Absolute Left Ventricular Ejection Fraction Research Articles

Impact of Diabetes and Glycemia on Cardiac Improvement and Adverse Events Following Mechanical Circulatory Support.

Type 2 diabetes is prevalent in cardiovascular disease and contributes to excess morbidity and mortality. We sought to investigate the effect of glycemia on functional cardiac improvement, morbidity, and mortality in durable left ventricular assist device (LVAD) recipients. Consecutive patients with an LVAD were prospectively evaluated (n=531). After excluding patients missing pre-LVAD glycated hemoglobin (HbA1c) measurements or having inadequate post-LVAD follow-up, 375 patients were studied. To assess functional cardiac improvement, we used absolute left ventricular ejection fraction change (ΔLVEF: LVEF post-LVAD-LVEF pre-LVAD). We quantified the association of pre-LVAD HbA1c with ΔLVEF as the primary outcome, and all-cause mortality and LVAD-related adverse event rates (ischemic stroke/transient ischemic attack, intracerebral hemorrhage, gastrointestinal bleeding, LVAD-related infection, device thrombosis) as secondary outcomes. Last, we assessed HbA1c differences pre- and post-LVAD. Patients with type 2 diabetes were older, more likely men suffering ischemic cardiomyopathy, and had longer heart failure duration. Pre-LVAD HbA1c was inversely associated with ΔLVEF in patients with nonischemic cardiomyopathy but not in those with ischemic cardiomyopathy, after adjusting for age, sex, heart failure duration, and left ventricular end-diastolic diameter. Pre-LVAD HbA1c was not associated with all-cause mortality, but higher pre-LVAD HbA1c was shown to increase the risk of intracerebral hemorrhage, LVAD-related infection, and device thrombosis by 3 years on LVAD support (P<0.05 for all). HbA1c decreased from 6.68±1.52% pre-LVAD to 6.11±1.33% post-LVAD (P<0.001). Type 2 diabetes and pre-LVAD glycemia modify the potential for functional cardiac improvement and the risk for adverse events on LVAD support. The degree and duration of pre-LVAD glycemic control optimization to favorably affect these outcomes warrants further investigation.

A Comparison of the Association of Septal Scar Burden on Responses to LBBAP-CRT and BVP-CRT

BackgroundLeft bundle branch area pacing (LBBAP) is an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT). However, despite the presence of left bundle branch block, whether cardiac substrate may influence the effect between the 2 strategies is unclear. ObjectivesThis study aims to assess the association of septal scar on reverse remodeling and clinical outcomes of LBBAP compared with BVP. MethodsWe analyzed patients with nonischemic cardiomyopathy who had CRT indications undergoing preprocedure cardiac magnetic resonance examination. Changes in left ventricular ejection fraction (LVEF) and echocardiographic response (ER) (≥5% absolute LVEF increase) were assessed at 6 months. The clinical outcome was the composite of all-cause mortality, heart failure hospitalization, or major ventricular arrhythmia. ResultsThere were 147 patients included (51 LBBAP and 96 BVP). Among patients with low septal scar burden (below median 5.7%, range: 0% to 5.3%), LVEF improvement was higher in the LBBAP than the BVP group (17.5% ± 10.9% vs 12.3% ± 11.8%; P = 0.037), with more than 3-fold increased odds of ER (OR: 4.35; P = 0.033). In high sepal scar subgroups (≥5.7%, range: 5.7%-65.9%), BVP trended towards higher LVEF improvement (9.2% ± 9.4% vs 6.4% ± 12.4%; P = 0.085). Interaction between septal scar burden and pacing strategy was significant for ER (P = 0.002) and LVEF improvement (P = 0.011) after propensity score adjustment. During median follow-up of 33.7 (Q1-Q3: 19.8-42.1) months, the composite clinical outcome occurred in 34.7% (n = 51) of patients. The high-burden subgroups had worse clinical outcomes independent of CRT method. ConclusionsRemodeling response to LBBAP and BVP among nonischemic cardiomyopathy patients is modified by septal scar burden. High septal scar burden was associated with poor clinical prognosis independent of CRT methods.

Long-term efficacy of left bundle branch pacing and biventricular pacing in patients with heart failure complicated with left bundle branch block.

