Changes In Left Ventricular Ejection Fraction Research Articles

Definition and management of arrhythmia-induced cardiomyopathy: findings from the EHRA SIC survey

Abstract Background Arrhythmia-induced Cardiomyopathy (AiCM) represents a subtype of heart failure (HF) in the context of a sustained arrhythmia. However, clear definitions and management recommendations for AiCM are lacking. Purpose The European Heart Rhythm Association Scientific Initiatives Committee (EHRA SIC) conducted a survey to determine the current definitions and management of patients with AiCM among European and non-European electrophysiologists. Methods A 25-item online questionnaire was developed and distributed among EP research network centres between September 4th and October 5th 2022. Results Out of the 206 respondents, 16% were females and the most (33%) were between 40-49 years old. Most of the respondents were EP-Specialists (81%) working at a University Hospital (47%). While most participants (67%) agreed that AiCM should be defined as a left ventricular ejection fraction (LVEF) impairment after new onset of an arrhythmia and/or LVEF recovery after treatment of the culprit arrhythmia, only 35% identified a specific LVEF drop/improvement to diagnose AiCM, the majority (50%) agreeing with a 10% change in LVEF (Figure) but with the rest of the experts choosing a wide range of values (from 5 to 20% LVEF drop). Most respondents used all available therapies in AiCM patients: catheter ablation was chosen by 93%, electrical cardioversion by 83%, antiarrhythmic drugs by 76% and adjuvant HF treatment were used by 76%. 83% of respondents indicated that adjuvant HF treatment should be started at first diagnosis of HF prior to antiarrhythmic treatment and 84% agreed that the therapy should be stopped within six months after LVEF normalization. Responses for the optimal time point for the first reassessment of LVEF during FU varied markedly (1 day to over 6 months after antiarrhythmic treatment). Conclusion This EHRA Survey reveals varying practices in defining and managing AiCM among European and non-European physicians. There is an unmet need for a consensus in the definition and management of AiCM patients to improve patient care.Figure

Non-invasive electrocardiographic assessment of arrhythmic risk in ischaemic cardiomyopathy patients undergoing revasularisation

Abstract Background Ventricular arrhythmias are a leading cause of death in patients with ischaemic cardiomyopathy (ICM). Ischaemia is thought to increase arrhythmic risk and coronary revascularisation is frequently undertaken to reduce this risk, although the recent REVIVED-BCIS2 trial did not show a difference in the incidence of death, device therapies or sustained arrhythmias in patients assigned to have percutaneous coronary intervention (PCI) compared to optimal medical therapy alone(1). Purpose We assessed the mechanistic effects of revascularisation on arrhythmic risk in patients with ICM using non-invasive electrocardiographic imaging (ECGi). Methods Patients were eligible if they had a left ventricular ejection fraction (LVEF) <40%, extensive coronary disease (BCIS Jeopardy Score≥6) and were scheduled to undergo revascularisation with coronary artery bypass grafting or PCI. ECGi assessment was performed using a 252-electrode vest with anatomical co-registration using a CT thorax. Patients underwent stress perfusion cardiac magnetic resonance (CMR) imaging; both ECGi and CMR were conducted at baseline and 3 months post revascularisation(Figure 1). The primary outcome measure was dispersion of repolarisation measured using global activation recovery interval (ARI) dispersion. Secondary outcome measures included repolarisation time (RT) dispersion, mean ARI and LV ARI dispersion. We also assessed the relationship between ARI dispersion, revascularisation and left ventricular scar burden. Data are presented as mean ± SD or median [IQR]. Results Thirty patients were recruited between 2020-2023; age 67±11 years, 90% male, BMI 28±5 and baseline LVEF was 29±8%. Twelve patients underwent CABG, 18 (60%) had PCI. The BCIS jeopardy score was 10 [9-11] at enrolment and decreased to 2 [0-4] after revascularisation. The LV scar burden at baseline was 15.1±6.5% and the change at 3 months was -0.5±5% (p=0.70). ARI dispersion and LV ARI dispersion were correlated with LV scar burden (r=0.62,p=0.01 and 0.71,p=0.002 respectively). No differences were seen in ARI dispersion (44.5 vs 44.1, p=0.86) or secondary outcome measures before and after revascularisation (RT dispersion: 45.5 vs 44.7, p=0.49; Mean ARI: 281.3 vs 282.6, p=0.74; ARI dispersion: 44.5 vs 44.1, p=0.86; LV ARI dispersion: 38.4 vs 36.7, p=0.39)(Figure 2). The LVEF change on CMR at 3 months was +6.9±10%; no relationship was seen between change in LVEF and ARI dispersion. Conclusion Arrhythmic risk assessed by non-invasive ECGi was not altered by coronary revascularisation. LV ARI dispersion was highly correlated with scar burden, which is not altered by revascularisation. Future work includes analysis of perfusion data. Our results support the findings of the REVIVED arrhythmia study that revascularisation does not reduce arrhythmic risk in patients with ICM(1). ECGi derived LV ARI dispersion correlates with scar and may represent a non-invasive arrhythmic risk assessment tool.Figure 1Figure 2

