bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4088: Isolated Potentials and Pace-Mapping to Guide Ablation for Ventricular Tachycardia in Patients with Non-Ischemic Cardiomyopathy
Authors: Kuhne Michael , Sarrazin Jean-Francois , Wells Darryl , Chalfoun Nagib , Crawford Thomas , Boonyapisit Warangkna , Veerareddy Srikar , Billakanty Sreedhar , Wong Wai Shun , Ebinger Matthew , Good Eric , Chugh Aman , Jongnarangsin Krit , Pelosi Frank , Oral Hakan , Morady Fred , Bogun Frank M
Published: July 2021

Background
: Isolated potentials (IPs) during sinus rhythm are indicators of fixed scar in patients with prior infarcts. IPs in conjunction with pace-mapping (PM) have been helpful to guide ablation of post-infarction ventricular tachycardia (VT). The purpose of this study was to determine the value of IPs in conjunction with PM to guide VT ablation in patients with non-ischemic cardiomyopathy.

Methods
: 32 consecutive patients (23 male, age 56±13 years, ejection fraction 0.30±0.14) with VT and non-ischemic cardiomyopathy were analyzed. Thirty/32 patients had an implanted cardioverter defibrillator (ICD). Electroanatomic maps of the left (n=21) and right ventricle (n=13), the coronary sinus (n=3), and the epicardium (n=4) were obtained during baseline rhythm. PM was performed at sites with low voltage (<1.5mV). Radiofrequency energy was delivered at sites with concealed entrainment or matching pace-maps. Mean follow-up time was 10±9 months.

Results
: 173 VTs (cycle length 359±86 ms) were induced. Appropriate ablation sites with IPs during sinus rhythm were recorded in 19/32 patients (59%) (group A). In these patients, a total of 195 appropriate target sites were identified for 56/100 induced VTs (56%); 136/195 sites (70%) displayed IPs. In the remaining 13 patients, no target sites with IPs were identified (group B) despite combined endocardial and transcutaneous epicardial mapping in 3/13 patients. In these 13 patients, a total of 96 appropriate target sites were identified for 25/73 induced VTs (34%). Fifteen/19 patients (79%) in group A were non-inducible at the end of the procedure compared to 2/13 patients (15%) in group B. During a mean follow-up of 10±9 months, 15/19 patients (79%) in group A compared to 1/13 patients (8%) in group B remained arrhythmia free (p=0.0002).

Conclusion
: IPs in conjunction with PM are helpful in identifying critical isthmus areas for ablation of VT in patients with non-ischemic cardiomyopathy. Differences in the extent of fixed scar tissue may be the reason for differences in the prevalence of IPs, and this might explain better ablation results in some patients with non-ischemic cardiomyopathy.
Abstract 4090: Substrate Modification Using Electroanatomically-guided Linear Ablation During Sinus Rhythm To Treat Post-infarction Ventricular Tachycardia
Authors: Deneke Thomas , Lemke Bernd , Boesche Leif-Ilja , Calcum Bernd , Muegge Andreas , Lawo Thomas , Grewe Peter H
Published: July 2021

Catheter ablation of ventricular tachycardia (VT) in the setting of ischemic cardiomyopathy can be performed to modify the underlying substrate. We evaluated the efficacy of a linear VT ablation procedure based on sinus rhythm (SR) substrate maps to treat ischemic VT in consecutive patients.

Methods: In 110 consecutive patients with ischemic VT (56% not tolerated) catheter ablation was attempted. During SR left ventricular scar mapping was performed identifying scar tissue (bipolar voltages 1.5mV). Regionalization of VT-exit regions was performed based on pace-mapping within the scar border zone. Ablation was directed towards the identified exit region performing linear ablation along the scar border. ICD-holter interrogation was performed during follow-up.

Results: A mean of 2.7±1.6 different VTs were inducible per patient (total 286). In 97% (107) of all patients (74% of all inducible VTs ablated: 213/286) the clinical VT was successfully ablated. In 68 patients (62%) no sustained monomorphic VT (complete success) was inducible at the end of the ablation procedure whereas in 39 patients (35%) VTs (partial success) were still inducible. Over a median follow-up of 12 months (6 –39) 88 (80%) patients were free from any ventricular arrhythmia. 19 successfully ablated patients had recurrences in between 6 to 36 months post intervention but the number of episodes treated by the ICD was significantly reduced (16±4 within 3 months (3±2) (p=0.02). No difference in patients with tolerated compared to non-tolerated VTs were detected (recurrences in 7/48 (15%) tolerated and 15/62 (24%) non-tolerated; p=0.13). There was a significant difference in freedom from any VT in patients with complete (88%) versus partial success (72%) (p=0.04).

Conclusions: Substrate modification targeting only the scar-border zone including the VT exit site based on SR-maps is highly effective in suppressing the occurrence of a clinical VT in patients with remote myocardial infarction (97%). Based on the electro-anatomical findings complete freedom from any ventricular arrhythmia over a median of 1 year can be achieved in 80% of all patients. No difference in regard to freedom from any ventricular arrhythmia can be documented in patients with tolerated and non-tolerated VTs.
Abstract 4114: Identification of Gap Lesions Following Failed Atrial Fibrillation Ablation: Using Three-Dimensional Delayed Enhancement MRI to Guide Re-ablation Procedure
Authors: Badger Troy J , Oakes Robert S , Fish Eric N , Segerson Nathan M , Akoum Nazem W , Burgon Nathan S , Rao Swati N , Shabaan Akram , DiBella Edward V , MacLeod Rob S , Marrouche Nassir F
Published: July 2021

Objectives.
Pulmonary vein antrum (PVA) isolation is a common ablation strategy to treat patients with atrial fibrillation (AF). Incomplete lesion formation around the PVA is thought to contribute to recurrence of AF. We report a new multi-step approach to ensure complete PVA scarring by using 3D delayed enhancement MRI (DE-MRI) models of the LA to show regions needing ablation during repeat procedure.

