bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17180: Longitudinal Dissociation in the His Bundle: Persistent Bundle Branch Block Can be Corrected by Permanent His Bundle Pacing
Authors: Vijayaraman Pugazhendhi , Ellenbogen Kenneth A , Dandamudi Gopi
Published: July 2021

Introduction:
Focal disease in the main body of the His bundle (HB) is the cause for majority of the bundle branch block (BBB) patterns on EKG. Temporary distal HB pacing (HBP) has previously been shown to correct BBB in high number of patients. Anecdotal reports have confirmed abolition of BBB by permanent HBP.

Hypothesis:
The aim of our study is to report the incidence of correction of BBB during permanent HBP in patients undergoing pacemaker (PM) implantation.

Methods:
Permanent HBP was attempted in 185 patients referred for PM implantation. Pts with QRS duration (d) ≥110 ms and BBB were included in the study. Pts with normal QRS or CHB were excluded. HBP was performed using the Medtronic SelectSecure 3830 pacing lead. Baseline QRSd, paced QRSd, correction of BBB and HB pacing threshold were recorded.

Results:
Fifty patients met the inclusion-exclusion criteria. Mean age 73±12 yrs; men 65%, HTN 81%, DM 30%, CAD 38%, AF 42%, SSS 39%, AV disease 61%, RBBB 31, LBBB 14, IVCD 5). Permanent HBP was successful in correcting BBB in 42 (84%) patients. Underlying BBB was corrected by HBP in 29 of 31 (94%) patients with RBBB; 11 of 14 (79%) patients with LBBB; 1 of 5 (20%) patients with IVCD. Baseline QRSd improved from 141±15 ms to 124±17 ms. HBP threshold at implant was 1.5±1.3 V @ 0.5 ms.

Conclusions:
Permanent HBP corrected underlying BBB in the vast majority of patients with right or left BBB (40 of 45, 89%) compared to only 1 of 5 (20%) patients with IVCD. This confirms that focal disease in the main HB is the cause for BBB in the patients referred for PM implantation.
Abstract 17186: In Vivo Platelet Activation in Impaired Glucose Tolerance and During Progression of Type 2 Diabetes: a Cross-sectional and Longitudinal Study
Authors: Ciaffardini Flavia , Davì Giovanni , Di Fulvio Patrizia , Formoso Gloria , Liani Rossella , Pagliaccia Francesca , Patrono Carlo , Petrucci Giovanna , Pitocco Dario , Rocca Bianca , Santilli Francesca , Simeone Paola , Tanese Luigi , Tripaldi Romina , Vazzana Natale , Zaccardi Francesco
Published: July 2021

Introduction:
Impaired glucose tolerance (IGT) reflects the progression from normoglycemia to type 2 diabetes mellitus (DM). IGT and DM are associated with high cardiovascular disease (CVD) morbidity and mortality.

Hypothesis:
Enhanced platelet activation has been previously reported in DM, but whether this pertains to IGT is unknown.

Methods:
We investigated in vivo platelet activation, as reflected by the urinary excretion of 11-dehydro-TXB2 (TXM), in IGT and DM patients with a diagnosis documented either <12 months (new-DM) or ≥12 months (established-DM) from study entry. Patients were studied repeatedly up to 46 months to assess changes in platelet activation over time. Some patients were given standard 500 kcal meals at 8am, 1 and 6pm and TXM was measured repeatedly during a 12-hr period.

Results:
We enrolled 49 IGT patients (19M, age 56±9 yrs), 59 new-DM (36M, 61±10 yrs) and 61 established-DM (34M, 62±7 yrs, DM duration 9.7±6.1 yrs) patients diagnosed according to the ADA criteria, not on antiplatelet drugs. Median TXM values at study entry were comparably enhanced in the 3 groups (1,189 [897-1,503], 1,277 [897-1,870], and 1,217 [885-1,494] pg/mg creatinine in IGT, new- and established-DM, respectively; p=0.39). Urinary TXM excretion showed limited intra-subject variability over time, as shown in the Figure. There was no convincing evidence of a circadian variation in TXM excretion. Two-hour, post-meal glucose variations (8-10am or 1-3pm) did not affect subsequent TXM values.

Conclusions:
We conclude that the potential benefits and risks of antiplatelet therapy should be considered in IGT management, because persistent platelet activation might contribute to CVD progression and its thrombotic complications. Given the stability of high TXM excretion in DM, this non-invasive biomarker of platelet activation should be tested as a predictor of vascular events during long-term follow-up.
Abstract 17189: Superior Vena Cava as the Substrate of Various Forms of Atrial Tachycarrhythmias: Consideration into the Mechanism and Tachycardia Circuit
Authors: Yamabe Hiroshige , Kanazawa Hisanori , Hoshiyama Tadashi , Ito Miwa , Ogawa Hisao
Published: July 2021

Background:
The superior vena cava (SVC) is known to possess the myocardial sleeves extending from the right atrium which has been shown to be a substrate for various atrial tachyarrhythmias. However, the precise mechanisms and electrophysiologic feature of these atrial tachyarrhythmias, originating from the SVC has not been elucidated well.

Objective:
The purpose of this study was to define the mechanisms and electrophysiologic characteristics of atrial tachyarrhythmias originating from the SVC.

Methods:
In 21 patients with atrail tachycarrhythmias originating from the SVC, the mechanism and tachycardia circuit were examined by the contact or non-contact mapping system (EnSite NavX or 3000).

Results:
There were 5 reentrant atrial tachycardia (AT), 4 focal ATs and 12 atrial fibrillation (AF). Three reentrant ATs showed a macro-reentrant activation around the SVC sleeve with critical slow conduction zone (SCZ) in the SVC and the remaining 2 showed a localized reentry within the SVC. Four focal AT showed a focal discharge source in the SVC. In 8 of 9 ATs, SCZ or focal discharge source was observed at the area extending from the anterior to lateral portions of the SVC. All 12 AF were initiated by the repetitive discharge from SVC and was maintained by the meandering reentrant activation within the SVC involving the junction between the SVC and right atrium during AF. All 9 ATs were terminated by the radiofrequency energy delivery to the SCZ (n=4) and the focal discharge source (n=3) or isolation of SVC (n=2). All 12 AF were terminated by the circular application of radiofrequency energy delivery around the junction between SVC and right atrium, resulting in the SVC isolation in 9 patients.

