bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11990: LMNA Cardiomyopathy Mimicking Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Kato Koichi , Ohno Seiko , Makiyama Takeru , Horie Minoru
Published: July 2021

Background and Objectives:
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease characterized by RV dilatation and ventricular arrhythmias. Desmosomal gene mutations are the major cause of ARVC. LMNA mutations have been known to lead dilated cardiomyopathy, other systemic diseases, and more recently, ARVC. In this study, we performed extensive genetic screening for LMNA in ARVC patients and assessed the clinical characteristics of patients with LMNA mutations.

Methods:
Study cohort consisted of 57 ARVC probands (definite; 45). Coding exons of LMNA, 4 desmosomal protein genes (PKP2, DSP, DSG2, DSC), and also 3 long QT syndrome related genes (KCNQ1, KCNH2, SCN5A) were amplified and sequenced by using illumina next generation sequencer. Clinical characteristics of LMNA mutation carriers and those of desmosomal mutation carriers were compared by using student t test.

Results:
Among 57 clinically-diagnosed ARVC probands, we identified desmosomal mutations in 32 probands (56.1%) and two LMNA mutations in two probands. The first LMNA mutation, p.M1K was detected in 62-year-old male, and the second one, p.W514X was in 70-year-old male. Both patients showed RV dilatation, non-sustained ventricular tachycardia, and complete atrioventricular block. His younger brother also died from ARVC. The proband’s daughter and son, who are currently in their 30s, have the same M1K mutation, however, have not had any signs of ARVC yet. In the family member with W514X mutant, the proband’s father suddenly died in his 40s and 45-year-old daughter who had the same W514X mutation, showed RV dilatation and brady-AF. In probands with LMNA mutations compared to those with desmosomal mutations, the age of onset was significantly older (38.6±18.1 vs 60.0±2.8), and their heart rate was significantly slower (61.1±12.5 vs 47±1.4). Both probands with LMNA mutations underwent pacemaker therapy, which is rare in patients with desmosomal mutations (2/2 vs 1/32 ). In family members with LMNA mutations, none of mutation carriers had showed ARVC until their 50s.

Conclusion:
Our patients with LMNA mutations developed ARVC with bradyarrhythmia after age of 50. Genetic screening for LMNA gene is important for ARVC, especially in cases with bradycardia.
Abstract 11993: Three Year Clinical and Imaging Data of the Paclitaxel-Eluting Absorbable Magnesium Scaffold (Dreams) From the Biosolve-I Study
Authors: Haude Michael , Erbel Raimund , Erne Paul , Verheye Stefan , Vermeersch Paul , Degen Hubertus , Böse Dirk , Waksman Ron , Weissman Neil , Prati Francesco , Koolen Jacques
Published: July 2021

AIMS:
In order to assess the long term safety, clinical performance and the bioabsorption process of the paclitaxel-pluting absorbable magnesium scaffold (DREAMS) 3-year clinical data and multi-modality imaging outcomes are reported.

METHODS AND RESULTS:
Forty-six subjects were enrolled in the first-in-man BIOSOLVE-I study in two different cohorts with clinical follow-up at 1, 6, 12, 24 and 36 months; angiographic and IVUS follow-up for cohort 1 at 6-month and for cohort 2 at 12-month. A subgroup of patients underwent OCT and vasomotion testing. The primary endpoint is Target Lesion Failure (TLF) at 6-month for cohort 1 and at 12-month for cohort 2. For some patients also 18-month and 24-month imaging data are available.TLF rate at 36-month was 6.8% including 2 TLRs and 1 peri-procedural MI occurring at the 12-month follow-up angiography; no events emerged from 12- to 36-month. No cardiac death or scaffold thrombosis was observed.

Vasoconstriction after acetylcholine at 6-month (delta=-10.04%; p=0.0008 versus baseline) followed by vasodilatation after nitroglycerine (delta=8.69%; p<0.0001 versus baseline) demonstrates the uncaging aspect of the absorption process with no further change at the 12-month follow-up. Six-month virtual histology (VH) data showed a significant decrease in the dense calcium by 39.5% (p=0.0015) remaining stable from 6- to 12-month follow-up.This decrease is interpreted as a surrogate assessment for the bioabsorption process of the scaffold material.

Echogenicity data using the decrease in intensity of the ultrasound signal to quantify the change in strut structure demonstrate a continuous decrease in % hyperechogenicity over the follow-up period, with the most pronounced changes within the first 6 months (22 to 16% p<0.001).

