bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13977: Low Operative Mortality Achieved With Surgical Septal Myectomy: Role of Dedicated Hypertrophic Cardiomyopathy Centers in the Management of Dynamic Subaortic Obstruction
Authors: Maron Barry J , Dearani Joseph A , Ommen Steve R , Maron Martin S , Schaff Hartzell V , Nishimura Rick A , Ralph-Edwards Anthony , Sherrid Mark V , Swistel Daniel G , Balaram Sandhya , Rastegar Hassan , Rowin Ethan J , Smedira Nicholas G , Lytle Bruce W , Desai Milind Y , Lever Harry M
Published: April 2024

Background:
Treatment of progressive heart failure, due to left ventricular (LV) outflow tract obstruction has been a major component of hypertrophic cardiomyopathy (HCM) disease management for 50 years. Septal myectomy has been the primary treatment option to abolish gradients and relieve heart failure symptoms. The role of myectomy in HCM management has depended on effectiveness in relieving heart failure symptoms, but also an acceptable operative risk.

Methods:
Over the most recent 15-year period, we reviewed 3,700 consecutive isolated myectomy operations performed at major North American HCM institutions. Composite operative mortality (first 30 days) was only 0.4%. Seventeen operative deaths were at ages 24 to 82 (≥70 years), and only 6 occurred after 2010. Notably, 2 of the 4 Mayo Clinic deaths were in patients with prior alcohol septal ablation. Septal myectomy, when performed in experienced HCM centers, was much safer when compared to operative mortality with coronary artery bypass grafting (2.3%); valve replacement (3.5%); mitral valve replacement specifically (5.7%) (STS Database), similar to atrial or ventricular septal defect closure and 15-fold less than myectomy in community hospital or low volume surgical settings.

Conclusions:
Surgical myectomy performed in dedicated HCM centers with experienced surgeons and staff is one of the safest open-heart procedures currently practiced, with a mortality rate as low as 0.4%. The large mortality discrepancy for myectomy between community hospitals and dedicated HCM centers underscores that this operation should be considered a specialized procedure best performed in high volume HCM institutions.
Abstract 14020: Practice Trends in the Care of Infants With Hypoplastic Left Heart Syndrome: A Report From the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC)
Authors: Carlo Waldemar F , Cnota James F , Anderson Jeffrey B
Published: April 2024

Introduction:
The NPC-QIC was established in 2008 to improve outcomes of hypoplastic left heart syndrome (HLHS) patients during the interstage period using quality improvement to reduce unnecessary practice variation. Our objective was to evaluate early and recent interstage practice variation within the collaborative.

Methods:
Data from the first 100 patients (6/2008 - 1/2010) representing 18 centers were compared with the most recent 100 patients (1/2014 - 11/2014) from these same centers.

Results:
Prenatal diagnosis increased from 72% to 82% (p = 0.09). There were no differences in gestational age or weight at Norwood. A composite of any preoperative risk factor (mechanical ventilation, acidosis, renal insufficiency, arrhythmia, NEC, sepsis) occurred more frequently in the early era (58% vs 34%, p <0.01). While mean age at Norwood was similar (8.3 vs 6.6 days, p = 0.2), the standard deviation for this variable was significantly lower in the recent era (10.5 to 6.4 days, p = 0.03). Use of RV-PA conduit increased (69% to 84%, p = 0.02). Rates of complete discharge communication with both the primary care physician (31 to 97%, p < 0.01) and primary cardiologist (44 to 97%, p < 0.01) increased substantially. There was no change in interstage feeding strategies between eras. Use of interstage outpatient surveillance program increased (76% to 99%, p < 0.01) with all participants in the late era monitoring both oxygen saturation and weight.

Conclusions:
Among NPC-QIC centers contributing patients to both early and recent cohorts, there were significant changes in preoperative risk factors, Norwood surgical strategy, discharge communication, and interstage surveillance. Practice variation in timing of Norwood has been reduced. Further study is required to determine an association between these practice trends and decreased mortality.
Abstract 14123: Circulating miRNAs as Biomarkers of Afterload, Acute Vascular Reactivity, and Ventricular-Vascular Coupling in Pediatric Idiopathic Pulmonary Arterial Hypertension: Initial Clinical Studies
Authors: Kheyfets Vitaly O , Truong Uyen , Dunning Jamie , Hunter Kendall , Sucharov Carmen C , Ivy Dunbar , Miyamoto Shelley , Shandas Robin
Published: April 2024

Introduction:
Although it is known that structural remodeling of the pulmonary arteries (PA) leads to increases in right ventricular (RV) afterload in pediatric idiopathic pulmonary arterial hypertension (iPAH), evaluating such changes early in the process continues to be challenging. Since biological markers such as microRNAs may manifest earlier than functional markers, and since such markers may be detected using simple blood draws, identifying correlations between microRNAs and RV or pulmonary vascular functional parameters would be particularly useful in tracking this disease.

Methods:
Blood was collected for 14 pediatric patients with iPAH while undergoing right heart catheterization (RHC). Taqman Low Density Arrays (TLDA) was used to quantify miRNA expression in each patient. RHC data was used to compute pulmonary vascular impedance, ventricular-vascular coupling (VVC), and other hemodynamic markers. VVC was computed from the pressure tracing using the single beat pressure method (Vanderpool RR, et al. Heart 2015;101:37–43).

