bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4480: Triggering Mechanisms of Coronary Stent Thrombosis: D
ata from the Dutch Stent Thrombosis Registry
Authors: Zwart Bastiaan , van Werkum Jochem W , Heestermans Antonius A , Kelder Johannes C , Zomer A C , van ‘t Hof Arnoud W , Verheugt Freek W , ten Berg Jurriën M
Published: July 2021

Background The occurrence of stent thrombosis (ST) is only partially explained by known clinical, angiographic and procedural determinants and little is known about superimposing triggering mechanisms of ST. Given a degree of similarity in pathophysiology between ST and myocardial infarction we sought to examine the role of timing of onset, vigorous physical exertion, emotional stress and infection as potential triggers of ST.

Methods Patients (
n
=437) with
“definite”
ST were recruited consecutively in the setting of a large multicenter observational cohort study. Patients were interviewed with well-validated questionnaires to identify one of the following triggers:

timing of onset of chest pain for ST

performance of vigorous (≥ 6 MET) physical activity in the 2 hours preceding ST,

presence of emotional stress (experiencing a serious life event in the 14 days preceding the ST according to the Social Readjustment Rating Scale or feelings of anger in the 24 hours of ST) and

presence of a documented active infection at the time of ST.

Results A total of 363 patients with
“definite”
ST (83.1%) were able to supply adequate information. Overall, a significant trigger was identified in 83 patients (22.9%). Analysis of the different categories of ST revealed a higher prevalence of triggers with an increasing time-interval between index PCI and ST. A trigger was present in 8 (6.6%) patients with acute ST, in 40 (28.0%) patients with subacute ST, in 13 (28.3%) patients with late ST and in 22 (42.3%) patients with very late ST. Analysis of circadian variation showed a steep peak incidence of ST in the morning hours from 7–12 hours.

Conclusions Triggering mechanisms such as time of the day, physical exertion, emotional stress and infection may play an important role in a considerable number of patients presenting with ST. The prevalence of these triggers are particularly high in patients with late and very late ST.
Abstract 4489: Transesophageal Echocardiography Evaluation of Percutaneous Repair of Mitral Valve Using CARILLON
™
Device. Single-Center Procedural Results in Consecutive Patients
Authors: Jerzykowska Olga , Kalmucki Piotr , Woloszyn Maciej , Grotowski Tomasz , Link Rafal , Smuszkiewicz Piotr , Siminiak Tomasz
Published: July 2021

Background
: Despite recent advancements, Functional Mitral Regurgitation (FMR), secondary to dilated cardiomyopathy remains a common clinical problem. Conventional cardiac surgery therapies have high procedural risk and therefore new techniques for percutaneous repair of mitral valve are being developed.

Aim.
The purpose of the study was to verify the acute efficacy of percutaneous mitral valve repair in patients with FMR by transesophageal echocardiography (TEE)

Methods
: We analyzed consecutive cases of percutaneous mitral valve repair with CARILLON
™
Mitral Contour System
™
(Cardiac Dimensions® Inc.) performed in a single center. The technique is based on implantation into the coronary venous system, where the device applies tension to the mitral ring in order to improve coaptation of the leaflets. TEE was performed during the procedure in the cath lab. Measurements before and immediately after the device release at the end of the procedure are given.

Results
The procedure was attempted in 17 cases of secondary MR with no apparent organic changes on the leaflets. Successful implantation of the device was performed in 13 patients (12M and 1F, aged 48 – 67 yrs). The TEE parameters of the MR significantly changed after the procedure as compared to before the procedure, including vena contracta (0.43±0.13 vs 0.68±0.16cm, p=0.024), EROA (0.21±0.06 vs 0.27±0.08cm
2
, p=0.019) and MR jet area/LA area (37.31 ±11,51 vs 53.82±14,14%, p=0.001). In 4 patients the device was recaptured due to compromised circumflex artery (3pts) and/or lack of measurable improvement in TEE (2 pts). No procedural complications were observed.

Conclusion
The implantation of CARILLON
™
system is feasible and safe in patients with Functional MR. Initial observations on efficacy justify completion of large clinical trials aiming at establishing the role of the technique in clinical practice.
Abstract 4498: Role of Self-Expanding Drug-Eluting Axxess Stent in Bifurcation Lesions: Intravascular Ultrasound Findings of AXXESS, AXXENT and DIVERGE Trials
Authors: Koo Bon-Kwon , Hasegawa Takao , Miyazawa Akiyoshi , Chang Hyeonsoo , Ako Junya , Dens Josef , Verheye Stefan , Grube Eberhard , Honda Yasuhiro , Fitzgerald Peter J
Published: July 2021

Backgrounds
Bifurcation location remains one of the most challenging lesion subsets even in the era of drug-eluting stents. AXXESS stent is a self-expanding drug-eluting stent designed to be placed in the proximal part of the main vessel, at the level of the carina. This stent has flared configuration so as to properly expand into the bifurcation anatomy. This study was performed to assess the efficacy of the AXXESS stent on the treatment of left main and non-left main bifurcation lesions using intravascular ultrasound (IVUS).

Methods
Volumetric IVUS data from 3 multi-center trials using AXXESS stent in bifurcation lesions (AXXESS trial: non-left main bifurcation, N=37, AXXENT trial: left main bifurcation, N=21 and DIVERGE trial: non-left main bifurcation, N=56) were analyzed. All IVUS analyses were performed at an independent core laboratory. To adjust the difference in length of measured segments, the parameter of volume index was derived from each volume parameter using the formula of volume/measured length (mm
3
/mm). Percent neointimal volume was defined as neointimal volume divided by stent volume.

