bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2511: Impact of Olmesartan on Progression of Coronary Atherosclerosis; - A Serial Volumetric IVUS Analysis from the OLIVUS Trial -
Authors: Hirohata Atsushi , Yamaji Hirosuke , Murakami Masaaki , Hirose Eiki , Ohkawa Keisuke , Ishizawa Makoto , Sato Shinji , Morota Tadashi , Miyoshi Tohru , Hatanaka Kunihiko , Yamawaki Hitoshi , Komatsubara Issei , Yamamoto Keizo
Published: July 2021

Prior intravascular ultrasound (IVUS) trials suggest slowing of coronary plaque progression with some medicines but have not shown convincing evidence of regression using angiotension-II receptor blocking agents (ARB). A prospective, double-blind, randomized, multicenter trial (Impact of OLmesartan on progression of coronary atherosclerosis; evaluation by IntraVascular UltraSound [OLIVUS]) was performed in 247 stable angina pectoris patients with native coronary artery lesions. When these patients underwent percutaneous coronary intervention for culprit lesions, IVUS was performed in their non-culprit vessels (without angiographically documented coronary stenosis [<50%]). Patients were randomly assigned to receive 20 mg of Olmesartan or control, and treated with a combination of β-blockers, calcium channel blockers, diuretics, nitrates, glycemic control agents and/or statins per physician’s guidance. Patients already on ACE inhibitors or other ARBs were excluded. Serial IVUS examinations (baseline and 14-months follow-up) were performed to assess coronary plaque volume. Volumetric IVUS analyses (mean measured length:41.2 ± 8.7mm) included lumen (LV), plaque (PV), vessel volume (VV), percent plaque volume (% PV), percent change in total PV (PCPV) and percent change in % PV (PC%PV). At baseline, patient characteristics and all IVUS parameters were identical between the two groups. However, follow-up IVUS showed significantly decreased PCPV and PC%PV in the Olmesartan group, despite similar blood pressure (table

). In addition, multivariate analysis identified Olmesartan administration as one of the factors that decreased plaque volume (β-coefficient −0.29 (95%CI, −0.7 to 0.4), p<0.01). These observations suggest a positive role in potential plaque regression through the administration of Olmesartan, an angiotension-II receptor blocking agent, for patients with stable angina pectoris.
Abstract 2555: Vascular Brachytherapy an Effective Therapy for Patients with Drug-Eluting Stent Restenosis
Authors: Bonello Laurent , Kaneshige Kimberley , de Labriolle Axel , Roy Probal , Steinberg Daniel H , Slottow Tina L Pinto , Xue Zhenyi , Torguson Rebecca , Suddath William , Satler Lowell , Pichard Augusto , Waksman Ron
Published: July 2021

The rates of drug-eluting stent (DES) in-stent restenosis (ISR) exceeds 10% in difficult subsets of patients and lesions. The optimal management of DES ISR remains unclear. Vascular brachytherapy (VBT) was proven to be effective for the treatment of bare metal stent (BMS) ISR but its outcome for DES ISR has not established. We aimed to investigate the safety and efficacy of VBT for DES ISR lesions. Ninety-nine consecutive patients who presented with ISR following DES implantation in 122 lesions were subjected to conventional PCI with adjunct VBT using either a beta radiation system [Beta Rail in 74 patients (82.2%) and the Galileo system in 13 patients 14.4%] or gamma radiation [Checkmate system in 3 patients (3.3%)]. Patients were followed clinically for MACE during 1-year follow-up. More than half of the patients had a previous coronary artery bypass surgery. A high proportion of patients (55%) had complex ISR with diffuse or proliferate pattern and 31.1% had recurrences of ISR to the same site. Procedural success was documented in all patients post-VBT with uneventful course during hospitalization. At 12 months’ follow-up the TLR rate was 11.1% and the overall MACE rate was 24.4%. Patients with multiple episodes of ISR to the same site had a MACE rate of 32%. There were no reports of stent thrombosis in any of the patients. VBT for the treatment of DES ISR was found to be effective and safe and should be considered a viable tool for the treatment of DES ISR, in particular in complex patients with multiple recurrences.
Abstract 2557: The Appraisal-Trial: Evaluating RESTEN-MPTM in Patients with Bare Metal Stent de novo Native Coronary Artery Lesions
Authors: Philipp Sebastian , Böse Dirk , Kordish Igor , Brachmann Johannes , Coburg Klinikum , Hardt Stefan , Sack Stefan , Erbel Raimund
Published: July 2021

Background: Although the use of drug-eluting stents has been shown to limit neointimal hyperplasia, currently available DES may adversely affect re-endothelialization, possibly precipitating late cardiac events. The aim of this study was to evaluate the efficacy and safety of a microbubble delivery of c-myc antisense peptide in preventing restenosis after coronary stenting in de novo stenosis with intravascular ultrasound.

Methods: A BMS was implanted in de novo coronary artery lesions (RD ≥ 2.5- ≤4.0mm; TL ≥ 15- ≤ 30mm in length). Serial intravascular ultrasound analysis were performed in 25 lesions. A dose of 16mg RESTEN-MPTM (AVI BioPharma/Global Therapeutics LLC) was intravenously administered after stenting and again 24 hours later.

Results: A total of 50 patients were enrolled, 34 in Essen, 13 in Coburg and 3 in Heidelberg. Before stenting, the MLD and length of stenosis was determined by QCA. 18 Patients had a LAD lesion, 21 LCX, 12 RCA. 84% (43/51) of the lesions were either Type B2 or C lesions. At six month follow-up, angiography with a QCA was performed. Generally the neointimal proliferation was minor and open vessel lumen could be demonstrated during follow-up. Of the 30 patients currently studied at six-months in the IVUS sub-study, six patients required TLR. Late lumen loss by QCA was 0.47±0.09mm. Volume stenosis by IVUS was 26 ± 4 %. Generally the neointima proliferation was minor and open vessel lumen could be demonstrated during follow-up.

