Severe Ventricular Dysfunction Research Articles

#2334 Elevated serum admission creatinine in acute heart failure hospitalizations: lifting the veil to understand outcome differences

Abstract Background and Aims Organ crosstalk in heart failure and kidney dysfunction is prevalent and is associated to a high event rate. In this setting elevated serum creatinine (sCr) at acute decompensated heart failure (ADHF) admissions is a strong risk factor for poor outcomes. Current accepted cardiorenal syndrome (CRS) classification is based on timing and initial organ dysfunction and fails at capturing its nature and prognosis. We sought to describe patient (P) profile and outcomes in P hospitalized for ADHF with high admission sCr in function of current CRS classification and assess for stratifying predictors. Method We conducted an observational, analytical and cross-sectional study, with prospective and consecutive data acquisition. We included P over 18 years-old, who were admitted to the Intensive Care Telemetry Unit in our Hospital between July, 2011 and Dec, 2023 due to ADHF. P who received a heart transplant during index admission or those on chronic dialysis were excluded. Clinical, epidemiological and biochemical variables were registered. Renal dysfunction was defined under admission sCr >1.4 mg/dl and divided according to Ronco et al classification, as initially cardiac (type 2) or renal (type 4) origin. We constructed multivariate logistic and survival regression models, with selection of relevant predictors by resampling and regularization of a Lasso regression model. Statistical significance was considered with a 5% of alpha error level. Analysis was conducted using R (R Core Team, 2023). Results A total of 1868 consecutive P were included. P population consisted in type 2: 124 and type 4: 258 P, respectively. We found no differences in gender (p = 0.47), while type 4 were older (75 ± 12 vs 71 ± 12; p < 0.01). Ventricular dysfunction was more severe in type 2 (left ventricular ejection fraction 34 ± 17 vs 41 ± 16%; p < 0.001). While ischaemic heart disease was more prevalent in type 4 (32.8 vs 23.5%; p = 0.001), idiopathic cardiomyopathy was more frequent in type 2 (18.8 vs 7.2%; p = 0.001). Clinical phenotypes differed between groups, being clinical hypoperfusion more frequent in type 2 (32.4 vs 12.3%; p < 0.001). Admission sCr was higher in type 4 (1.9 [0.8] vs 1.6 [0.58] mg/dl; p < 0.001), as was 1st day natriuresis (81 vs 67 mEq; p = 0.01). Both groups experienced a similar diuretic resistance rate (21.2 vs 17.1%; p = 0.34), while type 4 received rescue ultrafiltration more frequently (11.3 vs 3.5%; p < 0.01). Type 2 received a higher inotropic support rate (47.1 vs 19.5%; p < 0.01) and had a longer length of stay (9 vs 7 days; p = 0.01). In-hospital (11.8 vs 11.3%; p = 0.99); 6-month and 1-year mortality rates (66.8 vs 72.8% and 55.1 vs 64.6% respectively; p = 0.3). In a similar way, 1-month (94.8 vs 94.7%), 6-month (72 vs 74.7%) and 1-year readmission rates (59.2 vs 60.9%; p = 0.6) were similar in both groups. A multiple logistic regression model (AUCROC 0.82) identified admission sCr (OR 2.6; CI 95% 2.2-3.2; p < 0.001), inotropic need (OR 1.87; CI 95% 1.4-2.6; p < 0.001), anasarca phenotype (OR 1.63; CI 95% 1.06-2.5; p = 0.02), moderate to severe right ventricular dysfunction (OR 1.4; CI 95% 1.03-1.9; p = 0.03) as independent predictors for a descending sCr behavior during hospitalization, while the lower T3 levels were associated with less probability for a descent of sCr (OR 0.21; CI 95% 0.1-0.46; p < 0.001). Conclusion Organ crosstalk in ADHF hospitalizations was associated with a high event rate. One-year mortality and readmission rates were similar in both groups. Renal support therapies were more frequent under lower kidney reserve conditions. Ventricular dysfunction and systemic congestion phenotype are relevant to a better understanding for potential reversibility at the admission time and may promote actions for outcome enhancing.

