Median Left Ventricular Ejection Fraction Research Articles

Effect of early catheter ablation of atrial fibrillation in patients with heart failure.

According to current guidelines, pulmonary vein isolation as first-line therapy should be considered for patients with atrial fibrillation (AF), however, optimal timing of the procedure is still unknown in patients with heart failure (HF). We aimed to evaluate the effect of early catheter ablation (CA) in patients with HF and left ventricular ejection fraction (LVEF) below 50%. We analyzed data from a structured registry comprising 227 patients with paroxysmal or persistent AF and HF with LVEF < 50% who underwent radiofrequency CA between 2015 and 2022. Early CA was defined as a procedure performed within 12 months of AF diagnosis. The median follow-up duration was 1748 (1176.3-2353.5) days, with a minimum follow-up of 365 days. Our endpoints were AF recurrence after a 3-months blanking period and all-cause mortality. Among the 227 patients with a median age of 64.3 years, 97 (42.7%) experienced AF recurrence and 55 (24.2%) died during the follow-up period. The median LVEF was 40% for early CA and 38% for delayed CA (p = .053). Early CA significantly reduced AF recurrence (HR = 0.25 [0.15-0.42], p < .001), however, the timing of procedure did not affect all-cause mortality (p = .16). These findings were consistent regardless of AF subtype or the burden of comorbidities, as assessed by the CHA2DS2-VASc score. The timing of CA of AF appears to be an important factor in patients with HF. Early CA reduced AF recurrence, although it does not impact all-cause mortality. We found similar results regardless of AF subtype or burden of comorbidities.

Newly diagnosed heart failure in patients with atrial fibrillation referred for catheter ablation - identifying patients with arrhythmia-induced cardiomyopathy

Abstract Introduction Atrial tachyarrhythmias are primary drivers in the development of arrhythmia-induced cardiomyopathy (AiCM). The restoration of sinus rhythm in patients with an AF (atrial fibrillation) based AiCM results in enhancement of left ventricular ejection fraction (LV-EF). This study aims to assess the prevalence of undiagnosed and unexplained heart failure among patients with AF referred for catheter ablation and seeks to phenotype these patients. Methods Our registry, a prospective, observational clinical cohort that recruits patients with heart rhythm disorders at a large tertiary-care center since March 2021 was interrogated for AF patients. These patients underwent screening for heart failure based on clinical, laboratory, and imaging characteristics. Undiagnosed heart failure at baseline, lack of heart failure medication and absence of known structural heart disease were considered suspicious for AiCM. Results A total of 1225 patients were analyzed. 35.2% were female, median age 67 (IQR 59;75) years, median LV-EF 55.0 (IQR 50;60) % and median N-terminal pro B-type natriuretic peptide (NT-proBNP) 686 (IQR 210;1630) mg/dl. NYHA class I was reported in 28.3% cases, NYHA class II in 32.2%, NYHA class III in 20.2% and NYHA class IV in 2%. At baseline, 263 patients (17.6%) had an LV-EF &amp;lt; 50% of those 110/263 (42%) with suspected AiCM. Patients with suspected AiCM were 67 (IQR 58;76) years old, 40.9% were female, median LV-EF was 41.0 (IQR 35;41) % and NT-proBNP at admission was 1681 (IQR 775;2352) mg/dl. Patients with suspected AiCM had a significantly reduced TAPSE (19 vs. 22 mm; p&amp;lt;0.001), showed generic characteristics of heart failure (NTproBNP: p&amp;lt;0.001, NYHA class: p=0.049), while EHRA score was significantly lower (p=0.006). In contrast, patients with known cardiomyopathy of non-AiCM origin at baseline and EF &amp;lt; 50% (n=153) had significantly higher LAVI (44.8 vs. 38.8 ml/m2; p=0.002), were predominantly male (76.5 vs. 59.1 %; p=0.004) and had lower GFR (60.2 vs. 68.5 ml/min; p=0.002) compared to AiCM patients. Among 29/110 suspected AiCM patients with available TTE at follow-up (within 12 months post-catheter ablation), 26/29 exhibited an improved LV-EF (40% at baseline vs. 54% at FU; p&amp;lt;0.001). 3/3 patients without LV-EF improvement exhibited arrhythmia recurrence. Conclusion Primary AiCM was suspected in 42% of all AF patients with reduced LV function referred for catheter ablation. These patients exhibited a different phenotype compared to the remaining cohort. After catheter ablation, ejection fraction improved in 90% of AiCM patients. These findings call for structured HF screening in clinical routine in AF patients. In the future, validated scores are required to enable early rhythm control for these patients.Proportion of patients with HFrEFCourse of EF after catheter ablation

Lower dose radiotherapy did not alter cardiac function and was not pro-arrhythmic: results of the small prospective HALO trial

