Moderate Dysfunction Research Articles

Sudomotor dysfunction is associated with impaired left ventricular diastolic function in persons with type 2 diabetes: a cross-sectional study.

The incidence of preserved ejection fraction heart failure has significantly increased in persons with type 2 diabetes mellitus (T2DM). Left ventricular (LV) diastolic dysfunction is an early and important manifestation of preserved ejection fraction heart failure. The onset of heart failure in persons with diabetes is associated with diabetic neuropathy. However, the relationship among sudomotor function, which is an early manifestation of small fiber neuropathy, and LV diastolic function remains unclear. This study aimed to explore the association between sudomotor function and LV diastolic function in persons with T2DM. In total, 699 persons with T2DM were enrolled and divided into three groups according to electrochemical skin conductance (ESC) assessed using the SUDOSCAN device: "no dysfunction" group (NSF), "moderate dysfunction" group (MDF), and "severe dysfunction" group (SDF). LV diastolic function was assessed using Doppler echocardiography. To evaluate the relationship between ESC and echocardiographic parameters, Pearson's correlation analysis was performed. Additionally, logistic regression analysis was used to determine the association between LV diastolic function and ESC. A receiver operating characteristic (ROC) curve was constructed to evaluate the performance of sudomotor function indicators in detecting impaired cardiac diastolic function. There were 301 persons (43.06%) in the NSF group, 232 (33.19%) in the MDF group, and 166 (23.75%) in the SDF group. Compared to the NSF group, the MDF and SDF groups had higher A and E/e' and lower e' values (all p < 0.05). Pearson's correlation analysis showed that A and E/e' were negatively associated with foot ESC (FESC) and hand ESC (HESC), whereas e' was positively associated with FESC and HESC (all p < 0.05). After adjusting for confounding factors, binary logistic regression analysis showed that ESC was independently associated with impaired LV diastolic function (p = 0.003). The area under the ROC curve values for FESC and HESC were 0.621 and 0.635, respectively (both p < 0.05). Deteriorating sudomotor function was associated with reduced diastolic function indicators. ESC can be used as a biomarker for detecting LV diastolic impairment.

Disrupted propionate metabolism evokes transcriptional changes in the heart by increasing histone acetylation and propionylation

Propiogenic substrates and gut bacteria produce propionate, a post-translational protein modifier. In this study, we used a mouse model of propionic acidaemia (PA) to study how disturbances to propionate metabolism result in histone modifications and changes to gene expression that affect cardiac function. Plasma propionate surrogates were raised in PA mice, but female hearts manifested more profound changes in acyl-CoAs, histone propionylation and acetylation, and transcription. These resulted in moderate diastolic dysfunction with raised diastolic Ca2+, expanded end-systolic ventricular volume and reduced stroke volume. Propionate was traced to histone H3 propionylation and caused increased acetylation genome-wide, including at promoters of Pde9a and Mme, genes related to contractile dysfunction through downscaled cGMP signaling. The less severe phenotype in male hearts correlated with β-alanine buildup. Raising β-alanine in cultured myocytes treated with propionate reduced propionyl-CoA levels, indicating a mechanistic relationship. Thus, we linked perturbed propionate metabolism to epigenetic changes that impact cardiac function.

The relationship between family function and the incidence of overweight/obesity in children and adolescents in Chengdu city, Sichuan province of China: based on latent profile analysis

BackgroundOverweight/obesity in children and adolescents has become a global health problem, and family function may be associated with its occurrence. Studies exploring the association between family function and overweight/obesity in children and adolescents were performed in Western and Taiwan, China. To date, related studies haven’t been conducted in Mainland China.ObjectivesTo investigate the current status of overweight, obesity, and family function among children and adolescents in Chengdu, China, and to explore their associations.MethodsChildren and adolescents in five primary and middle schools were chosen by cluster sampling. Body Mass Index was used to measure the status of overweight and obesity, and the Chinese family assessment instrument was adopted to assess family function. Latent profile analysis and stepwise logistic regression were applied to identify family classification and explore the relationships between family function and overweight/obesity.ResultsA total of 7616 (84.92%) children and adolescents out of 8968 completed the study with qualified-filled questionnaires. Nine hundred and sixty-six (12.68%)participants were overweight and 656 (8.61%) were obese. The family function was categorized into three profiles: mild (63.93%), moderate (12.32%), and severe (23.75%) dysfunction. The prevalence of overweight was 12.16%, 14.71%, and 13.05% for mild, moderate, and severe family dysfunction, respectively. And the prevalence of obesity was 8.19%, 10.77%, and 8.62% respectively. Participants in moderate and severe dysfunction families were more likely to be overweight (moderate: OR = 1.27, 95% CI:1.01 ~ 1.59, P = 0.04; severe: OR = 1.38, 95% CI:1.15 ~ 1.66, P = 0.001) and obese (moderate: OR = 1.35, 95% CI:1.02 ~ 1.79, P = 0.03; severe: OR = 1.55, 95% CI:1.23 ~ 1.96, P < 0.001). Sociodemographic data such as gender, residence, grade, pocket money per week, the number of siblings, and the education level of the mother were all associated with the risk of being overweight/obese in children and adolescents.ConclusionsThe problems of being overweight or obese exist among children and adolescents in Chengdu. And the risk of being overweight or obese increases along with the decrease in family function.