Results
During follow-up, AXXESS stent volume index was increased by 27.6±20.2% (from 8.5±2.8 to 10.6±3.3mm
3
/mm). Percent neointimal volume obstruction was 3.4±4.2%. Lumen volume index was increased by 22.4±19.9% (from 8.5±2.8 to 10.3±3.2mm
3
/mm). Patients with 9 month follow-up IVUS had more NIV obstruction than with 6 month follow up (4.3±5.0 vs. 2.5±3.0%, p=0.03). There was a trend toward more stent expansion in non-left main bifurcation lesions than in left main bifurcation lesions (30±16% vs. 19±29%, P=0.1). However, percent neointimal volume obstruction was not different according to the location of lesions (P=0.5). Late acquired incomplete stent apposition was occurred in only 1 case.

Conclusion
This combined IVUS analysis suggests that AXXESS stent seems to be an effective treatment option for wide range of bifurcation lesion morphologies.
Abstract 4510: Pulmonary Hypertension before Transcatheter Aortic Valve Implantation Is Reversible and Lacks Prognostic Significance
Authors: Al Ali Abdullah M , Munt Brad , Altwegg Lukas , Humphries Karin , Carere Ronald , Cheung Anson , Lichtenstein Samuel V , Moss Robert , Pasupati Sanjeevan , Thompson Christopher R , Ye Jian , Webb John
Published: July 2021

The prognostic significance of pulmonary hypertension (PH) and the potential for reversibility in the setting of aortic stenosis (AS) have been debated. We examined the clinical correlates and prognostic significance of PH in high risk elderly patients with symptomatic severe AS undergoing transcatheter aortic valve implantation (AVI). AVI was performed in 143 patients. Adequate echocardiographic estimation of baseline pulmonary artery systolic pressure was available in 115 (80%). Patients were divided into 3 groups according to baseline pulmonary artery pressure estimated by transthoracic echocardiogram: I: <30 mmHg, II: 30 –50 mmHg and III: >50 mmHg. Clinical and echocardiographic follow-up was obtained at 1, 6 and 12 months after AVI. Group I consisted of 17 patients (15%), group II 58 patients (50%) and group III 40 patients (35%). At baseline the three groups were similar in terms of age, functional status, presence of severe pulmonary disease, aortic valve area and mean gradient. Patients with severe PH (group III) were more likely to have left ventricular dysfunction (LVEF <50%) than patients with mild to moderate PH (groups I and II) (52% vs. 21%, p=0.002) and had more severe mitral regurgitation (grade ≥ 3 in 68% vs. 41%, p =0.0002). At one month, systolic pulmonary artery pressure fell significantly in group III (11.0 ± 14.3 mmHg, p=0.0008) and this reduction was maintained at 6 months. However, the changes in group I (increase of 7.1 ± 8.7 mmHg, p=0.07) and group II (decrease of 0.9 ± 9.3 mmHg, p=0.53) were not significant. Mortality at one year following AVI was 21%, but was not related to severity of PH. Using group III as a reference, hazard ratios were 0.83 (95% CI: 0.24 –2.9) for group I and 0.88 (95% CI: 0.4 –1.9) for group II. In elderly patients with severe AS treated with transcatheter AVI, severe PH is associated with more depressed left ventricular function and more severe mitral regurgitation. Severe PH is associated with a significant and greater fall in pulmonary pressure following AVI and does not influence one year survival.
Abstract 4562: Real-time Transthoracic Three-dimensional Echocardiography Provides Valuable Management Information in Double Outlet Right Ventricle: An Echocardiographic-surgical Correlative study
Authors: Inage Akio , Takahashi Ken , Rebeyka Ivan , Ross David , Smallhorn Jeffrey F
Published: July 2021

Objective:
To assess the incremental value of real-time transthoracic three-dimensional echocardiography (RT3DE), over two-dimensional echocardiography (2DE) in determining the adequacy of the interventricular communication (IC) and surrounding structures in double outlet right ventricle (DORV).

Background:
The IC size which is crucial to the management of DORV is different from the “hole” closed by the surgeon. If the IC communication is too small post operative left ventricular outflow tract obstruction can occur.

Methods:
Twenty patients with DORV, mean age of 1.2 years (range 0 day to 8 years) and mean body weight of 7.1 kg (range 3.1 to 21.8 kg), were examined with RT3DE, as well as 2DE. Full volume RT3DE data sets were acquired in all, using either an X3–1 or X7–2 Matrix-Array transducer (Philips Medical System). Data analysis was performed using offline Philips QLabs. We measured end diastolic (ED) and end systolic (ES) area of the IC and the “hole” closed by the surgeons by RT3DE and 2DE, and adjusted them by body surface area (BSA). As well, we measured the tricuspid to aortic and tricuspid to pulmonary valve distance (TV-AV and TV-PV distance) by RT3DE and determined the relationship of the tricuspid valve to the IC.

Results:
Four patients had an associated muscular VSD. The mean ED and ES IC area/BSA were 7.33 ± 3.94 and 4.25 ± 1.86 cm
2
/m
2
by RT3DE and 3.41 ± 1.9 and 2.00 ± 1.29 cm
2
/m
2
by 2DE respectively. The mean ED and ES “surgical hole” area/BSA were 10.62 ± 3.94 and 6.52 ± 2.65 cm
2
/m
2
by RT3DE and 5.90 ± 2.47 and 4.27 ± 1.36 cm
2
/m
2
by 2DE respectively. ED and ES IC and “surgical hole” areas were significantly different between RT3DE and 2DE (P value ranges: 0.024 to < 0.001). 2DE tended to underestimate IC and the “surgical hole” size. The TV-AV and TV-PV distance relationship by RT3DE could be determined and was consistent with current surgical practice for DORV. The precise relationship of tricuspid valve attachments in the vicinity of the IC were readily determined by RT3DE, but not by 2DE.