Results:
miR-21, which frequently appears in the PAH literature, was well correlated with pulmonary vascular resistance index (PVRi) (r = 0.81, P < 0.001, see Fig. 1a). Fig. 1b shows that the ratio of miR-150/571 is an excellent predictor of VVC (r = 0.91, P < 0.05). Random Forest statistical machine learning identified miR-683 as a classifier of acute vascular reactivity, confirmed with receiver operating curves (AUC = 0.88, see Fig. 1c)

Conclusion:
Over a dozen circulating miRNAs were identified as potential biomarkers for pediatric iPAH from the aforementioned arrays, with several having strong correlations to afterload and acute vascular reactivity. The ratio of miR-150 (recognized as biomarker of PAH) and miR-571 (recognized as biomarker of heart failure) appears particularly promising as a predictor of ventricular-vascular decoupling.
Abstract 14145: Stroke Volume Index Predicts Mortality of Patients Undergoing Transcatheter Aortic Valve Implantation With Concomitant Mitral Regurgitation
Authors: Anousakis-Vlachochristou Nikolaos , Toutouzas Konstantinos , Drakopoulou Maria , Stathogiannis Konstantinos , Latsios George , Synetos Andreas , Tsiamis Eleftherios , Tousoulis Dimitris
Published: April 2024

Introduction:
Patients with severe aortic stenosis frequently suffer from concomitant mitral regurgitation (MR), which implicates cardiac hemodynamic and clinical status.

Hypothesis:
We assessed the hypothesis that moderate/severe MR increases mortality of patients undergoing trancatheter aortic valve implantation (TAVI) and evaluated the possible predicting ability of pre-implantation echocardiographic assessment.

Methods:
We prospectively enrolled 119 patients, retrieved clinical and echocardiographic data before and 6 months after TAVI and divided patients in two groups: none/mild and moderate/severe MR. Clinical follow-up performed in a two-year period. A low mean gradient was assumed when <40 mmHg, a low stroke volume index (SVi) when <35ml/m2 and a low ejection fraction when <45%. Statistical analysis of all-cause mortality performed with the Kaplan-Meier method and further evaluated with Cox proportional hazards analysis.

Results:
Seventy six patients (64%) had none/mild and 43 (36%) had moderate/severe MR. The baseline characteristics where evenly distributed among groups except for gender, coronary artery disease, chronic obstructive pulmonary disease and pulmonary arterial systolic pressure. The median follow-up time was 23 months (mean 22±13 months). During follow-up period the cumulative probability for mortality was significantly different between groups (none/mild MR: 14.5%, moderate/severe MR: 34.9%, p=0.006). In multivariate analysis, low SVi predicted mortality adjusted for moderate/severe MR and the variables that differed at baseline [HR: 5.1, 95% CI (2.21, 11.92), p=0.001], while other echocardiographic variables did not contribute to the final model although significant in univariate analysis.

Conclusions:
Patients undergoing TAVI with concomitant moderate or severe MR had increased risk for mortality in a two-year period. Pre-implantation low stroke volume index independently predicted mortality.
Abstract 14172: Abrogation of S100A1 Exacerbates Right Ventricular Dilation and Fetal Gene Expression in the Sugen/hypoxia Model of Pulmonary Arterial Hypertension in Mice
Authors: Teichert-Kuliszewska Krystyna , Tsoporis James N , Desjardins Jean F , Izhar Shehla , Parker Thomas G
Published: April 2024

Background:
S100A1, a Ca
2+
-sensor protein, is expressed in myocardium and endothelial cells and regulates cardiac muscle contractility. Previously, we demonstrated that under basal conditions
in vivo
, S100A1 knockout mice (KO) exhibited a significant elevation in right ventricular systolic pressure (RVSP), accompanied by an increase in RV hypertrophy. Since RV dysfunction occurs with progression of pulmonary arterial hypertension (PAH), we aimed to determine the impact of deleting S100A1 on progression of PAH in the Sugen-hypoxia (SUHx) model in mice.

Methods and Results:
C57BL6 (WT) and S100A1 KO mice (n=10 per group) were injected once weekly subcutaneously with SU (20mg/kg) and exposed to chronic Hx (10% O
2
) for 3 weeks. PAH was assessed by hemodynamic parameters, RV morphology and echocardiography. RV and lung tissue were collected for molecular analysis. In WT and S100A1 KO mice exposed to SUHx, RVSP was similar 31.0±1.90 vs.31.4±2.08, respectively. In RV and lung tissue of WT mice, S100A1 mRNA and protein decreased approximately 40% in response to SUHx. SUHx induced similar increases in RV weight calculated as the Fulton index (0.43±0.06 in WT vs. 0.41±0.04 in S100A1KO) but in contrast to WT, S100A1 KO demonstrated a 3.7- and 1.5- fold increase in the mRNA levels of the hypertrophic genes, atrial natriuretic factor and beta-myosin heavy chain, respectively (p<0.05). In S100A1 KO mice SUHx reduced heart rate (S100A1KO - 305.41±54.69 vs. WT- 443 ±54.82 bpm, p< 0.001) compared to WT. Furthermore, serial echocardiographic assessment indicated increased RV dilation in the S100A1KO compared to the WT in response to SUHx as assessed by increases in RV internal diameter in both diastole (S100A1KO, 1.92±0.08 vs. WT, 1.53 ±0.08, p=0.004) and systole (S100A1KO, 1.34±0.1 vs. WT, 0.97±0.01, p=0.02).

Conclusion:
Our results show that PAH is associated with decreased expression of S100A1 in the RV and lack of S100A1 increases RV dilation and expression of fetal gene markers in the SUHx model. S100A1 may serve to limit severity of RV structural changes in PAH and represents a potential therapeutic target in this disease.
Abstract 14181: Poor Long-Term Prognosis in Patients With Inflammatory Dilated Cardiomyopathy Diagnosed by Immunohistochemistry-Based Criteria
Authors: Sugano Yasuo , Nakayama Takafumi , Yokokawa Tetsuro , Nagai Toshiyuki , Ogo Keiko O , Ikeda Yoshihiko , Ueda Hatsue I , Nakatani Takeshi , Yasuda Satoshi , Ogawa Hisao , Anzai Toshihisa
Published: April 2024

Background:
Dilated cardiomyopathy (DCM) is highly heterogeneous and the future clinical course is almost unpredictable due to its diversity in each individual patient. Inflammatory DCM (DCMi) is defined by World Heart Federation (WHF) criteria as 14/mm
2
or more infiltrating T-lymphocytes or activated T-cells (including up to 4 macrophages) in the endomyocardial biopsy of a dilated heart. However, detail characteristics and long-term prognosis in patients with DCMi have not been fully understood.