Risk of atrial arrhythmias in patients with ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy

BackgroundIn arrhythmogenic right ventricular cardiomyopathy (ARVC), risk of atrial arrhythmias (AAs) persists after ventricular tachycardia (VT) ablation. ObjectiveThe purpose of this study was to determine the type, prevalence, outcome, and risk correlates of AA in ARVC in patients undergoing VT ablation. MethodsProspectively collected procedural and clinical data on ARVC patients undergoing VT ablation were analyzed. Risk score for typical atrial flutter was determined from univariate logistic regression analysis. ResultsOf 119 consecutive patients with ARVC and VT ablation, 40 (34%) had AA: atrial fibrillation (AF) in 31, typical isthmus-dependent atrial flutter (AFL) in 27, and atrial tachycardia/atypical flutter (AT) in 10. Seventeen patients (43%) with AA experienced inappropriate defibrillator therapy, with 15 patients experiencing shocks. Ablation was performed for typical AFL in 21 (53%), AT in 5 (13%), and pulmonary vein isolation for AF in 4 (10%) patients and prevented AA in 78% and all AFL during additional mean follow-up of 65 months. Risk score for typical flutter included age >40 years (1 point), ≥moderate right ventricular dysfunction (2 points), ≥moderate tricuspid regurgitation (2 points), ≥moderate right atrial dilation (2 points), and right ventricular volume >250 cc (3points), with score >4 identifying 50% prevalence of typical flutter. ConclusionAAs are common in patients with ARVC and VT, can result in inappropriate implantable cardioverter-defibrillator shocks, and typically are controlled with atrial ablation. A risk score can be used to identify patients at high risk for typical AFL who may be considered for isthmus ablation at the time of VT ablation.

Long-term impact of anatomic subtype in hypoplastic left heart syndrome after Fontan completion

BackgroundAortic atresia (AA)/mitral stenosis (MS) is a well-known risk factor for survival after Norwood; however, the effect of anatomical subtypes in those who survive surgical palliation is unknown. MethodsWe performed a retrospective single-center study of patients with classic hypoplastic left heart syndrome (HLHS) who underwent Fontan at our center between August 1989 and July 2017. Clinical outcomes, as well as ventricular and atrioventricular-valve (AVV) function, were determined for each patient, and the effects of HLHS subtype were estimated using multivariable statistical analyses. ResultsWe included 418 patients with HLHS (AA/mitral atresia [MA] 153, AA/MS 100, aortic stenosis [AS]/MS 154, and AS/MA 11). The median follow-up period was 8.6 (interquartile range, 2.9-15.8) years. Overall transplant-free survival, cumulative incidence of AVV failure, and ventricular failure, which were defined by moderate dysfunction or greater or the necessity of surgical interventions, were 70.1%, 35.9%, and 17.9% at 20 years, respectively. Of the 3 major subtypes, AA/MS was associated with lower survival rate (AA/MA 74.6% vs AS/MS 79.1% vs AA/MS 56.1% at 17 years, P = .04). The subanalysis between AA/MA and AA/MS revealed AA/MS tended to have a greater rate of ventricular failure without a significant difference of AVV failure (AA/MA 11.2% vs AA/MS 26.2% at 17 years, P = .053). ConclusionsThe survival risk of the anatomic subtype AA/MS persisted long term after Fontan completion and was likely due to a greater rate of single ventricle rather than AVV failure. These findings suggest that the abnormal pressure overload condition of the hypoplastic left ventricle created by AA/MS has a detrimental effect on single right ventricle function.