Conclusions:
SVC provides the focal discharge source and the substrate of SCZ of AT. These critical area for maintaining AT mostly located at the antero-lateral portions of the SVC. Focal discharge source and substrate for meandering reentry within the SVC also maintained the SVC origin AF. These unique electrophysiologic characteristics of SVC provide the substrate of various forms of atrial tachycarrhythmias.
Abstract 17213: Serum Alkaline Phosphatase Elevation is an Independent Predicting Factor of Worsening Renal Function in the Patients with Acute Heart Failure
Authors: Yamazoe Masahiro , Mizuno Atsushi , Nishi Yutaro , Niwa Koichiro , Isobe Mitsuaki
Published: July 2021

Background:
Worsening renal function (WRF) has been associated with poor outcome in the patients with acute heart failure (AHF). Recently, venous congestion had been paid attention to the important predictor of WRF in AHF. Abnormal serum alkaline phosphatase (ALP) was reported as a biological marker of liver congestion and of the extent of right sided filling pressure in AHF. In this study, we evaluated the relationship between ALP and development of WRF in AHF.

Method:
We enrolled consecutive patients hospitalized due to AHF in cardiovascular center of St Luke’s International Hospital, Tokyo, Japan from January, 2004 to December, 2013. We excluded the patients either on dialysis, estimated glomerular filtration rate (eGFR) under 15 ml/min/m2, or primary liver disease. We defined WRF as elevation of serum creatinine of 0.3 mg/dl or above raised from admission to discharge. We classified patients into tertiles by baseline measurements of ALP. We performed multivariate analysis to make the prediction model of WRF.

Result:
Total 1245 patients (age 76.4±12.9 years old, male 54.8%) were enrolled. During hospitalization, 166 (13.3%) patients developed WRF. Patients were classified into tertiles (<77, 77 to 203, >203 IU/L). Compared with the lowest ALP tertile, middle and the highest ALP tertile groups developed WRF more frequently (8.4% vs 15.5% vs 16.8%, P=0.003). In multivariate logistic regression, after adjustment of age, gender, and other risk factors, we found eGFR (Odds ratio (OR) 0.978, 95%Confidence Interval (CI) 0.967 to 0.987, P<0.001), diabetes mellitus (OR 1.83, CI 1.19 to 2.80, P=0.005), norepinephrine use (OR 1.65, CI 1.04 to 2.61, P=0.03), albumin (OR 0.507, CI 0.337 to 0.764, P=0.001), middle tertile ALP (OR 1.81, CI 1.07 to 3.06, P=0.02), and highest tertile ALP (OR 2.08, CI 1.24 to 3.48, P=0.005) compared with lowest tertile were independent variable to predict WRF.

Conclusion:
Our study showed that elevated serum ALP is an independent predicting factor for WRF in the patients with AHF.
Abstract 17230: Respiratory Sinus Arrhythmia Quantified from Standard ECG for Risk Stratification of Post-Infarction Patients
Authors: Sinnecker Daniel , Barthel Petra , Müller Alexander , Laugwitz Karl-Ludwig , Schmidt Georg
Published: July 2021

Objectives:
Respiratory sinus arrhythmia (RSA) reflects modulation of the sinoatrial node discharge frequency by the autonomic nervous system. Impaired autonomic function is associated with adverse outcome in cardiac patients. We developed a method for calculating RSA from standard ECG recordings and investigated its association with mortality in survivors of acute myocardial infarction.

Methods:
Consecutive patients (n=941, mean age 61 years, 19% female) presenting with acute myocardial infarction and sinus rhythm were enrolled between May 2000 and March 2005 and followed up until August 2010. The main study outcome was 5-year all-cause mortality. Patients underwent 30-minute ECG recordings. Auxiliary respiratory muscle activity derived from high pass-filtered ECG signal was used to define respiratory phase. The influence of expiration on RR intervals (RRI) was assessed by bivariate phase-rectified signal averaging (PRSA), and RSA
PRSA
was quantified by Haar wavelet analysis. RSA
PRSA
≤0 was defined as abnormal.

Results:
During the follow-up, 72 patients died. Five-year mortality rates in patients with normal and abnormal RSA
PRSA
were 4% and 14%, respectively. Under univariable analysis, RSA
PRSA
was a significant predictor of death (p<0.001), as were GRACE score (p<0.001), LVEF (p<0.001), and the presence of diabetes mellitus (p<0.001). Under multivariable analysis, RSA
PRSA
, GRACE score, LVEF, and diabetes mellitus were independently and significantly associated with outcome.

Conclusions:
Respiratory sinus arrhythmia, quantified by bivariate PRSA from standard ECG recordings, is an independent predictor of mortality risk in post-infarction patients.
Abstract 17250: Serum vs. Imaging Biomarkers of Myocardial Injury in Duchenne Muscular Dystrophy: Findings from the E-SCAR DMD Trial
Authors: Raman Subha V , Hor Kan N , Mazur Wojciech , Halnon Nancy , Tran Tam , Smart Suzanne , McCarthy Beth , Kissel John T , Taylor Michael D , Jefferies John L , Rafael-Fortney Jill , Roble Sharon , Cripe Linda H
Published: July 2021

Introduction:
Cardiomyopathy has become a leading cause of death in Duchenne muscular dystrophy (DMD). We previously showed that early mineralocorticoid receptor antagonist therapy reduces myocardial damage in a preclinical model of DMD. The Eplerenone for Subclinical Cardiomyopathy in DMD (E-SCAR DMD, NCT01521546) is a multicenter randomized placebo-controlled clinical trial evaluating eplerenone in boys with preserved left ventricular ejection fraction (LVEF) and evident myocardial injury by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR).