VENTRICULAR ARRHYTHMIAS IN A UNEXPECTED CARDIAC MAGNETIC RESONANCE

Abstract Background Electrical storm in a widespread inflammation of the myocardium represent a very challenge condition and recognizes a broad spectrum of etiology. Case Presentation A 59–year–old man, without significant prior medical history, came to our attention because, following an emergent hernioplasty procedure, he displayed anterior ST–segment elevation and elevated troponin levels (150.000 ng/L). An echocardiogram revealed an estimated left ventricular ejection fraction (EF) of 39% with anterior hypokinesia. Coronary angiography showed no abnormalities. Cardiac magnetic resonance imaging demonstrated ring–like edema and ring–like late gadolinium enhancement in the left ventricle on T2–weighted and PSIR sequences, with no involvement of the right ventricle. Additionally, there was an increase in extracellular volume. Despite several laboratory tests to investigate infectious or autoimmune causes, the etiology remained inconclusive. To further explore the cause, an endomyocardial biopsy was performed. However, the patient experienced an unstable electrical storm three days later. Management Recurrent ventricular tachycardia (VT) was initially treated with esmolol, amiodarone, and procainamide, but with limited success. Due to VT–induced hemodynamic instability, the patient was sedated with propofol and intubated. Endomyocardial biopsy (EMB) confirmed lymphocytic myocarditis. In light of the hemodynamic instability and refractory electrical storm, the patient was promptly cannulated for veno–arterial extracorporeal membrane oxygenation (VA–ECMO) and started on methylprednisolone. Although there was an apparent resolution of VT, the patient experienced new episodes, necessitating percutaneous stellate ganglion block and an upgraded treatment plan that included mycophenolate mofetil. Given the high burden of arrhythmias, severe ventricular dysfunction, and the lack of response to medications, the patient is now awaiting cardiac transplantation. Conclusion Transmural edema and ring–like late gadolinium enhancement (LGE) in the early phase are predictors of a poor prognosis. In cases of hemodynamic deterioration and refractory electrical storms, it is crucial to promptly initiate mechanical support. Cardiac transplantation remains the sole treatment option for individuals who do not respond to antiarrhythmic and immunosuppressive drugs.

A case of pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension - a happily completed odyssey

Chronic thromboembolic pulmonary hypertension is a rare condition that is usually a consequence of prior acute pulmonary embolism. It is caused by persistent obstruction of pulmonary arteries by organized thrombi resulting in redistribution of blood flow and secondary pulmonary microvascular remodelling. Thus, pulmonary vascular resistance and pulmonary artery pressure are increased leading to right ventricle pressure overload, development of right heart failure and death. In eligible patients pulmonary endarterectomy is the standard of care and it can result in complete normalization of haemodynamics and right ventricular morphology and function. We present the case of a patient with chronic thromboembolic pulmonary hypertension with severe right ventricular dilation and dysfunction and refractory heart failure. After successful pulmonary endarterectomy we observed almost complete normalization of hemodynamics and restoration of right ventricular dimensions and function, as well as significant clinical improvement.

Rhythm Disorders in Pulmonary Arterial Hypertension (PAH) - What Therapeutic Options are Available?

Rhythm disorders in PAH are rare. In practice, they pose a therapeutic management challenge. Right ventricular dysfunction associated with hypoxia influences the prescription of antiarrhythmics; some of them are even contraindicated. We report three cases of idiopathic PAH complicated by atrial flutter (2 cases) and atrial fibrillation (1 case). The patients experienced right heart failure after a stabilization phase with specific vasodilators (bosentan, sildenafil, iloprost). They were treated with oral amiodarone, alongside treatment for right heart failure. Potassium levels were normal. Beta-blockers were not prescribed due to severe right ventricular dysfunction with arterial hypotension. Unfortunately, two patients developed hyperthyroidism secondary to amiodarone. Through these observations, we will discuss the different therapeutic options in these situations, referencing the literature.

Biatrial myopathy in heart failure with preserved ejection fraction.

Left atrial (LA) myopathy is increasingly recognized as an important phenotypic trait in heart failure (HF) with preserved ejection fraction (HFpEF). Right atrial (RA) remodelling and dysfunction also develop in HFpEF, but little data are available regarding the clinical characteristics and pathophysiology among patients with isolated LA, RA, or biatrial myopathy. Patients with HFpEF underwent invasive haemodynamic exercise testing, comprehensive imaging including speckle tracking strain echocardiography, and clinical follow-up at Mayo Clinic between 2006 and 2018. LA myopathy was defined as LA volume index >34 ml/m2 and/or LA reservoir strain ≤24% and RA myopathy by RA volume index >39 ml/m2 in men and >33 ml/m2 in women and/or RA reservoir strain ≤19.8%. Of 476 consecutively evaluated patients with HFpEF defined by invasive exercise testing with evaluable atrial structure/function, 125 (26%) had no atrial myopathy, 147 (31%) had isolated LA myopathy, 184 (39%) had biatrial myopathy, and 20 (4%) had isolated RA myopathy. Patients with HFpEF and biatrial myopathy had more atrial fibrillation, poorer left ventricular systolic and diastolic function, more severe pulmonary vascular disease, tricuspid regurgitation, ventricular interdependence and right ventricular dysfunction, and poorer cardiac output reserve with exercise. There were 94 patients with events over a median follow-up of 2.9 (interquartile range 1.4-4.6) years. Individuals with biatrial myopathy had an 84% higher risk of HF hospitalization or death as compared to those with isolated LA myopathy (hazard ratio 1.84; 95% confidence interval 1.16-2.92, p = 0.01). Biatrial myopathy identifies patients with more advanced HFpEF characterized by more severe pulmonary vascular disease, right HF, poorer cardiac reserve, and a greater risk for adverse outcomes. Further study is required to define optimal strategies to treat and prevent biatrial myopathy in HFpEF.

Test Bench for Right Ventricular Failure Reversibility: The Hybrid BiVAD Concept.