AV nodal ablation in atrial fibrillation: long term outcomes

Abstract Background Ablation of the atrioventricular (AV) node, following the insertion of a permanent pacemaker, is a treatment option for symptomatic atrial fibrillation (AF) where rate control is poor, despite maximally tolerated pharmacological intervention or percutaneous AF ablation [1], and yet there is limited data on long-term outcomes. Purpose The purpose of this study is to investigate post AV node ablation follow up outcomes, including the incidence and timeframe of conversion of paroxysmal to persistent AF; incidence and timeframe of upgrade to biventricular pacemakers; and mortality. Methods This observational descriptive study looked at the post-procedure follow-up outcomes of patients who underwent AV node ablation at our centre between March 2015 and June 2019. Retrospective analysis of prospectively collected data was analysed. The demographics of the patients, including their age, gender, co-morbidities, pre-ablation left ventricular ejection fraction (LVEF) and medications were recorded. The follow up outcomes investigated included the change in LVEF, the proportion of patients whose AF converted from paroxysmal to persistent, the proportion of patients requiring upgrade to biventricular devices, and deaths within 6 months of ablation. Outcomes were compared between those who had a biventricular pacemaker pre-ablation and those who had single/dual chamber pacemakers. Results 296 patients with a mean age of 72.7± 8.5 years and a female to male ratio of 54.1% : 45.9% were included. 94 patients (31.8%) had paroxysmal AF pre- ablation. 51.6% of those who had paroxysmal AF pre-ablation converted to persistent AF over a median period of 3 years (interquartile range, 3 years). Among those who had a biventricular pacemaker pre-ablation, 56.5% of those with paroxysmal AF converted to persistent, compared to 47.4% of those with a dual pacemaker pre-ablation p=ns Among patients with dual chamber pacemakers, those who remained in paroxysmal AF post-ablation had a mean CHADVASC score of 3.2 (range of 1-6) compared to 3.7 (range of 2-6) in those whose AF converted to persistent (p=0.19). 9 patients (3%) died within less than 6 months of the procedure, with 1 patient dying within 6 days. 13% of the patients originally having a single or dual chamber pacemaker required an upgrade to a biventricular pacemaker over a median period of 1.25 years (interquartile range 1.1 years). All the patients who required an upgrade to a biventricular pacemaker had normal LVEF pre-ablation except for one patient who had mild LV impairment. Conclusions A significant proportion of patients with paroxysmal AF converted to persistent AF following AV node ablation and having a biventricular pacemaker did not offer benefit in keeping people in paroxysmal AF.A considerable number of people required an upgrade to biventricular pacemaker over a short time frame even though they had normal LVEF pre AV nodal ablation.

Improvement in Left Ventricular Function of the Resected Myocardium after Septal Myectomy in Patients with Aortic Valve Replacement

Background: Some surgeons have previously advocated for a more aggressive concomitant septal myectomy to address left ventricular outflow tract obstruction; however, concerns about the surgical complications of post-septal myectomy remain. Here, we aimed to assess the clinical, echocardiographic, and pathological findings following concomitant septal myectomy with surgical aortic valve replacement. Methods: We reviewed 21 patients who underwent surgical aortic valve replacement and concomitant septal myectomy from April 2014 to September 2019. The global and regional left ventricular ejection fraction changes between the perioperative periods were analyzed using two-dimensional speckle-tracking echocardiography. The resected myocardium was pathologically assessed. Results: No operative mortality was observed during the study period. Transthoracic echocardiography showed no significant differences in preoperative and postoperative left ventricular ejection fraction (68.1 ± 9.9% vs. 68.6 ± 6.0%, p = 0.82) or interventricular septum thickness (11.9 ± 1.4 mm vs. 11.5 ± 1.5 mm, p = 0.23). Interventricular septum thickness at the end-systolic phase, which is the maximum septal wall thickness, was significantly reduced postoperatively (27.7 ± 9.3 mm vs. 22.6 ± 5.5 mm, p < 0.05). The basal, mid, and apical septal areas improved with septal myectomy by 80%, 230%, and 27%, respectively, compared to perioperative echocardiography (basal septal, 80 ± 23%; mid septal, 230 ± 830%; apical septal, 27 ± 350%). Pathological examination of the resected myocardium revealed marked endocardial thickness (mean, 914 µm) with focal fibrosis. Conclusions: In aortic valve stenosis patients with septal hypertrophy, concomitant septal myectomy with surgical aortic valve replacement improved regional myocardial function and eliminated left ventricular outflow tract obstruction by removing thickened endocardium and prominent fibrosis.