Summary: Microbubble delivery of c-myc antisense seems to be effective in reducing neointimal tissue proliferation without the problem of late stent thrombosis, because the proliferation seems to be attenuated but not fully blocked.
Abstract 2566: Intravascular Ultrasound Guidance may Modify Neointimal Coverage Following Sirolimus-Eluting Stent Implantation
Authors: Sera Fusako , Uematsu Masaaki , Kotani Jun-ichi , Awata Masaki , Morozumi Takakazu , Watanabe Tetsuya , Onishi Toshinari , Iida Osamu , Minamiguchi Hitoshi , Kawamoto Kenji , Yano Masamichi , Ikeoka Kuniyasu , Okamoto Shin , Tanaka Nobuaki , Yasui Haruyo , Ishihara Takayuki , Dohi Tomoharu , Nanto Shinsuke , Nagata Seiki
Published: July 2021

Background:
Although sirolimus-eluting stent (SES) has significantly reduced in-stent restenosis, insufficient neointimal coverage may result in adverse outcomes. Intravascular ultrasound (IVUS) guided percutaneous coronary intervention improves the patency of bare-metal stents at follow-up. IVUS guidance at the time of SES implantation may also optimize neointimal coverage following stenting.

Methods:
We evaluated 55 SES implanted lesions using both angioscopy and IVUS at follow-up (12±7 months). The lesions were divided into two groups: IVUS guided implantation (group I, n=40); angiography alone (group A, n=15). Neointimal coverage was classified into 4 grades by angioscopy: no coverage (
G0
); struts bulged into the lumen, but were covered and still translucently visible (
G1
); struts were visible, but not clear (
G2
); and struts were embedded and invisible (
G3
). Minimal stent area (MSA), external elastic membrane (EEM), lumen cross-sectional area (CSA) and plaque burden were measured by IVUS at follow up. Both proximal and distal references were used. Stent expansion was assessed by stent expansion index (SEI) = MSA/reference EEM CSA.

Results:
Lesion and procedural characteristics were similar between the groups both at stent implantation and at follow-up. Although the post-procedural quantitative angiographic data were not different between the groups, distribution of the angioscopic grades of neointimal coverage at follow-up were significantly different (group A = 1.0±0.5 grades versus group I = 1.5±0.6 grades, p=0.01). IVUS measurements at follow up showed larger plaque burden at the proximal reference sites (54±12% versus 46±9%, p=0.02) and smaller SEI (0.35±0.09 versus 0.46±0.10, p=0.001) in group A than in group I.

Conclusions:
IVUS guidance at the time of SES implantation may modify angioscopic grades of the neointimal coverage, possibly optimizing neointimal coverage and preventing thrombosis.
Abstract 2594: Remote Ischemic Preconditioning Protects the Brain Against Injury Following Hypothermic Circulatory Arrest
Authors: Kaakinen Hanna , Loukogeorgakis Stavros P , Tsang Viktor , Niemelä Eija , Tuominen Hannu , MacAllister Raymond J , Deanfield John E , Yannopoulos Fredrik , Mäkelä Tuomas , Alestalo Kirsi , Kiviluoma Kai , Anttila Vesa , Juvonen Tatu
Published: July 2021

Ischemic preconditioning (IPC) is an innate mechanism that protects tissues from injury during ischemia and reperfusion. IPC has systemic effects that protect tissues remote from those undergoing preconditioning (remote IPC; RIPC). RIPC can be elicited by applying brief periods of ischemia to tissues with ischemic tolerance (skeletal muscle) yet protect vital organs that are more susceptible to ischemic damage. Using a porcine model, we determined if RIPC of the limb is protective against brain injury caused by hypothermic circulatory arrest (HCA). 12 piglets were randomized to control and RIPC groups before undergoing cardiopulmonary bypass (CPB) and 60 minutes HCA at 18oC. RIPC was induced by 4 cycles of 5-minute ischemia alternating with reperfusion of the hind limb (inflation of pneumatic cuff to 200mmHg) prior to CPB. Intracranial pressure and temperature, brain lactate concentration and electroencephalographic (EEG) activity were monitored for 8 hours after HCA. Assessment of neurological status was performed daily for 7 days post-operatively, using a species-specific quantitative behavioral score. All animals were sacrificed and brain tissue was harvested for histopathological analysis. Data were analyzed using 2-way ANOVA or student’s t-test. Study groups were balanced for baseline and intra-operative parameters; no differences were observed in intracranial pressure and temperature. Brain lactate concentration was significantly lower (p<0.0001, ANOVA) and recovery of EEG activity faster (p<0.05, ANOVA) in the RIPC group compared to control. RIPC had a beneficial effect on neurological function during the 7-day follow-up period (behavioral score; p<0.0001 vs. control, ANOVA). Histopathological analysis demonstrated a significant reduction in total cerebral injury in RIPC animals compared to controls [injury score; median (interquartile range): control 6.4 (5.0 – 8.0) vs. RIPC 1.6 (0.5–2.5), p<0.001, t-test]. These data demonstrate, for the first time, that RIPC protects the brain against HCA-induced injury, resulting in accelerated recovery of neurological function. RIPC might be neuroprotective in patients undergoing surgery with HCA and improve long-term outcomes. Clinical trials to test this hypothesis are warranted.
Abstract 2597: Aortic Atresia Is Associated with an Inferior Postoperative Systemic, Cerebral and Splanchnic Oxygen Transport Status in Neonates with Hypoplastic Left Heart Syndrome after the Norwood Procedure
Authors: Zhang Gencheng , Van Arsdell Glen , Holtby Helen , Cai Sally , Radi Osman Al , Li Jia
Published: July 2021