When heart transplantation and myocardial recovery are unlikely, patients presenting with biventricular cardiogenic shock initially treated with extracorporeal membrane oxygenation (ECMO) may benefit from a mechanical support upgrade. In this scenario, a micro-invasive approach is proposed: the combination of the double-lumen ProtekDuo cannula (Livanova, London, UK) and the Impella 5.5 (Abiomed, Danvers, MA) trans-aortic pump that translates into a hybrid BiVAD. All consecutive ECMO patients presenting with biventricular cardiogenic shock and ineligibility to heart transplantation from August 2022 were prospectively enrolled. The clinical course, procedural details, and in-hospital events were collected via electronic medical records. A total of three patients, who were temporarily not eligible for heart transplantation or durable LVAD due to severe acute pneumonia and right ventricular (RV) dysfunction, were implanted with a hybrid BiVAD. This strategy provided high-flow biventricular support while pulmonary function ameliorated. Moreover, by differentially sustaining the systemic and pulmonary circulation, it allowed for a more adequate reassessment of RV function. All the patients were considered eligible for isolated durable LVAD and underwent less invasive LVAD implantation paired with a planned postoperative RVAD. In all cases, RV function gradually recovered and the RVAD was successfully removed. The Hybrid BiVAD represents an up-to-date micro-invasive mechanical treatment of acute biventricular failure beyond ECMO. Its rationale relies on more physiological circulation across the lungs, the complete biventricular unloading, and the possibility of including an oxygenator in the circuit. Finally, the independent and differential control of pulmonary and systemic flows allows for more accurate RV function evaluation for isolated durable LVAD eligibility reassessment.

Impact of integrated care in patients with heart failure with reduced ejection fraction: a report from the WARCEF trial

Abstract Background In recent years there has been more and more attention to the concept of ‘integrated care’ for patients with cardiovascular diseases. Integrated care strategies have been thought to provide comprehensive evaluation and management of patients characterized by complex chronic conditions and high prevalence of comorbidities. Purpose To propose and evaluate an integrated care management for patients with heart failure with reduced ejection fraction (HFrEF). Methods We performed a secondary analysis of the WARCEF trial, which randomized HFrEF patients with sinus rhythm at baseline to Warfarin and Aspirin. We propose the ABC-HF as a strategy of integrated care management. ABC-HF stands on three pillars: i) Adherence to Guideline-Directed-Medical-Therapy, defined as ACE inhibitors/ARBs plus Beta-Blockers plus MRAs; ii) Better symptom control, defined as NYHA category I-II; iii) Comorbidities optimisation, as per guideline-directed management of hypertension, previous myocardial infarction, previous stroke, peripheral vascular disease, (incident) atrial fibrillation, etc. Patients were managed adherent to the ABC-HF strategy if all the three conditions were fulfilled. Main outcome was the composite of ischemic stroke, intracranial hemorrhage, all-cause death. Results A total of 2,264 patients were available for analysis (mean [SD] age 60.8 [11.4] years, 450 [19.9%] females). Overall, 254 (11.2%) patients were managed adherent to ABC-HF: 199 (8.8%) adherent to no criteria; 905 (40.0%) to one criterion; and 906 (40.0%) to two criteria. Over a mean (SD) follow-up of 3.55 (1.78) years there were 602 (26.6%) events. Patients managed adherent to ABC-HF reported a lower rate of composite outcome compared to those non-adherent (16.1% vs. 27.9%, p<0.001). A Cox multivariate regression analysis adjusted for age, sex, ejection fraction, randomized treatment, and Minnesota physical domain score showed that clinical management adherent to ABC-HF was associated with a reduction in the risk of the primary composite outcome (HR 0.54, 95% CI 0.38-0.76). A progressively higher number of ABC-HF criteria fulfilled was associated with a progressively lower risk [Figure 1]. Conclusion In a cohort of HFrEF with severe ventricular dysfunction, adherence to ABC-HF, as an integrated care management for HF patients, is associated with a lower risk of adverse outcomes. Higher numbers of ABC-HF criteria fulfilled is associated with a progressively lower risk.ABC-HF Criteria and Risk of Composite Ou

Is staging for cardiac damage in aortic stenosis associated with MACE in cancer patients with prior radiotherapy or chemotherapy that underwent transcatheter aortic valve replacement?

