Baseline Left Ventricular Ejection Fraction Research Articles

Myocardial work in patients with heart failure and ischemic cardiomyopathy according to the mode of coronary revascularization

BackgroundThe association of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) on myocardial function, as reflected in myocardial work (MyW) parameters, in patients with ischemic cardiomyopathy and heart failure (HF) is unknown. MethodsWe analyzed data from 68 patients who were hospitalized with chronic HF due to ischemic cardiomyopathy and stratified them according to the mode of revascularization. All patients underwent a 2D speckle tracking echocardiography exam performed by the same expert sonographer and had complete MyW data including global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). ResultsThe mean age of patients was 70 ± 10 years and 86.8% were men. The mean left ventricular ejection fraction (LVEF) in overall cohort was 31.6 ± 9.5%. Both subgroups did not significantly differ in terms of baseline LVEF, comorbidities, and pharmacotherapy. Compared with those who received PCI, patients revascularized with CABG had significantly greater GWI (821 vs. 555 mmHg%, p = 0.002), GCW (1101 vs. 794 mmHg%, p = 0.001), GWE (78 vs. 72.6%, p = 0.025), and global longitudinal strain (−8.7 vs. −6.7%, p = 0.004). Both patient subgroups did not significantly differ with respect to GWW (273 vs. 245 mmHg%, p = 0.410 for CABG and PCI, respectively) and survival during the median follow-up of 18 months (log-rank p = 0.813). ConclusionPatients with HF and ischemic cardiomyopathy revascularized with CABG had greater myocardial work performance when compared with those revascularized with PCI. This might suggest a higher degree of functional myocardial revascularization associated with the CABG procedure.

Role of collateral circulation in the recovery of left ventricular function after recanalization of chronic coronary total occlusion

Aim. To obtain extended data on the impact of collateral circulation on the recovery of left ventricular (LV) function after recanalization of chronic coronary total occlusion (CTO), especially in patients with reduced left ventricle ejection fraction (LVEF).Material and methods. This single-center, prospective, non-randomized study included 20 patients with single-vessel CTO with reduced LVEF (<50%), confirmed by magnetic resonance imaging (MRI), who underwent successful recanalization. All patients were divided into 2 groups depending on the severity of collateral circulation. After 1, 3 and 6 months, MRI was repeated to assess LV function recovery.Results. All patients had prior myocardial infarction, while in 70% of cases — in the area of the occluded artery. A previous attempt to recanalize CTO was noted in 30%. The mean baseline LVEF according to echocardiography was 38,80±6,72%. The most common target vessel was the right coronary artery (n=17, 85%), followed by the circumflex and anterior descending arteries — 1 (5%) and 2 (10%) patients, respectively. In the group with high collateral circulation, the initial LVEF according to MRI was higher compared to the group with mild collateral circulation (35,8±7,33% vs 30,7±8,82%, p=0,17). After 6 months, MRI showed significant changes in end-diastolic volume (from 226±71,1 ml to 203±55,2 ml) and LV endsystolic volume (from 153±72,8 ml to 118±57,6 ml), as well as mean increase in LVEF by 3,3%, 4,8% and 5,2% at 1, 3 and 6 months, respectively (p=0,01 compared with baseline). The predictors of LVEF recovery in multivariate regression analysis were the initial LVEF according to MRI, and the filling rate of distal CTO bed on coronary angiography (R2=0,63).Conclusion. Successful percutaneous coronary intervention with CTO improves LV function in patients with ischemic cardiomyopathy, regardless of the degree of collateral circulation. LV function recovery generally occurs within 3 months after revascularization.

Mineralocorticoid receptor antagonist initiation during admission is associated with improved outcomes irrespective of ejection fraction in patients with acute heart failure.