Abstract Background Stereotactic arrhythmia radiotherapy (STAR) is a highly promising bail-out treatment for patients with therapy-refractory ventricular tachycardia (VT). Despite precise, noninvasive targeting of the pro-arrhythmic area, surrounding healthy cardiac tissue inadvertently receives low-dose radiation. There is a historical notion that collateral cardiac damage from radiation of extra-cardiac structures can cause heart failure and arrhythmias. In the HALO trial, where non-small cell lung cancer (NSCLC) patients treated with stereotactic ablative radiotherapy (SABR) received relatively low-dose radiotherapy to the heart, detailed cardiac safety after radiotherapy was therefore evaluated. Objective The aim of this study was to prospectively evaluate cardiac function after collateral radiotherapy on the heart in patients with NSCLC treated with SABR. Methods The HALO trial was a prospective observational trial evaluating cardiac adverse effects in patients treated with SABR for early stage NSCLC. Patients with a tumour within 3cm of the pericardium were eligible to participate. The mean radiotherapy dose per segment was calculated by semi-automated angulation and segmentation using an in-house developed tool. The heart was segmented according to the AHA 17-segment model. Patients underwent cardiac magnetic resonance imaging (CMR) pre-treatment, 3 and 12 months after treatment. CMR strain-analysis was conducted by two independent observers using cvi42 software. Longitudinal, radial and circumferential strain were measured both globally and segmentally and evaluated for dose-dependent effects. Results Ten patients were included in this study. Two patients dropped out before first follow-up and were not included in this analysis. Median age was 66 years (range 58-81) and four were male (50%). Median distance between the tumour and pericardium was 0.46cm (range 0.00-2.80). Patients were treated with 8 fractions of 7.0-7.5 Gy (n=6), 5 fractions of 11.0 Gy (n=1) or 3 fractions of 18.0 Gy (n=1). Median global cardiac radiotherapy dose was 6.7 Gy (range 0.1-17.9). Pre-treatment, median left ventricular ejection fraction as measured on CMR was 65% (range 40-75), global longitudinal strain was -15% (-20 - -9), global circumferential strain was -17% (-26 - -9) and global radial strain was 28% (11-60). These did not significantly change comparing 3 months and 12 months after treatment with pre-treatment. As can be appreciated from Table 1, there were no dose-dependent effects on segmental longitudinal, radial and circumferential strain both 3 months or 12 months after SABR. There were no ventricular arrhythmias observed during follow-up. Conclusion In this small study, collateral radiotherapy in patients with NSCLC treated with SABR did not significantly alter cardiac function as measured on CMR, and no relevant pro-arrhythmic effects were observed during short term follow-up. Extending the research into a larger dataset is warranted.

Genotype, phenotype and outcomes of patients with hypertrophic cardiomyopathy referred for ablation of ventricular tachycardia

Abstract Background Sustained monomorphic ventricular tachycardia (SMVT) is the most common ventricular arrhythmia (VA) subtype in patients with hypertrophic cardiomyopathy (HCM) who have received an implantable cardioverter defibrillator (ICD). However, data on catheter ablation (CA) are limited and available series typically report results of non-genotyped patients with relatively mild hypertrophy and/or apical aneurysms. Purpose This study describes genotype, phenotype and outcome of consecutive HCM patients referred for CA ablation of refractory SMVT. Methods and results Nine out of 787 patients referred for catheter ablation of SMVT between 01/2016 – 10/2023 had a HCM phenotype, 8/9 with dominant septal hypertrophy, none with LV outflow tract obstruction, and only 1/9 with an apical aneurysm. The median maximal wall thickness was 25 mm (IQR 20,2 – 26,9 mm) and the median left ventricular ejection fraction 34 % (IQR 26-42%). Six patients had a class IV/V variant in the myosine binding protein C (MYBPC3) gene, in 3 no disease-causing variant was identified. All patients with MYBPC3 mutation presented with an electrical storm/incessant VT refractory to antiarrhythmic drugs (AAD), including amiodarone (6/6) and amiodarone + class I AAD (3/6). In an attempt to control VT, 4/6 patients with a MYBPC3 variant required ≥2 ablation including bail out strategies (transcoronary alcohol-ablation, bipolar ablation, half-saline), surgical substrate resection and intraoperative cryoablation (3/6) and radiotherapy (2/6). After a median follow-up of 25 months (IQR 2-75) after the last intervention, all patients with MYBPC3-variants had VT recurrence, 3/6 died and 1/6 underwent heart transplantation. In contrast, patients without class IV/V variants, did not require bail-out strategies; VT recurred in one (single episode) and one patient died, 24 months after CA. The time course of the disease, management and outcome for patients with and without disease causing mutation is illustrated, with the first ablation as center line (figure). Conclusions Only 1 % of patients referred for CA of SMVT to a high-volume center had a HCM phenotype. A MYBPC3 variant was identified in 67%, and, in contrast to prior reports, 89% had severe hypertrophy. VT free survival appears to be particularly poor in MYBPC3 variant carriers despite availability of all treatment modalities. In these patients, early screening for advanced heart failure management including heart transplantation is important.