Abstract Background Staging classification for severe aortic stenosis (AS) based on the extent of cardiac damage has been correlated with outcomes in the general population. This is categorized based on the following echocardiographic findings: stage 1 (increase in the left ventricular mass index; E/e’>14; and left ventricular ejection fraction <50%); stage 2 (left atrial volume index >34ml/m2; moderate to severe mitral regurgitation and atrial fibrillation), stage 3 (systolic pulmonary hypertension> 60mmHg and moderate to severe tricuspid regurgitation) and stage 4 (moderate to severe right ventricular dysfunction); its applicability in a cancer population exposed to chemo+/- radiotherapy and its correlation with MACE has not been explored. Purpose To evaluate if this staging system predicts MACE (cardiovascular death, myocardial infarction, coronary revascularization, stroke, and hospitalization for heart failure) at 18 months after TAVR in cancer patients who were previously exposed to cardiotoxic therapies. Methods We retrieved data of patients that underwent TAVR from 2013 to 2021. 544 patients were included in this study and divided in 3 groups: 187 patients with prior chest Radiotherapy and Chemotherapy (RT/CT), 155 with CT only, and 202 cancer patients not exposed to CT or RT control group. This was further subdivided in two groups based on the staging system in: stage ≤ 2 and ≥3. Fisher's exact test or chi-square was used to compare categorical variables and clinical outcomes among groups and ANOVA for continuous variables. Echocardiographic findings and correlation with the outcome were evaluated by a multivariable Cox model analysis and assessed by a proportional hazards model for time to event. Kaplan–Meier curves were performed to determine the event-free survival rate. Significance was considered as a p<0.05. Results RT/CT had a higher prevalence of moderate to severe mitral regurgitation (11.8%) p <0.001 and tricuspid regurgitation (13.9%) p=0.02. Stage ≥3 was (24.1%) in the RT/CT, (9.4%) in CT, and (16.1%) in controls p= 0.004. Additionally, stage ≥3 was a predictor of MACE at 18 months: RT/CT group HR 6.43 (3.06 – 13.1) p<0.001, CT HR 4.49 CI (2.27 – 8.89) p<0.001 and control HR 2.20 CI (1.13 – 4.26) p=0.02 (Table 1). MACE at 18 months for stage ≥3 was higher for all groups vs. stage ≤ 2. MACE at 18 months after TAVR was significantly higher in stage >3 for RT/CT (57.4%) and CT only (61.2%) vs. CL (27.2%) p<0.001 (Figure 1B). Conclusions In addition to predicting aortic stenosis risk in cancer patients before TAVR, cardiac damage staging is a strong predictor of MACE at 18 months in patients post-RT/CT and CT and suggests that these patients may benefit from earlier stratification for TAVR prior to reaching stage 3. Future studies with longer follow-up should be explored to evaluate its usefulness in this complex population.

Cardiac magnetic resonance correlates of staging algorithm in patients with asymptomatic severe aortic stenosis

Abstract Background The staging algorithm recently proposed to risk stratify patients with severe aortic stenosis (AS) has not been largely applied to patients who are asymptomatic. While the presence of severe tricuspid regurgitation, pulmonary hypertension and right ventricular dysfunction (stages 3-4) is expected to be low, the prevalence of left ventricular damage (LV), mitral regurgitation, left atrial (LA) dilation and atrial fibrillation (stages 1-2) can be higher in patients with asymptomatic severe AS. The cardiac magnetic resonance (CMR) correlates of the staging algorithm have not been described. Purpose To investigate the distribution of patients with asymptomatic severe AS in the staging algorithm and its differences with CMR findings. In addition, differences in CMR data between patients presenting with AS-related adverse events at 1-year follow-up and patients free of events were compared. Methods Patients with asymptomatic severe AS (aortic valve area, AVA<1.0 cm2) and preserved LV ejection fraction (EF) (>50%) that were referred to CMR were included. Biomarkers, echocardiographic and CMR data were assessed retrospectively. CMR-derived parameters included LV and right ventricular (RV) volumes and systolic function, LA volumes and tissue characterization were reported at baseline and compared with AS-related events (a composite of all-cause mortality, symptoms onset, or need for aortic valve replacement) during 1-year follow-up. Results Of 97 patients included (73±9 years old; 36% males), 3 (%) patients were classified in Stage 0, 34 (35%) in Stage 1, 59 (61%) in Stage 2, and 1 (1%) in Stage 3 or 4. Compared to stage 1, patients in stage 2 were older (P=0.006) and had a higher prevalence of overweight (P=0.037), hypertension (P=0.018), NT-proBNP (P=0.030) and hsTnT (p=0.011) levels. On CMR, they showed higher LV volumes and mass index, larger LA volumes and reduced LA ejection fraction, but no differences on myocardial tissue characteristics (Table 1). Regarding prognosis, 45 (46.5%) patients presented AS-related events at 1-year follow-up. Those with events were mainly in stage 2 (36%) and presented higher NT-proBNP levels despite showing no differences in AVA. On CMR, those with events had lower LVEF, greater LV to RV end-diastolic volume ratio, greater left atrio-ventricular coupling index, reduced LA function and a higher extension of late gadolinium enhancement (Table 2). Conclusions In our cohort, most patients with severe asymptomatic AS were in stage 2. Stage 2 patients presented a higher degree of left-chambers remodelling on CMR compared to patients in stage 1. Patients in stage 2 or with lower LVEF, LV remodelling or reduced LAEF on CMR were those with an increased risk for events at follow-up.