Heart failure (HF) guidelines recommend initiation and optimization of guideline-directed medical therapy, including mineralocorticoid receptor antagonists (MRAs), before hospital discharge. However, scientific evidence for this recommendation is lacking. Our objective was to determine whether initiation of MRA prior to hospital discharge is associated with improved outcomes. We performed a secondary analysis of 6197 patients enrolled in the RELAX-AHF-2 study. Patients were divided into four groups according to MRA therapy at baseline and discharge. At baseline 30% of patients received MRA therapy, which increased to 50% of patients at discharge. In-hospital initiation of an MRA was observed in 1690 (27%) patients, 1438 (23%) patients remained on MRA therapy, 418 (7%) patients discontinued MRA treatment, and 2651 (43%) patients did not receive an MRA during hospital stay. Compared with patients who did not receive MRA therapy, in-hospital initiation of an MRA was independently associated with lower risks of mortality (multivariable hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.60-0.96; p = 0.02), cardiovascular death (HR 0.77, 95% CI 0.59-1.01; p = 0.06), hospitalization for HF or renal failure (HR 0.72, 95% CI 0.60-0.86; p = 0.0003) and the composite endpoint of cardiovascular death and/or rehospitalization for HF or renal failure (HR 0.71, 95% CI 0.61-0.83; p < 0.0001) at 180 days. These results were independent of baseline left ventricular ejection fraction. In patients hospitalized for acute HF, in-hospital initiation of an MRA was associated with improved post-discharge outcomes, independent of left ventricular ejection fraction and other potential confounders.

Early prediction of left ventricular function improvement in patients with new-onset heart failure and presumed non-ischaemic aetiology

ObjectivesTo determine baseline characteristics predictive of left ventricular ejection fraction (LVEF) recovery in patients diagnosed with heart failure with reduced ejection fraction (HFrEF) and presumed non-ischaemic aetiology.MethodsWe prospectively recruited patients...

Dronedarone Versus Sotalol in Antiarrhythmic Drug-Naive Veterans With Atrial Fibrillation.

Sotalol and dronedarone are both used for maintenance of sinus rhythm for patients with atrial fibrillation. However, while sotalol requires initial monitoring for QT prolongation and proarrhythmia, dronedarone does not. These treatments can be used in comparable patients, but their safety and effectiveness have not been compared head to head. Therefore, we retrospectively evaluated the effectiveness and safety using data from a large health care system. Using Veterans Health Administration data, we identified 11 296 antiarrhythmic drug-naive patients with atrial fibrillation prescribed dronedarone or sotalol in 2012 or later. We excluded patients with prior conduction disease, pacemakers or implantable cardioverter-defibrillators, ventricular arrhythmia, cancer, renal failure, liver disease, or heart failure. We used natural language processing to identify and compare baseline left ventricular ejection fraction between treatment arms. We used 1:1 propensity score matching, based on patient demographics, comorbidities, and medications, and Cox regression to compare strategies. To evaluate residual confounding, we performed falsification analysis with nonplausible outcomes. The matched cohort comprised 6212 patients (3106 dronedarone and 3106 sotalol; mean [±SD] age, 71±10 years; 2.5% female; mean [±SD] CHA2DS2-VASC, 2±1.3). The mean (±SD) left ventricular ejection fraction was 55±11 and 58±10 for dronedarone and sotalol users, correspondingly. Dronedarone, compared with sotalol, did not demonstrate a significant association with risk of cardiovascular hospitalization (hazard ratio, 1.03 [95% CI, 0.88-1.21]) or all-cause mortality (hazard ratio, 0.89 [95% CI, 0.68-1.16]). However, dronedarone was associated with significantly lower risk of ventricular proarrhythmic events (hazard ratio, 0.53 [95% CI, 0.38-0.74]) and symptomatic bradycardia (hazard ratio, 0.56 [95% CI, 0.37-0.87]). The primary findings were stable across sensitivity analyses. Falsification analyses were not significant. Dronedarone, compared with sotalol, was associated with a lower risk of ventricular proarrhythmic events and conduction disorders while having no difference in risk of incident cardiovascular hospitalization and mortality. These observational data provide the basis for prospective efficacy and safety trials.

Efficacy of Tafamidis in Patients with Ala97Ser Hereditary Transthyretin Cardiac Amyloidosis: A Six-Month Follow-Up Study.