Hypothesis:
To better define biomarkers of early disease, we hypothesized that LGE has greater sensitivity vs. serum biomarkers for myocardial injury in DMD cardiomyopathy.

Methods:
Boys with DMD age ≥ 7 years were enrolled across 3 centers. LGE-CMR images were acquired using comparable techniques across 3T scanners, and core laboratory LGE quantification was performed blinded to laboratory findings as a percentage of LV mass using software based on the full-width half-maximum technique. Troponin-I, creatine kinase (CK) and CK isoenzymes were measured from blood samples obtained at the time of CMR examination using standardized clinical assays.

Results:
42 boys age 16 ± 7 years had preserved LVEF (57 ± 6%), and LGE-positive regions averaged 5.0 ± 2.6% of LV myocardium. While 100% had evident myocardial injury by LGE, 43% had measurable CK-MB and only 18% had detectable troponin-I in serum (Figure). %LGE was higher (5.4 ± 2.7 vs. 3.3 ± 1.8%, p<0.05) and LVEF was lower (55.4 ± 4.9 vs. 59.0 ± 7.1%, p < 0.01) in boys with detectable vs. those with undetectable troponin-I, whereas detectable CK-MB did not predict higher %LGE or lower LVEF.

Conclusion:
DMD patients with abnormal myocardium by LGE-CMR may have no detectable abnormalities by serum biomarkers, underscoring the importance of myocardial injury imaging in identifying patients with subclinical cardiomyopathy who may benefit from early treatment.
Abstract 17262: Outcomes following High Risk Surgery provided as an Alternative to Transplant in patients with End-stage Heart Disease
Authors: Kawajiri Hiroyuki , Garrard Lisa , Manlhiot Cedric , Ross Heather , Delgado Diego , Billia Filio , McDonald Michael , Rao Vivek
Published: July 2021

Background:
Heart transplant (Tx) and ventricular assist device (VAD) have become established treatments for end stage heart failure; however, both treatments still have unsolved problems. Patients referred for Tx or VAD are often found to have cardiac lesions amenable to surgical intervention. We examined the results of conventional surgery in patients with severe left ventricular dysfunction to explore the possibility of high risk surgery as an alternative option.

Methods:
We reviewed our institutional database and identified all surgical patients referred to our senior author with severe LV dysfunction (EF<20%). We then selected patients who were initially referred for consideration of Tx or VAD, but were instead offered conventional surgery. All patients underwent evaluation for Tx candidacy and thus were prospectively stratified into Tx eligible (Tx-E) or Tx non-eligible (Tx-NE) groups. We compared outcomes stratified by Tx eligibility as well as by type of surgery.

Results:
A total of 133 patients were enrolled. 68 patients were Tx-E, and 65 were Tx-NE. Tx-E patients were younger than Tx-NE (57±8 vs 70±8 year-old, p<0.01). Isolated CABG was performed in 77 patients, while 56 had other procedures. In-hospital mortality was 8.8% in Tx-E, and 15.4% in Tx-NE (p=0.29). Kaplan-Meier analysis demonstrated that survival in Tx-E was comparable to ISHLT Tx data, while survival in Tx-NE was comparable to INTERMACS DT data (Figure1). When stratified by type of surgery, in-hospital mortality was lower for isolated CABG (6.5% vs 19.6%, p=0.03). Isolated CABG seemed to have comparable survival to ISHLT Tx and INTERMACS DT by Kaplan-Meier analysis (Figure2).

Conclusion:
The mortality and morbidity in patients undergoing alternative surgeries appears to be similar to the contemporary results of Tx and VAD destination therapy. Particularly if the pathology of heart failure is graftable coronary artery disease, isolated CABG may be a good option for highly selected patients.
Abstract 17350: Multimarker Risk Stratification in Patients with Acute Myocardial Infarction
Authors: O’Donoghue Michelle L , Morrow David A , Desai Nihar , Sherwood Matthew , Murphy Sabina A , Cannon Christopher P , Gerszten Robert E , Sabatine Marc S
Published: July 2021

Background:
Circulating biomarkers have been evaluated largely individually for risk stratification in the setting of acute myocardial infarction (MI). The optimal multimarker strategy remains undefined.

Methods:
A total of 11 established and emerging biomarkers representing different pathobiological axes were studied. Specifically, MR-proADM, MR-proANP, copeptin, hsCRP, galectin-3, GDF-15, MPO, NT-proBNP, ST-2, PAPP-A and troponin T (TnT) were measured at presentation in 1258 patients from CLARITY-TIMI 28, a randomized trial of clopidogrel in ST-elevation MI (STEMI). Patients were followed for 30 days. Biomarker analyses were adjusted for age, sex, comorbidities, heart rate, blood pressure, creatinine clearance, Killip class, lytic type and timing, anterior MI and treatment arm. Forward stepwise selection was used to assess a multimarker strategy.

Results:
When examined individually (Figure, left), 7 biomarkers were each associated with an increased risk of CV death or heart failure through 30 days independent of standard clinical factors. In a multimarker model, 3 biomarkers emerged as independent and complementary predictors of CV death or HF: TnT, ST2, and MPO (Figure, right). A multimarker risk score significantly improved the C-statistic for predicting CV death or HF as compared with the TIMI STEMI Risk Score alone (AUC 0.75 to 0.82, P=0.001) as well as the NRI and IDI (P<0.01 for each).

Conclusions:
In patients with STEMI, a multimarker strategy that combines biomarkers across pathobiological axes of cardiomyocyte necrosis, hemodynamic stress and inflammation provides incremental prognostic information for risk stratification.
Abstract 17412: Vital Exhaustion and Incident Cardiovascular Disease: a Meta-Analysis
Authors: Thankachen Jincy , Bavishi Chirag , Cohen Randy , Rozanski Alan
Published: July 2021

Background:
A number of psychosocial conditions are associated with cardiovascular disease (CVD) events. One such condition is vital exhaustion (VE), defined as a combination of fatigue, increased irritability and feelings of demoralization. To date, a number of studies have examined the association between VE, fatigue (as a stand-alone entity) and subsequent cardiovascular events with varying results. In order to evaluate the potency of VE/fatigue as a CVD risk factor, we conducted a meta-analysis of existing studies concerning these factors in the literature.