Conclusion:
RT3DE provides useful and additive information, and offers simulated intraoperative visualization of true IC and the “surgical hole” in DORV as well as the surrounding structures.
Abstract 4565: Optimal Timing Of Stage-2 Palliation For Hypoplastic Left Heart Syndrome
Authors: Hickey Edward J , Caldarone Christopher A , Blackstone Eugene H , Yeh Thomas , Pizarro Christian , Williams William G , Jacobs Jeffrey P , Jacobs Marshall L , Tchervenkov Christo I , McCrindle Brian W
Published: July 2021

Background

Because optimal timing of stage-2 palliation of HLHS is contentious, we explored associations between length of time between stage-1 and stage-2 (“interstage interval”) and survival.

Methods

A multi-institutional cohort of neonates (N=703;1994 –2001) who underwent Norwood palliation for HLHS was studied. Survival models were constructed for each of stage-1 and stage-2 and their combined cumulative hazard was defined.

Results

A constant, persisting hazard for death was prominent ≈2 months after Norwood (“interstage death”). Risk factors for interstage death included: smaller weight at diagnosis, longer DHCA duration, smaller indexed tricuspid annulus, mitral stenosis, older age at Norwood, smaller distal arch dimension and sternal splinting (all
P
<.01, >50% bootstrap reliability). Following stage-2 palliation (N=404, median interval 5.8 months after Norwood), 32 died before subsequent Fontan completion. Risk factors for these deaths included: earlier stage-2 (
P
<.0001, 60% reliability), younger age at Norwood and smaller RV dimensions at diagnosis. Performing stage-2 within 2 months of Norwood conferred exponential increased risk of death. Cumulative hazard exposure (figure

) was minimized with interstage interval ≈ 3 months. For low risk patients intervals >4 months were optimal. For high-risk children survival was optimized with ≈ 2 month interstage interval.

Conclusions

Optimal timing of stage-2 palliation is dependent on patients’ risk category. High-risk children may have improved survival by early progression to stage-2; no such benefits are seen for lower risk children. The interstage interval will not be safely reduced below 2 months.
Abstract 4568: Surgical Management of Complete Atrioventricular Septal Defect: Associations with Surgical Technique, Age and Trisomy 21
Authors: Atz Andrew M , Hawkins John , Lu Minmin , Cohen Meryl , Jaggers James , McCrindle Brian W , Margossian Renee , Mosca Ralph , Colan Steven , Lacro Ron , Minich L LuAnn
Published: July 2021

Background:
Surgical strategies vary for repair of complete atrioventricular septal defect (AVSD). The impact of age, surgical technique and trisomy 21 on contemporary outcomes is poorly defined.

Methods:
From 6/04 to 2/06, 124 children with primary repair of complete AVSD were studied in a Pediatric Heart Network sponsored observational study. Demographic, procedural, and outcome data were obtained within 28 days of surgery and 6 months later.

Results:
Median age at repair was 115 days (9 – 396 days). Type of surgical repair was single patch (19%), double patch (71%), and single ASD patch with primary VSD closure (10%). Repair types varied significantly across centers (p=0.002) but there were no differences noted in residual atrial or ventricular septal defects or degree of mitral regurgitation (MR) by repair type within 28 days. Median intensive care unit (ICU) stay was 4 days, length of ventilation 2 days, total hospital stay 7 days; there were no differences by presence of trisomy 21(80% of cohort). A patch margin VSD was detected by echo within 28 days in 43% and at 6 months in 14% (p<0.05). A VSD > 3mm was seen in 6% at discharge and 1% at 6 months. At least moderate MR was present in 26% early and 22% at 6 months. Hospital mortality was 3/124 (2.4%); one within 30 days (0.8%). Overall survival at 6 months was 96% (119/124). Pleural effusion was the most common reported postoperative complication (20%). Earlier age at surgery was associated with longer time on ventilator (p=0.02), longer ICU stay (p=0.03) and use of circulatory arrest (p=0.01). Older age was associated with longer duration of aortic cross clamp time (p=0.05). Age at repair was not associated with residual abnormalities including residual VSD and moderate or greater MR at 6 months. .

Conclusions:
Contemporary outcomes following repair of complete AVSD are excellent regardless of repair type or presence of trisomy 21. Although a residual VSD may be detected by echo in 43%, most are trivial and resolve by 6 months. Earlier age at surgery is associated with increased resource utilization but has no influence on incidence of residual VSD or significant MR.
Abstract 4579: Endogenous Brain Natriuretic Peptide (BNP) Protects Against Apoptosis of Ischemic Human Astrocytes in an Autocrine Fashion
Authors: Katoh Chisato , Tomita Hirofumi , Metoki Norifumi , Saitoh Genta , Osanai Tomohiro , Ken Okumura
Published: July 2021