Hereditary transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and fatal disease. A97S (p.Ala117Ser) is the most common transthyretin genetic mutation in Taiwan. Tafamidis is a transthyretin stabilizer, and it has been shown to improve outcomes. However, its effect on A97S ATTR-CM subtypes remains unknown. This study aimed to investigate the efficacy of tafamidis in patients with hereditary A97S ATTR-CM after 6 months of treatment. We retrospectively analyzed ATTR-CM patients who received tafamidis (61 mg/day) treatment at National Taiwan University Hospital. Functional status, biochemistry and echocardiography were measured at baseline and after 6 months of tafamidis treatment. The outcome measure was to compare the N-terminal pro-brain natriuretic peptide (NT-proBNP) level at baseline and after 6 months of tafamidis treatment. Twenty patients were enrolled in this study. Their mean age was 63.0 ± 5.8 years and 75% were men. The baseline left ventricular (LV) mass index was 200.9 ± 63.9 g/m2, and the baseline LV ejection fraction was 58.9 ± 13.5%. After 6 months of treatment, the log NT-proBNP level significantly improved from 2.9 ± 0.6 to 2.7 ± 0.5 (p = 0.036). Subgroup analysis showed that the LV posterior wall thickness and left atrial diameter were significantly higher in the patients with improved NT-proBNP, suggesting the benefits of tafamidis for ATTR-CM patients with severe cardiac involvement. The patients with hereditary A97S ATTR-CM in this study had decreased levels of NT-proBNP after 6 months of tafamidis treatment, and this reduction was especially pronounced in those with more severe cardiac involvement.

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.

Changes in left ventricular systolic function for 1 year in patients with acute heart failure &amp;lt;50 years of age

Abstract Funding Acknowledgements Type of funding sources: None. Background Though old age is an important risk factor for cardiovascular disease including heart failure (HF), HF can develop in young patients and can have a greater impact on a quality of life because they are active individuals. Purpose We evaluated the clinical characteristics and prognosis according to change of left ventricular (LV) function in younger patients with acute HF. Methods Study data were obtained from a multicenter cohort that included patients hospitalized for acute HF. Patients who were under 50 years of age and had available data regarding baseline and one-year follow-up left ventricular ejection fraction (LVEF) were included in this analysis. Patient were classified into two groups according changes in LVEF: the improved or stationary group whose LVEF improved or maintained at one-year follow-up; the aggravated LVEF group whose LVEF deteriorated at one-year follow-up. Results Among 437 patients, 14.6% of patients had experienced worsening of LVEF at the one-year follow-up. The patients in aggravated LVEF group had a worse clinical profile than patients with improved or stationary LVEF. During follow-up (median 1946 days), a total of 56 patients (12.8%) died. Among them, the aggravated LVEF group had higher incidence of all-cause death (32.8% vs. 9.4%, p &amp;lt; 0.001). The aggravated LVEF group showed significant lower cumulative all-cause death free survival rate than improved or stationary LVEF group (Figure). In addition, the aggravated LVEF group had significantly higher incidence of cardiac death (14.1% vs. 2.9%, p &amp;lt; 0.001), readmission (76.6% vs. 55.5%, p = 0.002), readmission due to cardiac cause (57.8% vs.30.8%, p &amp;lt; 0.001), and HF readmission (51.6% vs. 26.0%, p &amp;lt; 0.001). After adjusting for confounding factors, Cox regression analysis showed that use of angiotensin converting enzyme inhibitors at discharge was independently associated with 63% reduced risk of aggravated LVEF (Odds ratio 0.37, 95% confidence interval 0.168–0.791, p = 0.001). Conclusions Poor clinical prognosis is expected if LVEF worsens after 1 year in young patients with HF. Clinicians need to be aware of the deteriorating characteristics of young HF patients and provide delicate treatment.

Mortality After Total Thyroidectomy for Amiodarone-Induced Thyrotoxicosis According to Left Ventricular Ejection Fraction.