Left bundle branch block cardiomyopathy: an intriguing and defiant entity from diagnosis to treatment

Abstract Introduction and objectives Left bundle branch block cardiomyopathy (LBBB-CM) is an increasingly recognized entity, where electromechanical dyssynchrony seems to play a central role in left ventricular dysfunction (LVD) development. This is a challenging and scarcely studied topic, as causality dilemma between LBBB and LVD is still unsolved. Our aim is to increase current evidence on the subject by analyzing a population of idiopathic LBBB patients (pts) who developed, at some point, LVD not explained by other causes. Methods Retrospective study of LBBB adult pts screened from a large tertiary care hospital electrocardiographic database from 2011 to 2017. After careful evaluation, only possible LBBB-CM pts with serial follow-up (FU) echocardiographic and clinical data were included in the analysis. Results 53 pts were identified as possible LBBB-CMP. At baseline, 44% presented left ventricular ejection fraction (LVEF)&amp;gt;50%, while 56% had LVD. 51% were female and mean age at first-ever LBBB report was 59 years-old. All cohort presented echocardiographic mechanical desynchrony, and additional testing to exclude other causes of LVD (non-invasive ischemia testing in 78%; coronariography in 68%; cardiac magnetic resonance in 38%). Median FU time was 10 years. Worst-LVD was reported as severe in 49% of pts, moderate in 23% and mild in 28%. Median time-to-dysfunction in those with initial LVEF&amp;gt;50% was 8 years. 77% of pts presented heart-failure (HF) symptoms. 40% and 42% presented at least 1 CV event and CV hospitalization, respectively. Most events and/or hospitalizations were due to acute decompensated HF. 2 CV deaths were observed. Cardiac resynchronization therapy (CRT) devices were implanted in 47% of pts. All presented clinical improvement after implantation, and LVEF significantly increased (pre-CRT median LVEF of 24% vs 48% post-CRT; p&amp;lt;0.001). When comparing pts with vs without CRT (Figure 1), better LVEF improvements were achieved in CRT group (median LVEF improvement of 27% in CRT vs 11%; p&amp;lt;0.001). Repeating the latter analysis in pts who only presented at least moderate dysfunction, higher LVEF increase was also reported in CRT group (median LVEF improvement of 27% in CRT pts vs 14%; p=0.002), and significantly more CRT pts recovered LV function (50% CRT vs 14% non-CRT; p=0.028). Notably, no differences were found in rates of medical HF therapy between groups (p=1). Conclusion Our data shows LBBB-CM as a diagnosis of exclusion, where careful evaluation of other LVD etiologies should be performed and discarded. We highlight important morbidity rates in this population, namely HF hospitalizations, as well as the apparently critical role of CRT implantation in these pts. All our CRT pts responded excellently to the therapy. Thus, our study raises awareness to the emerging question of whether this entity can be reversed after LBBB correction with CRT and if early intervention would be desirable.Figure 1

Predictors of tricuspid regurgitation and right ventricular remodelling following percutaneous atrial septal defect closure

Abstract Background Atrial septal defects (ASD) are one of the most common congenital heart defects, and if left unrepaired, life expectancy is decreased due to pulmonary hypertension (pHTN), atrial arrhythmias, and heart failure. Residual right ventricular (RV) dilation or dysfunction despite ASD closure can lead to worse outcomes. Purpose There is insufficient data on predictors of poor RV remodelling following ASD closure in adults. In this study, we aimed to identify risk factors of persistent RV dilation or dysfunction despite percutaneous ASD closure. Methods Patients undergoing primary percutaneous ASD closure between 1/2010-6/2021 were followed for a year. Patients with hemodynamically insignificant or iatrogenic ASDs, pHTN and Eisenmenger syndrome were excluded. Non-linear multiphase mixed–effects cumulative logistics regression model was used to assess the trend of the individual’s degree of TR, RV dysfunction and size over time. This was further stratified by age group (≥40 and &amp;lt;40). Partial dependence plot was used to study the association between age, body surface area (BSA), degree of RV and left ventricle (LV) dysfunction pre-procedurally with the likelihood of lack of RV remodelling. The association between ASD size and the likelihood of sustained RV dysfunction following ASD closure was also studied. Results A total of 185 patients met the inclusion criteria. The median age was 41 and 63% were female. The mean follow-up time of 3.6 months (range 1 day to 4.5 years). 249 echocardiograms were retrieved. Results showed a transient worsening of TR in the first 3 months post-ASD closure, which was more pronounced in older patients (≥40) (Figure 1). A larger ASD size was associated with a higher likelihood of early moderate or greater RV dysfunction (Figure 2). All patients had some degree of RV remodelling following the procedure. Older patients (≥40) were more likely to have RV dysfunction at the time of closure. Older age, RV and LV dysfunction, and high BSA were associated with poor RV remodelling or persistent RV dilation a year after ASD closure (Figure 3). Conclusions Patients who underwent percutaneous ASD closure with at least one of the following risk factors: age greater than 40, larger ASD, ventricular dysfunction, and high BSA require closer long-term follow-up given the reduced RV remodelling. Future studies are needed to elucidate the effect of poor RV remodelling on functional capacity, arrhythmic burden, and progression of TR and long-term outcomes.