The plasma brain natriuretic peptide (BNP) level is increased in the acute phase of human stroke, but its source and function are unclear. Recently, we showed that the BNP level was higher in atherothrombotic cerebral infarction (69.1±9.4 pg/ml) than in control subjects (31.1±5.4 pg/ml), and that the BNP level in ischemic stroke was positively correlated with the NIH Stroke Scale (r=0.41, p<0.05) and infarct volume (r=0.34, p<0.05). Astrocytes provide metabolic and trophic support to neurons and modulate synaptic activities. At the early stage of brain ischemia, astrocytes are swollen, and their damage may compromise postischemic neuronal survival. We tested the hypothesis that human astrocytes produce BNP under hypoxia, and this endogenous BNP protects against apoptosis in an autocrine fashion. The human astrocyte cell line, U373MG, was exposed to hypoxia (O
2
≤1%) for 24 hours. The ratio of BNP to GAPDH mRNA was increased by 7.7±.0 fold after 12-hour hypoxia and further increased by 8.6±1.6 fold after 24-hour hypoxia compared with that in 3-hour normoxia (both, p<0.01). The protein expression assessed by Western blot was increased by 2.0±0.4 fold at 24 hours (n=5, p<0.05). Tyrosine phosphorylation of c-Src was observed by 2.0±0.2-fold increase at 30 minutes. These responses to hypoxia were all blocked by pretreatment with PP1 at 50μM, an inhibitor of c-Src. Apoptosis was measured by detecting caspase activation by flow cytometry, and it was increased by 2.5±0.1 fold after 24-hour hypoxia compared with that in normoxia. To investigate the role of up-regulated BNP in apoptosis, we performed the loss of function test by transfecting a specific siRNA for NPPB that suppressed BNP by more than 80%. The activity of caspases in the BNP knockdown cells was increased by 3.2±0.2 fold after 24-hour hypoxia compared with that in normoxia (n=5, p<0.001), and it was greater than that in the cells transfected with non-targeting siRNA. These results indicate that hypoxia increases BNP gene expression through the c-Src-dependent signaling cascade in the human astrocytes. Endogenous BNP shows brain protection via the anti-apoptotic effect. BNP may be useful in the treatment of ischemic brain diseases.
Abstract 4625: Dantrolene Inhibits Spontaneous Ca
2+
Release as a Substrate for Catecholaminergic Polymorphic Ventricular Tachycardia (PSVT) by Correcting Defective Inter-Domain Interaction within the Ryanodine Receptor
Authors: Kobayashi Shigeki , Yano Masafumi , Suetomi Takeshi , Ono Makoto , Xu Xiaojuan , Uchinoumi Hitoshi , Tateishi Hiroki , Okuda Shinichi , Yamamoto Takeshi , Matsuzaki Masunori
Published: July 2021

We previously reported that dantrolene, a therapeutic agent for malignant hyperthermia (MH), prevented abnormal Ca
2+
leak by correction of the defective inter-domain interaction between N-terminal (1– 600) and central (2000 –2500) domains in MH-type ryanodine receptor (RyR). These N-terminal and central domains of the RyR, harbor many mutations associated with MH in RyR1 and CPVT in RyR2. Here, we examined the effect of dantrolene on the Ca
2+
release in CPVT-associated RyR2

R2474S/
+

knock-in (KI) mice model. In KI (but not in wild-type:WT) mice (n=6), ventricular tachycardia was observed during or after exercise with treadmill (6/6), which was prevented by pretreatment of dantrolene (20 mg
−1
kg
−1
day
−1
, for 7 days). Cardiac sarcoplasmic reticulum (SR) vesicles were isolated (n=4), then RyR2 was fluorescently labeled with methylcoumarin acetamido (MCA) using DP

2460
–
2495

(DPc10), harboring the CPVT mutation site; R2474S, as a site-directing carrier. Only in KI (but not WT) SR, cAMP (1 μM) reduced stabilizing interactions between N-terminal and central domains (viz. domain unzipping), as assessed by the quenching of the MCA fluorescence by a large-size fluorescence quencher. Dantrolene (1 μM) inhibited the cAMP-induced domain unzipping (in KI) without effect on the cAMP-induced increase in Ser2808 phosphorylation that showed no difference between WT and KI. Using a quartz crystal microbalance technique (a highly sensitive mass-measuring technique), dantrolene was found to specifically bind to the domain 601– 620 of RyR2. In isolated, saponin-permeabilized cardiomyocytes, local Ca
2+
release events were measured using a confocal microscopy with Rhod-2; [Ca
2+
] was buffered at 30 nM by 0.5 mM EGTA. In KI, the frequency of Ca
2+
sparks (SpF: s
−1
· 100 μm
−1
) was much more increased in response to 1μM cAMP (9.7±0.4 in WT; 14.5±0.4 in KI, p<0.01). In the co-presence of dantrolene (1 μM), the increase in SpF in KI was markedly inhibited. In conclusion, dantrolene, by normally restoring the defective inter-domain interaction, seems to correct the hyper-activated channel gating caused by RyR2 mutation, thereby inhibiting spontaneous Ca
2+
release leading to lethal arrhythmia.
Abstract 4628:Efficacy of Bepridil in Patients with Symptomatic Brugada Syndrome-The Relationship Between The Effects of Bepridil and SCN5A Mutation-
Authors: Murakami Masato , Nishii Nobuhiro , Nagase Satoshi , Nakamura Kazufumi , Morita Hiroshi , Oka Takefumi , Ohe Tohru , Kusano Kengo F
Published: July 2021

Background
: It has been reported that Bepridil prevents ventricular fibrillation (VF) in patients with symptomatic Brugada syndrome (BrS) because it depresses I
to
current. But the relationship between the effects of Bepridil and SCN5A mutation in patients with BrS is not known.

Methods and Results
: Low-dose (100mg/day) Bepridil was administered for seven patients (three with SCN5A mutation, four without SCN5A mutation; all men; age, 33 to 74 years) of BrS. If the effect was insufficient, Bepridil was escalated to 200mg/day. Three patients with SCN5A mutation had many VF episodes (patient A 22/72, B 11/38 and C 10/26; VF events/months) before low-dose Bepridil. But after low-dose Bepridil, most VF episodes were controlled (patient A 0/27, B 1/30 and C 1/29; VF events/months). All of four patients (patient D, E, F and G) without SCN5A mutation had relapses of VFs in a short term after low-dose Bepridil. One patient (patient E) suspected to have proarrhythmia needed cessation of Bepridil. In the other three patients, 200mg/day of Bepridil was administered. It was effective for one patient (patient G), but not effective for the other two patients (patient D and F). In patients with SCN5A mutation, parameters of signal-averaged electrocardiography (SAECG) were improved after low-dose Bepridil. But there was no improvement in SAECG of patients without SCN5A mutation (figure

).