Methods.
Five patients who suffered AF recurrence following PVAI elected to undergo a second procedure. All 5 patients received DE-MRI scans 3 months following each procedure. 3D segmentation of the LA was performed to evaluate for complete PVA scarring. Application of a color look-up table was used to illuminate scar tissue. Regions of healthy PVA myocardium was marked following the failed ablation and targeted during repeat procedure.

Results.
All patients showed incomplete PVA scarring after the first ablation. All patients had increased PVA scarring following the repeat procedure. 4 (80%) patients were free of AF (determined by 8 day Holter recordings, ECG and event monitoring) at 3-month follow-up. The figure

below shows lack of continuous scar (orange/white) around the left and right PVA following the failed procedure. Gap lesions of healthy myocardium (blue) were identified and targeted (yellow arrows) prior to repeat ablation. Following the successful repeat procedure, all four PVA had continuous scar lesions.

Conclusion.
3D DE-MRI models of the LA may identify gaps in RF lesions following failed PVA isolation. These 3D models may assist in procedure planning for the second ablation procedure by identifying the regions necessary for re-ablation.
Abstract 4117: A Comparison of Cardiac MRI Peri-Infarct Border Zone Quantification Strategies for the Prediction of Ventricular Tachycardia Inducibility
Authors: Rubenstein Jason C , Lee Daniel , Wu Edwin , Kadish Alan , Passman Rod S , Goldberger Jeffrey J
Published: July 2021

Peri-infarct border zone (BZ) as quantified by delayed-enhancement cardiac MRI (CMR) has been proposed as a risk stratification tool, and is associated with increased mortality, but has been measured by various methods in the literature. We assessed which BZ analysis best predicts inducible arrhythmia during electrophysiological study (EPS).

Methods: CMR was performed in 47 patients with CAD referred for EPS to assess for ventricular tachyarrhythmias (VT). CMR data was analyzed for BZ quantification by three methods. Method I used pixels 2–3 standard deviations over the mean of normal tissue, expressed as % of LV mass. Method II (Yan) used the same pixels but is expressed as % of infarct size. Method III (Schmidt) used a full-width, half-max method. EPS results were classified as negative (non-inducible) or positive (monomorphic VT). Patients with indeterminate EPS outcomes (VF or polymorphic VT, n=9) were not included in this analysis.

Results: There were 38 subjects-age 60.2 ± 10.8 yrs, 68% male. During EPS, 20 patients were non-inducible and 18 had induced monomorphic VT (MVT). EF was not significantly different between non-inducible patients and those with MVT (33.4 ± 11.9% vs. 28.1 ± 9.3, p=0.13). Infarct size was significantly different (15.0 ± 11.6% vs. 26.4 ± 12.0%, p = 0.005). BZ by method I was significantly different (1.4 ± 1.3% vs. 3.1 ± 1.5%, p = 0.001), but not by method II (15.2 ± 21.3% vs. 8.0 ± 4.8%, p = 0.17) or method III (4.1 ± 4.5g vs. 3.7 ± 3.7g, p = 0.756). Multivariate analysis demonstrated that BZ by method I was an independent predictor of EPS outcome after controlling for infarct size (OR 1.97 per % change, 95% CI 1.04 to 3.73, p = 0.04). Method I BZ remained an independent predictor when controlling for both infarct size and EF, (OR 2.12 per % change, 95% CI 1.06 to 34.22, p = 0.03). Correlation between techniques was variable (Method I vs. Method II R=0.77, p=0.001; Method I vs. Method III R=0.03, p=0.86; Method II vs. Method III R=0.15, p<0.32).

Conclusion: This study demonstrates significant variability between the published methods for measuring BZ. We also show that large BZ by Method I is a stronger predictor of inducible MVT during EPS than EF and infarct size. BZ may be yet another CMR marker of elevated risk of arrhythmia, but requires more rigorous definition.
Abstract 4121: Clomipramine Infusion During Tilt Test To Imply The Neurocardiogenic Origin Of Syncopes And Presyncopes Of Unknown Aetiology
Authors: Cinquetti Gael , Perrier Eric , Deroche Jacques , Manen Olivier , Lerecouvreux Michel , De Serre De Saint Roman Charlotte , Plotton Christian , Carlioz Roland
Published: July 2021

The aim of this study was to prospectively evaluate the diagnostic accuracy for neurocardiogenic syncopes (NCS) of two Head-Up Tilt table test (HUT) strategies in 991 patients with syncopes/presyncopes of unknown aetiology after negative clinical and non invasive investigations. HUT is a widely accepted tool in the evaluation of patients with evidence of VVS but questions remain about the sensitivity and the use of provocative agents.Clomipramine (CP), a serotonin re-uptake inhibitor, was recently proposed as a new drug challenge test for the diagnosis of neurocardiogenic syncope (NCS). Group A : the first 341 pts (207 male ; mean age = 49,9 ± 23 years) were passively tilted at 60° for 30 minutes (min), then for 15 min with 2 μg/min isoproterenol infusion rate. Group B : the following 650 pts (383 male ; mean age = 48,3 ± 21 years) were tilted at 60° for 20 min with 5 mg CP infused during the first 5 min of tilt. A positive HUT was defined as reproducting the patient’s syncope or presyncope, associated with an abrupt fall in blood pressure (systolic blood pressure <80 mmHg) and/or concomitant bradycardia (<50 beats/min). Positives responses were classified in 3 types according to the Brignole’s modification of the VASIS classification. There was no significant difference between group A/B in sex or age. Group A : Positive HUT* : 103 (Sensitivity : 30,2%) Group B : Positive HUT* : 382 (Sensitivity : 58,8 %) (*) type 1 : 36 vs 157 ; type 2A : 8 vs 13 ; Type 2B: 9 vs 57 (14,9%) ; Type 3 : 50 vs 155. No adverse effect was noticed. CP during HUT increase significantly the accuracy of the test for NCS diagnosis, especially for type 2B answers, and patients <30 yo. The duration of the test is notably shortened, and the tolerance is remarkable. If previously reported specificity (87 to 94%) was confirmed, CP-HUT might be the most valuable tool in the evaluation of pts with syncopes/presyncopes of unknown aetiology.
Abstract 4128: Evaluating Sex Differences in Population-Based Utilization of Implantable Cardioverter Defibrillators (ICDs): The Role of Cardiac Conditions and Non-Cardiac Comorbidities
Authors: MacFadden Derek R , Tu Jack V , Chong Alice , Austin Peter C , Lee Douglas S
Published: July 2021

BACKGROUND:
Although sex differences exist in the use of ICDs, reasons for the disparities are poorly understood. We determined if age, comorbid conditions, or ICD indication explained the sex differences.