Prevalence and incidence of diastolic dysfunction in new-onset atrial fibrillation: implications for clinical and preclinical HFpEF

Abstract Background Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are closely associated diseases that frequently coexist. However, due to the overlapping symptoms, the diagnosis of HFpEF can be overlooked with symptoms being attributed to AF. Purpose We aimed to investigate the prevalence of diastolic dysfunction (DD) in patients with new-onset AF compared to sinus rhythm (SR), study changes in diastolic function parameters over time in the two groups and compare the incidence of DD at follow-up. Methods Adults with new diagnosis of AF and adults in SR were identified. Patients with previous cardiac surgeries, congenital heart disease, hypertrophic or infiltrative cardiomyopathy, primary mitral disease, left-sided valve disease, low ejection fraction, enlarged left ventricle, or with no 6-month follow-up echocardiogram were excluded. Diastolic function was assessed through 4 components: mitral medial e’ &amp;lt;0.07 m/sec, mitral medial E/e’ &amp;gt;15 in SR and &amp;gt;11 in AF, TR velocity &amp;gt;2.80 m/sec, and left atrial volume index &amp;gt;34 ml/m2, with severe DD (SDD) defined by ≥3/4 findings and moderate DD (MDD) by ≥2/4 abnormal diastolic function parameters. Annualized changes were calculated as the difference between follow-up and baseline values divided by years in between. In a secondary analysis, patients with new-onset AF were propensity score-matched to patients with SR in a 3:1 ratio based on age, sex, body mass index, and comorbidities. Results Overall, 1,747 patients with incident AF (median age 67 years; 34% females) and 29,623 in SR (median age 59 years; 51% females) were included. New-onset AF was independently associated with the presence of SDD vs SR (8% vs 2%) and MDD (25% vs 11%, p&amp;lt;.001 for both in adjusted analysis). Over median follow-up of 3.2 (IQR 1.6-5.8) years, annualized severity progression in each of the 4 diastolic function parameters was greater in the AF group (p&amp;lt;.001 for all), Table. The incidence rates of SDD and MDD were 3.7 and 8.8 per 100-person year, respectively, in AF versus 1.1 and 3.6 per 100-person years, respectively, in SR (p&amp;lt;.001 for both at univariate and multivariable analysis), Figure. Results were similar in the propensity-score matched analysis. Conclusions Patients with new-onset AF more commonly have moderate or severe diastolic dysfunction that indicates the presence of potentially overlooked clinical HFpEF (when symptoms exist) or preclinical HFpEF (when symptoms are absent) compared to patients in SR. In long-term follow-up, patients with AF display accelerated progression in DD; suggesting that therapies to prevent progression to symptomatic HFpEF may be highest value in this patient population.

Comparative prognostic value of different echocardiographic parameters of the subpulmonary left ventricle in adults with a systemic right ventricle

Abstract Introduction Adults with complex congenital heart disease and a systemic right ventricle (SRV) are at increased risk of SRV dysfunction, heart failure, and premature death. In the systemic left ventricle (LV), impaired global longitudinal strain (GLS) is a strong predictor of adverse outcome. In the subpulmonary LV, however, echocardiographic assessment lacks standardisation and the relative prognostic significance of metrics of subpulmonary LV function remain unknown. Purpose To assess the correlation and relative prognostic power of quantitative metrics of subpulmonary LV function in adults with an SRV. Methods All adults with an SRV who underwent echocardiography in 2011-2019 at our specialist centre and had sufficient data for quantitative multiparametric subpulmonary LV assessment were included. LV systolic function was assessed by fractional area change (FAC), 4-chamber global longitudinal strain (GLS) and free wall longitudinal strain (FWLS). Linear regression was used to assess the correlation between echocardiographic variables of subpulmonary LV function. Cox regression analysis was used to assess the relation between echocardiographic predictors and the combined endpoint of death or transplantation. TimeROC analysis was performed to assess risk variable performance. Results In total, 120 patients (43.5±12.1 years, 60.0% male, 37.5% congenitally corrected transposition of the great arteries) were included. Most patients (94, 79.0%) were in NYHA functional class I/II and two-thirds (79, 66.4%) were receiving ≥1 heart failure therapy. One half of patients (63, 52.5%) had at least moderate systolic SRV dysfunction at baseline assessment with a median SRV FAC of 27[22-32]%. Subpulmonary LV function was visually preserved in most patients (98, 81.7%), with a LV FAC of 47.0[40.0-52.9]%. Median GLS was -15.2[-19.7–11.8]% and LV FWLS -19.9[-24.4–12.8]%. There was a weak correlation between LV FAC and GLS (r=0.25). During a median follow-up of 4.9[3.4-5.6] years, 24(20.0%) patients died and 3(2.5%) underwent heart or heart-lung transplantation. The 5-year transplant-free survival was 78.9%, (95%CI: 71.7-86.8%). On univariable Cox analysis, LV FAC (/5%, HR 0.55, 95%CI:0.47-0.65, p&amp;lt;0.0001) and GLS (/5%, HR 1.6, 95%CI:1.1-2.31, p=0.01), but not LV FWLS (/5%, HR 1.25, 95%CI:0.99-1.58, p=0.06) emerged as predictors of death or transplantation. LV GLS did not remain predictive in a bivariable model including LV FAC. LV FAC outperformed GLS on timeROC analysis (5-year AUC 0.87 vs. 0.64, p&amp;lt;0.0001; Figure). Conclusions Impaired systolic function of the subpulmonary LV strongly associated with mortality and heart or heart-lung transplantation in adults with an SRV. Both LV FAC and GLS are related to outcomes and should be a part of comprehensive echo assessment. LV FAC, a marker longitudinal and radial contraction, may better reflect pathophysiological mechanisms of subpulmonary LV failure and has greater prognostic significance in SRV patients.5-year ROC curves of LV FAC and GLS