Left bundle branch pacing (LBBP) can physiologically correct complete left bundle branch block (CLBBB), and has become the best alternative to biventricular pacing (BiVP). To compare the efficacy of LBBP and BiVP in patients with heart failure (HF) complicated with CLBBB. This was a single-center retrospective study. Patients with HF complicated with CLBBB who underwent successful cardiac resynchronization therapy (CRT) in Wuhan Asian Heart Hospital from June 2018 to June 2023 were enrolled and divided into LBBP group and BiVP group according to the pacing method. The primary endpoints were the absolute increase of left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and echocardiographic response rate. Secondary endpoints were all-cause mortality, heart failure hospitalization (HFH), NT-proBNP, paced QRS duration, pacing threshold, and procedural duration. A total of 120 patients were enrolled in this study, including 60 patients in LBBP group and 60 patients in BiVP group. The median follow-up time was 37 ± 19 months. Compared with BiVP group, LBBP group had a more significant increase in absolute LVEF (ΔLVEF) (14.8 ± 9.9% vs. 10.7 ± 9.0%, P = 0.02), a more significant reduction in LVEDD (56.9 ± 10.9 mm vs. 61.1 ± 10.8 mm, P = 0.03), and a higher echocardiographic super response rate (65% vs. 45%, P = 0.02). There were no significant differences in all-cause mortality (1.7% vs. 10.0%, P = 0.11) and HFH (6.7% vs. 13.3%, P = 0.22). In terms of paced QRS duration (128.7 ± 14.1 ms vs. 137.5 ± 16.5 ms, P = 0.002), pacing threshold (0.72 ± 0.21 V/0.4 ms vs. 1.39 ± 0.51 V/0.4 ms, P < 0.001), procedural duration (134.1 ± 32.2 min vs. 147.7 ± 39.4 min, P = 0.04), the LBBP group was superior to the BiVP group. In nonischemic cardiomyopathy (NICM) patients with HF combined with CLBBB and LVEF ≤ 35%, LBBP is better than BiVP.

Hand-Held Echocardiography by Advanced Practice Providers in Patients with Congestive Heart Failure.

The performed hand-held echocardiography (HHE) was evaluated and interpreted by trained advanced practice providers (APPs) on hospitalized CHF patients for image quality and interpretation by comparing with expert echocardiographer and SE findings. Congestive heart failure (CHF) is associated with increased hospital admissions and mortality. While a standard echocardiogram (SE) is the gold standard for cardiac assessment, it is not readily available. Hospitalized CHF patients require rapid assessment for expedited treatment. Over 6 months, five trained APPs performed HHE on hospitalized CHF patients and interpreted: (a) left ventricular (LV) size, (b) LV ejection fraction (LVEF), and (c) right atrial pressure (RAP). The study echocardiographer reviewed and blindly interpreted the HHE images and compared them with APPs and SE findings. Kappa statistics determined the degree of agreement between APPs and the study echocardiographer's interpretation of the HHE images and SE. A total of 80 CHF patients (age 73 ± 14 years, 58% males; LVEF (by SE) 45 ± 19%; 36.3% body mass indexes ≥ 30 kg/m2) were enrolled. HHE interpretation by APPs had a good agreement for LVEF (kappa 0.79) with the study echocardiographer and SE (kappa 0.74) and a good agreement for RAP (kappa 0.67) with the study echocardiographer. The correlation between the absolute LVEF interpretation by the study echocardiographer on HHE and SE was r = 0.88 (p < 0.0001). Trained APPs obtained diagnostic-quality HHE images and interpreted the LV function and RAP in CHF patients in good agreement with the study echocardiographer. LVEF by HHE correlated with LVEF by SE. Our study suggests trained APPs can use HHE to evaluate LVEF and RAP in CHF patients, leading to expedited and optimized treatment.

Abstract 17782: Reverse Remodeling as a Survival Predictor in Chagas Cardiomyopathy

Introduction: Chagas cardiomyopathy (CC) has a worse prognosis than other etiologies. Reverse remodeling (RR) is consistently associated with better mortality and morbidity outcomes in heart failure with reduced ejection fraction (HFrEF) of non-chagasic etiology. Still, the impact on CC has been poorly studied. Hypothesis: RR improves survival in patients with CC. Methods: From January 2006 to September 2021, the medical records of 1049 patients with positive serology for Trypansosoma cruzi infection associated with left ventricular ejection fraction (LVEF) &lt;40% were reviewed. RR was defined as a 10% absolute increase in LVEF or absolute LVEF &gt; 40% on the second echocardiogram. Participants were divided into 2 groups: negative RR (NRR) and positive RR (PRR). Results: 221 patients had PRR and 828 NRR. At baseline, the median age in the PRR group was 59 years versus 56 years in the NRR (p &lt;0.001), with 48.2% males in the RRP group versus 58.9% in the RRN (p 0.005). Regarding treatment, only the use of furosemide showed a difference (63.3% in the PRR and 75.4% in the NRR; p &lt;0.001). Regarding baseline ECOTT: the median of LVEF was 30.5% in PRR and 29% in NRR (p &lt;0.001), median LV Diastolic Diameter (DD) (PRR 60 mm; NRR 64mm; p &lt;0.001); median LV Systolic Diameter (SD) (PRR 50 mm; NRR 55 mm); the presence of moderate to severe mitral insufficiency (PRR 37.8%; NRR 50.6%; p &lt;0.001). In the second ECOTT, the PRR group had a median LVEF of 41%, LVDD of 58 mm, and LVSD of 44 mm. In both the univariate analysis and the adjustment made by the multivariate analysis by COX regression, the PRR was an independent predictor associated with all-cause death (HR 0.625, 95% CI 0.421-0.928; p 0.020). Median survival time (and 95% CI) was 8,8 (8,4-9,2) years in the NRR group and 11,4 (10,8-13,8) in the PRR group. Survival was significantly better for PRR than NRR (p &lt;0.001, pairwise Log-Rank comparison). Conclusions: This study suggests a positive association between PRR and increased survival in patients with CHD and HFrEF. Previously published studies didn’t demonstrate this association, possibly due to the small number of patients included.