METHODS:
We examined all patients in Ontario, Canada, with cardiac arrest (CA, 1998 –2007), myocardial infarction (MI, 2002–2007), or heart failure (HF, 2005–2007), using the Canadian Institute for Health Information Database. MI and HF cohorts excluded those with prior CA, and included patients post-MADIT-2 and SCD-HeFT trials. Patients were followed until ICD implant using Cox regression, with hazard ratio (HR) >1.0 indicating greater likelihood of ICD implant in men.

RESULTS:
Among 9246 patients eligible for ICD implantation after CA, 237 (2.6%) women and 725 (7.8%) men received ICDs. In 105,516 primary prevention MI patients, 172 (0.2%) women and 836 (0.8%) men received ICDs. Among 61,160 primary prevention HF patients, 221 (0.4%) women and 852 (1.4%) men received ICDs. The rate of ICD implant was significantly higher in men across indications adjusting for age, prior arrhythmia, and comorbidities (Figure

). Post-CA, the HR for secondary prevention ICD was 1.92 (95%CI, 1.66 –2.23). Men were more likely to undergo ICD implant than women for primary prevention, with HRs 3.00 (95%CI, 2.53–3.55) post-MI and 3.01 (95%CI, 2.59 –3.50) in HF patients. Although death after primary prevention ICD did not differ by sex, mortality risk was higher in men after CA (HR 1.42; 95%CI, 1.03–1.95).

CONCLUSIONS:
Differences in ICD use for all indications were not explained by age or comorbidities. Despite increased use, men had reduced post-implant survival after cardiac arrest.
Abstract 4174: Adenosine-Stress CT Myocardial Perfusion Imaging: Comparison with Stress Myocardial Perfusion MRI in Patients with Coronary Artery Disease
Authors: Ishida Masaki , Sakuma Hajime , Kato Shingo , Nagata Motonori , Ishida Nanaka , Nakamura Mashio , Nakajima Hiroshi , Ito Masaaki , Takeda Kan
Published: July 2021

Background:
CT coronary angiography with vasodilator stress might be of great value in detecting both myocardial ischemia and morphological stenoses of the coronary arteries. Stress myocardial perfusion MRI has been shown to provide accurate assessment of presence and extent of myocardial ischemia in patients with coronary artery disease(CAD). The aim of this study was to determine the value of stress myocardial perfusion CT for the detection of myocardial ischemia by using stress perfusion MRI as a reference method.

Methods:
The study protocol was approved by the institutional review board and all participants gave written informed consent. Cardiac CT was performed in 12 patients with suspected CAD by using a 64-detector MDCT scanner. Beta-blocker was orally administered prior to CT study. During continuous injection of adenosine, contrast enhanced CT images of the heart were acquired with retrospectively gated helical CT protocol. Adenosine stress myocardial perfusion MRI was performed within 2 weeks from CT perfusion study in all patients. Stress myocardial perfusion MDCT and MR images were qualitatively assessed by two observers using a 16-segment model.

Results:
All patients completed stress CT study protocol without significant side-effect. Averaged heart rate was 62+/−10 beats/min in the baseline state and 74+/−14 beats/min during adenosine stress. Perfusion abnormality during stress was observed in 83 (43.2%) of 192 segments by MDCT and in 89 (46.4%) of 192 segments by MRI. On a vessel based analysis, stress CT and stress MRI findings are concordant in 30 (83.3%) of 36 territories. The sensitivity, specificity and accuracy of adenosine stress myocardial perfusion CT for the predicting abnormal perfusion on stress perfusion MRI was 84.6%, 80% and 83.3%, respectively.

Conclusion:
Adenosine stress myocardial perfusion CT can be successfully performed in patients with CAD. Excellent agreement between stress myocardial perfusion CT and MRI observed in this study indicates the value of stress CT approach for comprehensive assessment of morphology and functional significance of CAD.
Abstract 4186: Magnetic Resonance Late Enhancement in Dilated Cardiomyopathy is Related with Complex Ventricular Arrhythmias
Authors: Almeida Ana G , Marques João S , Sargento Luis M , David Cláudio , Dias Nuno C , Lopes Mário G
Published: July 2021

Late enhancement (LE) by cardiovascular magnetic resonance (CMR) has been found in about two-thirds of patients with dilated cardiomyopathy (DCM). However, the functional significance of this finding is not well established. The aim of this study was to assess, in patients (pts) with DCM, the relationship of LE with complex ventricular arrhythmias.

Methods: 38 consecutive pts (44±8 years-old, 26 men) with DCM were included, after exclusion of ischemic heart disease by coronary angiography and secondary cardiomyopathies by clinical and laboratory investigation. Functional class and plasmatic NT-pro-BNP were assessed. All underwent CMR:

short-axis SSFP encompassing all LV; LV volumes and ejection fraction (EF) were obtained;

LE (segmented inversion-recovery fast gradient-echo sequence), 10 –15 mn after 0.2mmol/kg of Gd-DTPA acquired in 2, 3, 4-chambers and short-axis views; LE was classified in subendocardial or midwall and quantified using plannimetry of LE contours, 6SD from remote myocardium; a fibrosis index was obtained from LE mass/myocardial mass.