To report cardiac outcomes after total thyroidectomy for amiodarone-induced thyrotoxicosis according to the baseline left ventricular ejection fraction in a tertiary referral center. Retrospective, monocentric. The tertiary health care system. Patients who underwent total thyroidectomy for amiodarone-induced thyrotoxicosis between 2010 and 2020 with age >18 and available preoperative left ventricular ejection fraction were included in this study. Patients were dichotomized into: group 1 with left ventricular ejection fraction ≥40% (mildly reduced/normal ejection fraction), and group 2 with left ventricular ejection fraction <40% (reduced ejection fraction). There were 34 patients in group 1 and 17 to group 2. The latter were younger (median 58.4 [Q1-Q3 48.0-64.9] vs. 69.8 years in group 1 [59.8-78.3], p = .0035) and they presented more cardiomyopathy (58.8 vs. 26.5%, p = .030). Overall, the median time until surgery referral was 3.1 [1.9-7.1] months and 47.1% underwent surgery after restoration of euthyroidism. Surgical complications accounted for 7.8%. In group 2, the median left ventricular ejection fraction was significantly improved after surgery (22.5 [20.0-25.0] vs. 29.0% [25.3-45.5], p = .0078). Five-year cardiac mortality was significantly higher in group 2 (p < .0001): 47.0% died of cardiac causes versus 2.9% in group 1. A baseline left ventricular ejection fraction <40% and a longer time until surgery referral were significantly associated with cardiac mortality (multivariable Cox regression analysis, p = .015 and .020, respectively). These results reinforce the idea that surgery, if chosen, should be performed quickly in patients with left ventricular ejection fraction <40%.

Left ventricular ejection fraction and long-term outcomes in women presenting with signs and symptoms of ischaemia

BackgroundAlthough women are known to have a relatively higher left ventricular ejection fraction (LVEF) compared with men, a sex-neutral LVEF threshold continues to be used for clinical management. We sought...

Effect of left ventricular ejection fraction Spectrum on 1-Year mortality in patients with acute ischemic stroke or transient ischemic attack.

We aimed to investigate the association of the left ventricular ejection fraction (LVEF) spectrum with 1-year clinical outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). In a prospective registry for the Third China National Stroke Registry (CNSR-III), AIS or TIA patients with echocardiography records during hospitalization were recruited. All LVEFs were categorized into intervals of 5% in width. The lowest and highest intervals are ≤40% and >70%, respectively. The primary outcome was all-cause death at 1 year. Cox proportional hazards regression analysis was performed to investigate the association between baseline LVEF and clinical outcomes. This analysis included a total of 14,053 patients. In total, 418 patients died during 1-year follow-up. Overall, LVEF ≤60% was associated with a higher risk of all-cause death compared to LVEF >60%, independent of demographic and clinical characteristics (aHR 1.29 [95% CI 1.06-1.58]; p = 0.01). The cumulative incidence of all-cause death was significantly different among the eight LVEF groups that survival declined successively with the decrease of LVEF (log-rank p ≤ 0.0001). Patients with AIS or TIA with decreased LVEF (≤60%) had a lower 1-year survival rate after onset. LVEF 50%-60% even within the normal range, may still contribute to poor outcomes in AIS or TIA. Comprehensive evaluation of cardiac function after acute ischemic cerebrovascular disease should be strengthened.

Cardiotoxicity of BRAF/MEK Inhibitors: A Longitudinal Study Incorporating Contemporary Definitions and Risk Scores

BackgroundRapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors have revolutionized treatment for patients with BRAF-mutated melanoma. Although left ventricular systolic dysfunction associated with these therapies has been reported in clinical trials, the real-world incidence is poorly defined, as are risk factors for its development. ObjectivesThis study sought to characterize the incidence, time course, and risk factors for cancer therapy–related cardiac dysfunction (CTRCD) in patients with melanoma receiving BRAF and MEK inhibitors. MethodsPatients with melanoma treated with BRAF and MEK inhibitors at a cancer hospital network between June 1, 2017, and June 30, 2020, were included retrospectively. CTRCD was defined as mild, moderate, or severe according to International Cardio-Oncology Society (ICOS) definitions. Baseline cardiotoxicity risk stratification was performed using the Heart Failure Association/ICOS tool. ResultsOf the 63 patients included, 27% developed CTRCD (17% mild and 10% moderate). No patients developed severe CTRCD or symptomatic heart failure. CTRCD occurred most frequently in patients considered to be at “low” and “medium” baseline risk of cardiotoxicity (82%). The baseline left ventricular ejection fraction and global longitudinal strain were not different in patients who developed moderate CTRCD vs those who did not. Left ventricular internal diameters in diastole and systole were larger in patients who developed moderate CTRCD compared with those who did not (left ventricular internal diameter in diastole: 4.9 ± 0.6 cm vs 4.3 ± 0.6 cm; P = 0.023; left ventricular internal diameter in systole: 3.3 ± 0.4 cm vs 2.8 ± 0.5 cm; P = 0.039). ConclusionsBRAF and MEK inhibitor–associated CTRCD is common. The utility of the Heart Failure Association/ICOS risk stratification tool appears limited in this group, and better risk prediction tools are needed. The long-term consequences of CTRCD, particularly mild CTRCD, warrant evaluation in larger prospective studies.