Obstructive sleep apnea and acute decompensated heart failure

Abstract Funding Acknowledgements None. Background Acute decompensated heart failure is a condition with a high frequency of hospitalizations and mortality. Screening and treatment for obstructive sleep apnea can be helpful in these patients. Purpose To determine the frequency of obstructive sleep apnea in patients with acute decompensated heart failure. To add CPAP home therapy to standard medical treatment for heart failure. To follow patients for 1 year. Methods We conducted a single-centre, prospective cohort study form 150 consecutive patients hospitalized for exacerbation heart failure in the cardiology department. 81 patients meet inclusion criteria – Apnea-Hypopnea index (AHI) > 5, Epworth Sleepiness Scale (ESS) > 8, NYHA class II/III and NTproBNP>900 pg/ml. Patients with OSA were offered to purchase a CPAP device for the home. They were divided into two groups with CPAP and no-CPAP. All patients receiving optimal medical treatment. The follow-up period was 1 year. At the end of the period, patients underwent a physical examination, an echocardiography, and ESS. In the non-CPAP group, 29 patients were followed up and 13 patients dropped out due to mortality. In the CPAP group, 16 patients were followed up, with 1 dropped out. Sleep apnea screening was performed with ApneaLinkTM. Echocardiographic assessment of left ventricular ejection fraction (LVEF) and the E/e‘m ratio. Results From 81 with sleep apnea 72.8% (n=59) has obstructive sleep apnea (OSA) and 27.2% (n=22) has central sleep apnea (CSA). Of the 59 patients with OSA, 17 patients (28.8%) purchased a device and continued therapy at home, while 42 patients (71.2%)on optimal drug therapy without CPAP. There is a statistically significant difference in BMI in the group with CPAP compared to the no-CPAP group at the beginning and at the end of the follow-up (CPAP group at the start 36.47±7.3 vs. the end 33.3±5.7, p=0.001 and no-CPAP group at the start 36.35±7.34 vs. the end 35.74±7.46 , p=0.356). A similar relationship is found in systolic blood pressure(SBP) and diastolic blood pressure(DBP). SBP in CPAP group at start 136.2±6.2 mmHg vs. end 123.1±5.9 mmHg; р<0.001. relative to no-CPAP group – start 131.2±9.8 mmHg vs. end 131.3±7.7 mmHg; р=0.965. DBP in CPAP group at start 85.9±6.7 mmHg vs. end 77.3±5.3 mmHg; р<0.001 and no-CPAP group start 82.1±7.4 mmHg vs. end 81.7±5.7 mmHg, р=0.644. There is a significant change in LVEF between the two groups at the beginning and at the end of the follow-up (in CPAP group at start 47.5±8.7, vs. at end 50.07±7.5; р=0.005, between no-CPAP at start 52.5±6.9 vs. at end 52.2±7.1; р=0.389). The CPAP group had a median survival of 11.7 months vs. 10.1 months in no CPAP group(Log Rank (Mental-Cox) p=0.044 ). Conclusion Obstructive sleep apnea is a common comorbidity in patients with acute decompensated heart failure. The addition of CPAP therapy in these patients improved BMI, SBP, DBP and increases LVEF. All this improves the prognosis for these patients.

No sex differences in the cardiac responses during high altitude sojourn to 4300 m

Ascent to high altitude reduces oxygen availability and provokes compensatory cardiovascular responses. Females may exhibit attenuated hypoxic ventilatory responses compared to males, which could subsequently exaggerate the cardiovascular response to high altitude among females. The purpose of this study was to examine sex differences in cardiac responses during high altitude sojourn in young, healthy males and females. We hypothesized that females would exhibit a greater reduction in arterial oxygen saturation, and greater cardiac dysfunction compared to males. 17 healthy adults (8 males, 24±4 yrs, BMI 25.7±3.1 kg/m2; 9 females, 23±4 yrs, BMI 24.5±3.0 kg/m2) underwent cardiac assessment via echocardiography at 1400 m and after an 8-day ascent to 4300 m. Left ventricular (LV) systolic function was assessed via ejection fraction and fractional shortening. Diastolic function was assessed as the ratio between early and late mitral filling velocities (E:A ratio). The subendocardial viability ratio (SEVR) was derived from carotid tonometry, and carotid pressure waves were integrated with echocardiography derived measures of left ventricular ejection to estimate a left ventricular pressure-volume loop and calculate stroke work. Ascent from 1400 m to 4300 m resulted in reduced end-tidal CO2 (-Δ8±3 [males], -Δ8±2 mmHg [females], p<0.001), oxygen saturation (-Δ11±3 [males], -Δ11±5 % [females], p<0.001), and LV fractional shortening (-Δ7.9±7.5% [males] -Δ1.0±6.4 % [females], p=0.028) in both groups. Despite greater stroke work among males (p=0.002), high altitude-induced changes were not statistically different compared to females (+Δ35±184 [males], +Δ3±113 mL/mmHg [females]). Changes in LV ejection fraction (-Δ1.9±14.4 [males], -Δ1.5±18.7 % [females]) mitral E:A (-Δ0.33±0.53 [males], -Δ0.09±0.64 au [females]), and SEVR (-Δ0.06±0.33 [males], +Δ0.15±0.20 au [females]) from 1400 to 4300 m were not statistically different between sexes. Ascent from 1400 to 4300 m decreased end-tidal CO2, arterial oxygen saturation, and select metrics of LV systolic function (e.g., fractional shortening), but LV diastolic function, stroke work, and SEVR was preserved in both males and females. We observed no apparent sex differences in the effects of 8-day sojourn to 4300 m on arterial oxygen saturation, or cardiac systolic and diastolic function. Additional research is necessary to confirm these results in the context of longer-term altitude exposure and acclimatization, and in older populations (middle-aged and older adults). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

ASSESSMENT OF SAFETY AND FEASIBILITY OF ROTATIONAL ATHERECTOMY (RA) VERSUS CONVENTIONAL STENTING IN PATIENTS WITH CHRONIC TOTAL OCCLUSION (CTO) LESIONS