Abstract 15979: En Bloc Heart-Lung Transplantation and Vascular Reconstruction With Native Tissue in a Patient With Situs Inversus Totalis

Case: A 62-year-old male with primary ciliary dyskinesia, bronchiectasis, dextrocardia, ccTGA, VSD, ASD, and severe ventricular dysfunction was listed for HLTx. Suitable organs became available from a 21-year-old male donor after brain death. The right sided aorta, persistent left superior vena cava (LSVC), RIJ, and LCFV were cannulated for CPB. The bloc was procured in the typical fashion along with the donor’s pericardium and intact innominate vein. During the recipient cardiectomy, the LSVC was transected proximally, and right atrial (RA) tissue preserved in continuity with the left inferior vena cava (LIVC). To achieve situs solitus positioning of the mediastinum, a pericardial sling was created by plicating the right pericardium to the diaphragmatic pericardium, and the left pericardium was augmented with excess donor pericardial tissue to create a neo-pericardium in the left chest. The recipient’s RA tissue was used to extend the LIVC by forming a cavoatrial conduit and anastomosed to the donor RA, which required a slightly counterclockwise rotation of the cardiac axis and facilitated positioning the left phrenic nerve posterior to the apex. The tracheal and aortic anastomoses were performed in the typical fashion. The donor innominate vein was of sufficient caliber and length to complete the anastomosis to the recipient LSVC and the donor RIJ was ligated. Discussion: HLTx remains the only definitive therapy for patients with combined end-stage cardiopulmonary disease. The leading indication for HLTx is congenital heart disease. Accordingly, centers performing HLTx must be experienced in complex vascular reconstructions and concomitant procedures to address a broad spectrum of anatomical variants. With thoughtful pre-operative planning, close communication with the procurement team, and surgical experience, these procedures may be performed without the use of synthetic materials that predispose to infectious and thromboembolic complications.

Abstract 14647: EchoNext: An ECG-Based Deep Learning Model to Detect Structural Heart Disease

Introduction: Early detection of structural heart diseases (SHD) can help improve patient outcomes. Electrocardiogram (ECG) based deep learning (DL) models have the potential to identify patients (pts) with undiagnosed disease in need of further testing such as echocardiography. Most models have focused on detecting a single abnormality. A few studies have attempted detection on a comprehensive aggregate set of outcomes, but with limited scope and external validation. Hypothesis: An ECG DL model can identify pts at risk for SHDs, with stable external validation performance regardless of hospital type (academic/community), clinical setting (inpatient/outpatient/emergency department), or demographics (race/ethnicity). Methods: We identified 426,659 ECG-echo study pairs since 2008 from 5 NewYork-Presbyterian-affiliated (NYP) hospitals, including Columbia, to train the EchoNext DL model. ECGs were associated with SHD if acquired within one year prior to an echo reporting left ventricular (LV) ejection fraction ≤45%, LV wall thickness ≥1.3cm, moderate or severe valvular disease, moderate or large pericardial effusion, moderate or severe right ventricular dysfunction, or pulmonary artery systolic pressure ≥45 mmHg. EchoNext was tested on unseen data from four other NYP hospitals, including Cornell. Results: In the external dataset (n=21,421 pts), 33% were identified with SHD. EchoNext achieved an area under the receiver operating characteristic curve (AUROC) of 0.85, with robust results with respect to individual hospital (AUROC range: 0.82-0.87), clinical setting (0.78-0.84), and patient race/ethnicity (0.84-0.86; Figure). Conclusion: EchoNext demonstrated excellent performance in detecting SHD in the largest multi-institutional, multi-racial external validation of such a model to date. This model may allow AI-enabled reflex referral to echocardiography from ECG. Prospective trials are ongoing to validate.

Left ventricular assist devices for treatment of refractory advanced heart failure: the Western Australian experience.

Left ventricular (LV) assist devices (LVADs) can prolong survival and improve quality of life in end-stage heart failure. Review outcomes of the Western Australian LVAD programme. Retrospective database and medical record review. One hundred forty-seven LVADs have been implanted in 23 years, of which 95 were newer-generation devices (HeartWare HVAD [HW], HeartMate II and HeartMate 3). Presented data refer to these devices only. Most patients (94%) were classed as bridge-to-transplant or -candidacy/decision, with the remainder classed as 'destination therapy' (DT). Mean LV ejection fraction was 20%, and 36% had severe right ventricular dysfunction. Sixty-two percent of patients had a nonischaemic cardiomyopathy. Following LVAD implant, the median length of stay in intensive care was 2 days, and in the hospital overall was 23 days. Ninety-six percent of patients survived to hospital discharge, and, following discharge, 98% of days with LVAD were spent as an outpatient. The median number of hospital readmissions was 1.5 per patient per year. LVAD-associated infection requiring admission or intravenous antibiotics at any time after implant occurred in 36%, significant gastrointestinal bleeding in 19% and stroke in 11%. The percentage of patients alive with LVAD still in situ at 1, 2 and 5 years was 94%, 88% and 62% respectively, which exceeds current international registry outcomes. All DT patients survived at least 4 years, spending 97% of days with LVAD as an outpatient. The two longest-surviving HW DT patients worldwide (11.3 and 10.5 years) are among this cohort. Excellent outcomes can be achieved with LVADs in appropriately selected patients.