Echocardiographic Measurements in Normal Healthy Adult Population of North India.

Interpretation of imaging modalities depends on robust normal reference limits. Ethnicity is an essential determinant of cardiac chamber sizes. Though few studies from India have focused on this research, it has yet to include the Kashmiri population. We aimed to study normal echocardiographic values of healthy Kashmiri adults and compare them with Western and Indian studies. It was a prospective observational study on healthy adults of Kashmir Valley. A comprehensive echocardiographic analysis following standardized protocols was performed. A total of 2245 study participants were analyzed. The mean age was 32.52±11.55 years. There were 1100 (49%) males. Males had higher absolute left ventricular volumes and mass, left atrial volumes, right ventricular diameter, and aortic size, while females had higher absolute left ventricular ejection fraction and early and late diastolic mitral inflow velocities. Males had higher indexed left ventricular end-systolic volume, while females had higher indexed left ventricular end diastole diameter, aorta diameter, right ventricle, and left and right atrial sizes. Left ventricular mass and diastolic parameters were significantly associated with age. Compared with the American Society of Echocardiography/European Association of Cardiovascular Imaging, absolute values of left ventricle size, volumes, mass, right ventricle size, aortic size, and left and right atrial size were higher than those in our study. Our study population had a higher left ventricle ejection fraction. Among indexed parameters, left ventricle volumes, left ventricle systolic diameter, aortic annulus, and left and right atrial volumes were still significantly higher in Western data. While comparing with Indian data, we noted significant regional differences. We provide normal reference values for our local population. We noted significant differences with Western as well as other Indian populations. Our study highlights the need for developing ethnic-specific reference values of various echocardiographic measurements.

Association of anthracyclines induced cardiotoxicity (AIC) in patients with early breast cancer (eBC) with germline BRCA1/2 (gBRCA1/2) mutation: BRCAN study.

567 Background: BRCA1/2 genes play a critical role in genome stability and DNA repair in human cells, including cardiomyocytes. In animal models, loss of cardiomyocyte-specific BRCA1/2 is associated with DNA damage, apoptosis, cardiac dysfunction, and cardiac mortality following anthracyclines (A) exposure. However, whether these preclinical findings translate to humans still remains unclear. We conducted the BRCAN study to assess the impact of gBRCA1/2 status on AIC in a cohort of patients with eBC. Methods: This is a single center retrospective/prospective study including patients diagnosed with HER2-negative eBC treated with A based chemotherapy in the neo/adjuvant setting, known gBRCA1/2 status, left ventricular ejection fraction (LVEF) ≥ 50% at baseline and no previous significant cardiovascular events. During follow-up, we performed myocardial dysfunction blood biomarkers (MDBB), cardiac ultrasound and quality of life questionnaires (QoL). Primary objective was to assess the absolute LVEF change from baseline in BRCA1/2 mutation carriers (gBRCA1/2mut) versus non-carriers (gBRCA1/2wt). Secondary objectives were comparing MDBB and QoL in these groups. Results: 137 patients with eBC were included in the study (103 gBRCA1/2wt and 34 gBRCA1/2mut). Patients’ characteristics were similar between both groups in terms of age, baseline LVEF, radiotherapy (RT) on left side, total A accumulative dose, time from A exposure, antihypertensive or hypolipidemic agents use and smoking habit. Compared to baseline, LVEF % reduction was -4.7 [-12.0, 0.0] versus -9.5 [-18.0, -5.0] in gBRCA1/2wt and gBRCA1/2mut, respectively (p=0.027). To correct for confounding, we fit a regression model for the variables smoking habit, antihypertensive and hypolipidemic agents use. On average, LVEF % reduction in gBRCA1/2mut group was -4.5 [CI 95% -8.6, -0.4, p=0.032] compared to gBRCA1/2wt. No differences between MDBB (protein C-reactive, hsTn, NT-ProBNP, D-Dimer, ST-2 or Galectine-3) and QoL (MLHFQ and EQ5-D index) were detected between groups. Conclusions: Our data suggest that gBRCA1/2mut patients could represent a high risk population for AIC. A baseline comprehensive cardiovascular risk assessment and a closer follow-up should be recommended in these patients. Further research is needed on order to identify early predictive biomarkers for AIC. [Table: see text]

EMMY: The continued expansion of clinical applications of SGLT2 inhibitors.