Comparison of eplerenone and spironolactone treatment in patients with ischemic heart disease hospitalized due to ventricular tachycardia

Abstract Background The beneficial effects of mineralocorticoid receptor antagonists (MRAs) regarding sudden cardiac death (SCD) risk and cardiac remodeling are well known, moreover, they also reduce episodes of ventricular tachycardia (VT). However, superiority in effectiveness between receptor selective eplerenone and conventional spironolactone is unknown. Purpose Our aim was to assess the effect of eplerenone and spironolactone on ventricular tachycardia (VT) recurrence in patients with ischemic heart disease (IHD). Methods We collected data of 563 patients with IHD following hospitalization due to a sustained VT episode in a structured registry. Propensity score matching was performed based on age, hypertension, diabetes, history of acute myocardial infarction, left ventricular ejection fraction (LVEF) and presentation with incessant VT. The matched population consisted of 188 patients and was further analyzed. Predictors were assessed using univariate and multivariate Cox regression models. Kaplan-Meier curves were used for time-to-event analyses. Results The median age was 70 years with 81% being male. One third of the patients had an ICD implanted, while 43 (23%) had CRT. The median LVEF was 30%. Twenty-five (13%) patients presented with an electrical storm and 19 (10%) had incessant VT. In 86 cases (46%), the VT caused hemodynamic instability. Ablation was performed in 66 patients (35%), while 4 required mechanical circulatory support. During the median follow-up of 856 [399-1624] days, 69 patients had VT recurrence and 118 patients died. Eplerenone use significantly reduced the risk of VT recurrence compared to spironolactone (HR: 0.48 [0.29-0.78], log-rank p=0.003). This effect was consistent in the multivariate model as well (p=0.006). Conclusions Eplerenone use may be more beneficial in terms of VT recurrence in patients with IHD who present with a sustained VT. Further analysis is required to confirm these findings.

Absence of late gadolinium enhancement and outcomes of cardiac resynchronization therapy in non-ischemic dilated cardiomyopathy

Abstract Background Among patients with non-ischemic dilated cardiomyopathy (DCM) with indication for cardiac resynchronization therapy (CRT), there are no clear recommendations about who should receive a CRT-defibrillator (CRT-D) and who should have CRT-pacemaker (CRT-P). Absence of late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) has a high negative predictive value for ventricular arrhythmias (VA) and sudden death (SD) in DCM and is a predictor of reverse remodelling in several scenarios. Purpose To evaluate the association between absence of LGE and VA/SD or echocardiographic response to CRT in DCM patients treated with CRT. Methods Multicenter retrospective observational cohort study including consecutive DCM patients with de-novo CRT implant and with available CMR. The primary endpoints were: 1) a combined arrhythmic endpoint including appropriate defibrillator therapies, sustained VA and sudden death. 2) echocardiographic response to CRT, intended as an increase ≥10% in left ventricular ejection fraction (LVEF). Results We included 167 patients, 55% males, with median QRS duration of 160ms and median LVEF of 25%. LGE was present in 46% of cases (LGE+). A CRT-D was implanted in 73% of patients. Median follow-up was 63 months. Of note, among patients without LGE (LGE-) we did not record any event of the combined arrhythmic endpoint. The cumulative incidence of the arrhythmic endpoint was significantly higher in LGE+ than in LGE- patients (25% vs 0%, p&amp;lt;0.001) and LGE was an independent predictor of this endpoint (adjusted HR 42, p&amp;lt;0.001). The proportion of responders to CRT was significantly higher in LGE- than in LGE+ cases (81% vs 53%, p&amp;lt;0.001); absence of LGE was the strongest predictor of echocardiographic response to CRT at multivariate analysis (adjusted OR 4.1, p=0.001). Super-responders (i.e. those with LVEF≥50% at follow-up) were also more frequent among LGE- than LGE+ patients (46% vs 21%, p=0.001) and absence of LGE was an independent predictor of LVEF normalization (HR 2.6, p=0.03). Conclusions Among DCM patients who receive CRT, those without LGE have an extremely low (or null in this case) arrhythmic risk and, at the same time, they have a high probability of echocardiographic response to CRT. Thus, LGE- patients could be ideal candidates for CRT-P instead of CRT-D.