All underwent 24 H Holter monitoring, less than one month from CMR, and the number of ventricular arrhythmias (pairs, triplets or ventricular tachycardia) assessed.

Results: 22 pts were in NYHA class II and 17 in class III. Mean NT-pro-BNP was 512 ± 134 pg/ml, LV end-diastolic volume was 161±35mL/m2, mean EF was 31 ± 8%. LE was found in 26 patients (68%) and was always present in the midwall, involving a mean of 8 segments per patient (range 3–13); septal and anterior walls were the most frequently involved. There were repetitive ventricular arrhythmias in 29 pts. In comparison with pts without LE, pts with LE had higher NT-pro-BNP (917 vs 431 pg/ml, p=0.001), larger LV end-diastolic volumes (173 vs 143ml/m2, p=0.001) and lower EF (26% vs35%, p=0.001) and higher number of complex ventricular arrhythmias (p=0,0004). No relationship was found between the fibrosis index and the number of arrhythmias. Using multivariate analysis, the presence of LE was an independent predictor of ventricular arrhythmias (/p=0.002).

Conclusion: In patients with DCM, LE is significantly associated and an independent predictor of complex ventricular arrhythmias among LV volumes, ejection fraction and NT-pro-BNP,
Abstract 4188: Prognostic implications of Ischemic Myocardial Scar by Cardiac Magnetic Resonance in Patients with Normal Coronary Angiography and Dilated Cardiomyopathy
Authors: Valle Alfonso , Corbi Miguel , Nadal Mercedes , Estornell Jordi , Lucas Elena , Martinez Nieves , Restrepo Juan , Pirola Alesandro , Perez Leandro , Ridocci-Soriano Francisco
Published: July 2021

Background
. In patients (pts) with chronic heart failure, late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) is capable to distinguish left ventricular systolic dysfunction (LVSD) related or not to coronary artery disease (CAD). Moreover about 10% of pts with dilated cardiomyopathy (DCM) are actually «unrecognized » ischemic cardiomyopathy (ICM), possibly because of coronary recanalization after silent infarction. However, the prognostic implications of « unrecognized » ICM are not known.

Methods.
Three hundred consecutive pts with heart failure and LVSD underwent LGE-CMR and were followed prospectively during 833 days (12–2724). The primary endpoint was the composite of cardiac death or heart failure hospitalization. Pts were classified into 4 groups :

DCM without LGE (N 149) ;

DCM with midwall fibrosis (n 35) ;

ICM : ischemic scar and CAD (n 81) ;

« unrecognized » ICM : ischemic scar without CAD (n 30).

Results.
111 pts (38%) experienced events during follow-up.. There were non significant differences in event rate in patients with « unrecognized » ICM and ICM (53% and 63% respectively). By contrast the event rate in ICM groups were significantly higher than in pts with DCM (29% in group 1 and 31% in group 2 ; p = 0.000001) (Figure

). By multivariate analysis LGE was the strongest predictor of cardiac events (HR 1,7 CI 95% 1.07–2.88).

Conclusions
. In our series, pts with « unrecognized » ICM detected by CMR had a high risk of cardiac events during follow up similar to those pts with ICM. These findings had potentially important implications for routine use of CMR as a diagnostic and prognostic tool in patients with heart failure and systolic dysfunction.
Abstract 4201: A New Echo Index, Left Atrial Volume Index Over Late Diastolic Mitral Annulus Velocity Can Predict Elevated Left Ventricular Filling Pressures And Clinical Outcomes
Authors: Park Hun-Jun , Park Mahn-Won , Shim Byung-Joo , Lee Mi-Jung , Park Jae-Hong , Yoon Sung-Kyu , Baek Joo-Yeoul , Shin Woo-Seung , Koh Yoon-Seok , Shin Dong-Il , Jung Hae-Ok , Baek Sang-Hong , Ihm Sang-Hyun , Kim Pum-Joon , Seung Ki-Bae , Choi Kyu-Bo
Published: July 2021

Background: Another non-invasive method for prediction of elevated left ventricular filling pressure (LVFP) have attracted attention in clinical practice. Objectives: This study was to verify the clinical usefulness of left atrial volume index over late diastolic mitral annulus velocity (LAVi/A′) for the predictors of advanced (pseudonormal to restrictive physiology) diastolic dysfunction in the presence of elevated LVFP and clinical outcomes using right heart catheterization (RHC).

Methods: 163 patients (95 men, mean age 61±13 years) with dyspnea underwent comprehensive Doppler echocardiography, RHC and B-type natriuretic peptide (BNP) measurement. Using ROC curve, we compared the areas under the curves (AUC) of LAVi/A′, transmitral early diastolic/annular velocity ratio (E/E′), and BNP level for the prediction of advanced diastolic dysfunction. During a median follow-up of 13.3 months, the incidence of the composite outcomes of cardiac death or re-hospitalization for heart failure was compared based on the optimal cut-off value of LAVi/A′.

Results: The AUC of LAVi/A′ was comparable to that of BNP (0.91 vs. 0.90; p=0.78) and E/E′ (0.91 vs. 0.93; p=0.78) for prediction of advanced diastolic dysfunction. 68/163 (41.7%) patients had LAVi/A′ ≥4.0 and they had significantly higher BNP level and longer time difference between atrial reversal flow of pulmonary vein and transmitral late diastolic flow (AR
dur
-A
dur
) compared with those of LAVi/A′ <4.0 (BNP: 1207±1212 vs. 176±365 pg/ml; AR
dur
-A
dur:
24.6±21.1 vs. −3.3±15.9 msec, p<0.001, respectively). The LAVi/A′ had a reasonable correlation with mean PCWP (r=0.64, r
2
=0.41, p=0.001), which was comparable to that of E/E′ (r=0.60, r
2
=0.36, p=0.002). On Cox proportional hazard analysis, EF<50%, age ≥65 years, and LAVi/A′ ≥4.0 were independent outcome predictors with odds ratios of 4.8 (95% CI: 2.0 to 11.7), 3.8 (95% CI: 1.8 to 7.8), and 3.9 (95% CI: 1.5 to 9.8), respectively (p<0.01 for all).