Methods:
One hundred and sixteen consecutive patients between 2005 and 2007, who were finally diagnosed as DCM after right ventricular endomyocardial biopsy, were studied. Stored biopsy samples were immunohistochemically stained with antibodies specific for CD3 (T-lymphocytes) and CD68 (macrophages) to count the number of infiltrating cells into myocardium. We also collected each patient’s clinical characteristics, as well as prognostic data up to 9 years (mean 6.7 years) from diagnosis.

Results:
In total, 66 patients (57%) met the criteria for DCMi. Those patients showed no different baseline characteristics at diagnosis including age, sex, medications, past history, serum Na, creatinine, plasma BNP level, LV dimension, LV ejection fraction, and LV end-diastolic pressure compared to non-DCMi patients. During the observation period, 17 patients had poor clinical outcome of death or heart transplantation. Fifteen out of 66 patients with DCMi, despite only 2 out of 50 patients with non-DCMi, showed poor clinical outcome (23% vs 4%, p=0.007). Kaplan-Meier analysis revealed that DCMi patients had poorer long-term transplantation-free survival than non-DCMi patients (log-rank p=0.009, Figure).

Conclusions:
In our study, 57% of DCM patients fulfilled the immunohistochemistry-based criteria for DCMi defined by WHF. Patients who met the DCMi criteria had remarkably poor long-term prognosis regardless of similar baseline characteristics at diagnosis.
Abstract 14186: Is Mitral Valve Repair Superior to Mitral Valve Replacement in Elderly Patients? Short and Long-term Outcomes From the Past Two Decades
Authors: Silaschi Miriam , Chaubey Sanjay , Uzzamann Mohammad M , Khan Habib , Singh Mrinal , Deshpande Ranjit , Baghai Max , Wendler Olaf
Published: April 2024

Background:
Due to demographic changes a growing number of elderly patients present with mitral valve (MV) disease. Mitral Valve Repair (MV-repair) is the gold-standard treatment option for patients with MV disease. Nevertheless, in elderly patients there is still controversy if MV-repair improves outcomes of patients compared to mitral valve replacement (MVR).

We reviewed results after MV surgery in elderly patients treated at our institution over the past 20 years.

Methods:
Our in-hospital database was explored for patients who underwent MV surgery between 1994 and 2015. A comparative survival-analysis was performed for MV-repair vs. MVR patients. Cox-regression was applied to adjust for age, valve pathology, ejection fraction (EF) and combined procedures.

Results:
Of the 1776 patients identified, 356 (20.0%) were aged ≥75 years and received either MV-repair (n=224, 62.9%) or MVR (n=132, 37.1%). Patients with repeat cardiac surgery, endocarditis and concomitant aortic valve replacement were excluded. In 55.8% of MV-repair and 46.2% of MVR procedures were combined (p=0.10). Mean age was 79.3±3.1yrs (MV-repair) vs 78.4±2.9yrs (MVR: p=0.02). Logistic EuroSCORE was 14.8±1.3% (MV-repair) vs. 15.3±16.1% (MVR: p=0.77).

Median survival of all patients was 7.4years (95%CI: 6.8-8.1) compared to a survival of 8.5years (95%CI: 8.2-9.4) in the age matched UK population (Ratio 0.87; p=0.01). Thirty-day mortality was 6.3% (MV-repair) vs. 10.6% (MVR, p=0.16). Length of ICU-stay was 1.1±1.6 days vs. 1.0±1.0days (p=0.43). Overall 1-, 2-, 5- and 8-year survival after MV-repair (90.7%, 89.0%, 77.0% and 45.9% vs. 79.5%, 76.5%, 58.9% and 41.4%, p[logrank]=0.02) as well as adjusted survival at 1-, 2-, 5- and 8-years were significantly improved after MV-repair (91.1%, 90.2%, 81.0% and 52.5% vs. 77.7%, 76.1%, 56.2%, 37.0%, p<0.01). After MV-repair, impaired EF was an independent predictor of adverse outcome (p<0.01).

Conclusion:
Mitral valve surgery is a reliable treatment option with excellent long-term outcomes in elderly patients. Long-term outcomes can be improved in this patient group if mitral valves are repaired.
Abstract 14207: Racial Differences in the Incidence and Outcomes of Heart Failure in Commercially Insured Patients
Authors: Sangaralingham Lindsey R , Shah Nilay D , Roger Veronique L , Dunlay Shannon M
Published: April 2024

Background:
Epidemiologic studies have demonstrated that the incidence of heart failure varies by race and ethnicity, with the highest incidence occurring in blacks. However, whether these racial and ethnic variations extend to commercially insured populations and whether differences in early outcomes after diagnosis exist requires further exploration.

Methods:
We utilized administrative claims data from a large U.S. commercial insurance database to retrospectively identify privately insured and Medicare Advantage patients who were diagnosed with heart failure between 2006 and 2014. Published claims-based algorithms were used to identify patients with incident HF and categorize reasons for hospitalization after diagnosis.