Methods:
A systematic search of PubMed, EMBASE and PsychINFO (1972-May, 2014) was performed to identify all prospective studies involving subjects without baseline CVD, investigating the relationship between VE/fatigue and incident CVD. Unadjusted and adjusted effect estimates were extracted from individual studies. Pooled effect estimates were calculated with DerSimonian and Laird random effects models.

Results:
Eleven prospective studies with a total of 60, 610 participants and a mean follow-up period of 6.5 years were included in the analysis. A significant association was observed between VE/fatigue and incident CVD, using both unadjusted estimates [Pooled Relative Risk: 1.69 (CI: 1.31-2.18), p<0.001] and adjusted estimates from individual studies [Pooled RR: 1.36 (CI: 1.14-1.63), p=0.001]. Subgroup analysis by years of follow-up and type of VE/fatigue questionnaire yielded similar increased risk of incident CVD.

Conclusions:
VE/fatigue is a significant risk factor for incident CVD in healthy subjects, comparable in potency to some of the other common psychosocial risk factors for cardiac disease.
Abstract 17420: First Clinical Experience of Novel MRI Artifact Suppression Sequence in ICD Patients Undergoing Scar Delineation for Ventricular Tachycardia (VT) Ablation
Authors: Abdulghani Mohammed S , Asoglu Ramazan , Shin T. , Gullpalli R. , Huang Rui , Remo Benjamin , Klein Tommas , Hussien Ayman , Saliaris Anastasios , See Vincent , Synowski Stephen , Shorofsky Stephen , Jeudy Jean , Dickfeld Timm
Published: July 2021

Background:
Recent studies have suggested that CMR imaging can be safely performed in selected patients with implanted ICDs. However, metal artifacts significantly impact the evaluation of myocardial fibrosis when using standard late gadolinium enhanced (LGE) protocols.

Methods:
10 continuous patients scheduled for VT ablation underwent LGE CMR imaging (1.5T Siemens Avanto) for scar delineation using either the standard clinical late gadolinium enhancement (LGE) sequences (n=5) or a novel MR pulse sequence that used an inversion preparation pulse with a wide inversion bandwidth of 2.4kHz (n=5).

Results:
Standard LGE MR sequences produced a large central signal void with surrounding hyperintensity due to voxel dephasing. The new wide inversion bandwidth sequence reduced the artifact in the right ventricle from 21±7% to 1.2±1.3% (p<.001). Similarly, the new MRI sequence reduced the artifact in the LV from 44±9% to 4.5±5.7% (p<.001).

LV artifact location changed from 100% (inferior), 100% (septal), 100% (lateral) and 100% (anterior) to 0%, 0%, 0% and 60%, respectively. Similarly, the LV artifact present was present in the basal, mid and apical segment in 100%, 100%, and 100% in the old sequence but was reduced to 0%, 60%, and 20% in the new sequence (Fig.1).

While the artifact of the standard sequence prevented the reliable predictions of the voltage-defined scar during VT ablation, no significant low voltage area outside the imaged LGE areas were found in the patients imaged with the new MRI sequence.

Conclusions:
Widening the inversion bandwidth achieves a dramatic reduction in ICD metal artifact during LGE CMR imaging and allows a near completely evaluation of the whole myocardium. This allowed the reliable prediction of low voltage areas during VT ablation despite presence of ICD.
Abstract 17438: Misclassification of the Cause of Dyspnea by Resting Right Heart Catheterization: the Impact of Invasive Cardiopulmonary Exercise Testing
Authors: Santos Mário , Waxman Aaron B , Tracy Julie , Khalid Fariha , Opotowsky Alexander R , Systrom David M
Published: July 2021

Introduction:
Supine resting right heart catheterization (srRHC) is the standard method to differentiate pulmonary arterial hypertension (PAH) and heart failure with preserved ejection fraction (HFpEF), but most such patients complain of symptoms during exercise. We hypothesized that the upright invasive exercise phenotype of patients with unexplained exertional intolerance provides a distinct and additive perspective compared with supine resting RHC in the diagnosis of PAH and HFpEF.

Methods:
We reviewed results of consecutive patients with unexplained effort intolerance who underwent same day sequential srRHC and invasive cardiopulmonary exercise testing (iCPET) between March 2011 and October 2013. At rest, patients were classified with PAH if mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg and pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg; as HFpEF if PAWP > 15 mmHg; and as normal if none of the above hemodynamic criteria were met. At peak exercise, patients were categorized as exercise-induced PAH (eiPAH), exercise HFpEF (eHFpEF), normal (eNormal), or peripheral limitation according to the criteria displayed in the table.

Results:
Of 255 patients, 212 (83%) had normal srRHC. Of these, 46 (22%) had an abnormal iCPET result: eiPAH (n=24), eHFpEF (n=22). A resting mPAP > 18 mmHg discriminated eiPAH reasonably well (ROC AUC: 0.75; 95%CI: 0.67-0.83). Of those with abnormal srRHC, iCPET reclassified diagnosis for 16/43 (37%). Of the 30 patients who had HFpEF by srRHC, 12 (40%) had a normal cardiac hemodynamic profile during upright maximum exercise. 4 (31%) of the 13 patients with PAH at rest had no suggestion of intrinsic pulmonary vascular disease during exercise (3 eHFpEF and 1 non-cardiac limitation) with iCPET.