Conclusions: LAVi/A′ ≥4.0 is useful clinical predictors for advanced diastolic dysfunction in the presence of elevated LVFP and clinical outcomes.
Abstract 4303: Heme Oxygenase 1 Expression in Dendritic Cells Drives Cd4+ T Cell Activation in Transplantation Atherosclerosis
Authors: Noordeloos Annemarie M , Cheng C , van Deel E , Tempel D , Simoons M L , Lambrecht B , Duncker D J , Duckers H J
Published: July 2021

Although over-expression of heme oxygenase-1 (HO-1) attenuates transplantation arteriosclerosis, the mechanism by which HO-1 exerts its protective effect remains unclear. In order to investigate the effect of HO-1 expression specifically in the dendritic cell (DC) in the context of transplantation atherosclerosis, we studied the effect of HO1-deficient versus wildtype (WT) DCs on the T-cell priming response and outcome in a murine transplant arteriosclerosis model. At day 0 C57bl6 mice received either WT (N=7) or HO1-knockout DCs (N=7) pre-sensitized with Balb/c splenocytes lysate. At day 10 an allogenic aorta segment derived from Balb/c mice was transplanted into the carotid artery position of C57Bl6 mice. 14 days post transplantation, the grafts were harvested and analyzed by imumnohistology. Adoptive transfer of HO1-deficient DCs significantly increased neointimal hyperplasia as compared to WT DCs (116995 versus 38428 μm2 P<0.05). HO-1 deficient DCs also increased medial thickeness (15936 versus 12034 μm2 P<0.05), reduced intimal VSMCs content (46 versus 75% P<0.05) and resulted in more prominent medial cell infiltration (461 versus 232 μm2 P<0.05). In the transplanted aorta of the with HO-1 nullizygous DCs treated recipient group, an increase in CD4+ T-cell infiltration (9.5 versus 0.2% in WT P<0.05) and IgG deposition, concomitant to a decrease of CD8+ T cell infiltration (8.1 versus 14.3%, P<0.05) was observed. In line with these observations, in vitro analysis of HO-1 deficiency in DC function showed an increased priming potential for CD4+ T cells, thereby increasing the CD4+/CD8+ T cell ratio. Increased efficiency in CD4+ T cell priming by HO-1 deficient DCs was facilitated by a higher cell surface level of MHC II. Further studies indicated that HO-1 deficiency increased STAT1 phosphorylation, thereby enhancing CIITA gene expression that lead to increased MHC II levels on the DCs cell surface. HO-1 deficiency in dendritic cells increases vascular cell infiltration with a higher CD4+/CD8 T-cell ratio in vascular allografts resulting in an augmented form of transplantation arteriosclerosis. This effect is facilitated by a STAT1-CIITA-MHCII dependent intracellular pathway.
Abstract 4328: Integrated Network and Microarray Analysis to Identify New Biomarkers of Heart Failure after Myocardial Infarction
Authors: Devaux Yvan , Yvorra Céline , Vausort Mélanie , Jeanty Céline , Azuaje Francisco , Wagner Daniel
Published: July 2021

Purpose
: A significant proportion of acute myocardial infarction (MI) patients develop heart failure (HF). Early identification of patients at risk of developing HF after MI would be a major breakthrough. An approach combining the power of biological information networks and the precision of microarray analysis was undertaken to identify new biomarkers of HF.

Methods
: Since angiogenesis may be related to MI and HF, a protein-protein interaction (PPI) network was constructed by first extracting from the Entrez-Gene database a set of genes relevant to angiogenesis and MI. These genes were used as inputs to retrieve annotated interactions from the Human Protein Reference Database. Potential biomarkers were identified by network analysis. Gene expression profiles of blood cells taken at the time of MI in two groups of 16 patients (high ejection fraction (EF) at 1 month, EF≥45% and low EF at 1 month, EF≤40%) were obtained using oligonucleotide microarrays containing 25,000 genes and compared by Statistical Analysis of Microarrays (SAM). Prediction models based on machine learning were used to classify low and high EF patients.

Results
: SAM identified 525 genes differentially expressed between patients with high and low EF (fold-change ≥1.3). The PPI network included 556 nodes (proteins) and 686 edges (interactions). A network clustering algorithm identified 53 proteins highly specialized in growth and regulation processes. Out of these, 38 were found differentially expressed by SAM. Further filtering reported 3 genes as the optimal biomarker set: Vascular Endothelial Growth Factor B (VEGFB), Placental Growth Factor (PGF), both pro-angiogenic, and the anti-angiogenic protein Thrombospondin-1 (THBS1). Prediction models reported areas under the receiver operating characteristic curve (AUC) of 0.82 for this biomarker set.

Conclusion
: The classification performances achieved with the 3 biomarkers stresses the prognostic value of genes involved in angiogenesis. The network-based approach allowed us to identify powerful biomarkers, which could not be identified by applying standard gene expression data analysis only. Therefore, combined network and microarray analysis allows a systematic and less biased approach to biomarker discovery.
Abstract 4349: Usefulness of Echocardiographic Measures of Dyssynchrony in Patients with Borderline QRS Duration for Selection for Resynchronization Therapy
Authors: Oyenuga Olusegun , Hara Hideyuki , Tanaka Hidekazu , Kim Han-Na , Saba Samir , Gorcsan John
Published: July 2021