Results:
Among 148,827 patients with incident heart failure (mean age 72.2 years, 51% women), 70% were white, 15% black, 6% Hispanic, 3% Asian and 6% had unknown race/ ethnicity. The incidence of heart failure during the study period was 3.7 per 1000 person-years and was highest among blacks, followed by whites, Hispanics and Asians (9.9, 3.6, 2.5, and 2.0 per 1000 person-years, respectively). In total, 37% of patients were hospitalized at least once in the first year after diagnosis for a total of 93,358 hospitalizations. HF was the most common reason for hospitalization (13% of all hospitalizations), followed by arrhythmia (5%), sepsis (5%), pneumonia (4%), COPD (3%) and acute renal failure (3%). Reasons for hospitalization were similar across racial and ethnic groups. The rate of hospitalizations was highest the first month after diagnosis and then gradually declined. Black patients had the highest rates of hospitalization, while Asians had the lowest (Figure).

Conclusions:
Even among a commercially insured population that likely have fewer barriers to care, black patients had a higher incidence of HF and higher rates of hospitalization after initial diagnosis compared with other racial and ethnic groups.
Abstract 14223: Atrial Fibrillation, Clinical Outcomes, and Post-discharge Natriuretic Peptide Trajectory Among Patients Hospitalized for Heart Failure: Findings From the ASTRONAUT Trial
Authors: Greene Stephen J , Fonarow Gregg C , Subacius Haris , Maggioni Aldo P , Zannad Faiez , Solomon Scott D , Lewis Eldrin F , Böhm Michael , Gheorghiade Mihai
Published: April 2024

Introduction:
Heart failure (HF) clinical trials have used change in NT-proBNP as a surrogate endpoint, but the influence of atrial fibrillation/ flutter (AFF) on this endpoint is unclear. We investigated the association of AFF with change in NT-proBNP and clinical outcomes following HF hospitalization.

Methods:
Characteristics and outcomes of 1,358 patients from the ASTRONAUT trial were compared by presence/ absence of AFF on baseline ECG. Patients with history of AFF but without AFF on ECG were excluded. Full factorial repeated measures design using AFF and study randomization was used to predict NT-proBNP changes from baseline to 1, 6, and 12 months. Survival analysis was used to examine the correlation between AFF and outcomes.

Results:
Patient characteristics and outcomes are displayed in the Table. Among placebo patients, AFF was associated with higher NT-proBNP level at all time points, but larger reductions from baseline levels (p for interaction <0.01). These differences became non-significant after accounting for other clinical characteristics. The ability of aliskiren to lower NT-proBNP over time differed by AFF status (p for interaction <0.01, Figure). After adjustment for patient characteristics, AFF was not associated with cardiovascular mortality/ HF hospitalization or all-cause death at 12 months (all p≥0.15).

Conclusions:
Absolute levels and change from baseline in NT-proBNP over time differ in HF patients with and without AFF. The ability of a study drug to lower NT-proBNP may depend on the AFF prevalence in the population. AFF was not independently associated with clinical outcomes in this cohort.
Abstract 14266: The Association Between Ischemic and Jeopardized Myocardia and All-Cause Mortality in Patients With Peripheral Artery Disease
Authors: Hammad Tarek A , Yousefzai Rayan , Venkatachalam Sridhar , Lowry Ashley , Gornik Heather L , Jaber Wael , Bartholomew John R , Kim Soo Hyun , Cerqueira Manuel , Gray Bruce H , Blackstone Eugene H , Shishehbor Mehdi H
Published: April 2024

OBJECTIVE:
PAD is associated with increased all-cause mortality (ACM) and concomitant CAD. However, it is unclear whether uncovering the presence of coronary ischemia by a single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) would further help stratifying that excess risk.

Methods:
From 01/2000 to 01/2009, 4,294 patients underwent cardiac stress testing within 180 days of ankle brachial index (ABI) exam. Of these, 645 had PAD and SPECT MPI stress testing. Abnormal ABI was defined as ≤ 0.9 or prior peripheral revascularization. Myocardial ischemic burden and total jeopardized myocardium were represented by summed difference score (SDS) and summed stress score (SSS), respectively. Cox proportional hazard analyses were used to study the impact of SDS and SSS on ACM. Additionally using a hierarchical approach, we examined the step-wise addition of post-stress test coronary and peripheral revascularizations as time-varying covariates on outcomes.

Results:
Kaplan-Meier curves showed no significant differences in ACM between patients with ischemic myocardium (SDS > 0) and those without (SDS = 0), or between those with jeopardized myocardium (SSS > 0) and without (SSS = 0). Similarly in multivariable Cox analyses, the presence of ischemic or jeopardized myocardium remained with no significant impact on ACM in PAD, adjusted HR: 0.94, 95% CI: 0.53 - 1.69; P = 0.84 and adjusted HR: 1.16, 95% CI: 0.67 - 2.00; P = 0.59, respectively. Moreover, adjustment for post-testing coronary and peripheral revascularizations did not affect our results.

Conclusions:
Ischemic and jeopardized myocardia are not predictors of ACM in PAD, thus SPECT MPI does not appear to be a useful risk stratification tool in these patients.

Figure 1.

Unadjusted Comparison of All-Cause Mortality among PAD Patients according to the Presence of Ischemic Myocardium (Panel A) and Jeopardized Myocardium (Panel B)
Abstract 14271: Patiromer Controls Hyperkalemia in Resistant Hypertensive Patients on RAASi, With Diabetic Kidney Disease
Authors: Epstein Murray , Mayo Martha , Garza Dahlia , Stasiv Yuri , Zawadski Rezi , Berman Lance , Wilson Dan , Bakris George
Published: April 2024

Introduction:
Emerging treatments for hyperkalemia (HK) may have favorable effects on the risk:benefit ratio for pts with HTN and diabetic kidney disease (DKD) treated with RAASi. HK develops in ~7-14% of pts with HTN and DKD, which can limit RAASi dosing and potential cardio-renal benefit.

Hypothesis:
This post hoc analysis from the 52-wk AMETHYST-DN study examined the K
+
-lowering effect of patiromer, an investigational potassium binding polymer, in resistant HTN (RTN) pts with HK and DKD.