Conclusions:
In patients with exertional intolerance, iCPET reveals hemodynamic abnormalities which are overlooked with resting RHC and reclassifies a significant subset of apparent PAH and HFpEF patients by srRHC.
Abstract 17453: Clinical Features of Peripartum Spontaneous Coronary Artery Dissection
Authors: Tweet Marysia S , Hayes Sharonne N , Gulati Rajiv , Rose Carl H , Best Patricia J
Published: July 2021

Background:
Spontaneous coronary artery dissection (SCAD) is the principal cause of peripartum myocardial infarction (MI). Clinical features remain incompletely understood.

Methods:
Medical records of all women enrolled in a SCAD registry at the Mayo Clinic were reviewed to identify those who were either pregnant or ≤12 weeks postpartum at time of initial event. Diagnosis of SCAD was confirmed with coronary angiography in all cases. Obstetrical outcomes and incidence of recurrent SCAD events were assessed.

Results:
In total, 38 of 363 women enrolled in the registry met criteria for peripartum MI due to SCAD. Mean age at time of SCAD was 36±3 (range 27-42) years; 3 patients were pregnant at the time of initial event, and all pregnancies except 2 resulted in a live birth. Ten (26%) were diagnosed with multivessel SCAD (MV-SCAD). Most (60%) postpartum events occurred within 30 days of delivery. Antecedent co-morbidities included gestational hypertension/preeclampsia (9), fibromuscular dysplasia (7), gestational diabetes (4), and mixed connective tissue disease (1). Compared to US population birth data, women with peripartum SCAD were more likely to be ≤ 30 years at the time of first delivery (60% vs 42%) and more often multiparous (80% vs 59%). On long-term follow-up (median 3.7 years, IQR 1.1-7.1), 5 (13%) women experienced recurrent SCAD, with one episode occurring following a subsequent pregnancy. MV-SCAD was not associated with increased risk of recurrence (p=0.44).

Conclusion:
Women with peripartum SCAD are both older than the general obstetrical population at the time of first pregnancy and frequently multiparous at time of initial SCAD event. The highest frequency of SCAD was encountered during the first postpartum month, suggesting variations in hormonal and hemodynamic factors may contribute to SCAD events in susceptible women.
Abstract 17468: Left Ventricular Remodeling Index (LVRI) in patients after breast cancer therapy in the long-term follow-up
Authors: Heggemann Felix , Buggisch Hanna , Welzel Grit , Doesch Christina , Hansmann Jochen , Schoenberg Stefan O , Borggrefe Martin , Wenz Frederik , Papavassiliu Theano , Lohr Frank
Published: July 2021

Introduction:
Cardiotoxic side effects are of concern in long-term survivors of left-sided breast cancer therapy. 3-dimensional conventional radiotherapy (3DCRT) deposits high doses in defined regions of the heart. Intensity modulated radiotherapy (IMRT) reduces local high-dose exposition at the expense of exposing more heart tissue to lower doses. Cardio-MRI was performed in this study to assess MRI-morphologic and functional alterations after 3DCRT and IMRT/ additional chemotherapy, with IMRT only performed in patients that would have been exposed to unacceptably high heart doses with 3DCRT.

Methods:
49 patients with left-sided breast cancer (38 3DCRT and 11 IMRT; 20 patients with additional adjuvant chemotherapy (ACH) (13 3DCRT, 7 IMRT) were included prospectively. Baseline (pre-treatment) and 24 months post-treatment MRI was performed. With MRI, enddiastolic left ventricular mass (LVM), enddiastolic left ventricular volume (LVEDV) and stroke volume (SV) were assessed. LVRI was calculated with the formula LVM/LVEDV.

Results:
Mean dose for the whole heart was higher in IMRT than in 3DCRT patients (12.9±3.9 vs. 4.5 ±2.4 Gy). Larger regions received a higher radiation dose (>40Gy) in 3DCRT than in IMRT patients (3.3% vs. 1.3% of the whole heart). High local radiation dose > 50 Gy only occurred in the 3DCRT group (0.74% of the heart volume). After 24 months LVRI decreased significantly in patients with ACH (0.80 vs. 0.70, p=0.028). Non-significant decrease of LVRI was observed in the whole cohort (0.85 vs. 0.79), after IMRT (0.74 vs. 0.71), after 3DCRT (0.88 vs. 0.82) and without ACH (0.87 vs. 0.84). Decrease of LVRI in patients with ACH was caused by significant decrease of LVM (102.4 vs. 89.7 g, p=0.028) whereas LVEDV was stable (128.3 vs. 128.1g). In all groups, no significant decrease of SV could be assessed after 24 months.

Conclusions:
24 months after therapy, significant decrease of LVRI due to decreased LVM could be found only in patients with additional chemotherapy. Radiotherapy alone did not have a significant impact on LVRI, LVM and SV. Low doses to the whole heart with IMRT did not cause significant decreases in LVRI, LVM and SV.

LVM and LVRI are to be assessed in larger cohorts in patients with cancer therapy especially with additional chemotherapy.
Abstract 17489: Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Once-Daily ZS-9 for Treatment of Hyperkalemia: Achievement and Maintenance of K+ in Subgroup Analysis of Patients with Heart Failure not on RAAS Inhibitors
Authors: Singh Bhupinder , Rasmussen Henrik S , Lavin Philip T , Yang Alex , Packham David K
Published: July 2021

Introduction:
RAAS inhibitors (RAASi) have demonstrated improved outcomes for HF patients (pts) when given at high doses, but optimal treatment is limited by hyperkalemia (HK), eg, spironolactone withdrawal for K
+
>5.0 mEq/L (per package insert). Thus, HF pts do not benefit from these life-saving therapies due to HK. Current HK therapies (ie, SPS) have inconsistent and questionable efficacy and carry significant GI intolerability. ZS-9, a nonabsorbed cation exchanger that selectively traps K
+
in the gut, acutely restored and maintained K
+
in HK pts in a large Phase 3 study. To evaluate pts for whom HK was potentially RAASi-limiting, HF pts not on RAASi were evaluated.