Psychocognitive dysfunction in comorbid patients in the post-COVID period

Introduction. Currently, psychopathological symptoms are noted in a third of patients with COVID-19, according to published systematic reviews. Aim. To study psychocognitive function in comorbid patients depending on the coronavirus infection caused by SARS-CoV-2.Material and methods. The observational analytical cohort study included 223 patients with AF and comorbidity (ischemic heart disease, arterial hypertension, obesity, type 2 diabetes mellitus) aged 60–74 years, who were divided into 2 groups: 1st – 123 patients without COVID –19 and 2nd – 110 patients with a history of COVID-19 and the presence of PCS. The group of patients with a history of COVID-19 was retrospectively divided into 2 groups depending on the intake of sulodexide; patients in the subgroups were comparable. The work assessed psychological disorders (anxiety and depression) and cognitive status using specialized scales «HADS» and «SPMSQ».Results. In patients with COVID-19, compared with patients from group 1, there is a more pronounced depressive syndrome (p&lt;0.001); subclinical depression in 26% of patients (p&lt;0.001) and the absence of the latter in group 1; clinically pronounced depression was found in 15% (p=0.007). At the same time, the severity of subclinical symptoms of anxiety syndrome was noted in patients without COVID-19, and clinically significant anxiety was more often observed in recovered patients, although statistical significance was not achieved. When assessing cognitive function, it was found that moderate dysfunction was observed in patients with COVID-19 significantly more often (p=0.001). In the sulodexide group, only mild cognitive dysfunction was detected (14%), and the majority of patients taking sulodexide had no cognitive dysfunction.Conclusion. Thus, in comorbid elderly patients in the post-COVID period, an increase in the number of people with psychocognitive disorders was noted. In this regard, long-term follow-up of patients who have undergone COVID-19 is necessary, both for the dynamic assessment of underlying diseases and the analysis of psychocognitive status. In addition, it should be noted that the drug sulodexide, consisting of a heparin-like fraction and dermatan sulfate, has many pharmacodynamic (anti-inflammatory, angioprotective, anticoagulant, antifibrotic) and pharmacokinetic advantages (safety, the possibility of oral administration) can effectively prevent the development of cognitive dysfunction, which requires even further in-depth research.

Left Atrial Phasic Function via Cardiac Magnetic Resonance Imaging in Patients with Duchenne Muscular Dystrophy.

Cardiac dysfunction is a leading cause of morbidity and mortality in Duchenne muscular dystrophy (DMD). Left atrial (LA) function is a poorly understood concept in this patient population, and research suggests underlying structural changes that could affect atrial function. Cardiac magnetic resonance (CMR) imaging may provide an important non-invasive approach to evaluating LA function. This study was a single center retrospective review of consecutive CMR studies over a 1year period comparing LA phasic function within a cohort of DMD patients, and to those with structurally and functionally normal hearts. LA strain measurements including global reservoir, conduit, boost-pump strain, and LA volumes were obtained retrospectively. Spearman correlation analyses were performed on atrial strain measurements. 107 DMD and 79 normal CMR studies were included. The DMD cohort had worse systolic function (p < 0.001), smaller indexed max LA and left ventricular (LV) volumes (p < 0.001), and greater LA emptying fraction (p < 0.001). In the DMD cohort, emptying fraction decreased with advanced patient age (p < 0.001) and diminishing systolic function (p < 0.001). DMD patients with moderate or severe LV dysfunction demonstrated lower LA emptying fraction (p = 0.002), more impaired 2-chamber LA reservoir (p = 0.003), and LA pump (p = 0.006) and conduit strain (p = 0.018). DMD patients with preserved function have lower indexed LA volumes with higher LA emptying fractions than controls. Progression of disease and age is associated with decreased LA emptying fraction with early manifestations in reservoir and conduit strain. These findings suggest that strain markers of LA compliance and early left ventricular relaxation are associated with worsening cardiomyopathy in the DMD population.