Although echo dyssynchrony has not replaced routine selection criteria for cardiac resynchronization therapy (CRT) in patients with wide QRS, our objective was to test the hypothesis that dyssynchrony may assist in selection of patients for CRT with borderline QRS duration. We studied 119 heart failure patients referred for CRT; all were Class III-IV with ejection fraction (EF) ≤35%: 79 had Wide-QRS ≥130ms (169 ±28ms), and 40 had Borderline-QRS 100 –130ms (116 ±7ms). Dyssynchrony was assessed using tissue Doppler (TDI) longitudinal velocities from apical views (≥65ms opposing wall delay) and speckle tracking radial strain (≥130 ms septal to post. wall delay). Pulsed Doppler assessed interventricular mechanical delay (IVMD) (≥40ms), and filling time/RR interval (FT/RR ≤40%). Patients were followed for 8±5 months. Response to CRT was defined as ≥15% increase in EF. Overall, 77% of the Wide-QRS group were EF responders in contrast to 65% of the Borderline-QRS group. TDI was 87% sensitive and 67% specific for predicting response in the Wide-QRS group, but only 46% specific in the Borderline-QRS group. Radial dyssynchrony was the best predictor of response in the Borderline-QRS group with 80% sensitivity and 92% specificity. Although IVMD and FT/RR had low sensitivities, they were 100% specific. EF response to CRT is less frequent in patients with Borderline-QRS than in those with Wide-QRS. Radial dyssynchrony appears to be the best predictor of EF response in Borderline-QRS patients; IVMD and FT/RR were highly specific. A combined echo assessment of dyssynchrony has potential to assist in selection of patients for CRT with borderline QRS.
Abstract 4364: Gender-Specific Regulation of Ncx in Human Heart Failure
Authors: Mash Constance E , Sweet Wendy E , Moravec Christine S
Published: July 2021

We and others have previously reported increased protein levels of the sarcolemmal sodium-calcium exchanger (NCX) in failing (F) vs non-failing (NF) human hearts. In the non-failing cardiomyocyte, NCX transports calcium out of the cell following contraction, in an amount roughly equal to that which enters the cell through L type calcium channels upon depolarization. In the face of decreased sarcoplasmic reticulum calcium ATPase (SERCA) function in the F human heart, up-regulation of NCX is thought to be a compensatory change, helping to prevent calcium overload. It has also been demonstrated that NCX may work in reverse mode in F heart cells, providing for increased calcium influx during the action potential plateau. Recent studies have suggested that over-expression of NCX has different functional consequences in male and female animal hearts during metabolic inhibition as well as ischemia/reperfusion injury, yet studies demonstrating up-regulation of NCX in F human hearts have largely pooled male and female hearts. We have measured NCX and SERCA in a population of male and female F and NF human hearts. Nine patients were studied per group. F hearts were explanted from cardiac transplant recipients with diagnosis of dilated cardiomyopathy and NF hearts from unmatched organ donors. Immunoblotting was used to quantify NCX and SERCA, normalized to actin. NCX was increased in both male and female F hearts as compared to NF hearts, but the increase was proportionately greater in the male population (Normalized values: Male F 3.30 vs NF 1.0; Female F 2.60 vs NF 1.0). Comparison of NF hearts from males and females, however, demonstrated that levels of NCX protein are consistently higher in female than male hearts (Female NF 2.18 vs Male 1.0). SERCA protein was decreased in both male and female F hearts to equal degrees as compared to both groups of NF hearts (Male F 0.65 vs NF 1.0; Female F 0.65 vs NF 1.0), with no difference in NF levels between males and females (female NF 1.1 vs Male 1.0). These data suggest that NCX is regulated differently in male and female F human hearts, which may play a role in the ability of the heart to preserve adequate calcium cycling during cardiac dysfunction.
Abstract 4365: A Recombinant A-Type Natriuretic Peptide Improves Cardiac Function Probably through Suppression of Intracellular ROS in Heart Failure
Authors: Susa Takehisa , Kobayashi Shigeki , Suetomi Takeshi , Xu Xiaojuan , Ono Makoto , Uchinoumi Hitoshi , Tanaka Takeo , Okamura Takayuki , Kawamura Syuji , Yamamoto Takeshi , Yano Masafumi , Matsuzaki Masunori
Published: July 2021

Background: We previously reported that reactive oxygen species (ROS) causes Ca2+ leak through the ryanodine receptor (RyR), leading to contractile dysfunction, and eventually heart failure (HF). Here, we clarified an antioxidant action of carperitide, an exogenous A-type natriuretic peptide (ANP) in patients with heart failure and in isolated canine failing cardiomyocytes as well.

Methods and Results: In control subjects (N: n=10) and patients with HF (n=20), blood sampling was simultaneously performed from coronary sinus (CS) and artery (A) to measure 8-hydroxy-2-deoxyguanosine (8-OHdG: ng/ml), a marker of oxidative DNA damage. The serum 8-OHdG level was higher in (CS) than in (A) only in HF (HF: 0.57 ±0.33 in CS; 0.31 ± 0.16 in A; N: 0.17±0.07 in CS; 0.16 ± 0.06 in A), indicating that ROS is produced in failing cardiac tissue. The difference in the serum 8-OHdG between (CS) and (A) was increased as NYHA class elevates (r=0.65, p<0.01). The urine 8-OHdG/creatinine level (ng/mg) also correlated with the NYHA class (r= 0.62, p<0.001), LVEF (r=0.43, p <0.001) and PCWP (r=0.54, p<0.001). As protocol 1, we examined whether ANP (0.25 micrograms/kg/min, i.v.) decreases urine 8-OHdG/creatinine during the treatment of HF (n=8, for 3 days), as compared with that of nitroglycerin (NTG; n=8, for 3 days). Either treatment with ANP or NTG similarly improved hemodynamic parameters, such as cardiac index, PCWP, systemic vascular resistance, and pulmonary arterial resistance. In ANP-treated group, however, urine 8-OHdG/creatinine significantly decreased as compared with in NTG-treated group (ANP: 9.8±3.5; NTG:14.5±4.2, p<0.05). As Protocol 2, we produced canine tachycardia-induced HF model by 4-week’s rapid RV pacing (250 bpm) (EF 27±5%, n=6). Then, using the failing cardiomyocytes, we investigated the direct effect of ANP on intracellular ROS (by 2,7,-dichlorofluorescin diacetate fluorescence). In the failing cardiomyocytes, intracellular ROS markedly increased, as compared with normal cardiomyocyte. Interestingly, ANP (1×10 – 8 mol/L) significantly suppressed ROS production seen in failing cardiomyocyte.