Chronic total occlusion (CTO) sores in coronary arteries present a challenge in percutaneous coronary intervention (PCI) because of their complex anatomy and high rates of procedural failure. Objectives: In this comparative study, we aim to investigate the safety and feasibility of rotational atherectomy (RA) versus conventional stenting in patients with chronic total occlusion (CTO) lesions. Methods: This comparative study was conducted at Ayub teaching hospital from September 2023 to December 2023. Data was collected from 110 patients from both genders. Patients aged > 18 years and diagnosed with chronic total occlusion (CTO) lesions in coronary arteries confirmed by coronary angiography were included in the study. Baseline demographic and clinical data, including age, gender, comorbidities, and angiographic characteristics, were collected for each participant. Additionally, procedural details such as the type of intervention, rotational atherectomy, conventional stenting, procedural time, fluoroscopy time, contrast volume, and any adverse events encountered during the procedure were recorded. Results: Data were collected from 110 patients from both genders. The mean age of participants in the Rotational Atherectomy (RA) group was 62.4 ± 7.3 years, while in the Conventional Stenting group, it was 61.8 ± 6.9 years. There were 40 males and 15 females in the RA group, compared to 38 males and 17 females in the Conventional Stenting group. The prevalence of diabetes mellitus was 42.0% in the RA group and 45.5% in the Conventional Stenting group. Left ventricular ejection fraction (LVEF) was 53.7 ± 4.2% in the RA group and 54.1 ± 4.5% in the Conventional Stenting group. The RA group showed a success rate of 81.8%, and the conventional stenting group achieved a success rate of 90.9%. However, the RA group experienced slightly higher rates of major procedural complications (9.1% vs. 5.5%) and minor procedural complications (12.7% vs. 10.9%) than the conventional stenting group. Conventional stenting group, the mean change was -1.2 ± 0.7. Additionally, the incidence of target lesion revascularisation (TLR) was observed in 8 patients (14.5%) in the RA group and 12 patients (21.8%) in the conventional stenting group. Furthermore, major adverse cardiovascular events (MACE) occurred in 9 patients (16.4%) in the RA group and 11 patients (20.0%) in the conventional stenting group. Conclusion: It is concluded that both rotational atherectomy (RA) and conventional stenting are effective and safe treatment options for patients with chronic total occlusion (CTO) lesions. Our findings suggest that both strategies yield comparable procedural success rates, complication rates, and efficacy outcomes, including myocardial infarction frequency, troponin levels, and left ventricular ejection fraction changes.

Improved all-cause mortality with left bundle branch area pacing compared to biventricular pacing in cardiac resynchronization therapy: a meta-analysis.

Left bundle branch area pacing (LBBAP) has emerged as a physiological alternative pacing strategy to biventricular pacing (BIVP) in cardiac resynchronization therapy (CRT). We aimed to assess the impact of LBBAP vs. BIVP on all-cause mortality and heart failure (HF)-related hospitalization in patients undergoing CRT. Studies comparing LBBAP and BIVP for CRT in patients with HF with reduced left ventricular ejection fraction (LVEF) were included. The coprimary outcomes were all-cause mortality and HF-related hospitalization. Secondary outcomes included procedural and fluoroscopy time, change in QRS duration, and change in LVEF. Thirteen studies (12 observational and 1 RCT, n = 3239; LBBAP = 1338 and BIVP = 1901) with a mean follow-up duration of 25.8months were included. Compared to BIVP, LBBAP was associated with a significant absolute risk reduction of 3.2% in all-cause mortality (9.3% vs 12.5%, RR 0.7, 95% CI 0.57-0.86, p < 0.001) and an 8.2% reduction in HF-related hospitalization (11.3% vs 19.5%, RR 0.6, 95% CI 0.5-0.71, p < 0.00001). LBBAP also resulted in reductions in procedural time (mean weighted difference- 23.2min, 95% CI - 42.9 to - 3.6, p = 0.02) and fluoroscopy time (- 8.6min, 95% CI - 12.5 to - 4.7, p < 0.001) as well as a significant reduction in QRS duration (mean weighted difference:- 25.3ms, 95% CI - 30.9 to - 19.8, p < 0.00001) and a greater improvement in LVEF of 5.1% (95% CI 4.4-5.8, p < 0.001) compared to BIVP in the studies that reported these outcomes. In this meta-analysis, LBBAP was associated with a significant reduction in all-cause mortality as well as HF-related hospitalization when compared to BIVP. Additional data from large RCTs is warranted to corroborate these promising findings.

Perioperative Cannabinoids Significantly Reduce Postoperative Opioid Requirements in Patients Undergoing Coronary Artery Bypass Graft Surgery.

Background Opioids, commonly used to control pain associated with surgery, are known to prolong the duration of mechanical ventilation and length of hospital stay. A wide range of adjunctive strategies are currently utilized to reduce postoperative pain, such as local and regional nerve blocks, nerve cryoablation, and adjunctive medications. We hypothesized that dronabinol (a synthetic cannabinoid) in conjunction with standard opioid pain management will reduce opioid requirements to manage postoperative pain. Methods Sixty-eight patients who underwent isolated first-time coronary artery bypass graft surgery were randomized to either the control group, who received only standard opioid-based analgesia, or the dronabinol group, who received dronabinol (a synthetic cannabinoid) in addition to standard opioid-based analgesia. Dronabinol was given in the preoperative unit, before extubation in the ICU, and after extubation on the first postoperative day. Preoperative, intraoperative, and postoperative parameters were compared under an IRB-approved protocol. The primary endpoints were the postoperative opioid requirement, duration of mechanical ventilation, and ICU length of stay, and the secondary endpoints were the duration of inotropic support needed, left ventricular ejection fraction (LVEF), and the change in LVEF. This study was undertaken at Northwest Medical Center, Tucson, AZ, USA. Results Sixty-eight patients were randomized to either the control group (n = 37) or the dronabinol group (n = 31). Groups were similar in terms of demographic features and comorbidities. The total postoperative opioid requirement was significantly lower in the dronabinol group [39.62 vs 23.68 morphine milligram equivalents (MMEs), p = 0.0037], representing a 40% reduction. Duration of mechanical ventilation (7.03 vs 6.03h, p = 0.5004), ICU length of stay (71.43 vs 63.77h, p = 0.4227), and inotropic support requirement (0.6757 vs 0.6129 days, p = 0.7333) were similar in the control and the dronabinol groups. However, there was a trend towards lower durations in each endpoint in the dronabinol group. Interestingly, a significantly better preoperative to postoperative LVEF change was observed in the dronabinol group (3.51% vs 6.45%, p = 0.0451). Conclusions Our study found a 40% reduction in opioid use and a significantly greater improvement in LVEF in patients treated with adjunctive dronabinol. Mechanical ventilation duration, ICU length of stay, and inotropic support requirement tended to be lower in the dronabinol group, though did not reach statistical significance. The results of this study, although limited by sample size, are very encouraging and validate our ongoing investigation.