Novel uses for implanted haemodynamic monitoring in adults with subaortic right ventricles

BackgroundPulmonary hypertension (PH) is a common complication in patients with complete dextro-transposition of the great arteries (TGA) after atrial switch (D-TGA/AS) and congenitally corrected TGA (ccTGA). In this population with...

Abstract 12632: Clinical Outcomes Across Groups of Ejection Fraction and Grades of Diastolic Dysfunction

Introduction: Previous studies have examined the association of diastolic dysfunction (DD) with cardiovascular (CV) outcomes. Understanding how clinical outcomes for those with a normal ejection fraction (EF) and DD compared to those with reduced EF is important in mitigating CV risk and optimizing management. Methods: 153,305 patients with echocardiograms performed at our institution between 2009 and 2022 were included in this analysis and divided into 2 cohorts: A) Normal EF patients (n=136,455) who were further stratified by grade of DD; and B) low EF (EF&lt;50%, n=16,850) patients who were further stratified by EF into four groups. Patients were followed for CV hospitalization or death. Results: Over a median follow up of 3.42 years, 23,946 (16%) patients died. There were 31,113 (20%), 13,305 (9%), and 1,269 (1%) hospitalizations for any CV diagnosis, heart failure (HF), or cardiac arrest (CA), respectively. After adjustment for age, CAD, HF, DM, hypertension, AF and CKD, the risk of all-cause mortality and of CV or HF hospitalizations increased steadily with increasing grade of DD in patients with normal EF (Table). The same was observed in cohort B with worsening EF, to greater extent than in patients with preserved EF (Table). The risk of hospitalization for CA in patients with grade III DD, however, was comparable to that of patients with an EF &lt;25% (HR=0.97, 95% CI 0.58-1.62, p=0.90) and worse than patients in better EF quartiles (p&lt;0.001). Patients with grade II DD had a CA hospitalization risk comparable to those with EF between 36-40% (HR=1.11, 95% CI 0.79-1.57, p=0.54). Conclusions: Although systolic dysfunction is associated with worse overall death and HF hospitalizations than DD, the risk of CA in patients with grade II and III DD is comparable to that of patients with moderate and severe systolic dysfunction, respectively. Future studies are needed to examine the mechanisms of CA in DD, and optimal treatment strategies for these patients.

Abstract 16093: Hemodynamic Implications of Transseptal Access for Ventricular Tachycardia Ablation in Patients With Left Ventricular Assist Devices

Introduction: Ventricular tachycardia (VT) is common in patients with left ventricular assist devices (LVAD), and catheter ablation can be an effective treatment strategy. Although transseptal approach for LV mapping and ablation is often preferred, iatrogenic atrial septal defect (ASD) after transseptal access may theoretically result in clinically significant right-to-left shunting. The short- and long-term implications of transseptal puncture, including hemodynamic changes in LVAD patients, remain uncertain. Methods and Results: From 2013-2023, 15 LVAD patients (age 68.5±12 years; 2 women) underwent 18 VT ablation procedures with single transseptal access for LV ablation without ASD closure afterwards. Clinical VT was eliminated in 83%. No patients had prior PFO/ASD; Mean RVSP was 45mmHg, 6 (40%) had pulmonary hypertension, and 8 (53.3%) had moderate or severe RV dysfunction. All patients had previously failed at least 1 antiarrhythmic drug (amiodarone 100%; sotalol 33%; mexiletine 94%). Procedural complications occurred in 3 procedures (all related to vascular access, none directly related to transseptal access; 1 patient with interrupted IVC requiring transhepatic access had bleeding due to transection of intercostal artery requiring arterial embolization). Post-procedure echocardiograms (n=14; mean time to echo 90±116 days) showed no intra-cardiac shunting or persistent ASD. Right heart catheterization (pre: n=12; post: n=8, at mean follow-up 187±243 days) showed similar pre- and post-ablation RA pressures (11.6 vs 14.9 mmHg, p =0.24) and wedge pressures (14.9 vs 20.4 mmHg, p =0.8) with absence of significant shunting based on pre- and post-ablation arterial (95.2% vs 97.7%, p =0.06) and PA oxygen saturations (56.5% vs 51.3%, p =0.29). No episodes of clinically significant hypoxia occurred after ablation. Conclusion: Transseptal access for VT ablation can be safely performed in LVAD patients and is unlikely to result in clinically or hemodynamically significant residual shunting over long-term follow-up. Therefore, empiric ASD closure after transseptal access in all LVAD patients is likely unnecessary.

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.