Biomarkers to predict improvement of left ventricular ejection fraction after atrial fibrillation ablation

Abstract Background Atrial fibrillation (AF) and heart failure (HF) frequently coexist. Catheter ablation (CA) of AF is increasingly used in patients with AF and HF. However, prediction of improvement of HF after CA is challenging. Aim We aimed to evaluate the value of biomarkers, alone and in conjunction with a clinical tool (Antwerp score) to predict left ventricular ejection fraction (LVEF) recovery after CA in patients with AF and HF. Methods Patients undergoing CA for AF with depressed LVEF (&amp;lt;50%) were included. Plasma levels of 13 biomarkers were measured immediately prior to CA. Patients were categorized into "responders" (LVEF normalisation after CA in case of HFmrEF and at least 10% LVEF improvement and LVEF &amp;gt; 40% at follow-up in case of HFrEF) and "non-responders" (no LVEF recovery after CA). Models were constructed by comparing the plasma levels of the various biomarkers in responders and non-responders and by adjusting for age, sex, and Antwerp score and subsequent biomarkers were then combined according based on likelihood-ratios. The predictive power of the biomarkers alone and combined in outcome prediction, as well as improvement of the Antwerp score was then evaluated. Results Out of 1665 patients undergoing CA of AF, we included 208 patients with depressed LVEF (median age 63 years, 19% female, median LAVI 42 ml/m2, median LVEF 43%). The median follow-up time was 30 months [IQR 20-34] and the median time to LVEF recovery was 8 months [IQR 3-22]. Of these, 161 (77%) were responders and 47 (23%) were non-responders. Out of 13 biomarkers, four biomarkers (ANG2, GDF15, FGF23 and MyBPC3) were significantly different between responders and non-responders (p ≤0.001). A biomarker panel using these four biomarkers could predict LVEF recovery after CA for AF with an AUC of 0.72 (95%CI 0.64-0.81) overall, 0.69 (95%CI 0.59-0.78) in HFmrEF and 0.88 (95%CI 0.77-0.98) in HFrEF (Figure, A). Only ANG2 and GDF15 remained significantly associated with LVEF recovery after adjustment for age, sex, and the Antwerp score. The AUC of the Antwerp score for prediction of LVEF recovery improved from 0.75 (95% CI 0.67-0.83, Figure, B) to 0.78 (95% CI 0.70-0.86, Figure, C) in the overall population, from 0.71 (95% CI 0.61-0.81) to 0.74 (95% CI 0.64-0.84) in case of HFmrEF and from 0.87 (95% CI 0.78-0.97) to 0.92 (95% CI 0.85-0.99) in case of HFrEF when ANG2 and GDF15 were included in the model. Conclusion A biomarker panel using ANG2, GDF15, FGF23 and MyBPC3 performs similarly for prediction of LVEF recovery after CA in AF compared to the Antwerp score. The biomarkers ANG2 and GDF15 slightly improve the predictive value of the Antwerp score.Figure

Recovery of left ventricular systolic function in peripartum cardiomyopathy: an observational study from rural Tanzania

BackgroundThe aim of this study was to evaluate the recovery rate of the left ventricular systolic function of women diagnosed with peripartum cardiomyopathy receiving specialized care in rural Tanzania.MethodsIn this observational study, women diagnosed with peripartum cardiomyopathy at a referral center in rural Tanzania between December 2015 and September 2021 were included. Women diagnosed between February and September 2021 were followed prospectively, those diagnosed between December 2015 and January 2021 were tracked back for a follow-up echocardiography. All participants received a clinical examination, a comprehensive echocardiogram, and a prescription of guideline-directed medical therapy. The primary outcome was recovery of the left ventricular systolic function (left ventricular ejection fraction > 50%).ResultsMedian age of the 110 participants was 28.5 years (range 17–45). At enrolment, 49 (45%) participants were already on cardiac medication, 50 (45%) had severe eccentric hypertrophy of the left ventricle, and the median left ventricular ejection fraction was 30% (range 15–46). After a median follow-up of 8.98 months (IQR 5.72–29.37), 61 (55%) participants were still on cardiac medication. Full recovery of the left ventricular systolic function was diagnosed in 76 (69%, 95% CI 59.6–77.6%) participants. In the multivariate analysis, a higher left ventricular ejection fraction at baseline was positively associated with full recovery (each 5% increase; OR 1.7, 95% CI 1.10–2.62, p = 0.012), while higher age was inversely associated (each 10 years increase; OR 0.40, 95% CI 0.19–0.82, p = 0.012).ConclusionLeft ventricular systolic function recovered completely in 69% of study participants with peripartum cardiomyopathy from rural Tanzania under specialized care.