Aortic atresia (AA) has been identified as a risk factor for mortality after the Norwood procedure. We compared postoperative systemic and regional (cerebral and splanchnic) oxygen transport profiles in neonates with hypoplastic left heart syndrome with or without AA after the Norwood procedure. Systemic oxygen consumption (VO
2
) was measured using respiratory mass spectrometry postoperatively for 72 hrs in 17 neonates (n=9 in AA group and 8 in non-AA group). Arterial, superior vena cava, and pulmonary venous blood gases and pressures were measured at 2– 4 hr intervals to calculate cardiac output (CO), systemic vascular resistance (SVR), oxygen delivery (DO
2
) and oxygen extraction ratio (ERO
2
). Cerebral (ScO
2
) and splanchnic (SsO
2
) oxygen saturations were measured using near infrared spectroscopy. The doses of dopamine, vasopressin (up to 0.0008 unit/kg/min), phenoxybenzamine and milrinone were noted. When compared to non-AA group, AA group had lower CO (p=0.03), higher systolic arterial blood pressure (p=0.01) and SVR (p=0.002), lower DO
2
(p=0.07), VO
2
(p=0.003) and ScO
2
during the first 30 to 40 hrs. There was no significant difference in SsO
2
(p=0.12, n=7 in AA group and 3 in non-AA group). Despite a similar ERO
2
(p=0.5), AA group had higher lactate over 72 hrs (p=0.01). AA group received higher doses of vasopressin (p=0.005) and milrinone (p<0.0001), lower doses of dopamine (p=0.07), with similar use of phenoxybenzamine. Furthermore, VO
2
negatively correlated with vasopressin (p=0.05), positively correlated with milrinone (p=0.03) and dopamine (p<0.0001). When including the drugs, the inferior status in all the oxygen transport variables remained, and additionally adversely correlated with vasopressin (p from <0.0001 to 0.06), except for ScO
2
that positively correlated with dopamine, but not with other drugs. Aortic atresia is associated with an inferior status of systemic, cerebral and splanchnic oxygen transport in neonates after the Norwood procedure. Aggressive use of vasopressin worsens systemic and splanchnic oxygen transport status. Postoperative management strategies should be directed to improve both systemic and regional oxygen transport in this special group of patients.
Abstract 2600: Mitochondria Dysfunction Precedes Cardiomyocyte Apoptosis in the Pressure-Overloaded Neonatal Left Ventricle
Authors: Griffiths Eric R , Friehs Ingeborg , Scherr Elisabeth , Poutias Dimitrios N , McGowan Francis X , Nido Pedro J del
Published: July 2021

Objective:
In pressure overload LV hypertrophy (LVH) cardiomyocyte apoptosis has been recognized as a major contributor to the progression from compensated hypertrophy to failure. We hypothesize that the mitochondrial apoptotic pathway is the likely source via electron transport chain (ETC) dysfunction and oxidative stress with resultant activation of the intrinsic mitochondrial pathway.

Methods:
Neonatal rabbits underwent thoracic aortic banding at 10 days of age. Compensated hypertrophy (4wks), decompensated hypertrophy (6wks), and age-matched controls (n=4/group) were studied by serial echocardiography measuring LV mass/volume ratio (M/V) and fractional shortening (FS). ETC Complex I activities were determined by spectophotometry in isolated mitochondria (nmolesNADH/mg/min). Cardiomyocyte apoptosis (TUNEL staining) and Bcl-2/Bax ratios (immunoblotting) were measured. Data are expressed as median ± SEM with p≤.05 being significant by t-test.

Results:
At 4wks M/V ratio was significantly increased (control 1.47±0.11 vs. banded 2.01±0.18, p=.009) and FS was preserved. Complex I activity was significant decreased (control 1,355±123 vs banded 949±25, p=.04), however no significant loss of cardiomyocytes had yet occurred. By 6wks M/V ratio was significantly decreased (LV dilation; control 1.67±0.13 vs banded 1.26±0.09, p=.01) and FS was impaired (39.2±1.3 vs 27.7±4.3, p=.016). Complex I activity was further decreased (Control 940±47 vs Banded 773±21, p=.03). Bcl-2/Bax ratios were significantly decreased (control 0.97±.002 vs banded 0.9±.003, p=.028) with a resultant significant increase in cardiomyotcyte apoptosis compared to 4wk banded animals (3.93±0.86 vs 13.03±4.19 TUNEL pos nuclei/1000 nuclei, p=.05).

Conclusion:
In pressure overload hypertrophy, the transition from compensated LVH to failure and cardiomyocyte apoptosis is preceded by mitochondrial ETC dysfunction followed by a decrease in Bcl-2/Bax ratios. The likely mechanism is through increased reactive oxygen species generation and increased oxidative stress. Interventions to mitigate oxidative stress during compensated hypertrophy may prevent the onset of failure.
Abstract 2607: TGF-beta 1 as a Diagnostic Biomarker for Acute Aortic Dissection Type A in a Mouse Model of Marfan Syndrome
Authors: Matt Peter , Habashi Jennifer , Schoenhoff Florian , Black James , Grapow Martin , Eckstein Friedrich , Carrel Thierry , Huso David , Van Eyk Jennifer E , Dietz Harry C
Published: July 2021

Objectives:
Acute aortic dissection type A is the main cause of mortality in patients with Marfan Syndrome (MFS). The aim of this study was to develop a procedure to surgically induce an acute aortic dissection type A in a mouse model of MFS, and to discover a diagnostic biomarker of the aortic lesion.

Methods:
Ten fibrillin-1 deficient (Fbn1C1039G/+) and ten wild-type (WT) mice at 8 months of age were intubated, ventilated and the aorta exposed via hemisternotomy. We hypothesized that an aortic dissection type A could be induced by performing an aortic clamp injury. Serum samples were collected before and after induction (30 min) of the aortic lesion from the right femoral vein. Total (acid activated) TGF-beta 1 concentrations were measured by ELISA. Echo measurements of the aortic root were obtained from a parasternal long axis view in all mice.