Methods:
Hypertensive pts with mild (>5.0-5.5 mEq/L) and moderate (>5.5-<6.0 mEq/L) HK and DKD on RAASi were treated with patiromer in an 8-wk treatment initiation phase (TIP), followed by a 44-wk long-term maintenance phase (LTMP). Safety and efficacy were assessed/analyzed in a RTN cohort (defined at baseline [BL], as a SBP >140 mmHg on ≥4 classes of antihypertensive medication including a diuretic).

Results:
In AMETHYST-DN, 79/306 pts (67+7 yrs, 51% male) - 64 with mild HK, mean (±SEM) s-K
+
5.18 (0.03) mEq/l, and 15 with moderate HK s-K
+
5.77 (0.04) mEq/l - had RTN on RAASI. Mean (±SD) HR and SBP/DBP were 73 (10) bpm and 156 (10) mmHg / 83 (12) mmHg at BL. At BL stage ≥3b CKD was present in 51/79 pts (65%). Significant reductions in s-K
+
from BL occurred at each time point over the 52 wks /end of therapy (ET) (Figure). Investigators could add/modify non-RAASi antihypertensive medications, without known effect on s-K
+
, for BP control. Similar to the BP changes observed in the intent-to-treat population, at ET the change in mean (±SD) SBP/DBP was -18 (17) mmHg/ -9.0 (13) mmHg in the RTN group. Mean (±SD) change in eGFR from BL was –2.1 (12) mL/min/1.73m
2
. A total of 5/79 withdrew from study due to a patiromer related AE (hypokalemia 3, constipation 2). Doubling of serum Cr occurred in 7 pts; 1 death occurred during LTMP.

Conclusions:
Patiromer effectively controlled HK throughout a 52-wk period in a high-risk cohort of RTN pts, which enabled these pts to continue to use RAASi to control BP.
Abstract 14355: Sinus Rhythm Prior to Catheter Ablation Positively Impacts Ablation Outcome in Non-Paroxysmal Atrial Fibrillation Patients
Authors: Mohanty Sanghamitra , Mohanty Prasant , Trivedi Chintan , Gianni Carola , Gunes Mahmut F , Gokoglan Yalcin , Bai Rong , Burkhardt John David , Sanchez Javier , Hranitzky Patrick , Gallinghouse G. J , Al-Ahmad Amin , Horton Rodney , Di Biase Luigi , Natale Andrea
Published: April 2024

Background:
Catheter ablation of non-paroxysmal atrial fibrillation (NPAF) is associated with longer procedure times and lower long-term success rates than that of paroxysmal AF. We tested the hypothesis that NPAF patients entering the EP laboratory (lab) with sinus rhythm (SR) have shorter procedure time and better ablation-outcome than those with AF as the entry-rhythm.

Methods:
Total of 804 consecutive NPAF patients undergoing radiofrequency catheter ablation at our center were included in this prospective analysis. Based on the presenting rhythm in the EP lab, patients were classified into two groups; patients on SR (group 1, n=236, age 63±10 years, male 71%, LVEF 55.2±8.4, LA size 4.5±0.9 cm), patients in AF (group 2, n=568, age 64±10 years, male 69%, LVEF 54.4±11.4, LA size 4.6±0.6 cm). All patients were followed up for 38±6 months for arrhythmia recurrence by event recorder, ECG and Holter monitoring.

Results:
The baseline characteristics were not different between the groups. When comparing the procedural parameters between the groups, patients presenting with SR required significantly shorter radiofrequency time (64.1±30.7 min vs. 82.3±29.4 min in AF group, p<0.0001) and procedure times (143.9±91.2 min vs. 162.3±62.2 min in AF group, p=0.019).

At the end of follow-up, significantly higher recurrence rate was noted in those presenting with AF compared to patients on SR at the procedure; 264 of 568 (47%) vs. 80 of 236 (34%) respectively, log-rank p=0.002 (unadjusted hazard ratio 1.55 [1.17 - 2.05]) (figure).

After adjusting for AF type, age, gender, LA size, and LVEF in multivariable Cox model, patients presenting with AF at procedure were twice more likely to fail compared to those on SR (hazard ratio 1.91 (95% CI 1.19 to 4.15), p=0.001).

Conclusion:
Sinus rhythm prior to catheter ablation for non-paroxysmal AF decreases the duration of ablation and increases the long-term efficacy of the procedure.

Figure: Kaplan-Meier curve showing recurrence by study groups
Abstract 14364: Hemodynamic Evaluation of 30 Y-Graft Fontan Completions
Authors: Trusty Phillip M , Restrepo Maria , Fogel Mark A , Kanter Kirk , Yoganathan Ajit P , Slesnick Timothy C
Published: April 2024

Background:
Fontan completion, resulting in a total cavopulmonary connection (TCPC), is accomplished using either a traditional baffle or bifurcated Y-graft. The use of Y-grafts was originally hypothesized to provide more even hepatic blood flow distribution to the lungs, a factor related to pulmonary arteriovenous malformations. This study evaluates the hemodynamic performance of the largest Y-graft cohort to date, compares those results with a traditional baffle, and highlights Y-graft cases that exhibit both favorable and poor performance.

Methods:
Thirty Y-graft and 30 traditional baffle Fontan patients were analyzed. TCPC anatomies and vessel flow waveforms were reconstructed using cardiac magnetic resonance (CMR) images and phase-contrast CMR. Computational fluid dynamic simulations were performed to quantify TCPC power loss, resistance, and hepatic flow distribution (HFD). Comparisons between graft types and subanalysis of favorable versus poor performing Y-grafts were investigated.