Prognostic impact of prior LVEF in patients with heart failure with mildly reduced ejection fraction.

As there is limited evidence regarding the prognostic impact of prior left ventricular ejection fraction (LVEF) in patients with heart failure with mildly reduced ejection fraction (HFmrEF), this study investigates the prognostic impact of longitudinal changes in LVEF in patients with HFmrEF. Consecutive patients with HFmrEF (i.e. LVEF 41-49% with signs and/or symptoms of HF) were included retrospectively in a monocentric registry from 2016 to 2022. Based on prior LVEF, patients were categorized into three groups: stable LVEF, improved LVEF, and deteriorated LVEF. The primary endpoint was 30-months all-cause mortality (median follow-up). Secondary endpoints included in-hospital and 12-months all-cause mortality, as well as HF-related rehospitalization at 12 and 30months. Kaplan-Meier and multivariable Cox proportional regression analyses were applied for statistics. Six hundred eighty-nine patients with HFmrEF were included. Compared to their prior LVEF, 24%, 12%, and 64% had stable, improved, and deteriorated LVEF, respectively. None of the three LVEF groups was associated with all-cause mortality at 12 (p ≥ 0.583) and 30months (31% vs. 37% vs. 34%; log rank p ≥ 0.376). In addition, similar rates of 12- (p ≥ 0.533) and 30-months HF-related rehospitalization (21% vs. 23% vs. 21%; log rank p ≥ 0.749) were observed. These findings were confirmed in multivariable regression analyses in the entire study cohort. The transition from HFrEF and HFpEF towards HFmrEF is very common. However, prior LVEF was not associated with prognosis, likely due to the persistently high dynamic nature of LVEF in the follow-up period.

Changes in Cardiac Function Following Fulminant Myocarditis.

The natural history of myocardial dysfunction in patients with fulminant myocarditis is poorly understood. This study aims to evaluate changes in cardiac function in patients with fulminant myocarditis using a nationwide registry in Japan. This retrospective cohort study included patients with biopsy-proven fulminant myocarditis and available for left ventricular ejection fraction (LVEF). We described the LVEF on admission, at discharge, and 1 year after discharge. We divided patients into 2 groups based on LVEF at discharge (reduced ejection fraction of <50% or preserved ejection fraction of ≥50%) and analyzed changes in LVEF and prognosis according to groups. We included 214 patients (the median [first-third quartiles] age of the cohort was 48 [35-62] years, and 63 [38%] were female). Of 153 patients available for LVEF at 1 year, the median (first-third quartiles) LVEF increased from 33% (21-45%) on admission to 59% (49-64%) at discharge and further to 61% (55-66%) at 1 year. Of 153 patients, 45 (29%) and 22 (14%) had LVEF <50% at discharge and at 1 year, respectively. Comparisons between patients with LVEF <50% and those with LVEF ≥50% demonstrated that the former group had a higher adjusted probability of death or heart transplantation (hazard ratio, 8.19 [95% CI, 2.13-31.5]; P=0.002). Some patients with fulminant myocarditis had left ventricular dysfunction in the chronic phase. Patients with reduced left ventricular function at discharge had a worse prognosis than those with preserved left ventricular function. URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000045352; Unique identifier: UMIN000039763.

Predictors of improvement in left ventricular systolic function after catheter ablation in patients with persistent atrial fibrillation complicated with heart failure

AimsThe current management of patients with atrial fibrillation (AF) and concomitant heart failure (HF) remains a significant challenge. Catheter ablation (CA) has been shown to improve left ventricular ejection fraction (LVEF) in these patients, but which patients can benefit from CA is still poorly understood. The aim of our study was to determine the predictors of improved ejection fraction in patients with persistent atrial fibrillation (PeAF) complicated with HF undergoing CA.Methods and resultsA total of 435 patients with persistent AF underwent an initial CA between January 2019 and March 2023 in our hospital. We investigated consecutive patients with left ventricular systolic dysfunction (LVEF < 50%) measured by transthoracic echocardiography (TTE) within one month before CA. According to the LVEF changes at 6 months, these patients were divided into an improved group (fulfilling the ‘2021 Universal Definition of HF’ criteria for LVEF recovery) and a nonimproved group. Eighty patients were analyzed, and the improvement group consisted of 60 patients (75.0%). In the univariate analysis, left ventricular end-diastolic diameter (P = 0.005) and low voltage zones in the left atrium (P = 0.043) were associated with improvement of LVEF. A receiver operating characteristic analysis determined that the suitable cutoff value for left ventricular end-diastolic diameter (LVDd) was 59 mm (sensitivity: 85.0%, specificity: 55.0%, area under curve: 0.709). A multivariate analysis showed that LVDd (OR = 0.85; 95% CI: 0.76–0.95, P = 0.005) and low voltage zones (LVZs) (OR = 0.26; 95% CI: 0.07–0.96, P = 0.043) were significantly independently associated with the improvement of LVEF. Additionally, parameters were significantly improved regarding the left atrial diameter, LVDd and ventricular rate after radiofrequency catheter ablation (all p < 0.05).ConclusionsThe improvement of left ventricular ejection fraction (LVEF) occurred in 75.0% of patients. Our study provides additional evidence that LVDd < 59 mm and no low voltage zones in the left atrium can be used to jointly predict the improvement of LVEF after atrial fibrillation ablation.