Abstract 11661: Genotypic and Phenotypic Guided Antiarrhythmic Drug Management of Multifocal Premature Ventricular Contractions

Introduction: Antiarrhythmic selection for progressive and intractable PVCs unresponsive to first and second line regimens can prove challenging. Genetic analysis assists by targeting specific genes, such as the SCN5a gene, which encodes for the alpha subunit of cardiac sodium channel NaV1.5. Mutations are associated with autosomal dominant phenotypes of multifocal ectopic Purkinje-related premature Contractions (MEPPCs). Case: A 38 year old female with a history of syncope and moderate left ventricular systolic dysfunction status post AICD and a family history of SCD presented for follow-up with complaints of frequent palpitations. ECG and a 72 hour Holter monitor had multifocal PVCs of purkinje origin with a burden of 31%. Despite a therapeutic trial with sotalol and amiodarone in various doses, she remained unresponsive with multifocal purkinje-related PVCs. TTE revealed global LV hypokinesia with worsening LVEF, and a cardiac MRI revealed features suggestive of a dilated cardiomyopathy (DCM) phenotype. Whole exome DNA analysis showed a heterozygous missense mutation pArg814Tryp on exon 16 of the SCN5A gene. Her specific variant, R814W, is a gain-of-function variant responsible for the hyperexcitability of the Purkinje fibers, making it amenable to sodium channel blockade with flecainide. After starting gene-directed flecainide, her PVC burden drastically reduced from 31% to 3% on repeat Holter monitor after 2 months. She has remained asymptomatic with an improved LVEF. Discussion: This is a unique case of SCN5A channelopathy with a MEPPC phenotype demonstrating a dramatic response to genotype guided management of multifocal PVCs. Clinicians should include such phenotypes in their differentials for patients that fail first and second line treatment regimens and have significant family history. It is essential to offer genetic testing to patients with a MEPPC phenotype in a DCM setting to choose the appropriate therapy and prevent SCD.

Long-term experience in treatment of acute promyelocytic leukemia in Mexican children in a tertiary care hospital.

Acute promyelocytic leukemia (APL) is a rare myeloid leukemia subtype affecting adult and pediatric populations. APL constitutes 15-20% of all childhood AML in Latin America, compared to 7% in the non-Latino population. This leukemia has unique characteristics, such as its association with chromosomal translocations involving the retinoid acid receptor α (RARA) gene on chromosome 17. In addition, APL is also distinct from other AML subtypes due to its response to all-trans-retinoic acid (ATRA), which induces terminal granulocytic differentiation of blasts. Overall 5-year survival rates are generally reported to be greater than 80%. A study was conducted from January 2008 to December 2022 applying the IC-APL 2006 treatment protocol. This case series reports the clinical results of 22 children with APL. In all cases, the diagnosis was made by bone marrow aspiration and evaluation of the t(15:17) or t(11:17) transcripts. We identified 22 patients with APL, of whom 10 were female and 12 were male. Twelve patients debuted with coagulation abnormalities. The doses of anthracyclines varied according to the risk, with an average of 496.8 mgm2. The cardiological assessment was performed before and after chemotherapy, finding 2/22 patients with moderate sisto-diastolic dysfunction and one with mild pulmonary insufficiency at the end of treatment. There were 6/22 patients with complications related to ATRA treatment, the most frequent being pseudotumor cerebri. All complications were transitory and treated immediately without complications. In this series of cases, an overall survival of 90.6% and a relapse-free survival of 90.6% were recorded. The follow-up mean was 9.1 ± 3.8 years. APL is a highly curable disease when combined with ATRA and anthracyclines. In this series of cases, good long-term results were observed with the IC-APL 2006 protocol. However, in Latin America, the availability of drugs such as arsenic trioxide as the first line of treatment is an unresolved challenge.

Abstract 14792: Predisposing Risk Factors Affecting Reversibility of Left Ventricular Diastolic Dysfunction in Patients With Moderate Diastolic Dysfunction and Preserved Ejection Fraction

Introduction: Few data exist on factors affecting the reversibility of diastolic dysfunction (DD) especially in patients with preserved left ventricular ejection fraction (LVEF). Hypothesis: In the present study, we investigated the predisposing risk factors affecting the reversibility of DD in patients with moderate DD and preserved LVEF. Methods: A total of 600 patients with moderate DD and preserved LVEF who underwent follow-up echocardiography were enrolled between 2011 and 2020. We compared their index and follow-up echocardiography findings and determined the predisposing factor affecting the reversibility of DD. Results: Comparing the index and follow-up echocardiography findings showed that 379 (63%) patients had improved to normal or mild DD (improved group) and 221 (37%) patients had maintained or worsened DD (unimproved group). Among the clinical risk factors, the incidence of paroxysmal atrial fibrillation (PAF) was significantly higher in the unimproved group than in the improved group (11 vs. 18, p=0.007). After adjustment for other clinical factors, PAF was determined to be an independent predisposing risk factor for the unimproved group (odds ratio, 2.76; 95% CI: 1.28-6.21, p=0.01). At follow-up echocardiography, the mean E/A ratio and E/e' were significantly improved in patients without PAF but remained in patients with PAF. Conclusions: We identified that PAF was an independent predisposing risk factor for the unimproved group in patients with moderate DD and preserved LVEF. Therefore, further management of PAF might be required in patients with moderate DD and preserved LVEF to prevent adverse cardiovascular events.