Results:
The TCPC resistance distribution, HFD distribution, and the effect of LPA stenosis on power loss for Y-grafts and traditional baffles are shown in Fig. 1A-1C. TCPC resistance was significantly lower in traditional baffle patients. HFD was similar overall, with median and range of 40 (1-77) and 51 (1-99) for the traditional baffle and Y-graft, but show a discrepancy at extreme values with more unbalanced flow in the Y-graft cohort. Power loss was more sensitive to LPA stenosis in the Y-graft cohort. Prediction of Y-graft HFD is multi-factorial and six representative cases are shown in Fig. 1D.

Conclusions:
Y-grafts do not inherently provide more balanced HFD than traditional baffles. Traditional baffles are more energetically favorable and less sensitive to PA stenosis. Graft type should be considered on an individual basis as hemodynamic performance is based on a combination of factors, including global flow distribution, PA stenosis and SVC positioning.
Abstract 14571: Prospective Randomized Comparisonof Miniaturized Extracorporeal Circulation System (MECC) versus Conventional Extracorporeal Circulation System (cecc) in the Prevention of Postoperative Atrial Fibrillation (FA) and Other Clinical Results in Cardiac Surgery Patients
Authors: Ellam Sten , Korvenoja Pekka , Hartikainen Juha , Valtola Antti , Hippelainen Mikko , Pitkanen Otto , Halonen Jari
Published: April 2024

Introduction:
Postoperative atrial fibrillation (AF) is the most common arrhythmia to occur after cardic surgery with an incidence between 20-45 %. It is associated with increased morbidity, including increased risk of stroke and need for additional treatment and costs. The pathophysiology of postoperative AF is not fully understood.cardiac surgery with extracorporeal circulation is known to be associated with a systemic inflammatory response,which may be in part responsible for postoperative AF. furthermore,foreign surface contact,blood-air contact,abnormal blood flow and hemodilution are broblems related to extracorporeal circulation.

Hypothesis and Methods:
In this prospective,randomized,open labelled clinical study,240 cardiac surgery patients were randomized either miniaturized extracorporeal circulation (MECC) group or conventional extracorporeal circulation (CECC) group before the surgery. The main outcome measure was the incidence of postoperative atrial fibrillation (AF) during the hospital stay after surgery. Other end points were use of blood products and vasoactive agents and the first (CKMBm) value postoperatively.

Results:
The incidence of postoperative atrial fibrillation was 43/120 (35.8 %) in the conventional extracorporeal circulation group (CECC) compared with 42/120 (35.0%) in the miniaturized extracorporeal circulation group (MECC) (p=0.893). The use of perioperative vasoactive agents was significantly lower in the (MECC) group compared with (CECC) group . Furthermore, the first postoperative CKMBm value was significantly lower in (MECC) patient group than in (CECC) patient group. There were no difference in the use of blood products between the groups.

Conclusion:
The clinical use of MECC with cardiac operative patients is safe and results are optimal when this procedure is performed by experienced teams. There were no difference in the incidence of postoperatrive atrial fibrillation (AF) between the groups, but the use of vasoactive agents was lower in (MECC) patient group, than in (CECC) patient group and also the first postoperative (CKMBm) value was lower in the (MECC) group than in (CECC) group.
Abstract 14662: Targeted Delivery of an Anti-miR to Cardiomyocytes Using Ultrasound and Microbubbles Suppresses Hypertrophy
Authors: Kopechek Jonathan A , Carson Andrew R , McTiernan Charles F , Chen Xucai , Feroze Rafey , Lavery Linda , Hasjim Bima , Villanueva Flordeliza S
Published: April 2024

Introduction:
MicroRNAs (miRs) are dysregulated in various cardiovascular diseases and anti-miRs have been developed to therapeutically inhibit the activity of specific miRs. An anti-miR against miR-23a suppressed hypertension-induced cardiac hypertrophy in preclinical models, but clinical translation is limited by a lack of targeted cardiac delivery systems. Ultrasound (US) targeted microbubble (MB) destruction (UTMD) is a novel therapeutic delivery platform that utilizes MBs as nucleic acid carriers. We hypothesized that UTMD-mediated delivery of anti-miR-23a suppresses cardiomyocyte hypertrophy and assessed UTMD-mediated functional delivery of anti-miR-23a to cultured cardiomyocytes (CMs) in vitro to lay the groundwork for future in vivo translational studies.

Methods:
Neonatal CMs were isolated from hearts of 1 to 2 day old Sprague Dawley rats. MBs were loaded with LNA-modified negative control anti-miR (NC) or anti-miR-23a, added to CM cultures (anti-miR concentration 300 pM) and insonified with a clinical US imaging system (1.3 MHz, MI setting=1.6). CMs were exposed to 100 μM phenylephrine (PE) to induce hypertrophy. Levels of miR-23a and FOXO3a (miR-23a target) were assessed by qRT-PCR 48 hr after UTMD and normalized to that in NC treated CMs. To quantify hypertrophy, CM surface areas pre- and post-PE were measured by a blinded observer.

Results:
UTMD treatment with anti-miR-23a knocked down CM miR-23a levels by 51 ± 24% compared to UTMD treatment with NC (N=5-6 per group, p < 0.01). Expression of FOXO3a mRNA (miR-23a target) was 47 ± 16% higher following UTMD-mediated anti-miR-23a delivery compared to NC (N=3 per group, p < 0.05). The increase in CM surface area upon PE exposure was 22 ± 13% less with UTMD-mediated anti-miR-23a delivery compared to NC (N=3 per group, p < 0.05).

Conclusions:
To our knowledge, this is the first study of UTMD-mediated modulation of miR levels in cardiac tissue with an anti-miR. UTMD mediated delivery of anti-miR-23a to CMs caused knockdown of miR-23a levels, restored expression of downstream target mRNA levels, and suppression of CM hypertrophy. These results lay important groundwork for future in vivo studies leading to targeted clinical strategies to therapeutically modulate miRNA activity in the human heart.
Abstract 14795: Strain Imaging Corrected by RR-interval is a Superior Predictor of Outcome in Patients With Atrial Fibrillation
Authors: Dons Maria , Jensen Jan S , Olsen Flemming J , de Knegt Martina C , Fritz-Hansen Thomas , Biering-Sørensen Tor
Published: April 2024

Aims:
This study evaluates the prognostic value of strain in patients with atrial fibrillation (AF) and suggests a novel approach on how to take into account the varying heart cycle lengths in AF.