Global longitudinal strain as a predictor of mortality in patients with cardiogenic shock

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Aarhus University Dagmar Marshalls Fond. Background The assessment of left ventricular (LV) function through transthoracic echocardiography (TTE) is essential for guiding diagnosis and treatment in cases of cardiogenic shock (CS). Myocardial global longitudinal strain (GLS) provides an objective and reproducible measure of systolic function, independently predicting outcomes in acute heart failure, regardless of left ventricular ejection fraction (LVEF). However, whether assessment of GLS can predict mortality in patients with CS remains unknown. Purpose In this study, we aimed to evaluate the prognostic significance of GLS in patients with CS. Methods Data from cardiac intensive care unit (CICU) patients admitted between 2007 and 2018 with CS who received vasoactive agents and/or mechanical circulatory support were analysed. GLS (as absolute values) and biplane LVEF were measured via TTE performed within 24 hours of CICU admission. Patients with CS were categorised based on the GLS quartile: mild (GLS &amp;gt;9.7%), moderate (7.0% &amp;lt; GLS &amp;lt;9.6%), severe (5.0% &amp;lt; GLS &amp;lt; 6.9%), and very severe (GLS ≤ 4.9%). CICU and in-hospital mortality were compared across GLS categories, and the relationship between GLS and mortality was assessed using multivariable logistic regression. Results The study included 626 patients with a median age of 68.6 years, a median LVEF of 31% (IQR 24 to 40%), and a median GLS of 7.0% (IQR 5.0 to 9.7%). In-hospital mortality was 29.1%. As GLS deteriorated, there was an increasing need for vasopressors (P&amp;lt;0.001). Patients with progressively lower GLS exhibited significantly higher CICU and in-hospital mortality across the GLS quartiles (Figure A; P&amp;lt;0.001). Patients in the severe (adjusted OR 2.67; p&amp;lt;0.001) and very severe category (adjusted OR 3.54; P&amp;lt;0.001) had significantly increased risk of in-hospital death compared with mild category. In multivariable analysis, every 1% decrease in GLS corresponded to a 14% higher risk of in-hospital mortality (P&amp;lt;0.001). Finally, GLS outperformed LVEF for discrimination of in-hospital mortality (P=0.002), and when both measurements were included in the same multivariable model, only GLS remained significant. When patients were divided according to whether they had GLS and/or LVEF below the median value, patients with low GLS had higher mortality irrespective of the LVEF (Figure B). Conclusion In patients with CS, GLS assessment surpasses LVEF in its prognostic value and improves risk stratification. Routine evaluation of GLS should be considered for patients with CS.Figure AFigure B

Telephone-Based Guideline-Directed Medical Therapy Optimization in Navajo Nation

Underutilization of guideline-directed medical therapy for heart failure with reduced ejection fraction is a major cause of poor outcomes. For many American Indian patients receiving care through the Indian Health Service, access to care, especially cardiology care, is limited, contributing to poor uptake of recommended therapy. To examine whether a telehealth model in which guideline-directed medical therapy is initiated and titrated over the phone with remote telemonitoring using a home blood pressure cuff improves guideline-directed medical therapy use (eg, drug classes and dosage) in patients with heart failure with reduced ejection fraction in Navajo Nation. The Heart Failure Optimization at Home to Improve Outcomes (Hózhó) randomized clinical trial was a stepped-wedge, pragmatic comparative effectiveness trial conducted from February to August 2023. Patients 18 years and older with a diagnosis of heart failure with reduced ejection fraction receiving care at 2 Indian Health Service facilities in rural Navajo Nation (defined as having primary care physician with 1 clinical visit and 1 prescription filled in the last 12 months) were enrolled. Patients were randomized to the telehealth care model or usual care in a stepped-wedge fashion, with 5 time points (30-day intervals) until all patients crossed over into the intervention. Data analyses were completed in January 2024. A phone-based telehealth model in which guideline-directed medical therapy is initiated and titrated at home, using remote telemonitoring with a home blood pressure cuff. The primary outcome was an increase in the number of guideline-directed classes of drugs filled from the pharmacy at 30 days postrandomization. Of 103 enrolled American Indian patients, 42 (40.8%) were female, and the median (IQR) age was 65 (53-77) years. The median (IQR) left ventricular ejection fraction was 32% (24%-36%). The primary outcome occurred significantly more in the intervention group (66.2% vs 13.1%), thus increasing uptake of guideline-directed classes of drugs by 53% (odds ratio, 12.99; 95% CI, 6.87-24.53; P < .001). The number of patients needed to receive the telehealth intervention to result in an increase of guideline-directed drug classes was 1.88. In this heart failure trial in Navajo Nation, a telephone-based strategy of remote initiation and titration for outpatients with heart failure with reduced ejection fraction led to improved rates of guideline-directed medical therapy at 30 days compared with usual care. This low-cost strategy could be expanded to other rural settings where access to care is limited. ClinicalTrials.gov Identifier: NCT05792085.

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.

Is plasma citrulline a good marker of hemodynamic status in malnourished patients with anorexia nervosa?