Conclusion
: In patients of BrS with SCN5A mutation, low-dose Bepridil improved parameters of SAECG and controlled VF occurrence.
Abstract 4653: Isolation Of Pulmonary Veins Using A Novel Decapolar Catheter For Mapping And Ablation
Authors: Weber Stefan , Fredersdorf Sabine , Jilek Clemens , Heinicke Norbert , Jungbauer Carsten , Husser Oliver , Jeron Andreas
Published: July 2021

Background: Ablation of atrial fibrillation (AF) is one of the most time consuming procedures in interventional electrophysiology. Currently, the selection of catheters and ablation techniques is still a matter of debate. Due to the rapidly increasing demand of ablation procedures, technical advances would be helpful to reduce complexity and procedure time in AF ablation. Therefore we investigated the feasibility of a novel decapolar ablation catheter (PVAC) combined with a duty-cycled, low-power RF generator for pulmonary vein (PV) isolation. The system does not require 3D mapping and is the first to enable mapping, pacing and circular as well as segmental ablation with a single catheter.

Methods: AF mapping and ablation was performed in 15 consecutive patients with intermittent AF (mean age 58±12 years, 6 males) using the PVAC- catheter. To visualize the pulmonary vein anatomy, CT or MRI scan was performed in addition to PV angiography before ablation procedure. Additionally all patients underwent transesophageal echocardiography to rule out left atrial (LA) thrombi. Ablation procedure was performed by introducing the PVAC to the LA via single transseptal puncture. An optimal and stable catheter position for mapping and ablation was achieved by using a steerable sheath and an over the wire technique. RF energy was typically delivered for 60s for circular and 30 to 60s for segmental ablations. Ablation success was defined by disappearance of PV signals and complete exit block obtained by PVAC stimulation.

Results: Isolation of all four PVs could be achieved in 59/60 veins (98%). A very small and hypoplastic right inferior PV could not be reached. The median RF application time until all PV were isolated successfully was 23±7 min. First half of ablations were performed by circular RF application, second half with segmental applications until isolation. Procedure time for ablation was 81±14 min. Total fluoroscopy time was 31±9 min. There were no procedural complications.

Conclusion: Mapping and ablation of pulmonary veins can be performed safe and fast, with low procedure times using a single catheter without 3D navigation or assisted steering. Thus this system may be of high interest not only for high volume but all centers performing AF ablation.
Abstract 4788: Long-Term Survival of the Very Elderly Undergoing Aortic Valve Surgery
Authors: Likosky Donald S , Dacey Lawrence J , Baribeau Yvon R , Leavitt Bruce J , DiScipio Anthony W , Hernandez Felix , Cochran Richard P , Quinn Reed D , Helm Robert E , Charlesworth David C , Clough Robert A , Malenka David J , Olmstead Elaine M , Ross Cathy S , O’Connor Gerald T
Published: July 2021

Increasing numbers of the very elderly are undergoing aortic valve procedures. We describe the short and long-term survivorship for this cohort. We conducted a cohort study of 8,796 consecutive patients undergoing aortic valve surgery without (48.0%; AVR) or with (52.0%) concomitant coronary artery bypass graft (CABG) surgery (AVR-CABG) between November 10, 1987 through June 30, 2006. Patient records were linked to the Social Security Administration’s Death Master File. Survivorship was stratified by age strata and concomitant CABG surgery. During 44,,435 person years of follow-up, there were 3,236 deaths. Among AVR, there were 3,939 patients <80 yrs, 463 patients 80 – 84 yrs, and 174 patients 85 + yrs (29 patients ≥90 yrs). Among AVR-CABG patients, there were 3,312 patients <80 yrs, 656 patients 80 – 84 yrs, and 252 patients 85+ yrs (22 patients ≥90 yrs). Increasing age among patients undergoing isolated AVR was associated with female gender, more vascular disease and congestive heart failure, procedural urgency, while less diabetes. Increasing age among AVR-CABG patients was associated with female gender, left main stenosis, procedural urgency, more congestive heart failure, while less diabetes and lower ejection fraction. Median survivorship was better for patients undergoing AVR: 11.8 yrs (<80 yrs), 6.7 yrs (80 – 84 yrs), 6.1 yrs (85+yrs) than patients undergoing AVR-CABG: 9.3 yrs (<80 yrs), 6.3 yrs (80 – 84 yrs), and 5.6 yrs (85+ yrs), though this effect diminished with age. Octogenarians undergoing aortic valve surgery have a surprisingly favorable survivorship, with more than half of these patients still alive 6 years after their procedure. Concomitant CABG surgery diminishes this survivorship only slightly.

Percent of Patients Surviving by Age Group, Procedure and Time Period
Abstract 4833: Protective Effect of a Quinazoline-Type Poly(ADP-Ribose)Polymerase Inhibitor Against the Development of Hypertensive Cardiomyopathy and Heart Failure
Authors: Bartha Eva , Magyar Klara , Solti Izabella , Kereskai Laszlo , Kalai Tamas , Hideg Kalman , Sumegi Balazs , Toth Kalman
Published: July 2021

Purpose: Spontaneously hypertensive rat (SHR) is a suitable model for studies of hypertension and consequential left ventricular (LV) hypertrophy and heart failure. It is known, that activation of poly(ADP-ribose)polymerase enzyme (PARP) plays a role in the development of postinfarction myocardial remodeling. In our work we examined the effect of a PARP inhibitor (L-2286) against the development of hypertensive cardiopathy and heart failure in SHRs.