Abstract P3093: Early Myocarditis In The Desmoglein 2 Mutant Mouse Model Of Arrhythmogenic Cardiomyopathy

Arrhythmogenic cardiomyopathy (ACM) is an inherited disease caused by mutations in desmosome proteins. Patients with ACM are born with normal hearts but develop arrhythmias, fibrofatty infiltration, and sudden death. The desmoglein 2 (DSG2) mutant mouse is a well-established model of ACM that recapitulates the human phenotype of the disease. This mouse develops severe ventricular arrhythmias, systolic dysfunction, myocardial fibrosis and exercise induced sudden death. Here, we present evidence of early myocardial immune cell infiltration as well as an inverse relationship between cardiac function and adult myocardial cytokine expression in DSG2 mutant mice. We examined 20 week old adult DSG2 homozygote mice and wildtype littermate controls for systolic function using echocardiography, cytokine expression using rtPCR and fibrosis using masons trichrome staining. Consistent with previous studies we found ventricular fibrosis is significantly increased in mutant hearts (p=0.003). We demonstrate that osteopontin, an inflammatory cytokine released by macrophages, is highly expressed in these hearts (p=2.0x10 -4 ). We detected an inverse correlation between systolic function and the osteopontin expression levels in these mutant mice (p=0.0015, r=-0.8315, R 2 =0.6914). These results lead us to suspect that immune cell infiltration may contribute to the disease progression. Subsequently, we examined immune cell populations in 3 week old DSG2 hearts, a period of time before the development of fibrosis, systolic dysfunction or arrhythmias. We measured >40-fold higher number of CD45 + leukocytes (with increased Ly6G + neutrophils and Ly6C + monocytes) within the heart muscle of DSG2 homozygotes via flow cytometry (p=7.4x10 -5 ), consistent with myocarditis. These results suggest myocarditis precedes fibrosis in the DSG2 mutant mouse model. Our ongoing work is focused on further characterizing the immune response in early post-natal life in the DSG2 mouse heart and determining whether early myocarditis contributes to the phenotype in ACM. Our results highlight potentially novel therapeutic targets to prevent disease progression in ACM.

The Use of Impella 5.5 for Donor-Heart Hemodynamic Support in Heart Transplantation.

Primary graft dysfunction is a feared complication and cause of mortality post-heart transplant. Primary graft dysfunction may require mechanical circulatory support, such as venoarterial extracorporeal membrane oxygenation, which carries its own risk for complications. We developed a new mechanical circulatory support method for patients who underwent heart transplant bridged with Impella 5.5, which was then placed into the donor heart. Among 12 heart transplants, four required Impella 5.5 support. The average age was 55.8 years. The mean duration for postoperative mechanical circulatory support was 3.8 days, ranging from 2 to 5 days. No patients developed severe right ventricular dysfunction. In our limited study, complications and mortality associated with the replanted Impella 5.5 were both 0%.

Left Atrial Myopathy in Heart Failure With Preserved Ejection Fraction.

The left atrium (LA) plays an important role in facilitating left ventricular (LV) filling by acting as a reservoir, passive conduit, and active booster pump, as well as a regulator of blood volume through A-type natriuretic peptide secretion in response to stimulation by mechanical stretch of the cavity. LA myopathy has emerged as one of the most important non-LV contributors to disease progression in heart failure with preserved ejection fraction (HFpEF). LA dysfunction is common in HFpEF and is associated with more severe pulmonary vascular disease and right ventricular dysfunction, and increases the risk of incident atrial fibrillation or atrial functional mitral regurgitation, leading to limitations in cardiac output reserve and reduced exercise capacity. LA deformation assessed by 2-dimensional speckle-tracking echocardiography is useful for estimating abnormal hemodynamics or exercise capacity, discriminating HFpEF from non-cardiac dyspnea and is an independent predictor of adverse outcome in HFpEF. Thus, interventions directly targeting LA myopathy may improve outcomes in HFpEF with LA myopathy. This review provides information regarding the physiology of the LA in patients with HFpEF and discusses the importance of evaluation of LA function, management issues, and future directions through ongoing trials of medical interventions.

The Impact of Atrial Fibrillation on All Heart Chambers Remodeling and Function in Patients with Dilated Cardiomyopathy-A Two- and Three-Dimensional Echocardiography Study.

Atrial fibrillation is frequently seen in patients with dilated cardiomyopathy (DCM), and its presence impacts the function of the heart, with clinical and prognostic consequences. In this prospective single-center study, we aimed to assess the impact of atrial fibrillation on cardiac structure and function, using comprehensive two- and three-dimensional echocardiography. We included 41 patients with DCM and persistent or permanent atrial fibrillation (38 male, age 58.8 ± 11 years), as well as 47 patients with DCM and in sinus rhythm (35 male, age 58 ± 12.5 years). Cardiac chambers and mitral and tricuspid valves' structure and function were assessed via standard two-dimensional, speckle-tracking, and three-dimensional echocardiography (3DE). Patients with DCM and atrial fibrillation had a more impaired left ventricular global longitudinal strain, higher 3DE left atrial volumes, and reduced function compared to patients in sinus rhythm in the presence of similar left ventricle volumes. Mitral annulus configuration was altered in atrial fibrillation DCM patients. Also, right heart volumes were larger, with more severe atrial and ventricular dysfunction, despite similar estimated pulmonary artery pressures and severity of tricuspid regurgitation. Using advanced echocardiography techniques, we demonstrated that atrial fibrillation induces significant remodeling in all heart chambers.