Introduction: Myocardial infarction (MI) is a challenging clinical and public health problem and is a leading cause of morbidity and mortality worldwide. Heart failure (HF) is a common sequela of acute myocardial infarction (AMI), with an incidence of up to 40% among hospitalized patients and has important implications for treatment and prognosis. Sodium-glucose co-transporter 2 inhibitors (SGLT2i), such as empagliflozin, have been shown to reduce the risk of hospitalization and cardiovascular mortality in patients with symptomatic HF and have therefore been included in the European and American heart failure guidelines. However, trials investigating the effects of this drug class in patients following acute myocardial infarction are lacking. Study and Results: The EMMY trial was conducted to assess the safety and efficacy of empagliflozin in patients with acute myocardial infarction (AMI). A total of 476 patients with AMI were randomly assigned to empagliflozin (10 mg) or matching placebo once daily within 72 h of percutaneous coronary intervention. The primary outcome was the N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP) change over 26 weeks. Secondary outcomes included changes in echocardiographic parameters. NT-proBNP reduction was significantly greater in the empagliflozin group (-15% after adjusting for baseline NT-proBNP, gender, and diabetes status (P=0.026)). Absolute left-ventricular ejection fraction improvement was 1.5% (P=0.029) greater, mean E/e' reduction was 6.8% (P=0.015) greater, and left-ventricular end-systolic and end-diastolic volumes were lower by 7.5 mL (P=0.0003) and 9.7 mL (P=0.0015), respectively, in the empagliflozin group, compared with placebo. Seven patients were hospitalized for HF (3 in the empagliflozin group). Other predefined serious adverse events were rare and did not differ significantly between groups. Lessons learned: The EMMY trial shows that early use of the SGLT2 inhibitor empagliflozin after acute myocardial infarction (MI) improves natriuretic peptide levels and markers of cardiac function and structure supporting the use of Empagliflozin in HF related to a recent MI.

Sacubitril/Valsartan Treatment in Heart Failure Increases The Left Ventricular Ejection Fraction: A Bayesian Analysis

Introduction: Heart failure is an important leading cause of mortality and morbidity despite optimal medical treatment and device therapy. Sacubitril/valsartan, a first-generation drug, was approved to use heart failure treatment recently. There are limited studies on the relationship between sacubitril/valsartan and left ventricular contraction. In our study, we aimed to evaluate the changes in left ventricular ejection fraction (LVEF) after sacubitril/valsartan treatment. Patients and Methods: Fifty-two patients with heart failure and reduced ejection fraction (HFrEF) were enrolled in this study. The baseline demographic, clinical, and echocardiographic characteristics of 52 patients were compared using the Bayesian method. Results: Fifty-two patients with heart failure and reduced ejection fraction (HFrEF) were included in the final analysis (66.2 ± 9.3 years, 69.2% male). Sacubitril/valsartan initial dose was low in 44.2% of patients, and intermediate in 55.8%. In the low initial dose population, the increase in absolute LVEF was 3.87 (95% HDI 1.53-6.20) and in the intermediate initial dose population, the increase in absolute LVEF was 5.89 (95% HDI 4.18-7.61). In the female population, the increase in absolute LVEF was 5.56 (95% HDI 3.49-7.63) and in the male population 4.75 (95% HDI 2.91-6.58) respectively. Conclusion: In this study, we demonstrated that sacubitril/valsartan is associated with increased LVEF regardless of baseline clinical characteristics.

Development of a new score to predict left ventricular reverse remodelling in patients with nonischemic cardiomyopathy

Abstract Background and purpose Implantable cardioverter-defibrillator is indicated in patients with dilated non-ischemic cardiomyopathy (DCM) and severely depressed left ventricular ejection fraction (LVEF) after a wait-and-see period of 3–9 months under optimised medical therapy. However, in the first 6 months after the disease debut, around 2% of patients might suffer life-threatening arrhythmias. The appearance of left ventricular reverse remodelling (LVRR) in patients with DCM is associated with a lower incidence of ventricular tachyarrhythmias. Therefore, it is relevant an early identification of the patients who will experience LVRR during the follow-up. Our aim was to develop a score to predict the appearance of LVRR in patients with DCM. Methods From 2014 to 2021, 201 patients with DCM and LVEF ≤45% were prospectively evaluated in our tertiary care hospital. All patients underwent a transthoracic echocardiogram and 1.5 Tesla scanner cardiac magnetic resonance (MR) as part of the diagnostic workup. LVRR was defined as an increase in LVEF ≥10 points or absolute LVEF ≥50% associated with a reduction in left ventricular end-diastolic diameter ≥10%. Results The median age of our cohort (n=201) was 61.6 (14.7) years, and 68% were male. Most patients (&amp;gt;90%) were treated with beta-blockers or RASS blockers, and 72% with mineralocorticoid receptor antagonists. During a mean follow-up period of 37.6 (33.9) months 45% of patients had LVRR. Patients with LVRR had a lower cardiovascular mortality (3.33 vs 9.59%; p=0.153), lower mortality due to heart failure (0% vs 8.22%; p=0.023), and a lower incidence of ventricular tachyarrhythmias (1.67% vs 19.18%; p=0.001). Table 1 shows the echocardiographic, MR and clinical characteristics of patients who experienced LVRR. Variables significantly associated with LVRR in the univariable analysis and considered clinically relevant were included in a multivariable logistic regression analysis. The final model included the presence of right ventricular end systolic volume index (RVESVi) &amp;gt;50 ml/m2 (2 points), left bundle brach block (LBBB) echo pattern (1 point), female gender (1 point) and tachycardiomyopathy/idiopathic/alcoholic/chemotherapy induced cardiomyopathy as the potencial cause of DCM (1 point). The score showed a good discrimination, with an area under the ROC curve of 0.82 (95% CI 0.69 to 0.94), 84% sensitivity and 80% specificity. The presence of 3 or more points was associated with a high probability to had LVRR (0 points: 1%; 1 points: 17%; 2 points: 38%; 3 points: 64%; 4 points: 84%%; 5 points: 94% and 6 points: 98%) (Figure 1). Conclusion A new score with four variables (RVESV, LBBB echo pattern, female gender and tachycardiomyopathy/idiopatic/alcoholic/chemotheapy induced cardiomyopathy as potential cause) accurately predicts the probability of LVRR. Considering patients who experience LVRR have less cardiovascular events, this score may be a helpful tool for patients' risk stratification. Funding Acknowledgement Type of funding sources: None.