Effectiveness and Safety of Sacubitril/Valsartan in Heart Failure in India: A Retrospective Real-world (SAVE) Study

Background: Sacubitril/Valsartan is one of the pillars of heart failure (HF) management. Little is known about its uses or impact in real-world practice in the Indian population. We evaluated the effectiveness and Safety of Sacubitril/Valsartan in Heart Failure in India. Methods: This retrospective analysis involved newly diagnosed adult patients of HF (class I–IV, per physician clinical assessment and discretion), treated in a tertiary care hospital during period of February–April 2023 and received Sacubitril/Valsartan. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured in addition to demographics, clinical symptoms, comorbidities, and left ventricular ejection fraction (LVEF). Following three months of Sacubitril/Valsartan medication, changes in LVEF, NT-proBNP levels, and clinical symptoms (graded from 1 to 10, with 10 being the maximum severity) were assessed. Results: Out of 60 patients eligible for the study, 57% were males and 43% were females. Mean body weight was 60.26 ± 7.00 kg, while mean BP was 130/81 mmHg. 60% patients had both type 2 diabetes and hypertension as comorbidity. There was 23% improvement in LVEF (from mean LVEF of 34 to 42, P &lt; .0001), with a significant decrease in NT-proBNP levels (mean 1220.5 pg/mL to 118.1 pg/mL, P &lt; .0001) after treatment with Sacubitril/Valsartan for 3 months, resulted in marked improvement in clinical symptoms of breathlessness (mean score decreased from 6 to 2, P &lt; .05), edema (mean score decreased from 5.5 to 1.8, P &lt; .05) and palpitations (mean score decreased from 2.4 to 1.1, P &lt; .05. 50 mg BD was the most commonly used dose of Sacubitril/Valsartan (70% patients), followed by 100 mg BD (25% patients) and rest (5%) with 200 mg BD dose. Treatment with Sacubitril/Valsartan was well tolerated, with &lt;5% patients reporting hypotension. Conclusion: The findings of this real-world study suggest Sacubitril/Valsartan was associated with an increase in ejection fraction translating into symptomatic improvement in Indian patients of HF.

Abstract 679: TXB-001 is an upgraded conjugated anthracycline that targets tumors with reduced risk of cardiotoxicity, hand-foot syndrome and alopecia

Abstract TXB-001 is a well-optimized N-(2-hydroxypropyl)methacrylamide copolymer-based conjugated pirarubicin (THP) and a novel candidate for developing anticancer drugs. It exhibits tumor-specific accumulation due to the enhanced permeability and retention effects and prolonged circulation time compared with free THP. Its hydrazone bond is dissociated under lower pH conditions, providing selective and rapid release of THP in acidic tumor environments. Therefore, TXB-001 is expected to have high efficacy and low toxicity. Anthracycline anticancer drugs have been widely used for the treatment of several cancers, but their use is limited by several adverse effects (AEs), including cardiotoxicity, which is a life-threatening AE. Furthermore, the maximum lifetime cumulative dose is decided for each anthracycline in clinical use, which leads to discontinuation of the medication. Hand-foot syndrome (HFS) is a dose-limiting AE of DOXIL®, a liposomal formulation of doxorubicin (DOX), and although it is not a life-threatening condition, it significantly deteriorates quality of life (QOL). Alopecia is another common AE, which is relatively noninvasive but adversely affects mental health and reduces QOL. In this study, we confirmed the efficacy of TXB-001 in a mice triple-negative breast cancer (TNBC) model and evaluated the cardiotoxicity-, HFS- and alopecia-inducing effects of TXB-001 in mice and rats to compare the severity with existing anthracycline anticancer drugs, including DOXIL®. The pharmacokinetic (PK) analysis in several tissues, including plasma, tumor, heart, skin of the chest, and palmar and plantar areas, was also performed after a single intravenous administration in rodents. As a result, TXB-001 showed an equivalent or greater antitumor effects than other anthracyclines in the TNBC model, and the AEs were scarcely observed. TXB-001 did not decrease left ventricular ejection fraction, with no or little HFS-like changes compared with DOXIL®, which showed significant histopathological changes. TXB-001 also showed weaker alopecia-inducing effects than DOX, DOXIL®, and THP. In the PK analysis, TXB-001 was distributed in the tumor at a higher concentration than in other tissues, except for plasma. Hence, most of the THP, the active ingredient, was released in the tumor. The exposure of the heart in the TXB-001-treated group was one-tenth of that in the DOXIL®-treated group. Moreover, accumulation in the skin, especially in palmar and plantar areas, was observed for DOXIL®, but no accumulation in the skin was observed for TXB-001. This PK profile consistently demonstrated the antitumor activity of TXB-001, without AEs. TXB-001 reduces the chance of dose-limiting and QOL-threatening AEs, and thus, cancer patients can continue treatment, making it a more convenient anticancer drug in clinical use with a wide safety margin. Citation Format: Keiyu Oshida, Mikito Hirakata, Emi Tomikawa, Chizuka Sakai, Masashi Uchida, Rieko Shimozono, Akiko Izawa, Yoko Koga, Tsubasa Okano, Hideki Narumi, Lisa Munakata, Ryo Suzuki, Miki Nonaka, Yasuhito Uezono. TXB-001 is an upgraded conjugated anthracycline that targets tumors with reduced risk of cardiotoxicity, hand-foot syndrome and alopecia [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 679.