Cardiac safety of reduced surveillance for cancer therapy related cardiac dysfunction in patients with breast cancer treated with HER2-targeted therapy.

12083 Background: Non-anthracycline-based therapy is a treatment option for patients (pts) with HER2-positive breast cancer (BC) and is associated with lower risk of cancer therapy related cardiac dysfunction (CTRCD) compared to anthracycline-based treatment. Given the reduced CTRCD risk with non-anthracycline HER2-targeted therapies, updates to practice guidelines that recommend surveillance echocardiograms (TTE) every 3 months are needed. We evaluated the cardiac safety of reduced CTRCD surveillance in pts receiving non-anthracycline HER2-targeted therapies. Methods: Pts with BC treated with non-anthracycline HER2-targeted therapy were enrolled in this single-arm prospective study. Pts with previous anthracycline exposure, uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg), or significant cardiovascular disease were excluded. TTEs were performed at baseline, 6 months, and 12 months during HER2-targeted treatment. The primary endpoint was a cardiac event, defined by clinical heart failure (New York Heart Association Class III/IV) or cardiovascular death, with a prespecified non-inferiority margin of 2.9% relative to a cardiac event rate of 1.1% based upon prior studies. Secondary endpoints were CTRCD, defined by decline of left ventricular ejection fraction (LVEF) ≥10% to &lt; 53%, and interruption of HER2-targeted treatment secondary to CTRCD. Results: Between May 2019 and January 2022, 190 pts (age 52 ± 11 y) with HER2-positive BC were enrolled: 143 (75%) had stage I disease, 8 (4%) had diabetes, 38 (20%) had hypertension, and baseline LVEF was 64 ± 5% (Table). Additional TTEs outside the prespecified 6- and 12-month timepoints were performed for 35 (18%) pts, of which 20 were to assess for possible cardiac symptoms. After 1-year follow-up, there were 0 (0%; 97.5% CI 0- 1.9%) cardiac events. Two (1.1%) pts developed CTRCD and 1 (0.5%) pt had a temporary CTRCD-related treatment interruption. Conclusions: Reduced CTRCD surveillance every 6 months is feasible and safe for selected pts with HER2-positive BC receiving non-anthracycline HER2-targeted therapy. Our findings support the need to update cardio-oncology practice guidelines and allow for less frequent surveillance TTEs among pts at low-risk for CTRCD. Clinical trial information: NCT03983382 . [Table: see text]

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]

Impact of initial fluid resuscitation volume on clinical outcomes in patients with heart failure and septic shock

BackgroundFluid resuscitation is a key treatment for sepsis, but limited data exists in patients with existing heart failure (HF) and septic shock. The objective of this study was to determine the impact of initial fluid resuscitation volume on outcomes in HF patients with reduced or mildly reduced left ventricular ejection fraction (LVEF) with septic shock. MethodsThis multicenter, retrospective, cohort study included patients with known HF (LVEF ≤50%) presenting with septic shock. Patients were divided into two groups based on the volume of fluid resuscitation in the first 6 h; <30 mL/kg or ≥30 mL/kg. The primary outcome was a composite of in-hospital mortality or renal replacement therapy (RRT) within 7 days. Secondary outcomes included acute kidney injury (AKI), initiation of mechanical ventilation, and length of stay (LOS). All related data were collected and compared between the two groups. A generalized logistic mixed model was used to assess the association between fluid groups and the primary outcome while adjusting for baseline LVEF, Acute Physiology and Chronic Health Evaluation (APACHE) II score, inappropriate empiric antibiotics, and receipt of corticosteroids. ResultsOne hundred and fifty-four patients were included (93 patients in <30 mL/kg group and 61 patients in ≥30 mL/kg group). The median weight-based volume in the first 6 h was 17.7 (12.2–23.0) mL/kg in the <30 mL/kg group vs. 40.5 (34.2–53.1) mL/kg in the ≥30 mL/kg group (P <0.01). No statistical difference was detected in the composite of in-hospital mortality or RRT between the <30 mL/kg group compared to the ≥30 mL/kg group (55.9% vs. 45.9%, P=0.25), respectively. The <30 mL/kg group had a higher incidence of AKI, mechanical ventilation, and longer hospital LOS. ConclusionsIn patients with known reduced or mildly reduced LVEF presenting with septic shock, no difference was detected for in-hospital mortality or RRT in patients who received ≥30 mL/kg of resuscitation fluid compared to less fluid, although this study was underpowered to detect a difference. Importantly, ≥30 mL/kg fluid did not result in a higher need for mechanical ventilation.