Methods:
Pts (N=753) with K
+
5.0-6.5 mEq/L were randomized (1:1:1:1:1) to ZS-9 (1.25, 2.5, 5 or 10g) or placebo (PBO) orally 3x/day for 48hr (acute phase). Following this phase, pts with K
+
3.5-5.0 mEq/L (n=542) were randomized 1:1 to the same ZS-9 acute phase dose or PBO 1x/day on Days 3-15 (extended phase). Unpaired t-tests were used to compare serum K
+
in pts treated with ZS-9 vs PBO.

Results:
Of 753 pts, 83 (11%) had HF and were not on RAASi; 13 were in the 10g dose group. Mean baseline (BL) K
+
for these pts was 5.3 mEq/L. At 48hr (acute phase), K
+
declined significantly, compared with BL (-0.73 mEq/L; p<0.05). In the extended phase, pts who remained on ZS-9 (n=6) maintained K
+
(BL: 4.5 mEq/L, Day 15: 4.6 mEq/L; Figure). Of note, 86.4% of pts in the 10g dose group were normokalemic at 48hr, compared with only 47.8% of pts in the PBO group.

Conclusions:
In HF pts not on RAASi, ZS-9 was effective at restoring and maintaining normokalemia, suggesting that these patients were potential candidates for RAASi. The high percentage of pts on PBO who did not restore normokalemia is representative of real-life pts for whom HK may limit optimal RAASi. To support the potential for ZS-9 to enable optimal cardio-and renoprotection by RAASi, further studies that evaluate the ability to challenge HF pts with RAASi after HK resolution are warranted.
Abstract 17506: A Young Man with a Great Fall: Putting the Pieces Together
Authors: Tanna Monique S , Slater William
Published: July 2021

A 35 year-old-male with hypertension and schizoaffective disorder presented with a first episode of non-prodromal syncope and traumatic fall resulting in a mandibular fracture. Physical examination revealed orthostatic tachycardia, normal cardiovascular examination, and no abnormalities with carotid sinus massage. Electrocardiogram showed NSR at 66 bpm, a single PVC, QTc interval 493 ms, and abnormal ST-T wave contour in V2-V3. Laboratory evaluation revealed normal electrolytes, mildly elevated troponin (0.763), and no leukocytosis. Postural orthostatic tachycardia syndrome was considered unlikely given that syncope did not occur after prolonged standing, and that his use of trazodone and risperidone can both cause orthostatic tachycardia. Transthoracic echocardiography (TTE) revealed decreased systolic function (EF 45%), paradoxical septal motion, normal LV wall thickness, and no valvular disease. Cardiac MRI showed moderate biventricular systolic dysfunction, LVEF 43%, RVEF 33%, mild 4-chamber dilatation, and a small pericardial effusion. Mild T2 hyperintensity in the mid-ventricular septum and anteroseptum, and scattered foci of patchy delayed gadolinium enhancement within the mid-anteroseptal, anterior and anterolateral LV segments were consistent with acute myocarditis. The reported prevalence of myocarditis among patients with sudden death is highly variable and ranges from 2-42%. Various types of myocarditis are associated with arrhythmias, including lymphocytic myocarditis which was the likely diagnosis in our patient. Despite lack of guideline recommendations, we opted to protect our patient with a wearable cardioverter-defibrillator given case reports of successful use for recurrent malignant arrhythmias in myocarditis. Follow-up TTE two months later was normal with EF 60%. Although syncope in the younger population is often appropriately attributed to a neurally-mediated etiology, the current case highlights the need for clinicians to be attuned to the possibility of subclinical myocarditis causing malignant arrhythmias in this setting, in which case the patient may be at risk for recurrent arrhythmia and sudden death and may benefit from the use of a wearable cardioverter-defibrillator.
Abstract 17518: Good Attendance to Cardiac Rehabilitation is Associated with Achievement of Low C-Reactive Protein Levels in Patients after Acute Myocardial Infarction
Authors: Doi Takahito , Kumasaka Reon , Arakawa Tetsuo , Nakanishi Michio , Noguchi Teruo , Ohara Takahiro , Fukui Shigefumi , Nakao Kazuhiro , Yanase Masanobu , Takaki Hiroshi , Ishihara Masaharu , Yasuda Satoshi , Goto Yoichi
Published: July 2021

Backgrounds:
Cardiac rehabilitation with exercise training (CR/ET) has been reported to be associated with reduction in C-Reactive Protein (CRP). In patients with acute coronary syndrome receiving statin therapy, achievement of CRP levels below 2mg/L is known to be important for long-term event-free survival. However, the determinants of achieving low CRP after CR/ET are not fully understood.

Methods:
To address this issue, we studied 490 consecutive acute myocardial infarction (AMI) patients who participated in our CR/ET program and underwent measurements for serum CRP at the beginning and the end of the 3-month CR program. Patients with abnormally high CRP (>= 20mg/L at baseline, >=10mg/L at 3 months) or on hemodialysis were excluded. Patients were divided into 2 groups according to CRP levels at the end of the 3-month CR/ET: Low-CRP group (CRP<=2.0mg/L, n=414), and High-CRP group (CRP>2.0mg/dl, n=76).

Results:
At baseline, there were no significant differences between the two groups in age (Low-CRP group 64years vs High-CRP group 63years, NS), body mass index (BMI, 23 vs 23, NS), prevalences of diabetes, smoking habit and statin use, left ventricular ejection fraction (LVEF, 46 vs 44%, NS), or brain natriuretic peptide (BNP) levels (169 vs 164pg/ml, NS). Although the prevalence of dyslipidemia was significantly higher (76% vs 63%, p<0.05), baseline CRP levels (4.5mg/L vs 5.9mg/L, p<0.05) was significantly lower in Low-CRP group than High-CRP group. Notably, Low-CRP group had significantly greater number of attendance in CR/ET in 3 months than High-CRP group (18 vs 14times, p<0.01). Multivariate logistic regression analysis (incorporating age, sex, BMI, history of dyslipidemia, baseline LVEF, peak CK, number of attendance in 3-month CR/ET, BNP, CRP, and statin use) demonstrated that history of dyslipidemia, lower baseline CRP levels, and greater number of 3-month CR/ET attendance were independent determinants (all p<0.05) of achieving CRP levels below 2.0mg/L.