Methods:
Echocardiograms from 204 patients with AF during examination were analyzed. Peak global longitudinal strain (GLS) was averaged from the apical 4-chamber, 2-chamber and long axis view. To adjust for the varying heart cycle lengths, we indexed the strain measurements with the square root of the RR-interval, (GLS/√(RR)). The combined end-point included incident heart failure, stroke, myocardial infarction and all-cause mortality.

Results:
During a median follow-up of 2.4 years, 82 patients (40%) reached the combined endpoint. Significant predictors at baseline included age (p<0.001) and diabetes mellitus (p=0.014).

Decreasing GLS/√(RR) was significantly associated with the combined endpoint, and the risk of reaching the endpoint increased significantly per 1%/sec1/2 decrease in strain (HR 1.13, 95% CI 1.07-1.20, p<0.001), especially in the patients with the lowest values of GLS/√(RR)(Figure 1). GLS/√(RR) remained an independent predictor even after adjustment for various risk factors, LVEF and E/e’ (HR 1.10, 95% CI: 1.02-1.19, p=0.017). In contrast, GLS did not remain a significant predictor after adjusting for the same variables (p=0.07), neither did LVEF (p=0.11). Besides being associated with an adverse outcome, decreasing values of GLS/√(RR) was associated with lower LVEF, larger LV mass and larger LV dimension (p<0.001 for all).

Conclusion:
Decreasing GLS/√(RR) was significantly associated with increased risk of reaching the combined endpoint and remained an independent predictor after multivariable adjustment. Indexing the strain values with the square root of the RR-interval (GLS/√(RR)) can counteract the variable cycle length in AF patients and GLS/√(RR) offers a more convincing risk-stratification assessment in AF patients compared to GLS.
Abstract 14884: Visit-to-Visit Variability in Body Weight and Risk of Cardiovascular Outcomes: Insights From the Treating to New Targets Trial
Authors: Bangalore Sripal , Fayyad Rana , DeMicco David , Waters David D
Published: April 2024

Introduction:
Previous studies have demonstrated a relationship between body weight and cardiovascular events. However, whether visit-to-visit variability in body weight affects cardiovascular outcomes is not known.

Hypothesis:
Variability in body weight is associated with increase in the risk of cardiovascular events

Methods:
We evaluated patients enrolled in the TNT trial with at least one post baseline measurement of body weight. Visit-to-visit variability in body weight was evaluated using various measures of variability: Standard deviation (SD), average successive variability (ASV), coefficient of variation (CV), and variation independent of mean (VIM) with the first 2 measures used as the primary measures. Primary outcome was any coronary events (composite of coronary heart disease death, non-fatal MI, resuscitated cardiac arrest, revascularization or angina) with the secondary outcomes of any cardiovascular event (composite of any coronary event, cerebrovascular event, peripheral vascular disease or heart failure), death, MI or stroke.

Results:
Among the 9921 patients included in the analysis,in the adjusted model, each 1-SD (1.62 kg) increase in body weight variability (as measured by ASV) increased the risk of any coronary event by 6% (HR=1.06; 95% CI 1.04-1.08; P <0.0001), any cardiovascular event by 7% (HR=1.07; 95% CI 1.05-1.08; P <0.0001), death by 8% (HR=1.08; 95% CI 1.05-1.11; P <0.0001), myocardial infarction by 6% (HR=1.06; 95% CI 1.03-1.10; P = 0.0002) and stroke by 7% (HR=1.07; 95% CI 1.03-1.12; P=0.001) independent of treatment effect and mean body weight. The results were consistent with other variability measures.

Conclusions:
In subjects with coronary artery disease, visit-to-visit variability in body weight is a strong and independent predictor of cardiovascular events suggesting perhaps that the swings in body weight are harmful.
Abstract 14940: Determinants of Rehospitalization After Cardiac Surgery in Prolonged ICU Length of Stay Survivors
Authors: Manji Rizwan A , Arora Rakesh C , Singal Rohit K , Hiebert Brett , Menkis Alan H
Published: April 2024

Introduction:
Determining predictors of rehospitalization of prolonged ICU length of stay (prICULOS) post cardiac surgery (CS) survivors would help inform processes of care in regards to optimization of patients pre-discharge and having additional community supports for this vulnerable population.

Methods:
Data of CS patients with prICULOS (ICULOS of ≥5 days post CS) from Jan. 1, 2000 to Dec. 31, 2011 was extracted from linked administrative and clinical databases to describe rehospitalization parameters. Regression analysis was used to determine predictors of time to first rehospitalization.

Results:
Of 9209 CS patients discharged home and alive at 30 days (d), 596 (6.5%) experienced prICULOS. The 30d rehospitalization rate was 109/596 (18.3%) for prICULOS patients vs. 996/8613 (11.6%) for non-prICULOS patients (p<0.01). For the prICULOS cohort, the cumulative rehospitalization rate at 1 year was 44.3%, and the median hospital LOS for readmissions was 7d. The most common reason for rehospitalization was heart failure. Out of 54 prICULOS patients that died within 1 year of discharge post CS, 32 (59%) died in hospital during rehospitalization. Predictors of time to first rehospitalization are in the table. Median time to first hospitalization of patients with the risk factors in the table was 54d compared to a median time of 70d in patients without these factors. Any rehospitalization within 1 year was independently associated with increased risk of death [OR 2.91, p<0.01].