Results:
Transthoracic echocardiography of the aortic root performed prior to surgery showed significantly larger diameters in Fbn1C1039G/+ mice compared to WT (p<0.0001). Aortic clamp injury led in Fbn1C1039G/+ and WT mice to a reproducible aortic wall hematoma, and intimal tears. Hematoxylin-eosin stained histological sections revealed aortic dissection of the medial layer in Fbn1C1039G/+ mice but not in WT (p<0.001). Elastin-stained sections revealed a significantly higher elastic fiber fragmentation and disarray in Fbn1C1039G/+ aortas compared to WT (p<0.001). Aortic dissection in Fbn1C1039G/+ mice was limited to the ascending aorta. Mean TGF-beta 1 serum concentrations significantly increased after inducing the aortic lesion in Fbn1C1039G/+ mice (p=0.01; 130 ng/ml vs 412.9 ng/ml) but not in WT mice (p=0.2). Sham operated Fbn1C1039G/+ and WT mice showed no difference in TGF-beta 1 serum concentrations before and after surgery (p=0.7; n=4).

Conclusions:
We present a reproducible and in the short-term non-lethal mouse model of a surgically induced acute aortic dissection type A in MFS. TGF-beta 1 serum concentrations after inducing the aortic lesion significantly increased in Fbn1C1039G/+ mice but not in WT and Sham operated mice. TGF-beta 1 is a promising diagnostic biomarker for an acute aortic dissection type A in MFS.
Abstract 2641: Comparative Incidence, Case-Fatality and Survival Rates of Stroke and Acute Myocardial Infarction. The Dijon Vascular (DIVA) Project
Authors: Gentil Arnaud , Bejot Yannick , Lorgis Luc , Durier Jerome , Zeller Marianne , Osseby Guy Victor , Dentan Gilles , Beer Jean-Claude , Moreau Thibault , Giroud Maurice , Cottin Yves , Bocage CHU
Published: July 2021

Acute coronary and cerebrovascular events share common underlying arterial pathology. Although some studies have evaluated the epidemiology of these two diseases, many of them were limited by being conducted on selected populations. The aim of the Dijon Vascular Project was to evaluate the epidemiology of both stroke and acute myocardial infarction from a large population-based study and over a long period. We prospectively assessed all first-ever cases of stroke and acute myocardial infarction (AMI) in a population of 151,846 in the city of Dijon, France, from 2001 to 2006. The 30-day case fatality rates were assessed in both groups. We recorded 1660 events, including 1020 (61.4 %) strokes and 640 AMI (38.6 %). The crude incidence of stroke was 112 / 100,000 / year while that of AMI was 70.2 / 100 000 / year. Incidence rates of the two diseases rose steeply with age. In women, the incidence of stroke was higher than that of AMI, in particular at 65 years and older. In men, the incidence of stroke was lower than that of AMI below 55 years, was similar between 55 and 65 years and higher above 65 years. Case-fatality rates at 30 days were similar for stroke and AMI. Our findings confirm that the annual incidence of stroke is higher than that of AMI except in young men. These data implications for prevention strategies, acute care, clinical trial design for future therapies and health-care organizations.
Abstract 2670: Intracoronary Bone Marrow Cell Transfer After Myocardial Infarction: 5-Year Follow-up of the BOOST Trial
Authors: Meyer Gerd P , Wollert Kai C , Lotz Joachim , Rager Ulrike , Pirr Jens , Ganser Arnold , Drexler Helmut
Published: July 2021

The BOOST study (BOne marrOw transfer to enhance ST-elevation infarct regeneration) was the first randomized controlled clinical trial to investigate the effects of intracoronary bone marrow cell (BMC) transfer after ST-elevation myocardial infarction (STEMI). 60 patients with STEMI and successful percutaneous coronary intervention (PCI) with stent implantation were randomized 1:1 to a control (CON) or BMC group. Baseline mean left ventricular ejection fraction (LVEF) as assessed by cardiac magnetic resonance imaging (MRI) 4 days after PCI was 51.3% and 50.0% in the CON and BMC groups, respectively. As previously reported, BMC transfer led to a mean improvement of LVEF by 6.0 percentage points at 6 months (P=0.003) and 2.8 percentage points at 18 months (P=0.27) as compared to the CON group. Five years (61±11 months) after PCI, we have now assessed the clinical status and have repeated cardiac MRI in all surviving patients. 2 CON patients and 2 BMC patients had died after 5 years. The composite endpoint of death, recurrent MI, or hospitalization with heart failure occurred in 6 CON and 5 BMC patients. As compared to baseline, LVEF at 5 years had decreased by 3.3±9.5% in the CON group and by 2.5±11.9% in the BMC group (mean difference between BMC and CON, 0.8 percentage points; P=0.75). As compared to baseline, LV end-diastolic and end-systolic volume indices had increased and LV mass index had decreased at 5 years, with no significant differences between both groups. In patients with a higher baseline infarct transmurality (MRI late enhancement), BMC therapy prevented a deterioration of LVEF as compared to the CON group even at the 5-year time point (P<0.04). In conclusion, a single intracoronary application of bone marrow cells does not appear to promote a sustained improvement of LVEF in patients with STEMI and relatively preserved systolic function. It remains possible that BMCs are effective long-term in patients with more impaired systolic function and/or with preconditioning of the cells.
Abstract 2805: Assessment of Coronary Artery Disease Using Magnetic Resonance Coronary Angiography: A Multicenter Trial
Authors: Kato Shingo , Sakuma Hajime , Ishida Nanaka , Ishida Masaki , Nagata Motonori , Ichikawa Yasutaka , Kataoka Kazuhiro , Matsumoto Yuji , Seo Hiroshi , Ochiai Reiji , Hosp Koga , Kobayashi Yasuyuki
Published: July 2021

Background:
CT coronary angiography is widely used to assess the presence of significant coronary artery disease (CAD). However, CT approach is associated with low but nonnegligible cancer risk. The purpose of this prospective multicenter study was to evaluate the diagnostic performance of coronary magnetic resonance angiography (MRA) in the ability to identify patients with significant CAD compared with coronary angiography.