Conclusion: Exogenous ANP has a potent antioxidant action that may contribute to an improvement of hemodynamics in patients with HF.
Abstract 4370: Intramyocardial Administration of Erythropoietin Promotes Cell Proliferation, Induces Early Angiogenesis and Attenuates Cardiac Remodeling
Authors: Gäbel Ralf , Klopsch Christian , Furlani Dario , Li Wenzhong , Yerebakan Can , Wang Weiwei , Pittermann Erik , Dryndao Andreas , lenz solvig , Li Ren-Ke , Ma Nan , Steinhoff Gustav
Published: July 2021

Erythropoietin (EPO) protects the ischemic myocardium from heart failure development after myocardial infarction (MI). However, little is known about its intracardiac cell proliferation and early angiogenesis. We hypothesize that EPO may contribute to cell proliferation, angiogenesis and eventually induce a beneficial remodeling process. Following permanent LAD ligation in rats, EPO (3000 U/kg; n=99) or saline (n=95) was delivered along the infarction border. In control animals without MI (n=55) saline was injected intramyocardially. After 6 weeks follow-up, left ventricle was catheterized and analyzed for cardiac performance. The level of eNOS mRNA was dramatically increased 9.3 fold in non-infarcted area of EPO treated rats at 24 h detected by real time PCR and confirmed by immunohistology. We found a 45 % enhancement in Ki-67+ cell numbers near the infarction at 48 h after EPO treatment (n=6, P<0.001). Hematopoietic cell lineages including c-Kit+ and CD34+ cells were augmented in the peripheral blood after 48h. Capillary density was enhanced by 17% as early as 1 week (n=6, P<0.001). Myocyte apoptosis was reduced by 41% and 37% at border zone after 1 and 6 weeks (n=6, P<0.05). Cardiac troponin T level, a highly sensitive and specific indicator of myocardial cell death, was significantly reduced in peripheral blood 2 weeks after EPO injection (n=5, P<0.05). Cardiomyocyte size and interstitial fibrosis at 6 weeks were decrease by 13% and 23% (n=6, P=0.015, P<0.001). Intramyocardial EPO delivery enhanced left ventricular performance at baseline and Dobutamine stress conditions compared with MI rats (cardiac output: 65% and 71% increase at baseline and stress; end-diastolic pressure: 51% and 53% reduction respectively, n=11–14, P<0.05). To conclude, intramyocardial EPO delivery induces early cell poliferation, angiogenesis and attenuates post MI remodeling.
Abstract 4380: Transition from IV Epoprostenol to Oral/Inhaled Targeted Pulmonary Arterial Hypertension Therapy in Pediatric Idiopathic Pulmonary Arterial Hypertension
Authors: Melnick LE , Barst RJ , Rowan CA , Kerstein Diane , Brady D , Rosenzweig EB
Published: July 2021

Introduction
: Prior to the availability of oral/inhaled (inh) PAH drugs, i.e. 2001–2007, IV epoprostenol (EPO) was the only approved drug for pts un-responsive to calcium channel blockade (CCB). We report our experience transitioning selected pediatric IPAH pts from EPO (initiated prior to 2001) to oral/inh PAH drugs.

Methods
: We retrospectively reviewed all pediatric IPAH pts treated at Columbia Univ (1991–2008) who transitioned off EPO to oral/inh drugs. Pre-specified criteria for transition included: functional class (FC) I/II, mPAP<35mmHg, normal CO and age > 6 yrs at transition. Hemodynamic and exercise data were obtained at baseline (prior to EPO initiation), at peak EPO dose, and at least 2 mos after EPO discontinuation (d/c) on stable oral/inh drug doses. Data: m ± SD.

Results
: 13 IPAH pts (6 F) transitioned off EPO between 4/03–11/07 (max dose 100 ± 42ng/kg/min) to oral/inh drugs at 11.6 ± 3.6 yrs of age. Mean duration on EPO: 6.6 ± 3.4yrs (range 1.2–12yrs); f/u post EPO d/c: 10.4 ± 11.6 mos (range 2–42.8 mos). Treatment with EPO improved hemodynamics vs. baseline (p<0.05) with no significant changes in hemodynamics or exercise capacity off EPO. In addition, further improvement was reported in FC off EPO (p<0.002; n=13).

Conclusions
: In selected IPAH children who began EPO prior to the availability of oral/inh PAH drugs, transition to oral/inh PAH therapy appears safe with efficacy maintained. Whether early initiation of EPO improves long-term outcome vs. deferral of EPO until oral/inh therapy fails remains unknown; further studies with longer-term follow-up are warranted.
Abstract 4427: Electrocardiographic Left Ventricular Hypertrophy Predicts Long Term Fatal Outcomes in Elderly Hypertensives Despite Diuretic-Based Antihypertensive Treatment: 14-Year Follow-Up of the Systolic Hypertension in the Elderly Program (SHEP)
Authors: Vagaonescu Tudor , Wilson Alan C , Kostis John B
Published: July 2021

Background:
To assess if diuretic-based antihypertensive treatment improves long term fatal (cardiovascular) outcomes in the elderly with isolated systolic hypertension (ISH) and ECG documented left ventricular hypertrophy (LVH).

Methods:
Retrospective analysis of the SHEP database of 4,736 patients age ≥60 years and ISH and subsequent vital status ascertainment by matching to the National Death Index.