Response predictors to cardiac resynchronization therapy in chronic heart failure: a 10-year-cardiovascular center experience.

Cardiac resynchronization therapy (CRT) has been established as an effective therapy for heart failure with reduced ejection fraction. Randomized clinical trials have shown its impact on mortality and HF hospitalizations, as well as improvement of symptoms and quality of life. Finding clinical, electrocardiographic, and echocardiographic variables that may predict the response to cardiac resynchronization therapy (CRT). We performed a single-center, observational, analytic, and retrospective study that included 102 patients with heart failure (HF) diagnosis who underwent CRT according to guideline-directed therapy from January 2010 to April 2020 in a third-level center. CRT response was defined as an improvement of New York Heart Association functional class in at least 1 category associated with a recovery of ≥ 5% in the left ventricular ejection fraction (LVEF). Our study population was 102 patients of which 61 (59.8%) were men. The mean age at HF diagnosis was 54 ± 18.7 years. Ischemic heart disease was the etiology in 37 (36.3%) cases. Fifty-one (50%) patients were classified as responders. Responders had wider QRS, and lower LVEF and right ventricular fractional area change at baseline. After CRT, responders had a greater reduction of QRS duration, and improvement in LVEF, global longitudinal strain, and echocardiographic dyssynchrony parameters. Multivariate regression analysis showed that left bundle branch block (LBBB), left ventricular end-diastolic volume (LVEDV), tricuspid annular plane systolic excursion (TAPSE), and baseline difference of pre-ejection periods were predictors of a positive response to CRT in this population. LBBB, TAPSE, LVEDV, and pre-ejection time difference are independent variables that can predict adequate response to CRT.

Analysis of clinical features of heart failure in children with cardiomyopathy and improved ejection fraction.

The prognosis of children with heart failure varies considerably. After treatment, left ventricular ejection fraction (LVEF) can be improved in some children. The aim of this study was to analyze the clinical features of children with heart failure accompanied by cardiomyopathy and recovered ejection fraction [heart failure with recovered ejection fraction (HFrecEF)] and to identify the predictors of improved LVEF. Children diagnosed with heart failure in Beijing Anzhen Hospital Affiliated to Capital Medical University from 2018 to 2021 were retrospectively enrolled. According to the baseline and change of LVEF, the patients were divided into two groups: a reduced ejection fraction (HFrEF) group and an HFrecEF group. The t-test was used to evaluate the difference between the two groups. The predictive factors of ejection fraction improvement were analyzed with a logistic regression model. A total of 72 children were included in this study, including 31 (43.1%) in the HFrEF group and 41 (56.9%) in the HFrecEF group. Compared with children in the HFrEF group, children in the HFrecEF group were younger and had faster resting heart rates, lower creatinine, lower suppression of tumorigenicity 2 (ST2) expression, a lower platelet-to-lymphocyte (PLT:LYM) ratio, and smaller left atrial diameter. After a mean follow-up of 35.87 months, 26 cases returned to normal ejection fraction. In the HFrEF group, sudden cardiac death occurred in two cases, and four cases received heart transplantation. Logistic analysis showed that virus infection [odds ratio (OR) =1.279; 95% confidence interval (CI): 0.374-4.379; P=0.007], low ST2 expression (cutoff value =1.89 ng/mL: OR =1.042; 95% CI: 1.007-1.082; P=0.032), and treatment with intravenous immunoglobulin (IVIG) (OR =5.077; 95% CI: 1.458-17.684; P=0.011) were predictors of improvement in LVEF in patients with heart failure after treatment. In some patients with HFrecEF, LVEF eventually returned to normal. The combination of viral infection, low ST2 expression, and the application of IVIG therapy were found to be independent predictors of LVEF improvement in patients with heart failure after treatment.

Left ventricular ejection fraction: clinical, pathophysiological, and technical limitations.

Risk stratification of cardiovascular death and treatment strategies in patients with heart failure (HF), the optimal timing for valve replacement, and the selection of patients for implantable cardioverter defibrillators are based on an echocardiographic calculation of left ventricular ejection fraction (LVEF) in most guidelines. As a marker of systolic function, LVEF has important limitations being affected by loading conditions and cavity geometry, as well as image quality, thus impacting inter- and intra-observer measurement variability. LVEF is a product of shortening of the three components of myocardial fibres: longitudinal, circumferential, and oblique. It is therefore a marker of global ejection performance based on cavity volume changes, rather than directly reflecting myocardial contractile function, hence may be normal even when myofibril's systolic function is impaired. Sub-endocardial longitudinal fibers are the most sensitive layers to ischemia, so when dysfunctional, the circumferential fibers may compensate for it and maintain the overall LVEF. Likewise, in patients with HF, LVEF is used to stratify subgroups, an approach that has prognostic implications but without a direct relationship. HF is a dynamic disease that may worsen or improve over time according to the underlying pathology. Such dynamicity impacts LVEF and its use to guide treatment. The same applies to changes in LVEF following interventional procedures. In this review, we analyze the clinical, pathophysiological, and technical limitations of LVEF across a wide range of cardiovascular pathologies.