P54: Early mortality associated with combination Impella 5.5 and extracorporeal membrane oxygenation support as bridge to cardiac replacement therapy

Background: End stage heart failure is treated with durable left ventricular assist device (LVAD) or orthotopic heart transplant (OHT). Patients with severe ventricular dysfunction and/or cardiogenic shock may require temporary mechanical circulatory support (tMCS) while awaiting cardiac replacement therapy. Extracorporeal membrane oxygenation (ECMO) and the Impella 5.5 (Abiomed; Danvers, MA) are well-studied bridging therapies. However, investigations of concomitant ECMO and Impella 5.5 (ECpella 5.5) therapy are lacking. The aim of this study is to compare mortality at 30-days and at most recent follow-up across four groups with different tMCS bridging strategies. Methods: This is a retrospective study evaluating all patients who were bridged to durable LVAD or OHT between December 31, 2018 to January 31, 2023 at our institution. Patients were separated into the following groups: Group 1 (solo ECMO), Group 2 (solo Impella 5.5), Group 3 (ECMO followed by Impella 5.5), and Group 4 (Impella 5.5 followed by ECMO). Patient demographics and early (30-day) mortality were collected from chart review (table 1). Group comparisons for continuous variables were performed with analysis of variance (ANOVA), and chi-square test of independence and Fisher’s exact tests were used for outcome data comparisons between groups. Results: This study included 61 patients bridged to LVAD or OHT with ECMO and/or Impella 5.5. Mean (std) age was 49.4 (14.3) years and mean (std) time on tMCS was 10.5 (8.4) days. 49% of our cohort required solo ECMO (Group 1, n = 30), 25% required solo Impella 5.5 (Group 2, n = 15), 11% required Impella 5.5 following ECMO (Group 3, n = 7), and 15% required escalation to ECMO from Impella 5.5 (Group 4, n = 9). Mortality at 30-days for Group 1 was 16.7%. No patients died in the 30-day postoperative period in Groups 2-4. Mortality at most-recent follow-up was 33.3%, 6.7%, 28.6%, and 0% for Groups 1-4, respectively. ANOVA revealed significant between-group differences for days on tMCS (p < 0.01). Chi-square test of independence revealed no significant difference in overall mortality across treatment groups (p = 0.07). Further partitioning with pairwise Fisher’s exact tests between treatment groups revealed no significant differences in mortality at most recent follow-up. Conclusions: Limited data exists comparing mortality between different combinations of tMCS as bridge to cardiac replacement therapy, and even less is known about mortality associated with order of therapy initiation. This data demonstrates comparable mortality between solo ECMO, solo Impella 5.5, ECMO followed by Impella 5.5, and Impella 5.5 escalated to ECMO therapies. Large, randomized controlled trials are required to fully evaluate the impact of order of tMCS in bridging to cardiac replacement therapy. Table 1. - Patient demographics and outcomes ECMO (n = 30) Impella 5.5 (n = 15) ECMO + Impella 5.5 (n = 7) Impella 5.5 + ECMO (n = 9) Age, years 45.7 ± 17.3 55.1 ± 8.1 51.6 ± 11.7 51.0 ± 11.0 Female 20.0% 0.0% 14.3% 0.0% BMI 28.0 ± 6.2 26.5 ± 4.7 24.9 ± 4.0 29.8 ± 5.3 Time on MCS, days 9.0 ± 6.6 17.1 ± 11.6 6.7 ± 3.1 7.1 ± 3.1 Bridged to LVAD 50.0% 26.7% 85.7% 0.0% Bridged to OHT 50.0% 73.3% 14.3% 100.0% 30-day mortality 16.7% 0.0% 0.0% 0.0%

Risk Factors for Adverse Outcomes in Term Infants with CHD and Definitive Necrotising Enterocolitis.

To define the incidence of definitive necrotising enterocolitis in term infants with CHD and identify risk factors for morbidity/mortality. We performed a 20-year (2000-2020) single-institution retrospective cohort study of term infants with CHD admitted to the Boston Children's Hospital cardiac ICU with necrotising enterocolitis (Bell's stage ≥ II). The primary outcome was a composite of in-hospital mortality and post-necrotising enterocolitis morbidity (need for extracorporeal membrane oxygenation, multisystem organ failure based on the paediatric sequential organ failure assessment score, and/or need for acute gastrointestinal intervention). Predictors included patient characteristics, cardiac diagnosis/interventions, feeding regimen, and severity measures. Of 3933 term infants with CHD, 2.1% (n = 82) developed necrotising enterocolitis, with 67% diagnosed post-cardiac intervention. Thirty (37%) met criteria for the primary outcome. In-hospital mortality occurred in 14 infants (17%), of which nine (11%) deaths were attributable to necrotising enterocolitis. Independent predictors of the primary outcome included moderate to severe systolic ventricular dysfunction (odds ratio 13.4,confidence intervals 1.13-159) and central line infections pre-necrotising enterocolitis diagnosis (odds ratio 17.7, confidence intervals 3.21-97.0) and mechanical ventilation post-necrotising enterocolitis diagnosis (odds ratio 13.5, confidence intervals 3.34-54.4). Single ventricle, ductal dependency, and feeding related factors were not independently associated with the primary outcome. The incidence of necrotising enterocolitis was 2.1% in term infants with CHD. Adverse outcomes occurred in greater than 30% of patients. Presence of systolic dysfunction and central line infections prior to diagnosis and need for mechanical ventilation after diagnosis of necrotising enterocolitis can inform risk triage and prognostic counseling for families.