ObjectiveMalnourished patients with anorexia nervosa (AN) have lower plasma citrulline level compared to healthy controls. Citrulline is a non-essential amino-acid synthetized by the enterocyte and has functions affecting cardiovascular status. The aim of the study is to describe citrulline plasma level and to assess its relationship with hemodynamic status in a cohort of malnourished adult patients with AN. MethodsA retrospective observational study including malnourished patients with AN hospitalized between January 2018 and January 2019 for the treatment of severe malnutrition was carried out. Anthropometric measures, biochemical tests, and cardiac function indicators including doppler echocardiographic parameters were evaluated. ResultsForty-eight patients with a median age of 29 [21–35.5] years old and body mass index (BMI) of 12 [10.5–-13.4] kg/m2 were included. Median systolic blood pressure (SBP) and median diastolic blood pressure (DBP) were respectively 99 [90–110] mmHg and 68 [59–73] mmHg. Median left ventricular ejection fraction (LVEF) was at 65 [58–69] %. Plasma citrulline level was under the normal range in 58% of patients and was positively correlated with fat mass, stroke volume, and left ventricular end diastolic volume, but not BMI. ConclusionCitrulline level may be an innovative associated marker of hemodynamic status in malnourished patients with AN. Further research and prospective studies are needed to elucidate the specific pathways involved.

Impact of Tricuspid Repair on Surgical Death in Patients Undergoing Mitral Valve Surgery Due to Rheumatic Disease

BackgroundTricuspid valve repair during mitral valve replacement surgery remains a controversial topic. The risk-benefit ratio in some populations remains uncertain, especially in rheumatic heart disease patients. Therefore, we aimed to evaluate the impact of concomitant tricuspid repair on surgical mortality in patients undergoing cardiac surgery due to rheumatic mitral valve disease who have moderate to severe functional tricuspid regurgitation. MethodsThis is a prospective cohort study from January 1, 2017, to December 30, 2022. All patients over 18 years of age who underwent cardiac surgery to correct rheumatic mitral valve disease with concomitant moderate to severe tricuspid regurgitation were included. The primary outcome was a surgical death. In an exploratory analysis, clinical and echocardiographic data were obtained 2 years after the procedure. ResultsOf the 144 patients included, 83 (57.6%) underwent tricuspid valve repair. The mean age was 46.2 (±12.3) years with 107 (74.3%) female individuals, the median left ventricular ejection fraction was 61.0% (55-67), and systolic pulmonary artery pressure (sPAP) was 55.0 mmHg (46-74), with 45 (31.3%) individuals with right ventricular dysfunction. The total in-hospital mortality was 15 (10.4%) individuals, and there was no difference between the groups submitted or not to tricuspid repair: 10 (12.0%) vs. 5 (7.5%); p = 0.46, respectively. There was an association with one variable independently: the sPAP value, relative risk 1.04 (1.01-1.07), p = 0.01. The estimated cut-off value of sPAP that indicates higher early mortality through the receiver operating characteristic curve (area 0.70, p = 0.012) was 73.5 mmHg. ConclusionsPerforming tricuspid repair in individuals who were undergoing cardiac surgery to correct rheumatic mitral valve disease was not associated with increased surgical mortality. Our results suggest the safety of tricuspid repair even in this high-risk population, reinforcing the recommendations in current guidelines.

Biomarkers to predict improvement of left ventricular ejection fraction after atrial fibrillation ablation

BackgroundAtrial fibrillation (AF) and heart failure frequently coexist. Prediction of left ventricular ejection fraction (LVEF) recovery after catheter ablation (CA) for AF remains difficult. ObjectiveThe purpose of this study was to evaluate the value of biomarkers, alone and in combination with the Antwerp score, to predict LVEF recovery after CA for AF. MethodsPatients undergoing CA for AF with depressed LVEF (<50%) were included. Plasma levels of 13 biomarkers were measured immediately before CA. Patients were categorized into “responders” and “nonresponders” in a similar fashion to the Antwerp score derivation and validation cohorts. The predictive power of the biomarkers alone and combined in outcome prediction was evaluated. ResultsA total of 208 patients with depressed LVEF were included (median age 63 years; 19% female; median indexed left atrial volume 42 mL/m2; median LVEF 43%). At a median follow-up time of 30 months, 161 (77%) were responders and 47 (23%) were nonresponders. Of 13 biomarkers, 4—angiopoietin 2 (ANG2), growth differentiation factor 15 (GDF15), fibroblast growth factor 23, and myosin binding protein C3—were significantly different between responders and nonresponders (P ≤ .001) and combined could predict the end point with an area under the curve of 0.72 (95% confidence interval [CI] 0.64–0.81) overall, 0.69 (95% CI 0.59–0.78) in heart failure with mildly reduced ejection fraction, and 0.88 (95% CI 0.77–0.98) in heart failure with reduced ejection fraction. Only ANG2 and GDF15 remained significantly associated with LVEF recovery after adjustment for age, sex, and Antwerp score and significantly improved the accuracy of the Antwerp score predictions (P < .001). The area under the curve of the Antwerp score in the outcome prediction improved from 0.75 (95% CI 0.67–0.83) to 0.78 (95% CI 0.70–0.86). ConclusionA biomarker panel (ANG2 and GDF15) significantly improved the accuracy of the Antwerp score.