CONCLUSIONS:
DREAMS shows excellent safety and efficacy data with no death and no scaffold thrombosis up to 3 years in the BIOSOLVE-I trial. Multi-modality imaging documented the absorption process and the uncaging aspect of this device already at 6 months.
Abstract 12049: The Association of Subclinical Vascular Disease and Erectile Dysfunction at 9-Year Assessment: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Feldman David I , Billups Kevin L , DeFilippis Andrew P , Chitaley Kanchan , Greenland Philip , Stein James H , Budoff Matthew J , Dardari Zeina J , Blumenthal Roger S , Nasir Khurram , Blaha Michael J
Published: July 2021

Background:
In cross sectional studies, erectile dysfunction (ED) and overt clinical cardiovascular disease commonly coexist. However, the temporal relationship between subclinical vascular disease and subsequent identification of ED remains unclear.

Methods:
After excluding participants taking ED medications at baseline, we studied 1,862 asymptomatic men from the Multi-Ethnic Study of Atherosclerosis (MESA) with complete baseline multi-modality subclinical disease phenotyping who underwent ED assessment at MESA visit 5 (9.4 years after baseline). ED was defined by self-report per the single question self-assessment in the Massachusetts Male Aging Study. Using multivariable logistic regression (see figure legend for adjustments), we assessed the relationship between three different categories of baseline subclinical vascular disease with subsequent self-identification of ED. Subclinical vascular disease measures tested were: atherosclerosis: coronary artery calcium [CAC], carotid intima-media thickness [CIMT]; vascular stiffness: aortic distensibility, distensibility coefficient; vascular dysfunction: ankle-brachial index [ABI], flow-mediated dilation [FMD].

Results:
A total of 839 men (45%) self-reported ED 9.4 ± 0.5 years after baseline. The mean age for the study population was 63.9 ± 8.9. There was a graded association between number and severity of subclinical disease abnormalities and ED. Measures of atherosclerosis were most closely associated with ED (see figure). Of the specific subclinical disease measurements, only presence of CAC and CAC>100 retained significance in a fully adjusted model (OR 1.5, 1.2 - 1.9; OR 1.4, 1.1 - 1.9).

Conclusions:
Multiple vascular disease abnormalities tend to cluster in men who later self-report ED. Of the tested subclinical vascular disease domains, markers of subclinical atherosclerosis, in particular CAC, are most closely associated with subsequent ED nearly 10 years after baseline.
Abstract 12149: Impact of Elevated Cardiac Troponin and Increased Fibrosis on Clinical Manifestations in Hypertrophic Cardiomyopathy
Authors: Nakamura Takashi
Published: July 2021

Introduction:
Recently, in patients with hypertrophic cardiomyopathy (HCM), an abnormal serum concentration of cardiac troponin (cTn), which is a sensitive marker of myocyte injury, was reported to be an independent predictor of the adverse outcome. In addition, late gadolinium-enhancement (LGE) cardiac magnetic resonance (CMR) imaging, which has been used to uniquely characterize the extent of myocardial fibrosis, has prognostic value in HCM. However, the relationship between myocyte injury, fibrosis, and clinical events/manifestations remains unclear.

Hypothesis:
A combined analysis using cTn and LGE by CMR may help to identify the clinical events/manifestations in patients with HCM.

Methods:
Eighty-seven HCM patients receiving regular outpatient treatment underwent CMR (cine and LGE imaging). LV myocardial fibrosis mass index (FMI) was quantified and the distribution/pattern of LGE was analyzed using 17 segment model. Serum cTnI was measured within a week around CMR testing. cTnI elevation was defined as ≥ 0.05ng/mL. Clinical events were defined as heart failure (HF) admission, ventricular tachycardia (VT), atrial fibrillation, and syncope.

Results:
In total patients, mean age was 65.7 ± 15.0 years old and female patients were 41.4%. HF and VT events were observed in 22 (25%) and 16 (18%) patients, respectively. Both elevated cTnI and higher FMI were associated with the combined clinical events (P<0.01 and P<0.05, respectively). Elevated cTnI was associated not with HF (P=0.06), but with VT (P<0.001). In contrast, higher FMI was associated with HF (P=0.01), but not with VT (P=0.67). A grouping according to both cTnI and FMI showed the good stratification for clinical events as shown in the figure.