Heart Failure Duration and Mechanistic Efficacy of Sacubitril/Valsartan in Heart Failure With Reduced Ejection Fraction

BackgroundAlthough sacubitril/valsartan (Sac/Val) is indicated for the treatment of heart failure with reduced ejection fraction (HFrEF), gaps in care continue to exist for those with newer onset HFrEF vs those with longer durations of disease. Methods and ResultsWe categorized 794 persons with HFrEF (EF of ≤40%) according to a HF duration of less than 12 months, 12–24 months, 24–60 months, and more than> 60 months. After the initiation of Sac/Val, concentrations of N-terminal pro-B type natriuretic peptide, high sensitivity cardiac troponin T, and soluble ST2 were measured, and Kansas City Cardiomyopathy Questionnaire 23 scores were obtained serially from baseline to 12 months. The left ventricular ejection fraction was measured by echocardiography. Significant decreases in the concentrations of N-terminal pro-B type natriuretic peptide, high sensitivity cardiac troponin T, and soluble ST2 were observed regardless of HF duration (P < .001). Comparable gains in Kansas City Cardiomyopathy Questionnaire 23 scores were achieved in all HF duration categories. Moreover, consistent reverse cardiac remodeling in all HF duration categories occurred, with the absolute left ventricular ejection fraction improvement by 12 months across HF duration groups of 12.2%, 6.9%, 8.5%, and 8.6% for HF duration of less than 12 months, 12–24 months, 24–60 months, and more than 60 months, respectively. ConclusionsThe initiation of Sac/Val decreases prognostic biomarkers, improves health status, and reverses cardiac remodeling processes, regardless of HF duration. Brief lay summaryWe categorized 794 persons with heart failure owing to a low ejection fraction according to disease duration into 4 groups: less than 12 months, 12–24 months, 24–60 months, and more than 60 months. After the initiation of sacubitril/valsartan (Entresto), we found that regardless of the duration of heart failure significant improvements occurred in cardiac biomarkers, patients felt better with improved health status and on testing with cardiac ultrasound examination, improvement in heart size, and function occurred. These results suggest that, regardless of heart failure duration, patients with a reduced ejection fraction would benefit from use of sacubitril/valsartan for their care.

Empagliflozin in acute myocardial infarction: the EMMY trial.

Sodium-glucose co-transporter 2 inhibition reduces the risk of hospitalization for heart failure and for death in patients with symptomatic heart failure. However, trials investigating the effects of this drug class in patients following acute myocardial infarction are lacking. In this academic, multicentre, double-blind trial, patients (n = 476) with acute myocardial infarction accompanied by a large creatine kinase elevation (>800 IU/L) were randomly assigned to empagliflozin 10 mg or matching placebo once daily within 72 h of percutaneous coronary intervention. The primary outcome was the N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP) change over 26 weeks. Secondary outcomes included changes in echocardiographic parameters. Baseline median (interquartile range) NT-proBNP was 1294 (757-2246) pg/mL. NT-proBNP reduction was significantly greater in the empagliflozin group, compared with placebo, being 15% lower [95% confidence interval (CI) -4.4% to -23.6%] after adjusting for baseline NT-proBNP, sex, and diabetes status (P = 0.026). Absolute left-ventricular ejection fraction improvement was significantly greater (1.5%, 95% CI 0.2-2.9%, P = 0.029), mean E/e' reduction was 6.8% (95% CI 1.3-11.3%, P = 0.015) greater, and left-ventricular end-systolic and end-diastolic volumes were lower by 7.5 mL (95% CI 3.4-11.5 mL, P = 0.0003) and 9.7 mL (95% CI 3.7-15.7 mL, P = 0.0015), respectively, in the empagliflozin group, compared with placebo. Seven patients were hospitalized for heart failure (three in the empagliflozin group). Other predefined serious adverse events were rare and did not differ significantly between groups. In patients with a recent myocardial infarction, empagliflozin was associated with a significantly greater NT-proBNP reduction over 26 weeks, accompanied by a significant improvement in echocardiographic functional and structural parameters. NCT03087773.

