LVEF in patients with DMD and may be protective of adverse cardiovascular ill health.