Conclusions:
In HCM patients, both cTn and FMI were significant markers for clinical events in HCM patients. In particular, elevated cTn was strongly associated with VT. Combined analysis of cTn and CMR may be useful in clinical practice for HCM.
Abstract 12183: Strain Dispersion is an Early Subclinical Manifestation of Diabetic Cardiomyopathy Assessed by 3D Echocardiography
Authors: Upton Ross , Levelt Eylem , Gamble James , Clarke Kieran , Betts Tim , Neubauer Stefan , Leeson Paul
Published: July 2021

Introduction:
The risk of heart failure is increased in patients with type 2 diabetes mellitus (type 2 DM) independently of risk factors such as coronary artery disease. The causes of diabetic cardiomyopathy are multifactorial and not fully elucidated. 3D echocardiography deformation imaging provides a non-invasive assessment of the structure and function of the left ventricle (LV) and has been shown to improve risk evaluation in patients with congestive cardiac failure (CCF).

Objective:
The aim of this study was to assess the earliest subclinical manifestations of diabetic cardiomyopathy using deformation imaging.

Method:
20 patients (mean age 58.6±1.8) with early-onset, uncomplicated type 2 DM, 20 healthy volunteers (mean age 53.3±2.8) and 10 patients with advanced CCF (NYHA class III+IV) (mean age 69.2±3.0) were studied. Strain dispersion was assessed by calculating the standard deviation of time to peak longitudinal strain across 16 segments of the LV.

Results:
Diabetic patients were matched with the controls for age and gender. Strain dispersion was increased in patients with type 2 DM when compared to healthy controls (p= 0.001) and global longitudinal strain was decreased (p=0.001). Strain dispersion in type 2 DM and CCF cohorts yielded similar values and were not significantly different (46.5±6.4 vs 52.2±7.9, respectively p=0.3).

Conclusion:
Strain dispersion is increased in uncomplicated type 2 DM patients with a short duration of disease. 3D echocardiographic deformation imaging is a sensitive non-invasive tool that could be helpful in the assessment of subclinical cardiac involvement in patients with type 2 DM.
Abstract 12244: 48 Week Outcomes Using Targeted Biologic Inhibition Agents to Treat Aggressive Multivessel Pulmonary Vein Stenosis
Authors: Western Kara , Kieran Mark , Baird Christopher , Ireland Christina , Colan Steven D , Gauvreau Kimberlee , Marshall Audrey C , Sena Laureen , Jenkins Kathy J
Published: July 2021

Introduction:
Intraluminal pulmonary vein stenosis (PVS) can occur in isolation, with congenital heart disease (CHD), chronic lung disease, or both. PVS can progress rapidly with vessel atresia, pulmonary hypertension, and RV failure, and can be fatal within months (mos) of diagnosis. Previous research has demonstrated that intraluminal obstruction occurs due to neointimal proliferation of myofibroblast-like cells, which express VEGF and PDGFR.

Hypothesis:
Adjunct targeted inhibition of VEGF (bevacizumab) and PDGFR (imatinib mesylate) may reduce disease activity in patients (pts) with multivessel intraluminal PVS and prolong survival.

Methods:
This is a single-arm, prospective, open-label FDA approved study using bevacizumab and imatinib mesylate to treat progressive multivessel intraluminal PVS. Pts with obstruction of ≥ 2 veins (echocardiographic (Echo) mean gradient ≥ 4 mmHg) were included after aggressive surgical or catheter based relief of obstruction. All but 3 pts had ≥ 1 PVS surgery prior to initiation. Pts with CHD received imatinib mesylate only, those without CHD or who progressed on study also received bevacizumab. Follow-up included lung scan and Echo q 4-8 weeks (wks); CT scan or angiography q 24 wks. We report initial (31 of 44 enrolled pts) who have reached 48 wks or study endpoint.

Results:
Among 31 pts, 17 were treated for 48 wks; 3 transplanted; 11 discontinued drug < 48 wks. Mean age at diagnosis was 4 mos; drug initiation 9 mos. Two had isolated disease, 16 CHD, 3 lung disease, 10 both. Twenty-four pts received imatinib mesylate only; 7 both drugs. Median number of pulmonary veins involved was 4 (range 2-5); 12 pts had ≥ 1 atretic vessel at initiation. Pts received mean of 85% planned doses of drug. At 48 wks, 26/31 (84%) were alive, 2 post-transplant. Eight of 31 (26%) stabilized, 6/31 (19%) did not require any subsequent pulmonary vein intervention.