The effect of trastuzumab on cardiac function in patients with HER2‐positive metastatic breast cancer and reduced baseline left ventricular ejection fraction

We investigated the effect of trastuzumab on cardiac function in a real‐world historic cohort of patients with HER2‐positive metastatic breast cancer (MBC) with reduced baseline left ventricular ejection fraction (LVEF). Thirty‐seven patients with HER2‐positive MBC and baseline LVEF of 40% to 49% were included. Median LVEF was 46% (interquartile range [IQR] 44%‐48%) and median follow‐up was 18 months (IQR 9‐34 months). During this period, the LVEF did not worsen in 24/37 (65%) patients, while 13/37 (35%) patients developed severe cardiotoxicity defined as LVEF <40% with median time to severe cardiotoxicity of 7 months (IQR 4‐10 months) after beginning trastuzumab. Severe cardiotoxicity was reversible (defined as LVEF increase to a value <5%‐points below baseline value) in 7/13 (54%) patients, partly reversible (defined as absolute LVEF increase ≥10%‐points from nadir to a value >5%‐points below baseline) in 3/13 (23%) patients and irreversible (defined as absolute LVEF increase <10%‐points from nadir and to a value >5%‐points below baseline) in 3/13 (23%) patients. Likelihood of reversibility was numerically higher in patients who received cardio‐protective medications (CPM), including ACE‐inhibitors, beta‐blockers and angiotensine‐2 inhibitors, compared to those who did not receive any CPM (71% vs 13%, P = .091). Sixty‐five percent of patients who received trastuzumab for HER2‐positive MBC did not develop severe cardiotoxicity during a median follow‐up of 18 months, despite having a compromised baseline LVEF. If severe cardiotoxicity occurred, it was at least partly reversible in more than two‐thirds of the cases. Risks and benefits of trastuzumab use should be balanced carefully in this vulnerable population.

Left Ventricular Assist Device-Mediated Cardiac Recovery: Impact of Diabetes Mellitus and Glycemic Control

<h3>Purpose</h3> Type 2 diabetes mellitus (DM) and poor glycemic control portend a higher risk for cardiovascular morbidity and mortality. We sought to assess their impact on left ventricular assist device (LVAD)-mediated cardiac recovery in chronic advanced heart failure (HF). <h3>Methods</h3> Consecutive patients (N=477) receiving a durable continuous-flow LVAD were prospectively evaluated. After excluding patients with acute HF etiologies or inadequate follow-up after LVAD (<3 months), 396 patients were stratified based on pre-LVAD DM status into non-diabetics (n=121; no history of DM and HbA1c <5.7) and diabetics/prediabetics (n=275; history of DM or HbA1c ≥5.7). Diabetics/prediabetics were further divided into 3 groups: prediabetics, n=106; well-controlled DM (HbA1c <7%), n=90; or not well-controlled DM, n=79. The absolute left ventricular ejection fraction (LVEF) change (ΔLVEF = LVEF post-LVAD - LVEF pre-LVAD) within one year on LVAD support was compared between groups with linear regression. DM is frequently associated with ischemic cardiomyopathy (ICM), so patients were stratified a priori into ICM and non-ICM (NICM). <h3>Results</h3> Compared to non-diabetics, diabetics/prediabetics were older, more likely male, with a higher BMI, and more commonly had an ICM, remote history of hypertension, and a longer HF symptoms duration. The <b>Figure</b> depicts the ΔLVEF between the study groups stratified into ICM or NICM. After adjusting for age, sex, BMI, HF symptoms duration, and history of hypertension, patients with well-controlled DM responded more favorably compared to patients with poor glycemic control. Overall, NICM patients responded more favorably than ICM patients. <h3>Conclusion</h3> DM appears to negatively affect functional cardiac improvement on LVAD support and effective glycemic control seems to be beneficial in enhancing the favorable myocardial functional response. Further research is warranted to investigate the underlying mechanisms driving the differential responses.

Sacubitril/valsartan in everyday clinical practice: an observational study based on the experience of a heart failure clinic.

Heart failure (HF) is a growing public health problem. Sacubitril/valsartan is now recommended to be used in persistently symptomatic patients with left ventricular ejection fraction (LVEF) <40%, replacing angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs). In the present study, we aimed to characterise the challenges of sacubitril/valsartan use in everyday clinical practice. We assessed the medical records of patients with HF and reduced ejection fraction eligible for sacubitril/valsartan attending a HF clinic at a Portuguese University Hospital during 2018 (n=152). The number of eligible patients receiving the drug and the reasons for not prescribing sacubitril/valsartan were evaluated. Additionally, we assessed the tolerability of maximal doses of sacubitril/valsartan. New York Heart Association functional class (NYHA class) and LVEF before and after up-titration to maximal tolerated sacubitril/valsartan dose were compared. Median follow-up was 41 months. Of the 152 included patients, 75 (49%) were prescribed the drug. The two main reasons for non-prescription were patient financial barriers (31%) and hypotension (27%). Only 33% of patients on sacubitril/valsartan did reach maximal dose. Hypotension was the main limiting factor for dose optimisation. Duration of sacubitril/valsartan treatment showed a positive association with LVEF improvement during follow-up (6.6% absolute LVEF increase/year). NYHA functional class improved significantly from baseline through the end of follow-up. In every-day clinical practice, although sacubitril/valsartan was associated with a marked improvement in NYHA class and in LVEF, important financial and clinical barriers to the implementation of this therapy were identified.