Methods: Male 6-week-old SHR rats were treated with L-2286 (n=32, SHR-L) or placebo (n=32, SHR-C) for 50 weeks. Male CFY rats were used as aged-matched, normotensive controls (n=7, CFY). The phosphorylation state of signal transduction proteins were monitored by Western blotting. To detect the extent of fibrosis, histologic samples were stained with Masson’s trichrome. Plasma BNP activity was also determined. Before the study, after 24 weeks, and at the end of the treatment period echocardiography was performed.

Results: L-2286 treatment enhanced the phosphorylation of the prosurvival factors Akt-1/GSK-3β and PKC ϵ (p<0.01), while phosphorylation of JNK, p-38 MAPK, PKC pan (p<0.01), PKC α/β, δ (p<0.05) were significantly ameliorated in SHR-L group. Interstitial collagen accumulation and plasma BNP activity were significantly elevated (p<0.05) in SHR-L and SHR-C groups compared to the CFY group. These parameters were improved due to L-2286 treatment (p<0.01 and p<0.05, respectively). Echocardiography showed that the measured parameters did not differ significantly among the three groups at baseline. After 24 weeks, LV end-diastolic and end-systolic volumes and LV wall thickness increased (p<0.05 SHR-L and SHR-C vs. CFY). All these parameters decreased by L-2286 treatment (p<0.05 SHR-L vs. SHR-C). At the end of the study in SHR-L group LV hypertrophy with preserved LV ejection fraction, however in the SHR-C group an excentric hypertrophy with poor systolic function was observable. As a hard endpoint, the survival rate was significantly better in SHR-L group (p<0.05) compared to SHR-C group.

Conclusions: We demonstrated that PARP inhibition has a beneficial effect against the development of LV hypertrophy and heart failure in SHRs, due to the activation of PKC ϵ, and Akt-1/GSK-3β signaling pathways.
Abstract 4865: The Amplitude Ratio of the First to Second Heart Sound Mirrors Left Ventricular Systolic Function
Authors: Hsieh Bill P , Unver Kamil , McNulty Edward , Schiller Nelson B
Published: July 2021

Background:
In animal studies, the amplitude of the mitral component of the first heart sound (S1) is proportional to the rate of left ventricular pressure rise (dP/dt). To develop a clinical application for this property, we tested the hypothesis that the relative amplitudes of S1 and S2 (aortic component of second heart sound) represent left ventricular dP/dt and ejection fraction (EF) in humans.

Methods:
Phono-electrocardiographic recordings using a digital hand-held device (HD Medical Group Ltd) followed by an echocardiogram were performed within two hours of a clinically indicated cardiac catheterization. Left ventricular dP/dt was estimated by intracardiac manometer or Doppler echocardiogram, left ventricular EF was measured by biplane 2D. The largest positive to negative deflections of the first and second heart sound components were defined as S1 and S2. The ratios of S1 to S2 (S1/S2) were obtained from the right upper sternal border (RUSB), left upper sternal border (LUSB) and apical area. Normal EF and dP/dt were defined as ≥ 55% and ≥ 1000 mmHg/s respectively.

Results:
We studied 61 patients with dP/dt ranging from 400 to 2850 mmHg/sec, EF ranging from 11 to 78 %. Body mass index, P-R interval, pulmonary or systemic blood pressure were not different between the normal and reduced EF or dP/dt groups. Compared with the group with reduced dP/dt or EF, the median S1/S2 at LUSB and RUSB were significantly higher in those with normal dP/dt (1.52 vs 0.78 for LUSB; 1.31 vs 0.75 for RUSB, p<0.05) or EF (1.44 vs 0.95 for LUSB; 1.65 vs 0.83 for RUBS, p<0.05). On receiver operating curve analysis, S1/S2 at LUSB and RUSB, had significant discriminative values for detecting normal dP/dt (AUC = 0.82 for LUSB, 0.74 for RUSB) and EF (AUC = 0.72 for LUSB, 0.68 for RUSB). The sensitivity and specificity of S1/S2 ≥1 for detecting normal left ventricular systolic function (normal dP/dt or EF) were 72– 80% and 57–71% respectively.

Conclusion:
This study demonstrated that S1, corrected for S2, mirrors left ventricular systolic function. A ratio of S1 to S2 of ≥1 is a useful indicator of normal left ventricular systolic function defined by dP/dt ≥1000 mmHg/s or EF ≥55%. Digital phonocardiography appears promising as an adjunctive bed-side tool for assessing left ventricular systolic function.
Abstract 4867: Myocardial Effects of Beta-Blocker Therapy in the Failing Diabetic Heart
Authors: Hamdani Nazha , Van der Velden Jolanda , van heerebeek Loek , Borbely Attila , Boontje Nicky M , Steinen Ger JM , Paulus Walter J
Published: July 2021

Raised diastolic left ventricular (LV) stiffness importantly contributes to heart failure (HF) in diabetes mellitus (DM) and results from myocardial deposition of advanced glycation endproducts (AGEs), interstitial fibrosis, cardiomyocyte hypertrophy and elevated diastolic resting tension (F
passive
) of cardiomyocytes. The relative importance of these mechanisms for diastolic LV stiffness differs between HF with reduced LV ejection fraction (EF) (HFrEF) and HF with normal LV EF (HFnEF) as evident from more fibrosis in HFrEF and more hypertrophy and higher F
passive
in HFnEF. The present study therefore compared myocardial effects of β-blocker therapy in DM patients suffering of HFrEF (n=11) or of HFnEF (n=15). All patients had DM type 2 and were free of significant coronary artery disease. LV endomyocardial biopsies were used to assess AGEs deposition by carboxymethyllysine immunohistochemistry and collagen volume fraction (CVF) or cardiomyocyte diameter (MyD) by histomorphometry. Cardiomyocytes were also isolated from the biopsies, attached to a force transducer and stretched to 2.2 μm to measure F
passive
. AGEs deposition was expressed relative to an age and sex matched control group without DM. In both HFrEF and HFnEF groups, β-blocker therapy reduced DM-related myocardial AGEs deposition. In both HFrEF and HFnEF groups, β-blocker therapy also reduced MyD. In HFnEF, β-blocker therapy lowered CVF but raised F
passive
of cardiomyocytes.