Conclusion:
Good attendance in CR/ET program is significantly associated with achievement of CRP levels below 2.0mg/L at 3 months, independent of baseline CRP levels, history of dyslipidemia, and statin use.
Abstract 17519: Exercise Capacity Increase, Obesity, and Statin Therapy Are the Key Factor for Decrease C-Reactive Protein through Exercise Training after Acute Myocardial Infarction
Authors: Doi Takahito , Kumasaka Reon , Arakawa Tetsuo , Nakanishi Michio , Noguchi Teruo , Ohara Takahiro , Fukui Shigefumi , Nakao Kazuhiro , Yanase Masanobu , Takaki Hiroshi , Ishihara Masaharu , Yasuda Satoshi , Goto Yoichi
Published: July 2021

Backgrounds:
Cardiac rehabilitation with exercise training (CR/ET) has been reported to be associated with reduction in C-reactive protein (CRP) levels in patients with coronary artery disease. However, determinants of reduction in CRP through CR/ET after acute myocardial infarction (AMI) are not fully understood.

Methods:
We studied 490 consecutive AMI patients (age 63±11 years, male 83%) who participated in our CR/ET program and underwent measurements for serum CRP and peak oxygen uptake (PVO2) by symptom-limited cardiopulmonary exercise test at the beginning and the end of the 3-month CR program. Patients with abnormally high CRP (>= 20mg/L at baseline, >=10mg/L at 3 months) or on hemodialysis were excluded.

Results:
After the 3-month CR/ET, body mass index (BMI, 23.3 to 23.1, P<0.001) and CRP (4.7mg/L to 1.1mg/L, P<0.001) significantly decreased, and normalized PVO2 increased (77.4% to 84.9% P<0.001). The magnitude of changes in CRP (ΔCRP) were greater in patients with statin therapy than in patients without statin therapy (-2.9 +/- 0.4mg/L vs -3.9,+/- 0.3mg/L p<0.05). There were significant positive correlation between ΔCRP and HDL-cholesterol (r=0.14), and inverse correlations between ΔCRP and BMI (r=-0.09) and changes in %PVO2 (%ΔPVO2, r=-0.16). Multiple linear regression analysis (incorporating age, sex, baseline ejection fraction, BMI, Brain natriuretic peptide, Hemoglobin A1c, HDL-cholesterol, LDL-cholesterol, statin use, and %ΔPVO2) demonstrated that higher BMI, greater increase in PVO2, higher HDL-cholesterol, and statin use were the independent determinants (all p<0.05) of greater decrease in CRP. Diabetes and smoking status were not the independent determinants of CRP decrease.

Conclusion:
A greater increase in exercise capacity, in combination with obesity and statin use, significantly associated with a greater reduction in CRP in patients after AMI participating in CR/ET.
Abstract 17530: Characterization of Cardiac-resident Leukocyte Populations in the Steady-state and During Aging
Authors: Ramos Gustavo C , van den Berg Anne , Weirather Johannes , Hofmann Ulrich , Frantz Stefan
Published: July 2021

Although it is well acknowledged that immunological phenomena participate in several cardiac diseases, it has been deeply neglected the fact that the heart is already populated by resident leukocytes before the onset of any sign of disease. In the present work we comprehensively characterized the cardiac-resident leukocyte populations and addressed for the first time in the literature how these cells take part in cardiac physiology and aging. We compared cardiac function, structure and gene expression of healthy naïve C57BL6/J (WT) mice 10 (young), 30 (mid-aged) and 60 (aged) wk old. Flow cytometrical analysis of perfused-digested murine hearts revealed a cardiac-resident leukocyte population comprised of approx. 103 cells/mg (M2-macrophages > B-cells > T-cells > granulocytes). The frequency of resident leukocytes found in cardiac muscle was 17.4 fold higher than in skeletal muscle, suggesting that they might be relevant for cardiac physiology. Importantly, cardiac-resident leukocyte composition shifted towards a pro-inflammatory profile during aging. Additionally, qPCR analysis indicated a significant up-regulation of pro-inflammatory genes such as TNF, IL-1β and IFN-γ in aged mice (e.g. TNF mRNA expression level: 2.1 .10-4 ± 2.0 10-5 in young vs 1.5 .10-3 ± 2.6 .10-4 in aged mice; P < 0.05). Similar results were found regarding to pro-fibrotic and pro-hypertrophic genes expression (e.g. Coll-III, TGF-β and βMyHC). Furthermore, aged WT mice presented increased serum levels of autoantibodies against myosin and higher frequencies of activated T helper cells (CD4+CD69+) in mediastinal lymph nodes as compared to young mice. Echocardiographic and hemodynamic studies revealed that in parallel with increased inflammation, 60 wk old naïve mice spontaneously develop severe cardiac dysfunction (e.g. ejection fraction: 34.6% ± 5.19%). Altogether, these data demonstrated that the heart comprises an important and yet underappreciated resident leukocyte population in the steady-state and that shifts in its composition occur in parallel with the cardiac deterioration observed in aged mice.
Abstract 17543: DMPK E Disrupts Sarcomere Structure by Inhibition of SRF Transcriptional Activity
Authors: Elzenaar Ies , Damanafshan Amin , van der Made Inge , Pinto Yigal M , van Oort Ralph J
Published: July 2021

Background:
Heart failure is associated with elongation of cardiomyocytes and loss of sarcomeres. Although the transcription factor myocyte enhancer factor-2 (MEF2) has an important role in this adverse remodeling, the mechanism underlying the structural changes of cardiomyocytes remains to be elucidated. In a screen for MEF2 target genes, we have recently identified myotonic dystrophy protein kinase (DMPK) as a potential mediator of adverse cardiomyocyte remodeling. However, it remains to be determined whether DMPK levels are increased in failing hearts and if DMPK is sufficient to induce structural remodeling of cardiomyocytes.