Conclusions:
Multi-modal treatment including aggressive surgical and catheter based intervention and targeted inhibition of myofibroblast proliferation resulted in a 48 wk survival of 84% among pts with multivessel intraluminal PVS. These results suggest that targeted inhibition may play an important role in managing aggressive pulmonary vein disease.
Abstract 12311: Side Branch Angle Influences the Neointimal Coverage of Drug-Eluting Stent in Coronary Bifurcation Lesions: An Optical Coherence Tomography Study
Authors: Watanabe Makoto , Uemura Shiro , Dote Youko , Sugawara Yu , Goryo Yutaka , Ueda Tomoya , Okayama Satoshi , Saito Yoshihiko
Published: July 2021

Background:
Stent implantation for coronary bifurcation is intrinsically accompanied with inappropriate strut apposition around side branch (SB), which has potential risk for future development of stent thrombosis. Previous experimental studies indicated that side branch angle (SBA) influences the local flow turbulence and wall shear stress. The purpose of this study was to investigate the relation between SBA and the neointimal coverage of drug-eluting stent (DES) which were implanted in coronary bifurcation lesions.

Methods:
Forty-seven bifurcation lesions treated with DES were evaluated with FD-OCT in 39 patients (mean age; 65.7±13.9 y.o) at follow-up angiography. Each lesions were divided into the bifurcation lesions without kissing balloon technique (KBT) after stent implantation (non-KBT group; 28 lesions) and those with KBT (KBT group; 19 lesions). Neointimal coverage was assessed based on cross-sectional OCT images containing SB at 0.4mm interval, and separately evaluated in terms of jailing struts over the SB ostium (SO) and non-jailing struts attaching to the vessel wall (VW). BA was measured on the longitudinal reconstruction images of FD-OCT before stent implantation. Incidence of uncovered struts and neointimal thickness were measured.

Results:
In non-KBT group, the percentage of uncovered struts was significantly higher in lesions with SBA≦60°compared with those with SBA>60°at both SO and VW region (56.9±39.8% vs. 25.6±26.8%, p<0.05; 10.6±7.6% vs. 3.3±4.4%, p<0.01, respectively) and significant negative correlation was found between SBA and the percentage uncovered struts at both SO and VW regions (r=–0.55, p<0.01; r=–0.47, p<0.05, respectively). In KBT group, the percentage of uncovered struts was not significant difference between lesions with SBA≦60°and those with SBA>60°at both SO and VW region (36.7±35.3% vs. 36.6±34.8%; 10.9±10.4% vs. 8.6±12.7%, respectively) and no correlation was found between SBA and the percentage of uncovered struts at both SO and VW region.

Conclusions:
The neointimal coverage of DES was affected by in bifurcation lesion without KBT, but is not affected in bifurcation lesion with KBT. KBT has potential benefit for neointimal coverage of DES at coronary bifurcation lesion with narrow SBA.
Abstract 12318: Prevalence of Atrial Fibrillation in Patient With Celiac Disease
Authors: pattanshetty deepak J , Gajulapalli Rama Dilip
Published: July 2021

Background:
Inflammation is an established risk factor for Atrial Fibrillation (AF). Celiac Disease (CD) is a systemic autoimmune inflammatory disease. Given the nature of the CD, this group could be at high risk for developing AF. We aim to evaluate the prevalence of atrial fibrillation in patients with Celiac disease.

Methods:
Electronic health records (01/1999 to 09/2013) from 13 different healthcare systems were obtained utilizing a HIPAA-compliant, patient de-identified web application (Explore; ExplorysInc). Among a total of 22, 385,340 patients, 24,530 were diagnosed with CD. The remaining 22,360,810 patients without CD served as the control group. The demographics and comorbidities are abstracted for comparison.

Results:
There was a significantly higher prevalence of AF among CD compared to those without CD [5.6 % vs. 2.8%, p <0.0001)] with the odds ratio being 2.04 (95% CI 1.9 to 2.2). After excluding the patients with coronary artery disease in both groups, the prevalence of AF was still higher among 2.9 % in celiac disease group compared to control group (2.9 % vs. 1.4%, p <0.0001) with odds ratio being 2.05 (95% CI 1.9 to 2.2). Patient characteristics are compared in table 1.

Conclusions:
There was a two fold increase in the prevalence of AF in patients with celiac disease compared to those of control group , which could well be due to the autoimmune disease causing systemic inflammation. Further prospective studies are needed to study the association in detail.
Abstract 12332: Tethering of Mitral Leaflets Relates to Displacement of Papillary Muscles by Dislocation of Heart During Off-Pump Coronary Artery Bypass Surgery: Assessment of Mitral Valve Complex by Three-Dimensional Echocardiography in Porcine Model
Authors: Igarashi Takashi , Iwai-Takano Masumi , Takase Shinya , Yokoyama Hitoshi
Published: July 2021

Introduction:
It is considered that morphological changes of mitral valve complex and worsening of mitral regurgitation (MR) cause the hemodynamic deterioration during off-pump coronary artery bypass grafting (OPCAB) in ischemic heart disease.