Cardiotoxicity of CPX-351 vs 7+3 in patients with untreated high-risk acute myeloid leukemia.

7029 Background: CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, is approved for newly diagnosed, therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes in the United States and Europe. While CPX-351 demonstrated improved overall survival and a similar safety profile vs 7+3 in the phase 3 clinical trial (NCT01696084), the safety of CPX-351 related to cardiac function has not been fully described, an important consideration, due to the known cardiotoxicity risk from anthracyclines. This post hoc analysis assessed the impact of CPX-351 vs 7+3 chemotherapy on cardiac impairment in a subset of adults with newly diagnosed high-risk or secondary AML (sAML) from the phase 3 trial. Methods: In the phase 3 trial, 309 patients (60–75 years old; AML according to WHO 2008 criteria) were randomized 1:1 to receive CPX-351 (100 units/m2 on days 1, 3 and 5; days 1 and 3 for second induction) or 7+3 (cytarabine 100 mg/m2/day for 7 days [5 days for second induction] and daunorubicin 60 mg/m2 on days 1–3 [days 1–2 for second induction]). Cardiac impairment was determined by cardiac adverse events (AEs) as well as echocardiogram (ECHO) measures including left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), which were assessed at baseline and two follow-up visits. Results: The study population included 102 patients (CPX-351, n = 57; 7+3, n = 45) with normal baseline LVEF (LVEF &gt; 53%) and at least one post-baseline ECHO measure (LVEF or GLS). Median (min, max) age was 68 (60, 75) years for CPX-351 vs 66 (60, 75) years for 7+3. The mean cumulative dose of daunorubicin while on study was lower for patients receiving CPX-351 vs 7+3 (378 vs 570 mg, respectively). Lower proportions of CPX-351 vs 7+3-treated patients had LVEF &lt; 53% (12% vs 31%) or GLS ≤18% (25% vs 38%) at follow-up 1 or 2. A clinically significant change in LVEF ( &gt; 10% decrease from baseline and LVEF &lt; 53%) or GLS ( &gt; 12% relative decrease from baseline and GLS &lt; 18%) was less common in patients treated with CPX-351 vs 7+3 (9% vs 20% and 21% vs 44%, respectively) at follow-up 1 or 2. The frequency of any cardiac AE by treatment group was similar for both CPX-351 and 7+3 (40% vs 42%). Tachycardia was the most common cardiac AE in CPX-351-treated patients (21% vs 9% in 7+3-treated patients), while atrial fibrillation was the most common cardiac AE in 7+3-treated patients (11% vs 4% in CPX-351-treated patients). Conclusions: The results of this post hoc analysis of data from the phase 3 trial show that CPX-351 is associated with less cardiotoxicity in adults with newly diagnosed high-risk or sAML, when compared with 7+3. The lower mean cumulative doses of daunorubicin while on study with CPX-351 appear to result in better cardiac outcomes with CPX-351 vs 7+3 chemotherapy. Characteristics of CPX-351, such as liposomal delivery, may also contribute to this effect but require further study to confirm this. Clinical trial information: NCT01696084 .