Results:
348 subjects (7.35%) of SHEP participants had ECG documented LVH at baseline. Subjects with LVH had at baseline: higher SBP and pulse pressure (p<0.0001), carotid bruits (13% vs. 7%, p<0.0001) and previous history of myocardial infarction (8% vs. 4%, p=.0008) when compared with participants without LVH. There were no significant differences with regard to age, sex, heart rate, body mass index, smoking and alcohol use, previous history of stroke, diabetes, angina, and assignment to treatment or placebo group. Over 14.3 years (mean) of follow up subjects with baseline LVH experienced significantly more all cause mortality (51% vs. 40%, p<0.0001) and cardiovascular death (24% vs. 19%, p=0.002) than participants without baseline LVH. In the group of participants with LVH at baseline active treatment of hypertension did not decrease all cause mortality (51% vs. 50%, NS) or cardiovascular death (26% vs. 24%, NS). There was no statistically significant interaction between LVH and the assignment to treatment (antihypertensive medication vs. placebo). In a multivariable analysis, the adjusted Cox hazard ratio of developing any fatal outcome in the LVH group was 1.181 (95% CI 1.005–1.387, p=0.043) after adjusting for age, sex, race, history of myocardial infarction, diabetes, alcohol smoking status, education, blood pressure, and assignment to treatment or to placebo group.

Conclusion:
In the elderly with ISH the presence of LVH documented by ECG increased the risk for long term fatal outcomes despite treatment with diuretic-based antihypertensive therapy. Although active treatment lowered risk in the SHEP study, treated participants with LVH had a higher risk for fatal outcomes than treated subjects without LVH.
Abstract 4472: Validation of an Angiography based Algorithm to Calculate the Coronary Flow Reserve
Authors: Rittger Harald , Kuper Asher , Sinha Anil , Schmidt Martin , Rieber Johannes , Brachmann Johannes
Published: July 2021

Coronary Flow Reserve (CFR) is defined as the ratio between flow in a coronary vessel at maximum hyperemia and at rest. It is considered as a marker for the integrity of the coronary mircrocirculation. The measurement is typically performed using dedicated Doppler guidewires and pharmacologic stimulation (CFRdoppler). This measurement is costly, time-consuming and potentially harmful since the Doppler wire has to be advanced into the coronary artery. Today a new angiography based algorithm is available using the first pass kinetic of the injected contrast dye to calculate the CFR. The aim of the present study was, to compare this new algorithm with the conventionally Doppler wire technique. CFR measurements were performed during 27 coronary interventions (10 female, mean age 64 ± 11 years). CFR
doppler
(Flowire, Volcano corp.) was calculated as the ratio of average peak velocity (APV) during hyperemia (140μg/kg·min
−1
) and at rest. For calculation of angiographic CFR
angio
, two angiograms were analised, one at base line flow and one at hyperemia state. CFR was calculated by the ratio between the hyperemia representing numbers of the logarithmic Time Density Curve (TDC) linear slope, multiplied with the coronary cross-sections, and the respective baseline representing numbers. An excellent correlation was found between the CFR
doppler
and the CFR
angio
values: CFR
angio
= 1× CFR
doppler
(r=0.87; p<0.0001). The average absolute difference between both indexes was 0.36±0.31. Angiographic measurement of CFR is a feasible and valid method in daily routine with an excellent correlation to doppler-wire derived measurements and moreover less potential of adverse interventional health effects.
Abstract 4508: Endothelial Dysfunction is Associated with Coronary Lesion Complexity in Patients with Coronary Artery Disease
Authors: Matsuzawa Yasushi , Sugiyama Seigo , Sumida Hitoshi , Sugamura Koichi , Nozaki Toshimitsu , Ohba Keisuke , Hirota Shinichi , Konishi Masaaki , Matsubara Junichi , Kojima Sunao , Nagayoshi Yasuhiro , Ogawa Hisao
Published: July 2021

Endothelial dysfunction is an important step in the atherosclerosis progression, and associates with future cardiovascular events. Reactive hyperemia peripheral arterial tonometry (RH-PAT) is a noninvasive, automatic, and objective tool to evaluate endothelial dysfunction. Angiographic complex coronary lesions are involved in plaque vulnerability. We investigated whether finger values of RH-PAT could correlate with angiographic coronary plaque complexity in patients with coronary artery disease (CAD). RH-PAT was measured using Endo-PAT2000 in 171 patients who were referred to Kumamoto University Hospital for cardiac catheterization. We defined the two group as below, Control group; coronary artery stenosis > 25% (n = 36, age 63 ± 11, male 25 %), and CAD group; coronary artery stenosis > 25 % (n = 135, age 68 ± 11, male 74 %). Coronary lesions (single-vessel; n = 29, multi-vessel disease; n = 106) were classified as of simple appearance (n = 43) or complex appearance (n = 92) by coronary angiography. Values of RH-PAT were significantly lower in patients with CAD than Control (1.65 [1.50 – 1.86] versus 1.92 [1.80 – 2.28], P < 0.01), and were significantly lower in CAD patients with complex coronary appearance than patients with simple coronary appearance (1.55 [1.45 – 1.76] versus 1.81 [1.66 – 1.95], P < 0.01). All patients underwent selective coronary angiography, and the extent of coronary stenosis was assessed using the scoring system. RH-PAT was significantly correlated with coronary plaque Extent Score (Rs = −0.33, P < 0.01). Single logistic regression analysis demonstrated that high-density lipoprotein cholesterol, triglycerides, and RH-PAT value significantly associated with the presence of complex coronary lesions, and multivariable analysis including cardiovascular risk factors identified that lower RH-PAT value was the only factor associated with the complex coronary lesions (odds ratio 1.45, 95% confidence interval 1.14 – 1.84; P < 0.01). Endothelial dysfunction was significantly associated with angiographic complex appearance of coronary plaques in patients with CAD. CAD patients with lower RH-PAT values might be vulnerable patients with vulnerable plaques and vulnerable endothelium.