Abstract 11041: Time Course of Recovery from Left Ventricular Systolic Dysfunction in Patients with Arrhythmia and Newly Diagnosed Heart Failure

Background: Newly diagnosed heart failure and concomitant persistent arrhythmia often is a challenging situation for clinicians, especially if left ventricular systolic dysfunction (LVSD) is otherwise not explainable. The time to recovery of arrhythmia-induced cardiomyopathy (AIC) is not well known and the prevalence of this disease is likely underestimated. Purpose: As AIC only can be diagnosed after rhythm control (RC) and thereafter recovery from LVSD (diagnosis ex juvantibus), we aimed to characterize the time course of recovery and describe the prevalence in such a specific cohort. Method and Results: We prospectively screened 95 patients hospitalized for newly diagnosed and otherwise unexplainable LVSD (left ventricular ejection fraction (LVEF) &lt;50%) and coexisting tachyarrhythmia (atrial fibrillation/flutter + heart rate (HR) &gt;100/min) in three cardiological centers. Coronary angiography and cardiac magnetic resonance imaging were performed to exclude other causes for LVSD. RC was achieved by electrocardioversion, ablation, pharmacologically or a combination of those. 50 of 68 included patients (age 69±11y, 63% male, LVEF 35.6±8%, mean±SD) were free from recurrent arrhythmia after 6 months and analyzed: AIC was diagnosed by any increase of ≥15% in absolute LVEF or an LVEF ≥50% with an improvement of ≥10% 6 months after RC; all others were diagnosed idiopathic DCM. LVEF was assessed by echocardiography at presentation and at follow-up visits 2, 4, and 6 months after RC. 9 patients did not meet the AIC-criteria, resulting in a prevalence of 82% for AIC. At presentation, AIC vs. DCM had smaller left ventricles (LVEDD 53.6±7.5 vs. 59.7±3.1mm, P&lt;0.05; LVESD 44.4±6.6 vs. 51.6±5.1mm, P&lt;0.01), biomarkers did not differ: NT-proBNP 4525±4535 vs. 4793±4076pg/mL, P=n.s., Troponin T-hs: 46.8±108.8 vs. 22.9±15.7ng/L, P=n.s.. 2 and 4 months after RC, 58% and 73% of patients fulfilled AIC criteria. Conclusion: The prevalence of AIC in patients in this specific collective with newly diagnosed and otherwise unexplainable LVSD with concomitant persistent tachycardia is surprisingly high and the time course of recovery suggests that the final diagnosis cannot be established before 6 months after rhythm restoration.

Cardiovascular outcomes after cardiac resynchronization therapy in cardiac amyloidosis.

AimsCardiac resynchronization therapy (CRT) is highly effective in dilated cardiomyopathy (DCM) patients with impaired left ventricular ejection fraction (LVEF) and left bundle block branch. In cardiac amyloidosis (CA) patients, left ventricular dysfunction and conduction defects are common, but the potential of CRT to improve cardiac remodelling and survival in this particular setting remains undefined. We investigated cardiovascular outcomes in CA patients after CRT implantation in terms of CRT echocardiographic response and major cardiovascular events (MACEs).Methods and resultsOur retrospective study included 47 CA patients implanted with CRT devices from January 2012 to February 2020, in nine French university hospitals (77 ± 6 years old, baseline LVEF 30 ± 8%) compared with propensity‐matched (1:1 for age, LVEF at implantation, and CRT indication) DCM patients with a CRT device. CA patients had lower rates of CRT response (absolute delta LVEF ≥ 10%) compared with DCM patients (36% vs. 70%, P = 0.002). After multivariate Cox analysis, CA was independently associated with MACE (hospitalization for heart failure/cardiovascular death) [hazard ratio (HR) 3.73, 95% confidence interval (CI) 1.85–7.54, P < 0.001], along with the absence of CRT response (HR 3.01, 95% CI 1.56–5.79, P = 0.001). The presence of echocardiographic CRT response (absolute delta LVEF ≥ 10%) was the only predictive factor of MACE‐free survival in CA patients (HR 0.36, 95% CI 0.15–0.86, P = 0.002).ConclusionCompared with a matched cohort of DCM patients, CA patients had a lower rate of CRT response and consequently a worse cardiovascular prognosis after CRT implantation. However, CRT could be beneficial even in CA patients given that CRT response was associated with better cardiac outcomes in this population.

Cardiac resynchronization therapy via left bundle branch pacing vs. optimized biventricular pacing with adaptive algorithm in heart failure with left bundle branch block: a prospective, multi-centre, observational study.