Conclusions:
Survivors of prICULOS after CS have a high rate of rehospitalisation and nearly a 3 fold increase risk of death if needing rehospitalisation within 1 year of initial discharge. We have identified 6 independent risk factors associated with rehospitalisation that can be used to optimize patients pre-discharge as well as be used to identify patients that may need closer follow-up in the community to prevent rehospitalization.
Abstract 14984: Cervical Branch Re-entry in Patients With Type A Acute Aortic Dissection is Related to a Patent False Lumen in the Aortic Arch and Enlargement After Ascending Aortic Replacement
Authors: Yasuda Shota , Imoto Kiyotaka , Uchida Keiji , Isoda Susumu , Karube Norihisa , Kasama Keiichiro , Minami Tomoyuki , Miyamoto Takuma , Uranaka Yasuko , Goda Motohiko , Suzuki Shinichi , Masuda Munetaka
Published: April 2024

Background:
In some patients with Stanford type A acute aortic dissection (A-AAD) who undergo resection of the entry site by ascending aortic replacement, the aortic arch false lumen is not thrombosed postoperatively, leading to late enlargement. This is attributed to blood leaking into the false lumen at the distal anastomosis. In addition, we hypothesized that a re-entry tear occurring in the distal part of cervical branches can act as an entry after operation.

Patients and Methods:
We retrospectively studied 85 patients (49 men; mean age 62 ± 12 years). Computed tomographic (CT) scans were evaluated before and after ascending aortic replacement, performed from 2006 through 2014. Patients with intramural hematoma were excluded. The presence of a patent false lumen in one or more cervical branches on preoperative CT was defined as cervical branch re-entry.

Results:
On preoperative CT, 41 patients (48%) had cervical branch re-entry. The prevalence of hypertension (61% vs. 84%, P = 0.027) and sex (proportion of men, 71% vs. 45%, P = 0.02) differed significantly between patients who had cervical branch re-entry and those who did not. A total of 47 patients (55%) had a patent false lumen in the aortic arch, caused by reverse blood flow from the cervical branch re-entry site in 20 patients, leakage at the distal anastomosis in 13 patients, and both factors in 14 patients. The false lumen remained patent after operation in 34 (83%) of the 41 patients with cervical branch re-entry, as compared with 13 (30%) of the 44 patients without re-entry. The proportion of patients with a patent false lumen after operation was significantly higher in the presence of cervical branch re-entry before operation (P<0.01). The late follow-up rate was 85.9% (73 of 85 patients), with a mean follow-up of 46 ± 26 months. Significant risk factors for a late increase in aortic arch diameter to ≥10 mm were younger age (P = 0.02) and cervical branch re-entry (P = 0.02).

Conclusions:
The preoperative presence of a cervical branch re-entry in patients with A-AAD is related to a patent false lumen in the aortic arch early after ascending aortic replacement and is a risk factor for late aortic arch enlargement. Total aortic arch replacement should be considered in patients who have A-AAD with cervical branch re-entry.
Abstract 15231: Oncostatin M Receptor Deletion Decreases FGF23 After Transaortic Constriction in Mice and Receptor Activation Correlates With Increased FGF23 in Patients With Aortic Stenosis
Authors: Richter Manfred H , Lautze Hans-Jürgen , Hou Yunlong , Maringanti Ranganath , Skwara Adalbert , Schönburg Markus , Cetinkaya Ayse , Beiras-Fernandez Andres , Werner Isabella , Nolte Hendrik , Hölper Soraya , Braun Thomas , Kubin Thomas , Kostin Sawa , Walther Thomas
Published: April 2024

Objectives:
Fibroblast growth factor 23 (FGF23) is becoming increasingly recognized as biomarker for heart failure (HF). We have previously shown that oncostatin M (OSM) is the strongest cytokine which induces FGF23 secretion from cultured cardiomyocytes. Although the bone is regarded as the source of FGF23, we have also demonstrated that cardiomyocytes of patients with end-stage HF strongly express FGF23. In this study we tested the hypothesis that the hypertrophied, non-failing heart is a source of circulating FGF23 via OSM receptor (Oβ) activation.

Methods:
Transaortic constriction (TAC) was performed in WT and Oβ knock-out mice (OβKO). Sham operated mice served as control. We have analysed myocardial biopsies and serum from patients with aortic stenosis (AS) with preserved ejection fraction. Patients with kidney disease were excluded from the study. Serum from healthy volunteers served as a control. Proteome and transcriptome profiling of serum and tissue samples in mice and AS patients were performed by mass spectrometry, multiplex assays, RT-PCR, ELISA, confocal microscopy (CM) and Western blots (WB).

Results:
Four weeks after TAC, WT mice animals showed significant increases in circulating FGF23 in comparison to sham-operated mice (583±117 (n=10) vs 218±36 pg/mL (n=10); p<0.05). Furthermore, CM, WB and RT-PCR analysis consistently revealed up-regulation of FGF23 expression and increased Oβ mRNA levels (100±10% (n=8) vs 284±26% (n=8); p<0.01) in cardiomyocytes. Conversely, TAC-OβKO showed reduction of circulating FGF23 to Sham levels (215±39 pg/mL (n=11); p<0.02) and significantly decreased myocardial FGF23 expression as compared to TAC in WT mice. Similarly, AS patients showed a 2.7-fold higher expression of Oβ in comparison to control tissue (269±77 (n=8) vs 100±28% (n=4); p<0.05). FGF23 serum levels were elevated 4-fold in comparison to serum from volunteers (85±47 (n=19) vs 23±2 (n=16) RU/mL; p<0.01).

Conclusions:
Our data demonstrate that Oβ activation is responsible for the cardiac release of FGF23 into the circulation in TAC animals. Activation of Oβ and increased levels of FGF23 in patients with AS indicates that FGF23 is a potential biomarker in AS patients with compensated hypertrophy before the onset of HF.