Materials and Methods:
The subjects were recruited from 7 institutions. Free breathing coronary MR angiograms covering the entire coronary artery tree were obtained in 138 patients who were suspicious of CAD. Non-contrast enhanced images were acquired with a commercial 1.5T MR imager and five-element cardiac coils after sublingual administration of isosorbide dinitrate. Conventional X-ray coronary angiography was performed within 4 weeks after coronary MRA. MR and X-ray angiograms were sent to a core laboratory for blinded interpretation. Coronary MR angiograms were evaluated by two experienced investigators by using sliding partial MIP reconstruction. Quantitative X-ray coronary angiography analysis was performed with significant CAD defined as luminal narrowing of at least 50% of the diameter.

Results:
The mean imaging time of coronary MRA was 9.5 ± 4.9 minutes. The prevalence of significant disease on X-ray angiography was 45% (62/138). On a vessel-based analysis, the area under receiver operating characteristic (ROC) curve for the MRA compared with X-ray angiography was 0.90 (95% CI; 0.86 to 0.93). On a patient based analysis, the ROC area was 0.88 (95% CI; 0.81– 0.93). The sensitivity, specificity, positive and negative predictive values of coronary MRA by vessel analysis were 78% (95% CI; 68 – 86%), 86% (82–90%), 60% (51– 69%), 94% (90–96%). These values by patient analysis were 87% (95% CI; 76–94%), 71% (59 – 81%), 71% (59 – 81%), 87% (76–94%).

Conclusions:
In the current multicenter study using commercial 1.5T MR imagers and sliding partial MIP reconstruction, the diagnostic accuracy of coronary MRA compared to quantitative coronary angiography is good, reflected by an ROC area of 0.88 on patient-based analysis. High negative predictive value indicates that coronary MRA can be used for screening CAD.
Abstract 2865: Enhanced Left Ventricular Mass Regression Following Aortic Valve Replacement is Associated with Improved Long-Term Survival: A 15-year Study
Authors: Ali Ayyaz , Patel Amit , Abu-Omar Yasir , Mehta Anila , Ali Ziad , Bleiziffer Sabine , Freed Darren , Sheikh Ahmad Y , Athanasiou Thanos , Pepper John
Published: July 2021

Background
Aortic valve replacement (AVR) is followed by regression of LVH. More complete resolution of LVH is suggested to be associated with superior clinical outcomes, however its impact on long-term survival following AVR has not been investigated.

Methods
Demographic and clinical data were obtained retrospectively through casenote review. Transthoracic echocardiography was used to measure LVM pre-operatively and at annual follow-up visits. Patients were grouped according to their reduction in LVM at late follow-up: Group A < 25 grams, Group B 25–150 grams and Group C > 150 grams.

Results
211 patients underwent AVR between 1
st
January 1991 and 1
st
January 2001. Pre-operative LVM was 295 ± 118 g in A (n=63), 346 ± 97 g in B (n=75) and 539 ± 175 g in C (n=73), P <0.001. Mean time to last echocardiogram was 6.4 ± 3.3 years. LVM at late follow-up was 351 ± 160 g in A, 265 ± 95 g in B and 270 ± 90 g in C, P <0.001. Transvalvular gradients at follow-up were not significantly differerent between groups (A: 21 ± 21 mm Hg, B: 20 ± 15 mm Hg, C: 14 ± 11 mm Hg), P = 0.10. There was no difference in the prevalence of other factors influencing LVM regression such as IHD or hypertension. Ten year actuarial survival was significantly greater in patients with enhanced LVM regression when compared with the log-rank test (A: 49% ± 7, B: 67%± 6, C: 75% ± 6), P =0.03 (Figure 1

). LVM reduction > 150 grams was an independent predictor of long-term survival on multivariate analysis (P = 0.03).

Conclusion
Enhanced LVM regression at late follow-up in patients undergoing AVR is associated with improved long-term survival. Strategies to optimize post-operative LVM regression should be considered in view of potential prognostic benefit.
Abstract 2874: Bone Marrow-Derived Mononuclear Cell Transfer Is Associated with Superior Cardiac Recovery and Neovascularization as Compared to Nonmodified Mesenchymal Stem Cell Therapy in Chronic Myocardial Infarction
Authors: Mathieu Myrielle , El Oumeiri Bachar , Touihri Karim , Thoma Philippe , Metens Thierry , Hadad Ielham , Ray Lynn , Mazouz Naima , Naeije Robert , Heydrickx Guy , Bartunek Jozef , Mc Entee Kathleen
Published: July 2021

Background:
Cell type with optimal efficacy for cardiac repair remains under discussion. We conducted a randomized, blind and placebo-controlled study with head-to-head comparison of autologous bone marrow mononuclear cells (BMNC) and autologous non-modified mesenchymal stem cells (BMSC) therapy in a large animal model of chronic MI.

Methods:
Eleven weeks after coronary ligation, 24 dogs received intramyocardial injections of placebo (n = 8), BMNC (227.10
6
± 32.10
6
cells, n = 8) or nonmodified-MSC (232.10
6
± 40.10
6
cells, n = 8). Cardiac performance and remodelling were assessed up to 16 weeks follow-up (FU).

Results:
(Table

) BMNC injection induced a decrease in the WMSI at 8 and 16 weeks as compared to baseline (BL). In contrast, injection of the BMSC was associated with a moderate decrease at 16 weeks vs BL. Furthermore, LV end-systolic elastance (Ees) increased only after injection of BMNC and remained unchanged after BMSCs injection.