AimsThe purpose of our study was to evaluate the feasibility and efficacy of cardiac resynchronization therapy (CRT) via left bundle branch pacing (LBBP-CRT) compared with optimized biventricular pacing (BVP) with adaptive algorithm (BVP-aCRT) in heart failure with reduced left ventricular ejection fraction ≤35% (HFrEF) and left bundle branch block (LBBB).Methods and resultsOne hundred patients with HFrEF and LBBB undergoing CRT were prospectively enrolled in a non-randomized fashion and divided into two groups (LBBP-CRT, n = 49; BVP-aCRT, n = 51) in four centres. Implant characteristics and echocardiographic parameters were accessed at baseline and during 6-month and 1-year follow-up. The success rate for LBBP-CRT and BVP-aCRT was 98.00% and 91.07%. Fused LBBP had the greatest reduced QRS duration compared to BVP-aCRT (126.54 ± 11.67 vs. 102.61 ± 9.66 ms, P < 0.001). Higher absolute left ventricular ejection fraction (LVEF) and △LVEF was also achieved in LBBP-CRT than BVP-aCRT at 6-month (47.58 ± 12.02% vs. 41.24 ± 10.56%, P = 0.008; 18.52 ± 13.19% vs. 12.89 ± 9.73%, P = 0.020) and 1-year follow-up (49.10 ± 10.43% vs. 43.62 ± 11.33%, P = 0.021; 20.90 ± 11.80% vs. 15.20 ± 9.98%, P = 0.015, P = 0.015). There was no significant difference in response rate between two groups while higher super-response rate was observed in LBBP-CRT as compared to BVP-aCRT at 6 months (53.06% vs. 36.59%, P = 0.016) and 12 months (61.22% vs. 39.22%, P = 0.028) during follow-up. The pacing threshold was lower in LBBP-CRT at implant and during 1-year follow-up (both P < 0.001). Procedure-related complications and adverse clinical outcomes including heart failure hospitalization and mortality were not significantly different in two groups.ConclusionsThe feasibility and efficacy of LBBP-CRT demonstrated better electromechanical resynchronization and higher clinical and echocardiographic response, especially higher super-response than BVP-aCRT in HFrEF with LBBB.

Outcomes of Spironolactone Withdrawal in Dilated Cardiomyopathy With Improved Ejection Fraction.

Background: The feasibility of spironolactone withdrawal in dilated cardiomyopathy patients with improved ejection fraction remains unknown. This study sought to determine whether spironolactone can be withdrawn safely in this circumstance.Methods: Consecutive patients with idiopathic dilated cardiomyopathy and prescribed spironolactone at discharge were included in this prospective, observational cohort using the Risk Evaluation and Management in Heart Failure Trial (NCT02998788) database. Those patients who experienced an absolute left ventricular ejection fraction (LVEF) improvement ≥10% and a second measurement of LVEF >40% would choose whether to continue spironolactone therapy and be included in final analysis. The primary endpoint was dilated cardiomyopathy relapse within 12 months, defined as a more than 10% reduction in LVEF, a 15% or greater increase in LVESVi, a 2-fold rise in NT-proBNP, or clinical signs of heart failure.Results: Seventy patients achieved an ejection fraction improvement and were included in the final analysis, of whom 30 chose to continue spironolactone and 40 decided to withdraw. In primary endpoint analysis, 23 (58%) patients from the withdrawal group and 4 (13%) patients from the continuation group relapsed (relative risk for relapse: 4.31; 95% CI: 1.67–11.11; p < 0.001). Patients from the withdrawal group experienced more symptom aggravation than the continuation group. No secondary safety endpoint was recorded. Improvements in cardiac structure parameters were no longer observed after spironolactone withdrawal, while improvements persisted in continuation group.Conclusions: Most dilated cardiomyopathy patients with improved ejection fraction will relapse after spironolactone withdrawal. These results should be weighed before spironolactone withdrawal was attempted.

Cancer Therapeutics-related Cardiac Dysfunction in Patients Treated With Immune Checkpoint Inhibitors: An Understudied Manifestation.

The widespread use of immune checkpoint inhibitors (ICI) has become a mainstay of care for a variety of malignancies. However, these therapies portend a range of adverse effects, including a potentially fatal form of cardiotoxicity which to date has not been elucidated. We aimed to evaluate the baseline characteristics of ICI-mediated cardiotoxicity. We performed a retrospective study evaluating patients treated with ICI who performed at least 2 echocardiography examinations, before and after the initiation of ICI. Cardiotoxicity was defined as Cancer Therapeutics-related Cardiac Dysfunction (CTRCD) development, with an absolute left ventricular ejection fraction reduction of >10%, to a value <53%. Fifty-two patients were included with a male preponderance (65%) and a mean age of 66 (±12) years. Twelve (23%) patients developed CTRCD, of which 2 patients were diagnosed with myocarditis. Among the CTRCD group, patients tended to be older and more likely to have baseline diastolic dysfunction: lower e' septal (P=0.026), higher E/e' septal (P=0.035), and a trend of E/e' average (P=0.076). All-cause and cardiovascular hospitalizations were significantly more common among the CTRCD group (P=0.028 and 0.001, respectively). Higher prevalence of cardiovascular mortality was observed among the CTRCD group (25% vs. 2%, P=0.034). We evaluated the development of CTRCD among patients treated with ICI therapies. Our findings suggest that baseline diastolic parameters may be associated with CTRCD development assisting in the early diagnosis of ICI-induced cardiac injury.