Conclusion:
Myocardial effects of β-blocker therapy were uniformly beneficial for diastolic LV stiffness in DM patients suffering of HFrEF but not in DM patients suffering of HFnEF. In DM, HF phenotype could therefore affect outcome of β-blocker therapy.
Abstract 4876: LAMP2 Cardiomyopathy is a Particularly Adverse Phenocopy of Sarcomeric Hypertrophic Cardiomyopathy
Authors: Maron Barry , Roberts William C , Arad Michael , Ho Carolyn Y , Haas Tammy S , Spirito Paolo , Wright Gregory B , Almquist Adrian K , Baffa Gina , Seidman Jonathan G , Seidman Christine C
Published: July 2021

Mutations in the X-linked lysosome-associated membrane protein gene (LAMP2; Danon disease) produce a morphologic phenocopy of sarcomeric hypertrophic cardiomyopathy (HCM) in young patients, characterized by extreme left ventricular (LV) hypertrophy and pre-excitation. However, the natural history of this newly recognized cardiomyopathy is incompletely resolved. Seven young asymptomatic patients with LAMP2 cardiomyopathy were identified at ages 8 to 15 years; 6 were male. LV hypertrophy was particularly marked (septal thickness 25– 65 mm; mean 42±17) in the presence of nondilated LV cavity. On each ECG, Wolff-Parkinson-White pre-excitation pattern was associated with markedly increased voltages (74±38mm for R- or S-wave). Over the 7±3 year follow-up from initial cardiac diagnosis, all 7 patients experienced particularly adverse disease consequences associated with progressive LV wall thinning and cavity dilatation and systolic dysfunction (ejection fraction, 29±7%) by the ages of 12 – 24 years (mean 20). Of the 7 patients, 5 either died of progressive heart failure, had heart transplantation or were considered for a donor heart; 2 others had sudden death events, including one fatal ventricular tachyarrhythmia refractory to defibrillator therapy and one appropriate defibrillator shock in an asymptomatic female survivor. Pathologic examination of hearts at autopsy showed histopathologic findings compatible with both HCM due to sarcomere protein mutations (i.e., extensive myocyte disarray, intramural small vessel disease, myocardial replacement scarring), and also evidence of a storage disease process (i.e., clusters of myocytes with vacuolated sarcoplasm within fibrotic areas). Heart weights, 1266 and 1425 grams, are the most substantial recorded for hypertrophic cardiomyopathies. LAMP2 cardiomyopathy is a uniformly profound, and particularly deleterious disease entity, causing refractory heart failure with systolic dysfunction as well as sudden death in young patients < 25 years of age. This novel phenocopy of sarcomeric HCM underscores the power of molecular diagnosis for predicting prognosis, and should also raise consideration for intervention with early heart transplantation.
Abstract 4880: The Common Variant Rs9939609 In The FTO Gene Is Associated With Early-onset Myocardial Infarction
Authors: Merlini Piera A , Berzuini Carlo , Mannucci Pier M , Peyvandi Flora , Tubaro Marco , Lina Daniela , Notarangelo Maria F , Foco Luisa , Bernardinelli Luisa , Ardissino Diego
Published: July 2021

Background and objective Type 2 diabetes and increase in body mass index (BMI) are major risk factors for myocardial infarction. Recently the common variant rs9939609 in the fat mass and obesity-associated (FTO) gene was reported to associate with type 2 diabetes only through an effect on body mass index (BMI). In the present study we investigated whether rs9939609 variant in the FTO gene is directly associated with early-onset myocardial infarction.

Method The Italian genetic study of early-onset myocardial infarction is a nationwide prospective case-control study involving 1842 patients hospitalised for a first myocardial infarction before the age of 45 years, and 1842 healthy subjects matched for age, gender and geographical origin. The following baseline data were collected for each case and control: age, gender, family history, body mass index, smoking habits, hypertension, hypercholesterolemia, diabetes, cocaine use, physical activity and alcohol consumption. Genotyping was performed using a Sequenome MassARRAY platform.

Results The rs9939609 variant in FTO gene was significantly associated with early-onset myocardial infarction (odds ratio 1,25, 95% confidence interval 1.08 to 1.45; p=0.000015) with a multiplicative model of the effect. After adjusting for diabetes, BMI, hypercholesterolemia and smoking the rs9939609 risk allele was still significantly associated with early-onset myocardial infarction (odds ratio 1.20, 95% confidence interval 1.05–1.38; p=0.006), thus indicating that this variant has a direct effect on myocardial infarction, not mediated by BMI. As previously reported FTO genotype was also associated with an increase in BMI, more specifically the p-value of no association in the control group is equal to 0,01.

Conclusions The rs9939609 variant in the FTO gene was significantly associated with the risk of early-onset myocardial infarction and with the increase in BMI. The rs9939609 variant in the FTO gene directly influences the risk of early-onset myocardial infarction.
Abstract 4917: Clopidogrel Resistance and Coronary Artery Plaque Burden in Patients Undergoing Percutaneous Coronary Intervention
Authors: Chirumamilla Amala , Maehara Akiko , Mintz Gary S , Mehran Roxana , Caixeta Adriano , Brar Somjot S , Iyengar Srinivas , Rabbani Leroy , Oveido Carlos , Fiscella Damiana , Sfakianakis Konstantinos , Kreps Edward M , Collins Michael B , Singh Varinder , Leon Martin B , Stone Gregg W , Moses Jeffrey W , Dangas George
Published: July 2021

Background:
Clopidogrel anti-inflammatory effect and plaque burden are important factors for atherothrombotic process. Data are lacking on relationship of plaque burden and clopidogrel resistance in patients undergoing percutaneous coronary intervention (PCI)

Methods:
We identified 138 patients who had intravascular ultrasound during PCI between Jan 2007 to June 2007. Using the Verify Now Point-of-care assay, P2Y12 platelet reaction units (PRU) and percent inhibition of platelet activation (IPA) were measured 16 –24 hours after the loading dose of clopidogrel (600mg for patients not on clopidogrel daily, and 300mg for patients on clopidogrel 75mg daily) but before the next day of clopidogrel dose. CR was defined as PRU >200 or as IPA<10% or <20%.