Conclusions:
In the canine model of chronic MI, myocardial BMNC transfer is superior to non-modified BMSC to reduce infarct size, improve regional systolic function and cardiac contractility. Functional improvement is associated with favourable angiogenic environment and neovascularization.
Abstract 2887: Peri-Operative Beta-Blockers in Patients Undergoing Non-cardiac Surgery: A Meta-Analysis of 12,306 Patients from Randomized Trials
Authors: Bangalore Sripal , Chandrashekhar Shruthi , Pulimi Sandeep , Messerli Franz H
Published: July 2021

Background:
The 2007 ACC/AHA guideline on perioperative evaluation recommends perioperative β-blockers for non-cardiac surgery. However, some clinical trials seem to be at odds with these recommendations.

Methods:
PUBMED/EMBASE/CENTRAL search for randomized trials (RCTs) evaluating β-blockers for non-cardiac surgery. Efficacy outcomes of all-cause mortality, cardiovascular (CV) mortality, nonfatal MI, nonfatal stroke, heart failure, and myocardial ischemia (30 days), and safety outcomes of perioperative bradycardia, hypotension, and bronchospasm.

Results:
Among 33 RCTs which evaluated 12,306 patients, β-blockers were not associated with any significant reduction in the risk of all-cause mortality, CV mortality, or heart failure, but were associated with a 35% decrease in nonfatal MI, 64% decrease in myocardial ischemia at the expense of a 101% increase (Figure

) in nonfatal strokes. The beneficial effects were driven mainly by trials with high-bias risk, while analyses of low-biased trials showed a 28% and 101% increase in all-cause mortality and stroke with only a 29% and 59% reduction in nonfatal MI and 59%myocardial ischemia. For the safety outcomes, β-blockers were associated with a significantly increased risk of peri-op bradycardia and peri-op hypotension.

Conclusions:
In patients undergoing non-cardiac surgery, we estimate that treatment of 1000 patients with β-blockers results in 16 fewer nonfatal MI, but at the expense of 3 disabling strokes and 45 and 59 patients with clinically significant perioperative bradycardia and hypotension respectively, and suggests an increase in all-cause mortality.
Abstract 2935: Clinical-Instrumental Characteristics and Prognosis in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy: 30 Years of Experience in a Referral Center
Authors: Di Lenarda Andrea , Pinamonti Bruno , Merlo Marco , Pivetta Alberto , Pyxaras Stylianos , Dragos Andreea , Mazzone Carmine , Brun Francesca , Silvestri Furio , Sinagra Gianfranco
Published: July 2021

There are few studies regarding the clinical and instrumental presentation of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC); all available data derive from few specialized centers. We sought to describe clinical characteristics, instrumental findings and prognosis in a large cohort of patients (pts) with an ARVC diagnosis. From 1976 to 2006 all pts matching ARVC diagnostic criteria were enrolled in the Heart Muscle Disease Registry of Trieste and underwent a structured diagnostic protocol and follow-up. 104 pts were studied, 66% males, mean age 33±13 years; 84% were symptomatic at enrolment (mean duration 44±67 months); 75% had symptomatic arrhythmias (43% with previous sustained ventricular tachycardia or ventricular fibrillation (SVT/VF)), 36% syncope, 20% heart failure (12% in NYHA class III-IV). Familial ARVC were present in 46% of pts. ECG was abnormal in 72% (right bundle branch block 25%; epsilon potentials 15%; anterior negative T waves 51%; QRS dispersion >40ms 11%). At signal averaged ECG late potentials were present in 58% of pts. At 2D echo, mean right ventricle (RV) end-diastolic area was 30± 8 cm2 and RV fractional area contraction (FAC) 30±13%; RV aneurysms were present in 67%. RV systolic dysfunction (defined as FAC<40%) was present in 78%, characterized severe (FAC <30%) in 48%. Left ventricular systolic dysfunction was present in 27% of pts. Stress test was interrupted in 11% of cases for ventricular arrhythmias (55% SVT/VF). RV fibrofatty tissue was present in 52% of Nuclear Magnetic Resonance and in 59% of RV endomyocardial biopsy (performed respectively in 24 and 27% of pts). During a mean follow-up of 132±89 months, 3 pts were lost; 20 out of the remaining 101 pts (20%) experienced death/heart transplantation, 6 (3%) died for refractory HF; 4 pts (2%) underwent heart transplantation (HT); 6 pts (3%) died suddenly; one (0.5%) for extracardiac disease and 3 (1.6%) for unknown reason. Ten-year cumulative survival free from HT was 57%. In our population ARVC presentation was characterized by symptomatic, frequently sustained ventricular arrhythmias. Notably, LV involvement was present in approximately one third of pts at enrolment. In the long term, the overall prognosis was severe.
Abstract 2936: Obesity and Mortality in Patients with Heart Failure and Preserved Systolic Function
Authors: Kapoor John R , Heidenreich Paul A
Published: July 2021

Several large cohort studies document better survival in heart failure patients with decreased left ventricular ejection fraction (EF) and higher body mass index (BMI) compared to those with a lower BMI. It is unclear, though, if this “obesity paradox” applies to heart failure patients with preserved EF or if it extends to the very obese (BMI>35). We followed 1,235 consecutive patients with a prior diagnosis of heart failure and a preserved EF (≥50%) documented on echocardiography at one of three laboratories. We determined adjusted mortality and readmission rates at 1 year following the echocardiogram. Obesity (BMI>30) was noted in 542 patients (44%). The mean age of the cohort was 71 years, but this varied depending on BMI (73 years for BMI<25, 64 years for BMI> 35, p< 0.001). In a subset of patients with complete diastolic indices and LV mass measurements (n=405), 95% had objective evidence of diastolic dysfunction. Age-adjusted all-cause mortality (Figure