Impella as Bridge to Durable Left Ventricular Assist Device in Acute Myocardial Infarction Cardiogenic Shock Patients.

Implantation of durable left ventricular assist device (LVAD) in cardiogenic shock (CS) patients after acute myocardial infarction (AMI) poses specific challenges (small left ventricular size, acute infarct area, need for antithrombotic therapy, status Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) 1 with impaired organ function and derangements in coagulation and inflammatory parameters) which may affect outcomes. We reviewed data of all AMI-CS patients who were implanted LVAD after Impella support at a referral center with the aim to analyze feasibility, timing, and outcomes of durable LVAD implantation after tMCS with Impella due to AMI-CS. Twenty-one patients were treated between 2013 and 2023: all were in Society for Cardiovascular Angiography & Interventions (SCAI) class D-E and INTERMACS 1-2 at presentation, median LV ejection fraction (EF) and LV end-diastolic diameter (EDD) were 15 (10-20)% and 57 (54-60) mm, respectively. Eleven patients (52%) were supported with Impella CP, seven with Impella 5.0 (33%), and three (14%) with Impella 2.5. Axillary cannulation was performed in nine patients (43%). Five patients (24%) had concomitant venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. Median duration of Impella support was 12 (8-14) days. Overall, the use of Impella was characterized by low rate of complications and allowed successful bridge to durable LVAD in all patients, with 100% 30 day survival rate.

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

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

Longitudinal data of serum creatine kinase levels and motor, pulmonary, and cardiac functions in 337 patients with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) presents with skeletal muscle weakness, followed by cardiorespiratory involvement. The need for longitudinal data regarding DMD that could serve as a control for determining treatment efficacy in clinical trials has increased notably. The present study examined the longitudinal data of Japanese DMD patients collectively and assessed individual patients with pathogenic variants eligible for exon-skipping therapy. Patients with DMD who visited Kobe University Hospital between March 1991 and March 2019 were enrolled. Data between the patients' first visit until age 20 years were examined. Three hundred thirty-seven patients were included. Serum creatine kinase levels showed extremely high values until the age of 6 years and a rapid decline from ages 7-12 years. Both the median 10-m run/walk velocity and rise-from-floor velocity peaked at the age of 4 years and declined with age. The values for respiratory function declined from the age of 11 years. The median left ventricular ejection fraction was >60% until the age of 12 years and rapidly declined from ages 13-15 years. Examination of the relationship between pathogenic variants eligible for exon-skipping therapy and longitudinal data revealed no characteristic findings. We found that creatine kinase levels and motor, respiratory, and cardiac functions each exhibited various changes over time. These findings provide useful information about the longitudinal data of several outcome measures for patients with DMD not receiving corticosteroids. These data may serve as historical controls in comparing the natural history of DMD patients not on regular steroid use in appropriate clinical trials.

Prevalence and prognostic impact of bone disease in chronic heart failure with reduced ejection fraction.

Chronic heart failure is associated with a bone-catabolic state and increases the risk of osteoporosis and fractures. Prospective studies investigating the clinical relevance of bone disease in heart failure are lacking. We aimed to assess the prevalence and prognostic impact of osteoporosis and vertebral fractures (VFs) in chronic heart failure with reduced ejection fraction (HFrEF). Symptomatic outpatients with chronic heart failure and a previous diagnosis of overtly reduced left ventricular ejection fraction<40% on stable, optimal HFrEF therapy and left ventricular ejection fraction<50% at enrolment were included into a prospective single-centre study. Osteoporosis was determined with dual-energy X-ray absorptiometry and defined as a T-score≤2.5 at any site. VFs were assessed using X-ray of both thoracic and lumbar spine applying the semiquantitative Genant score. We enrolled 205 patients (22% women), with a median age of 66 (IQR 58-74) years. Median left ventricular ejection fraction was 37 (IQR 30-43) % and median N-terminal pro B-type natriuretic peptide was 964 (IQR 363-2173) pg/mL. Osteoporosis, as defined by bone mineral density, and at least one VF were prevalent in 31 (15%) and 29 patients (14%). Osteoporosis or VF were present in 55 patients (27%) and 5 patients (2%) had both osteoporosis and a VF. During a median follow-up of 4.7 (IQR 4.0-5.3) years, 18 patients (9%) died due to cardiovascular (CV) cause, and 46 patients (22%) had a worsening heart failure (WHF) hospitalization. In multivariate Cox regression analyses, presence of VF independently predicted CV death (HR 2.82, 95% CI 1.04-7.65, P=0.042), WHF hospitalizations (HR 2.39, 95% CI 1.18-4.82, P=0.015), and a composite endpoint of CV death and WHF hospitalizations (HR 2.44, 95% CI 1.23-4.82, P=0.011). Osteoporosis was not significantly associated with CV events. In a prospective study, bone disease affected every fourth patient with HFrEF, and patients with VF at baseline had a two-fold risk of subsequent CV death or WHF hospitalization. Prevalent bone disease, particularly VF, should be considered as a clinically relevant comorbidity in HFrEF.