Radionuclide Imaging Findings in Iatrogenic Stress in Cases with Reduced Left Ventricular Ejection Fraction

Objective: This study aims to contribute to the existing literature by assisting in the selection of stress protocols for patients with reduced left ventricular ejection fraction (LVEF). We also aim to provide insights into patient follow-up based on changes in post-stress LVEF determined by echocardiography. Methods: Our retrospective study encompassed 487 patients initially diagnosed with coronary artery disease. Left ventricular function was assessed using echocardiography and myocardial perfusion scintigraphy. Among them, 250 patients with LVEF values within normal limits constituted Group-1, while 237 patients with LVEF values below 50% formed Group-2. Exercise stress testing was performed using a treadmill according to the Bruce protocol. For vasodilator stress testing, intravenous adenosine infusion at a rate of 140 μg/kg/min was administered for 6 minutes. Tc-99m-sestamibi was intravenously administered (8-12 mCi) for stress imaging and (24-36 mCi) for rest imaging. Results: The median age of all patients in the study was 64 (52-79) years, with 283 (58.1%) being male. Myocardial perfusion, assessed by myocardial perfusion scintigraphy, revealed a fixed perfusion defect in all patients. Reversible perfusion defects were observed in 172 (35.3%) patients. Among patients with reduced echo-LVEF values, those who underwent exercise stress testing showed significantly lower post-stress EF values compared to those who underwent vasodilator stress testing (35 (25-42) vs. 36 (30-47), p: 0.0005). Post-stress LVEF was notably lower in patients with reversible perfusion defects, indicating a higher rate of LVEF decrease due to stress (p: 0.0005). Conclusion: Left ventricular ejection fraction (LVEF) serves as a valuable metric for assessing left ventricular function. The findings from this study support its utility in guiding the selection of a suitable stress protocol and monitoring patients during iatrogenic cardiac stress applications.

Changes in Left Ventricular Function and Outcomes After Trancatheter Edge-to-Edge Repair for Secondary Mitral Regurgitation

BackgroundTranscatheter edge-to-edge repair (TEER) improved outcomes in patients with heart failure (HF) and severe secondary mitral regurgitation (SMR) compared with guideline-directed medical therapy (GDMT) alone regardless of the severity of baseline left ventricular ejection fraction (LVEF). The study aimed to evaluate the effect of early changes in LVEF after TEER and GDMT alone in patients with HF and severe SMR. MethodsWithin the COAPT trial, we evaluated outcomes according to changes in LVEF from baseline to 30 days. The primary outcome was all-cause death or HF hospitalization (HFH) between 30 days and 2 years. ResultsAmong 432 patients with paired echocardiographic data, 182 (42.1%) had increased LVEF (LVEF change 6.0% ± 4.9%) and 250 (57.9%) had a decrease or no change in LVEF (LVEF change –6.6% ± 5.6%) from baseline to 30 days. LVEF at 30 days increased more frequently with GDMT alone compared with TEER plus GDMT (51.4% vs 33.0%; P = .0001). Between 30 days and 2 years, there were no significant differences in death or HFH in the increase LVEF and the decrease LVEF groups (58.8% vs 51.4%; multivariable-adjusted HR, 0.97; 95% CI, 0.87-1.08; P = .59). TEER plus GDMT reduced the 30-day to 2-year rate of death or HFH compared with GDMT alone consistently in patients with increase LVEF and decrease LVEF (Pint = 0.75). ConclusionsAmong patients with HF and severe SMR, early improvements in LVEF were more frequent with GDMT alone compared with TEER plus GDMT but were not associated with subsequent outcomes at 2 years. TEER reduced death or HFH during 2-year follow-up irrespective of early LVEF changes.

Cardiac resynchronization therapy for pacing induced cardiomyopathy: Role of baseline right ventricular pacing burden.

Cardiac resynchronization therapy (CRT) is indicated for patients with heart failure with reduced left ventricular ejection fraction (LVEF) and chronic right ventricular (RV) pacing burden ≥40% (pacing-induced cardiomyopathy, PICM). It is uncertain whether baseline RV pacing burden impacts response to CRT. We conducted a retrospective study of all CRT upgrades for PICM at our hospital from January 2017 to December 2018. Univariate and multivariable-adjusted changes in LVEF, and echocardiographic response (≥10% improvement in LVEF) at 3-12 months post-CRT upgrade were compared in those with RV pacing burden ≥90% versus<90%. We included 75 patients (age 74±11years, 71% male) who underwent CRT upgrade for PICM. The baseline RV pacing burden was ≥90% in 56 patients (median 99% [IQR 98%-99%]), and<90% in 19 patients (median 79% [IQR 73%-87%]). Improvement in LVEF was greater in those with baseline RV pacing burden ≥90%versus<90% (15.7±9.3%vs. 7.5±9.6%, p=.003). Baseline RV pacing burden ≥90% was a strong predictor of an improvement in LVEF ≥10% after CRT upgrade both in univariate and multivariate-adjusted models (p=.005 and .02, respectively). A higher baseline RV pacing burden predicts a greater improvement in LVEF after CRT upgrade for PICM.