Uptitrating Treatment After Heart Failure Hospitalization Across the Spectrum of Left Ventricular Ejection Fraction

BackgroundAcute heart failure (AHF) is associated with a poor prognosis regardless of left ventricular ejection fraction (LVEF). STRONG-HF showed the efficacy and safety of a strategy of rapid uptitration of oral treatment for heart failure (HF) and close follow-up (high-intensity care), compared with usual care, in patients recently hospitalized for AHF and enrolled independently from their LVEF. ObjectivesIn this study, we sought to assess the impact of baseline LVEF on the effects of high-intensity care vs usual care in STRONG-HF. MethodsThe STRONG-HF trial enrolled patients hospitalized for AHF with any LVEF and not treated with full doses of renin-angiotensin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. High-intensity care with uptitration of oral medications was performed independently from LVEF. The primary endpoint was the composite of HF rehospitalization or all-cause death at day 180. ResultsAmong the 1,078 patients randomized, 731 (68%) had LVEF ≤40% and 347 (32%) had LVEF >40%. The treatment benefit of high-intensity care vs usual care on the primary endpoint was consistent across the whole LVEF spectrum (interaction P with LVEF as a continuous variable = 0.372). Mean difference in the EQ-5D visual analog scale change from baseline to day 90 between treatment arms was slightly greater at higher LVEF values, but with no interaction between LVEF as a continuous variable and the treatment strategy (interaction P = 0.358). Serious adverse events were also independent from LVEF. ConclusionsRapid uptitration of oral medications for HF and close follow-up reduce 180-day death and HF rehospitalization after AHF hospitalization independently from LVEF. (Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-ProBNP Testing, of Heart Failure Therapies [STRONG-HF]; NCT03412201)

Replication of genetic associations of chemotherapy-related cardiotoxicity in the adjuvant NSABP B-31 clinical trial.

The cardiotoxic effects of doxorubicin, trastuzumab, and other anticancer agents are well known, but molecular genetic testing is lacking for the early identification of patients at risk for therapy-related cardiac toxicity. Using the Agena Bioscience MassARRAY system, we genotyped TRPC6 rs77679196, BRINP1 rs62568637, LDB2 rs55756123, RAB22A rs707557, intergenic rs4305714, LINC01060 rs7698718, and CBR3 rs1056892 (V244M) (previously associated with either doxorubicin or trastuzumab-related cardiotoxicity in the NCCTG N9831 trial of anthracycline-based chemotherapy ± trastuzumab) in 993 patients with HER2+ early breast cancer from the NSABP B-31 trial of adjuvant anthracycline-based chemotherapy ± trastuzumab. Association analyses were performed with outcomes of congestive heart failure (N = 29) and maximum decline in left ventricular ejection fraction (LVEF) using logistic and linear regression models, respectively, under an additive model with age, baseline LVEF, and previous use of hypertensive medications as covariates. Associations of maximum decline in LVEF in the NCCTG N9831 patients did not replicate in the NSABP B-31 patients. However, TRPC6 rs77679196 and CBR3 rs1056892 were significantly associated with congestive heart failure, p < 0.05, with stronger associations observed in patients treated with chemotherapy only (no trastuzumab) or in the combined analysis of all patients relative to those patients treated with chemotherapy + trastuzumab. TRPC6 rs77679196 and CBR3 rs1056892 (V244M) are associated with doxorubicin-induced cardiac events in both NCCTG N9831 and NSABP B-31. Other variants previously associated with trastuzumab-related decline in LVEF failed to replicate between these studies.

Role of RA-LV pacing in patients with symptomatic left bundle branch block with CRT - a single centre experience