Subcutaneous anakinra in the management of refractory MIS-C in France.

Multisystemic inflammatory syndrome in children (MIS-C) is a therapeutic emergency and can lead to myocardial dysfunction (17%-75%) and heart failure (52%-53%). Intravenous immunoglobulins (IVIG) and corticosteroids (CST) have been validated for the management of this condition. Recent reports suggest that an interleukin-1(IL-1) receptor antagonist, namely anakinra, may be a valuable add-on to the 2019 novel coronavirus disease (COVID-19) treatment for refractory patients. The purpose of this study was to describe the clinico-biological characteristics of patients treated with anakinra as well as the efficacy and safety of subcutaneous anakinra therapy in this condition. The prospective multicentre study of children hospitalized for MIS-C between March 2020 and September 2022, including 23 international paediatric centres, followed for a mean duration of 3.072 ± 3.508 months. The patient data were extracted from the Juvenile Inflammatory Rheumatism (JIR) cohort. The clinico-pathological characteristics, cardiac ultrasound data, and adverse events were reported in patients receiving anakinra. Of the 470 children admitted with MIS-C, 18 French patients (50% girls) with a mean age of 10.06 ± 3.9 years were treated with subcutaneous anakinra. Anakinra was used in two situations, macrophage activation syndrome (MAS) (4 patients) and heart failure (14 patients) with a median left ventricular ejection fraction (LVEF) of 39.5% (30%-45%). The average dose of anakinra received was 2.53 ± 1.3 mg/kg/day for a median duration of 3 days. Prior to introduction, 78% (n = 14/18) of the patients had received CST and 56% (n = 10/18) had received IVIG. Only two patients received IVIG alone and six received CST alone plus anakinra. In 10% of cases, IVIG was poorly tolerated from a cardiovascular point of view and was discontinued. Transient elevations in serum transaminases were noted in four patients on anakinra without the need for treatment or dose modification. In all patients, rapid (48 h) improvement in myocardial function was observed (LVEF > 55%) with a concomitant significant decrease in myocardial enzymes (p < 0.05). All patients survived with complete recovery of cardiac function without sequelae. Subcutaneous anakinra appears to be a safe and effective treatment for the management of heart failure or MAS in MIS-C patients. The value of IVIG in these two situations remains to be reviewed.

Longitudinal Cardiac Evaluation of Children with Multisystem Inflammatory Syndrome (MIS-C) Following COVID-19 by Conventional and Speckle-Tracking Echocardiography

Multisystem inflammatory syndrome in children (MIS-C), is a rare but severe, hyperinflammatory complication of COVID-19, in which cardiovascular abnormalities are frequently detected. In this prospective study, we describe the echocardiographic findings in patients with MIS-C, with the use of conventional Echocardiography and Speckle-Tracking Echocardiography (STE) with Left Ventricular (LV) Global Longitudinal Strain (GLS) analysis, in the acute and follow-up phase. In total, 25 MIS-C patients [64% females, mean (± SD) age: 8.3 (± 3.72) years] were included. In the acute phase, median (IQR) Troponin and NT-proBNP and mean heart rate, were 8.07 (14.52) pg/mL, 2875.00 (7713.00) pg/mL, and 102.87 (± 22.96) bpm, respectively. Median (IQR) LV Ejection Fraction (LVEF) was 66 (8)% and LVEF impairment was detected in 2/25 (8%) patients. On follow-up (mean time interval:9.50 ± 4.59 months), heart rate was significantly lower, with a mean value of 90.00 (± 14.56) bpm (p-value = 0.017). Median (IQR) LVEF was 66.00 (6.70)% (p-value = 0.345) and all 25 participants had normal LVEF. In 14/25 patients, additional LV-GLS analysis was performed. During the acute phase, mean LV-GLS was − 18.02 (± 4.40)%. LV-GLS was abnormal in 6/14 patients (42.9%) and among them, only one patient had reduced LVEF. On follow-up (median (IQR) time interval:6.93 (3.66) months), mean LV-GLS was -20.31 (± 1.91)% (p-value = 0.07) and in 1/14 patient (7.1%), the LV-GLS impairment persisted. In conclusion, in the acute and follow-up phase, we detected abnormal LV-GLS values in some patients, in the presence of normal LVEF, indicating that STE-GLS is a valuable tool for identifying subclinical myocardial injury in MIS-C.