Methods and Results:
Since the DMPK gene is subject to extensive alternative splicing, we performed RT-PCR and QPCR analysis of known DMPK splice variants in hearts from mice subjected to transverse aortic constriction (TAC) or sham surgery. This demonstrated a 1.6 fold increase in the DMPK E isoform in failing mouse hearts compared to controls (P<0.05). To test the role of this specific splice isoform, we generated adenoviruses expressing DMPK E or a kinase dead mutant DMPK E. Overexpression of wildtype DMPK E, but not of the kinase dead mutant, in cardiomyocytes resulted in severe loss of sarcomeric structure. Moreover, QPCR analysis showed a decrease in mRNA levels for several sarcomeric genes after overexpression of DMPK E. Since these genes are known targets of the transcription factor serum response factor (SRF) and DMPK is known to phosphorylate SRF, we tested the effect of DMPK E on SRF activity. Luciferase experiments demonstrated that DMPK E is an inhibitor of SRF transcriptional activity. Finally, immunostaining revealed a translocation of SRF from the nucleus to the cytosol upon DMPK E overexpression.

Conclusion:
Our data indicate that the expression of DMPK E is increased in heart failure. Moreover, increased expression of this DMPK splice variant results in a decrease in sarcomeric gene expression by translocation and inhibition of SRF. Together, these results assign a novel function to DMPK in adverse cardiomyocyte remodeling during heart failure development.
Abstract 17577: Searching for the Optimal Regimen of Potent P2Y12 Inhibitor in East Asian Patients with Acute Coronary Syndrome: A Pharmacodynamic Study
Authors: Kim Jang-Young , Lee Ji Hyun , Lee Jun-Won , Youn Young Jin , Ahn Min-Soo , Ahn Sung Gyun , Yoo Byung-Su , Lee Seung-Hwan , Yoon Junghan
Published: July 2021

Introduction:
The efficacy of prasugrel and ticagrelor has not been well evaluated in East Asian. We sought to compare the pharmacodynamic efficacy of prasugrel and ticagrelor by using VerifyNow P2Y12 assay (Accumetrics, San Diego, CA, USA).

Methods:
From 2012 January to 2014 April, we selected 83 patients who were administered ticagrelor 90 mg twice daily (n = 24), prasugrel 10 mg daily (n = 39), or prasugrel 5 mg daily (n = 20) after percutaneous coronary intervention due to acute coronary syndrome in our institute. After 3-4 weeks, on-treatment platelet reactivity (OPR) was measured by VerifyNow assay. According to the previous studies, we used 2 different criteria for the therapeutic window of OPR (East Asian criteria: 275≥PRU>85; Western criteria: 208 ≥PRU>85). We compared the OPR and the proportion of the therapeutic window between 3 groups.

Results:
The OPR was the lowest in the ticagrelor group, followed by the prasugrel 10 mg and prasugrel 5 mg groups (49.1 ± 29.9 vs. 83.7 ± 57.1 vs. 168.5 ± 60.8, p < 0.001).When we used the East Asian criteria, the prasugrel 5 mg group had the highest proportion of patients in the therapeutic window of OPR followed by prasugrel 10mg and ticagrelor groups ( 90.0% vs. 46.2% vs. 12.5%, p < 0.001). When using Western criteria, the prasugrel 5mg group still showed the highest proportion of patients with therapeutic window followed by prasugrel 10mg and ticagrelor groups (60.0% vs. 43.6% vs. 12.5%, p<0.001).

Conclusion:
Short-term administration of prasugrel 5mg highly led the patients into the therapeutic window of OPR (in both of East Asian and Western criteria), compared with prasugrel 10mg and ticagrelor 180mg group. The prasugrel 5mg daily might be the optimal maintenance regimen for East Asian patients.
Abstract 17581: Evidence for Circulating Stem Cells Derived from the Human Heart and Their Therapeutic Potential
Authors: Yang Han-Mo , Kim Ju-Young , Cho Hyun-Jai , Lee Joo-Eun , Lim So-Jung , Jin Sooryeonhwa , Park Kyung-Woo , Lee Sahmin , Lee Hae-Young , Kang Hyun-Jae , Oh Byung-Hee , Park Young-Bae , Kim Hyo-Soo
Published: July 2021

Introduction and Hypothesis:
Many studies have shown resident cardiac stem cells in myocardium as well as epicardial progenitor cells in epicardium. However, the presence of stem cells in the endocardium has not been elucidated. In this study, we identified circulating multipotent stem cells from human peripheral blood. Furthermore, we investigated the origin and the therapeutic potential of these cells.

Methods and Results:
We identified a new population of cells from human peripheral blood mononuclear cells, which were quite different from previously reported stem cells. Newly identified cells expressed genes such as Oct3/4, KLF4, Nanog, and c-Myc. Moreover, FACS analysis precluded the possibility that these cells might be hematopoietic stem cells. To investigate the origin of these cells, we collected peripheral blood from patients undergoing bone marrow, liver, heart, or kidney transplantation. After culturing these cells, we could confirm that these stem cells were derived from the human heart by identifying the HLA types or the STR (short tandem repeat) profiles. In addition, we demonstrated that Nuclear Factor of Activated T-cells (NFAT)-positive and CD31-positive circulating cells in peripheral blood were derived from NFAT-positive cells in the endocardium. These cells had multipotency, indicating the ability of differentiation not only into mesodermal lineages, but also into ectodermal or endodermal lineages. When injected into the mouse heart
in vivo
, these stem cells were differentiated into multiple lineages, resulting in the improvement of the heart function. We established more than 200 cell lines from peripheral blood of patients with coronary artery diseases, cardiomyopathies, hematologic diseases, liver diseases, and kidney diseases.

Conclusions:
We demonstrated the existence of novel circulating multipotent stem cells in human peripheral blood, which express NFAT. Interestingly, these cells are derived from the tissue-resident stem cells of the endocardium of the human heart. Our findings suggest that these stem cells obtainable from peripheral blood could be a promising tool for heart regeneration.