) at one year decreased with increasing BMI (31% if BMI < 25, 22% if BMI 25–29, 20% if BMI 30–35 and 19% if BMI>35, p=0.003). In a proportional hazards analysis that adjusted for patient history, demographics and laboratory values, the hazard ratios for total mortality (relative to a normal BMI) were 1.47 (95% CI, 1.06–2.05) for BMI<25, 0.95 (95% CI, 0.64 –1.42) for BMI 30 –35, and 0.83 (95% CI, 0.52–1.31), for BMI >35, p=0.046). Similar findings were noted for the composite endpoint of survival free from heart failure hospitalization. These data suggest that the obesity paradox applies to heart failure patients with preserved systolic function and extends to very obese patients (BMI>35).
Abstract 3052: Initial Human Experiences with a Non-Stented Coronary Sinus Device for the Treatment of Functional Mitral Regurgitation in Heart Failure Patients
Authors: Sack Stefan , Kahlert Philipp , Bilodeau Luc , Pierard Luc , Lancellotti Patrizio , Legrand Victor , Bartunek Jozef , Vanderheyden Marc , Hoffmann Rainer , Schauerte Patrick , Shiota Takahiro , Marks David , Ellis Stephen , Erbel Raimund
Published: July 2021

Recently, several approaches have been developed for percutaneous mitral valve repair. The percutaneous transvenous mitral annuloplasty system (PTMA
TM
, Viacor Inc., Wilmington, USA) is an indirect annuloplasty device deployed within the coronary sinus (CS). Its mechanism is based on reduction of the anterior-posterior diameter of the mitral annulus to decrease mitral regurgitation (MR) by reestablishing leaflet coaptation in functional MR. We report the ongoing first-in-human experience with this non-stented device. 27 heart failure patients (NYHA II–IV) with functional MR II–III were enrolled at 5 centers. Via subclavian access, a multi-lumen diagnostic catheter was positioned within the anterior interventricular vein of the CS. Nitinol rods of various length and stiffness patterns were subsequently introduced into the lumina in order to exert pressure to the posterior mitral leaflet and to reduce AP diameter. Under fluoroscopic and echo guidance, different rod combinations were evaluated for maximal effectiveness before exchanging the diagnostic system to the permanent device. After assuring significant MR reduction by the permanent implant, the whole device was implanted in a subcutaneous pocket. 8 patients were excluded prior procedure due to unfavorable CS anatomy. The remaining 19 patients proceeded through a complete diagnostic exam. While the device was ineffective in 6 cases, echocardiography revealed a significant reduction of MR in 13 patients. 9 of these patients underwent successful implantation of the permanent device. 4 devices were subsequently removed, one at 7 days due to device fracture and the other 3 when the patients were referred for annuloplasty surgery due to device migration or diminished efficacy. Sustained reduction in MR and AP dimensions was noted in the remaining 4 long-term implants. No procedure related adverse events with permanent sequelae were observed in all patients. Initial human experiences with the PTMA
TM
device demonstrate safety and feasibility of this method as well as sustained favorable geometric modifications of the mitral annulus with reduction of MR in responding patients.
Abstract 3094: Implantable Cardioverter Defibrillator Therapy for Congenital Long QT Syndrome: a Single Center Experience
Authors: Horner Justin M , Kinoshita Masayoshi , Haglund Carla , Friedman Paul , Ackerman Michael J
Published: July 2021

Background: Long QT syndrome (LQTS) is a potentially lethal yet highly treatable channelopathy underscored by marked heterogeneity that necessitates evidence-based and individualized therapeutic approaches. One such therapy is the implantable cardioverter defibrillator (ICD). Here, we sought to determine the percentage of patients (pts) with LQTS that received an ICD in our LQTS clinic and its short term outcomes.

Methods: An IRB-approved, retrospective analysis of the electronic medical records of 167 LQT1, 113 LQT2, and 29 LQT3 pts evaluated in our LQTS Clinic with subset analysis of those implanted with an ICD in our institution from January 2000 to June 2007.

Results: Forty-eight pts (15% of total, 33 females, 14 LQT1, 20 LQT2, and 14 LQT3) received an ICD. The average age at implant was 30 ± 12 years (range 8 – 52 years). Nearly two-thirds received an ICD as primary prevention. The QTc exceeded 500 ms in 18 (37.5%). With an average follow-up of 42 ± 32 months, 9 (19%) have had an appropriate, VF-terminating therapy including 3 with LQT1 and 6 with LQT2. Notably, 5 of the 6 LQT2 females have already received an appropriate ICD therapy whereas none of the LQT3 pts have received one. Secondary prevention indications (p = 0.006), LQT2 genotype (p = 0.03), QTc > 500 ms (p = 0.001), and surprisingly a negative family history (p = 0.0005) predicted those ICD pts most likely to receive an appropriate therapy. Importantly, none of the non-ICD treated pts (> 250) have died a LQT-related death during the same follow-up. Conversely, 9 pts have experienced an inappropriate shock including 6 with LQT3 and males were more likely to receive inappropriate therapies (p = 0.002).