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Cardiac Resynchronisation Therapy(CRT) is considered as the cornerstone of treatment for patients with heart failure and left ventricular conduction delay ( left bundle branch block) who remain symptomatic despite optimal medical therapy. However, it has been well documented that the responder and success rates of this therapy are highly variable. Contemporary response rates from clinical trials as well as real world data demonstrate non-response rates of between 30–50%. Suboptimal AV delay timing is the most prevalent modifiable factor on follow up for improving response rates. AV Fusion pacing describes the delivery of CRT pacing with a programming strategy to preserve intrinsic atrioventricular (AV) conduction and ventricular activation via the right bundle branch. This concept is utilised in the RA- LV pacing strategies, which have been described in literature. However, RA-LV only pacing raises certain practical , moral and ethical concerns as it has never been a part of contemporary guidelines nor a part of large randomised control trial. Purpose The purpose of this study was to study the clinical as well as hemodynamic effects of RA-LV pacing in patients with a conventional CRT device with a programmed subthreshold RV lead. Methods All patients with a convention CRT indication ( CRT-P as well as CRT-D), with acceptable intrinsic AV conduction, non pacing dependent and normal Right Ventricular function were enrolled into the study. A total of 60 consecutive patients between 2016-2021 were enlisted from after the implant and followed up in the Device clinic of the institution. The baseline as well as follow-up LV function, Battery life and QRS duration was recorded and analysed. Results Total of 60 patients were enlisted of which 30 were males and 30 females. There were 16 patients were with Ischemic Cardiomyopathy in this group. The average follow-up period was 3 year from implant. The mean baseline Left Ventricular Ejection Fraction was 29% while the mean follow-up Left Ventricular Ejection Fraction was 46.5%. The mean QRS duration at implant was 155msec and the mean follow-up QRS was 123 msec. The subset analysis of ischemic vs the nonischaemic cardiomyopathy groups revealed that both groups had a similar response rates to improvement of clinical as well as Echocardiographic parameters including LVEF. The mean follow up LVEF in the ischemic and nonischaemic groups were 44.5 &amp; 46.5% respectively. This finding suggests that the advantage of AV fusion pacing is not significantly impacted with underlying aetiology of the Cardiomyopathy. Conclusion RA-LV with RV subthreshold CRT is a reasonable strategy for achieving traditional response rates of CRT in patients with a good intrinsic AV conduction. This modality overcomes a large number of procedural as well as ethical roadblocks in the use of fusion pacing for CRT therapy optimisation.

CI-452766-3 LEFT BUNDLE BRANCH AREA PACING IN PATIENTS WITH SEVERELY REDUCED LEFT VENTRICULAR EJECTION FRACTION

Left bundle branch area pacing (LBBAP) has been used as an alternative to biventricular pacing (BiVp) to achieve cardiac resynchronization therapy (CRT). However, its use in patients with severely reduced left ventricular ejection fraction (LVEF) has not been described. To evaluate the outcomes of LBBAP compared to BiVp in patients with an LVEF ≦20%. In this multicenter study, consecutive adult patients with ischemic and non-ischemic cardiomyopathy and an LVEF <35% undergoing CRT were included. LBBAP was offered as a first line treatment strategy after thorough discussion with patients; the last consecutive patients in whom BiVp was performed were used as controls. Patients were analyzed according to their LVEF (≤20% vs. 21-35%) and the pacing strategy used (LBBAP vs BiVp). The primary outcome was a composite of HF-related hospitalization and all-cause mortality. Secondary outcomes included individual components of the primary outcome, procedural and fluoroscopy times, paced QRS duration, change in LVEF, final LVEF, and change in HF-related symptoms. A total of 342 patients (mean age 69.7±11.2, female 30.1%; 117 with LVEF ≤20%) were included. No significant differences in the primary outcome or HF-related hospitalization were found in patients with LVEF ≤20% compared to patients with an LVEF 21-35%, but patients with a baseline LVEF ≤20% had a higher all-cause mortality (OR: 2.35; 95%CI 1.018-5.436, p=0.047). There were no differences in the primary outcome in patients with LVEF ≤20% treated with LBBAP vs. BiVp. However, patients with an LVEF ≤20% treated with LBBAP had significantly lower fluoroscopy times (17.5±10.3 vs. 23.1±15.4 mins., p=0.03), shorter paced QRS durations (124.6±18.7 vs. 151.1±34.3 msec, p<0.001), greater improvements in LVEF (8.1±11.2 vs. 3±5.7%, p=0.011), higher final LVEF (26.7±12.9 vs. 21.1±7.2%, p=0.018) and were less symptomatic (NYHA class 1.83±0.93 vs. 2.27±0.88, p=0.018) than patients treated with BiVp, respectively. A baseline LVEF ≤20% was associated with significantly longer procedural and fluoroscopy times in patients undergoing LBBAP compared to a baseline LVEF 21-35%. Patients with a baseline LVEF ≤20% have a higher all-cause mortality than patients with an LVEF 21-35%. Patients with an LVEF ≤20% treated with LBBAP have lower fluoroscopy time, shorter paced QRS duration, significantly less HF related symtpoms, greater changes and higher final LVEF than patients treated with BiVp.