Abstract 16711: Outcomes of Severe Mitral Stenosis With the Revised Severity Criteria: Mitral Valve Replacement versus Percutaneous Mitral Valvuloplasty

Introduction: Mitral stenosis (MS) severity is determined by mitral valve area (MVA); the threshold for severe MS was raised from MVA of 1.0 cm 2 to 1.5 cm 2 in recent guidelines. Hypothesis: This study aimed to compare the clinical outcomes, according to percutaneous mitral valvuloplasty (PMV) versus mitral valve replacement (MVR) treatment strategy, of severe MS patients with the updated criteria for the subgroups categorized by MVA of 1.0 cm 2 and 1.5 cm 2 . Methods: From the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry of 3,140 patients, we included severe MS patients who underwent PMV or MVR between January 2000 and December 2021 except previous valvular surgery/intervention, at least moderate other valvular dysfunction, and thrombus at the left atrium/appendage. Moderately severe MS (MS-MS) and very severe MS (VS-MS) were defined as 1.0 cm 2 &lt;mva≤1.5 cm2 and MVA≤1.0 cm 2 , respectively. Primary outcomes were a composite of cardiovascular (CV) death and heart failure (HF) hospitalization. Secondary outcomes were a composite of primary outcomes and redo-intervention. Results: Among 442 patients (mean 56.5±11.9 years, women 77.1%), the MVR group (n=260) was older, had more comorbidities, higher echoscore, larger left chambers, and higher right ventricular systolic pressure than the PMV group (n=182). During a mean follow-up of 6.9±5.2 years with inverse probability weighted matching, primary outcomes did not differ, but the MVR group experienced fewer secondary outcomes (p=0.010). In subgroup analysis of MS-MS and VS-MS patients, primary outcomes did not differ. However, the MVR group in VS-MS patients showed better secondary outcomes (p=0.012) (Figure). Conclusions: PMV or MVR did not influence CV mortality or HF hospitalization in both MS-MS and VS-MS. However, due to increased early redo-intervention in the PMV group in VS-MS, MVR would be the preferable option without clear evidence of suitable morphology for PMV.

Abstract 15739: Fetal Echocardiographic Predictors of Perinatal Outcome in Congenital Atrioventricular Block

Background: Congenital atrioventricular block (AVB) is a rare disease with poor outcomes. Heart rate (HR) is a major prognostic factor. To date, no study has evaluated the contribution of cardiac output (CO), stroke volume (SV), and HR on outcomes. Methods: In this retrospective study we evaluated associations between fetal echocardiographic parameters and risk of a composite severe fetal adverse event (AE) in patients with congenital AVB. Results: Of the 58 cases of congenital AVB, 21 (36%) had the composite AE, defined as fetal hydrops (8/58, 14%), ≥ moderate ventricular dysfunction (LV 3/58, 5%; RV 6/58 11%), fetal demise (2/57, 4%), or premature birth at ≤ 35 weeks (17/55, 31%). Of the 55 live births, 3/55 (5%) patients died and 35/55 (64%) had a pacemaker placed in the neonatal period. In univariate analysis, lower HR z-score was associated with the composite AE (p = 0.002) and all individual components of the composite AE. Higher LV end diastolic volume was associated with the composite AE (p = 0.004), premature birth (p = 0.006) and neonatal pacemaker placement (p = 0.009). Higher LV SV was associated with the composite AE (p = 0.003) and with fetal hydrops (p = 0.031) and premature birth (p = 0.002). Higher combined CO (p = 0.038), presence of structural heart defect (p = 0.038) and heterotaxy (p = 0.01) were associated with fetal hydrops. In multivariate analysis, lower HR z-score (p = 0.044) and higher LV SV (p = 0.037) were associated with the composite AE. Longitudinal analysis showed the AE group had lower HR and higher SV throughout gestation and trends towards a greater decline in SV and CO (particularly RV CO) in the third trimester. Conclusions: Heart rate, not CCO, is the primary determinant of perinatal outcome in fetuses with high grade AVB. The compensatory increase in LV volume and SV in the patients with the lowest HR (and worst outcomes) maintains CCO in most fetuses with AVB and reflects the ability for fetal cardiac adaptation in the setting of prolonged severe bradycardia.