Results:
Mean age of patients was 66±11 years and 74% were males. PRU>200 was found in 53 patients (38.4%) and PRU ≤200 in 85 patients (61.6%). Presence of myocardial infarction, hyperlipidemia, renal disease, smoking history, stable or unstable angina at admission were similar between the PRU groups and between IPA groups. Hypertension, diabetes, older age and reference site plaque burden were higher in clopidogrel resistance (Table

). With use of alternative definitions, reference segment plaque burden was also higher in clopidogrel resistance patients: 0.50±0.12 vs 0.41±0.13 in <10% vs ≥10% platelet inhibition (p=0.05), and 0.49±0.12 vs 0.41±0.13 in <20% vs ≥20% platelet inhibition (p=0.03)

Conclusion:
Clopidogrel resistance patients have more high risk baseline characteristics and higher plaque burden at the reference vessel segment, implying diffuse intracoronary atherosclerosis compared to clopidogrel sensitive patients who underwent PCI
Abstract 4954: Risk Factors for Death or Transplant in Chronic Symptomatic Heart Failure in Children: Subanalysis of Pediatric Carvedilol Study
Authors: Blume Elizabeth D , Boucek Mark M , Hsu Daphne , LaSalle Bernie , Gauvreau Kimberlee , Shaddy Robert E
Published: July 2021

The Pediatric Carvedilol Study trial offers a unique opportunity to investigate patient characteristics and risk factors associated with death or transplant in a population of children with moderate heart failure symptoms. The database from the Pediatric Carvedilol Study trial includes 157 children enrolled with symptomatic heart failure (NYHA II–IV) and ejection fraction (EF)<40%. For this analysis, the patients were divided into by outcome into 2 groups: those who died or underwent heart transplant during the study period (D/HTx) and those who did not (non-D/HTx). Baseline variables were compared using standard parametric and non-parametric testing. Multivariate analysis was performed using logistic regression

Results: Of the 157 children, the median age at enrollment was 3 yrs (0.2–17.8yrs). Fifty-two percent were male, and 116/157 (74%) had a left ventricle (LV) as the systemic ventricle. All pts except 3 were NYHA/Ross class II-III, with a median EF of 25.7%, median BNP of 111, and median LVEDD z-score of 6.04. Overall incidence of D/HTx in the enrolled patients over the study period was 30/157 (19%), with 12 deaths and 18 transplants. Risk factors for D/HTx were older age (8.1yrs vs 2.1 yrs, p< 0.006), higher BNP levels at enrollment (250 vs 80, p<0.003) and worse AVV regurgitation (p<0.012), but not diagnosis of congenital heart disease, ventricular morphology, or qualitative assessment of systemic ventricular dysfunction. In the subgroup of patients with a systemic LV, the D/HTx group had a significantly larger EDD z-score (7.7 vs 5.8, p=0.05), but no difference in ejection fraction (25.9 vs 25.6, p=0.8) compared to the non D/HTx. In a multi-variate model after adjusting for age, LV EDD z-score and BNP at enrollment were significantly related to risk for D/HTx. For this pediatric population with chronic symptomatic heart failure, risk factors for death or transplant included older age, higher BNP, and AVVR. In the subgroup of patients with a systemic left ventricle, larger LV EDD z-score, but not lower EF, was significantly related to short term risk for death or transplant.
Abstract 4955: Analysis of Heart Transplant Waitlist Mortality for Children
Authors: Mahle William T , Vincent Robert N
Published: July 2021

Background: The outcomes following pediatric heart transplantation (tx) have continued to improve, but pre-tx attrition has been a major concern. Historically, the risk of death while awaiting tx has been greater in children than adults. We sought to determine if recent advances in medical management have reduced the risk of death for children awaiting heart tx.

Methods. An analysis of the Scientific Registry of Transplant Recipients was undertaken to determine the risk of death while awaiting tx for children as compared to adults. Deaths were determined from the Social Security Death Master File and Centers for Medicaid and Medicare Service.

Results: During the 10 yr study period the number of children listed for heart tx increased by an average of 1% each year. Over the same time the number of pediatric donors decreased slightly. The number of deaths per patient listed decreased significantly in the non-infant pediatric patients and adults (table

). In the infant population the proportion of deaths did not change over time and generally exceeded 20%. In the most recent era–for the first time–non-infant pediatric patients had proportionally fewer waiting list deaths than adults. When one examines the annual death rates expressed per 1,000 patient-yrs at risk the non-infant pediatric pts also showed a marked reduction from 409.4 to 185.7, p<.01, whereas the rates for infants showed no improvement 1688.8 to 1788.9.

Conclusion: For children ages 1–17yrs waiting list mortality has improved dramatically in spite of a static rate of pediatric organ donation, suggesting that improved medical management has contributed to improved survival. There has been no improvement in waiting list mortality in the infant population. Whether the increased use of ABO incompatible donor organs and the advent of ventricular assist devices for this population will reduce waitlist mortality for this vulnerable group remains to be determined.

Waiting List Mortality