Conclusions: The majority of pts with LQTS can be treated effectively without an ICD. In this study, potentially life-saving therapies have been rendered so far at a 5– 6%/year rate. Inappropriate shocks occurred with similar frequency. Secondary prevention, genotype, and QTc predicted those ICD recipients most likely to receive appropriate therapy. Although LQT3 status is commonly associated with an ICD recommendation, so far none of the LQT3 positive ICD recipients have needed their device. Instead, the greatest “save” rate has occurred among the LQT2 positive females deemed at high risk.
Abstract 4009: Endothelial Dysfunction has Great Impacts on the Development of Acute Coronary Syndrome and Fatal Cardiovascular Events
Authors: Murakami Tatsuaki , Moriuchi Ikuo
Published: July 2021

Endothelial dysfunction is thought to contribute to atherothrombogenic process, however we identify little about practical relationship between clinical evolution of acute coronary syndrome (ACS) and endothelial dysfunction. This study investigated whether endothelial dysfunction has clinical impact on development of ACS. Endothelial dysfunction was graded by ultrasonic measured reactive changes in lumen diameter of right brachial artery following transient forearm occlusion for 5 minutes (FMD; flow-mediated endothelium-dependent vasodilation) in consecutive 518 patients with suspected coronary artery disease. The enrolled patients were categorized into three groups according to the values of FMD, and their cardiovascular events were prospectively followed-up for no less than 36 months. For a mean follow-up period of 60 months with 100% follow-up, the patients with severe endothelial dysfunction (FMD<4%; Group-L, n=174), more frequently developed ACS than Group-M with mild endothelial dysfunction (4%≤FMD<8%, n=171) plus Group-H with preserved endothelial function (FMD 8% or more, Group-H, n=173) (p<0.001, by Kaplan-Meier analysis] and majority of the patients with fatal cardiovascular events belonged to group-L. Cox proportional hazard model analysis showed that severe endothelial dysfunction was the most powerful predictor for future development of ACS (hazard ratio=5.77, 95%confidential interval; 2.52–13.22, p<0.001) and fatal cardiovascular events (hazard ratio=10.34, 95%confidential interval; 1.26 –72.25, p=0.022). These results suggest endothelial dysfunction plays important roles on development of ACS and fatal cardiovascular events in the near future, and strategies based on practical status of endothelial function are required to prevent ACS and fatal cardiovascular events.

Cumulative Incidence
Abstract 4023: Aspirin “Resistance”: Role of Pre-existent Platelet Reactivity and Correlation Between Tests
Authors: Frelinger Andrew L , Li Youfu , Linden Matthew D , Tarnow Inge , Barnard Marc R , Fox Marsha L , Michelson Alan D
Published: July 2021

Background:

Aspirin “resistance” (i.e. hyporesponsiveness to aspirin in a platelet function test) has been widely reported, but the underlying mechanism is unclear. We examined the role of pre-existent platelet hyperreactivity in aspirin “resistance”. We also determined the correlation between aspirin resistance defined by serum thromboxane (TX) B
2
(the most specific test of aspirin’s effect) and other assays of platelet function.

Methods:

Platelet function measured before and after aspirin 81 mg daily for 7 days was analyzed by Spearman’s rank correlation. Normal subjects (n=165) were studied because virtually all clinically relevant patients are already taking aspirin. An additional advantage of the use of normal subjects is that the platelet response to stimuli is not influenced (with resultant increased scatter of the data) by an underlying disease, e.g. coronary artery disease, which causes platelet hyperreactivity.

Results:

The proportion of the post-aspirin platelet function predicted by the pre-aspirin platelet function was 28.3 ± 7.5% (mean ± asymptotic standard error) for serum TXB
2
, 39.3 ± 6.8% for urinary 11-dehydro TXB
2
, 4.4 ± 7.7% for arachidonic acid-induced platelet aggregation, 40.4 ± 7.1% for ADP-induced platelet aggregation, 26.3 ± 9.2% for the VerifyNow Aspirin Assay®, and 45.0 ± 10.9% for the TEG® PlateletMapping
™
System with arachidonic acid. Spearman rank order correlations were highly significant for comparisons between assays when both pre-aspirin and post-aspirin results were included in the analysis. However, residual serum TXB
2
levels post-aspirin treatment were not significantly associated with post-treatment results of any of the other assays. Platelet count correlated with pre-aspirin serum TXB
2
and VerifyNow Aspirin Assay, but not with any post-aspirin platelet function test.

Conclusions:

Aspirin “resistance” (i.e. hyporesponsiveness to aspirin in a laboratory test) is in part unrelated to aspirin but is the result of underlying platelet hyperreactivity prior to the institution of aspirin therapy.

Individuals identified as aspirin “resistant” defined by serum TXB
2
are not the same individuals identified by the other tests.
Abstract 4067: Responses to Symptoms among Older Patients with Acute Myocardial Infarction in Korea
Authors: Hwang Seon Young , Choi Myungja , Jeong Myung Ho
Published: July 2021

Background:
Older patients’ delay in seeking treatment for symptoms is longer than younger patients with acute myocardial infarction (AMI), and results in increased higher rates of mortality and medical expenses.

Objectives:
To identify their personal and cognitive responses to symptoms and related actions among older patients aged over 65 years with the first attack of AMI in Korea.

Methods:
Study sample included 89 older patients hospitalized at a University Hospital, a principal site of Korea Acute Myocardial Infarction Registry. Semi-structured interviews were conducted, after approval of institutional review board, on the 2
nd
to 5
th
day of their stay in the hospital following coronary intervention, lasted 30 – 40 min and tape-recorded.

Results:
Median delay time from symptom onset to hospital was 24 ± 136.6 hours and mean age was 73 ± 5.7 years. About 70% had an elementary school education or lower and chronic illnesses such as hypertension or diabetes. The 30% presented to hospital for their atypical symptoms rather than chest pain. Average length of hospital stay was 13 ± 8.3 days. Lower education, intermittent or progressive development of symptoms, and no attribution as cardiac problems increased patient delay. Many patients showed great patience with self-management to alleviate their discomfort in various ways, such as self-medication, letting blood from their finger, and laying down at home. Four describing themes for the delay behaviors emerged from the qualitative data that they had

never imagined that they could have a heart attack because they were not sick even if they had hypertension or diabetes,

attributed their symptoms to their chronic illnesses or natural complaints of older age,

already attempted a medical help for their non-typical symptoms like a flu, and

did not want to burden their families or medical expenses with their problems.

Conclusions:
The findings demonstrated unique coping responses to symptoms in Korean elders. Educational intervention for the elders at high risk group for AMI is needed to increase knowledge of AMI and facilitate their decision to seek immediate help following chest discomfort.