Management of cardiac arrhythmias in paediatric patients with TANGO2-deficiency disorder

Abstract Funding Acknowledgements Type of funding sources: None. Background TANGO2-deficiency disorder (TDD) is a rare paediatric condition caused by bi-allelic mutations in the TANGO2 gene. TDD is characterised by susceptibility to metabolic crises with rhabdomyolysis, encephalopathy, lactic acidosis, hypothyroidism and difficult to manage tachyarrhythmias. Aim We describe the electrocardiographic (ECG) findings at baseline and during metabolic crises in patients with TDD. Methods Retrospective, single-centre, case series study of patients with TDD (&amp;lt;18 years), with ECG and subcutaneous Holter monitoring, both during metabolic crises and compensated phases. Results During the period 2013-2021, 12 patients with TDD were found (median age 6.8 years, IQR 2-11.5 years). In the inter-crisis period, bradyarrhythmias were evidenced: 2/12 patients presented sinus bradycardia, 2/12 pauses of 4 and 10 seconds, 1/12 Wenckebach type block; and tachyarrhythmias: 1/12 presented paroxysmal supraventricular tachycardia and 1/12 flutter. 25% had long QT during non-acute phases (median QTc max 476 ms, IQR 456ms-530ms). There were 14 hospitalisations for metabolic crises. 57.1% had QTc interval prolongation, 35.7% ventricular tachycardias (4/14 monomorphic VT, 1/14 torsade de prongs) and 1/14 Brugada type 3 pattern. Three patients died in the context of severe metabolic acidosis and multi-organ involvement (2/12 due to VT and 1/12 due to cardiogenic shock, bradycardia associated with QTc of 635ms and severe ventricular dysfunction). Conclusions In paediatric patients with TDD, the most frequent ECG abnormality was QTc interval prolongation with or without metabolic crises. There is a high risk of tachyarrhythmias, mainly VT, being the main cause of death in children with TDD. Subcutaneous Holter monitoring is recommended. During metabolic crises, there should be close ECG monitoring.

P144 USE OF SACUBITRIL/VALSARTAN IN A GUCH PATIENT POPULATION. PRELIMINARY STUDY

Abstract Sacubitril/Valsartan (S/V) is used with optimal results in the therapy of heart failure (HF); reduces mortality and hospitalizations by 20% compared to ACE inhibitor therapy. There is a little data on the use of S/V in adult patients with congenital or acquired pediatric heart disease (GUCH). In these patients, HF is a real challenge for the cardiologist. HF in GUCH often has a different pathophysiology than usual, and interesting univentricular hearts in Fontan circulation, systemic right ventricle and patients undergoing multiple cardiac surgical procedures. The literature is poor in information and the guidelines do not give clear indications. We report our experience on a GUCH population. Starting from November 2019 we started S/V therapy in 13 GUCH patients with severe ventricular dysfunction, all in NYHA class III and already in optimal therapy for HF. Median age was 42.7 years (27–79 years); 8 males and 5 females. Basic heart disease: 4 patients with Fontan circulation, 3 patients with systemic right ventricle (TGA, operated according to Mustard), n. 2 complete CAV operated, n. 1 Ebstein‘s disease, n.1 Patent ductus arteriosus, n. 2 pediatric onset dilated cardiomyopathy. Median duration of follow–up 11.6 months (2–26 months). In n. 1 patient it was necessary to suspend the S/V due to skin itching, which resolved on diuscontinuation. The dosage was reduced in tree patients due to symptomatic hypotension (1 of these was taking Sildenafil). In n. In 1 patient there was a reduction in the glomerular filtration rate, which did not require discontinuation of the drug. After treatment: 6 patients are in NYHA class I, n. 3 pts in NYHA II class and 4 pts remained in NYHA III class. In the year preceding the start of S/V therapy, all patients cumulatively had n. 15 hospitalizations; in the year following the first six months of treatment, the number of hospitalizations decreased to no. 5 (4 for HF and 1 for severe anemia) The ejection fraction, evaluated by Simpson‘s method, remained stable. However, the limitations of the echocardiographic method in patients with such complex anatomy must be considered Conclusions The use of S/V is safe and effective in GUCH patients. However, larger studies and longer follow–up are needed.