Hypothesis:
Mitral valve tethering is caused by dislocation of papillary muscle and leads to exacerbation of ischemic MR and hemodynamics.

Methods:
In 9 healthy swine with median sternotomy, we positioned the beating heart using Starfish heart positioner
®
and Octopus 2
®
(Medtronic) as OPCAB model. In 4 positions for CABG, i.e., control, LAD-, RCA-, and LCX- positions, three-dimensional (3D) full volume images by echocardiography were acquired (iE33
®
and X5-1
®
, Phillips Healthcare) to assess mitral valve complex with hemodynamic parameters. We assessed the morphological changes of the mitral valve complex in 4 positions using by Real-view
®
(YD Co.) and Cardio-view
®
(TomTec).

Results:
Systolic arterial pressure was significantly lower in LCX position than in control position (LCX 48.9±2.5 vs control 69.8±2.7 mmHg, P<0.001). There were no significant differences in the mitral annular diameters in each position. On the other hand, there were significantly increased in the maximum tenting height (control 2.9±0.5, LAD 2.7± 0.3, RCA 3.7± 0.3, LCX 4.1± 0.3 mm, P<0.01) and the tenting volume (control 0.7±0.1, LAD 0.6±0.1, RCA 0.8±0.1, LCX 1.0±0.1 cm
3
, P<0.05) in LCX position compered to other positions. The angle α, i. e., the angle between the posterior papillary muscle-to-annulus line and the least-squares annular plane, were tended to decrease in LCX position, and there was a significantly relationship between the tenting volume and the angle α (r= -0.643, P<0.001). By the assessment of 3D-coordinates of the papillary muscles, posterior papillary muscle was displaced to medial site in LCX position compered to other positions (P<0.001).

Conclusions:
In the dislocated and rotated position of the heart, especially in LCX position, the tethering of the mitral valve leaflets was increased, and related to the displacement of posterior papillary muscle. This suggests that mitral valve tethering is caused by dislocation of papillary muscle and leads to exacerbation of ischemic MR and hemodynamics during OPCAB.
Abstract 12375: Vascular Inflammation Evaluated by 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography is Associated With Endothelial Dysfunction
Authors: Honda Akihiro , Tahara Nobuhiro , Tahara Atsuko , Igata Sachiyo , Nitta Yoshikazu , Kodama Norihiro , Mizoguchi Minori , Yamagishi Sho-ichi , Fukumoto Yoshihiro
Published: July 2021

Background:
Endothelial dysfunction is an initial step for atherosclerotic cardiovascular disease. However, involvement of vascular inflammation in endothelial dysfunction is not fully investigated in humans. We assessed the relationship between endothelial function and vascular inflammation evaluated by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging.

Methods and Results:
We examined endothelial function and vascular inflammation, which were evaluated by flow-mediated dilation (FMD) of the brachial artery functionally and FDG-PET imaging of carotid arteries, respectively, in 128 subjects (83 males and 45 females; mean age 61.8 ± 10.0 years) who underwent a risk-screening test for cardiovascular disease in Kurume University Hospital. Vascular inflammation of the carotid arteries was measured by blood-normalized standardized uptake value, known as a target-to-background ratio (TBR). Mean percent change in vasodilation (percent change over the baseline values; %FMD) and carotid TBR were 5.60 ± 2.24 % and 1.43 ± 0.22, respectively. %FMD was less in men than in women. In univariate analysis, %FMD was inversely correlated with age (p=0.011), systolic blood pressure (p=0.014), carotid artery maximum intima-media thickness (p=0.014), HbA1c (p=0.020), visceral fat volume (p=0.005), or TBR values (p<0.001). Multiple stepwise regression analysis revealed that age (p=0.034), visceral fat volume (p=0.002), and TBR values (p<0.001) were independently associated with decreased %FMD (R2=0.245).

Conclusions:
We found here that vascular inflammation in the carotid arteries evaluated by FDG-PET was one of the independent association of decreased %FMD, thus suggesting that vascular inflammation might contribute to endothelial dysfunction in humans.
Abstract 12427: Racial Disparities in Hospitalization for Atrial Fibrillation: The Nationwide Inpatient Sample 2001-09
Authors: Kwan Gene F , Enserro Danielle M , Walkey Allan J , Wiener Renda S , Benjamin Emelia J , Magnani Jared W
Published: July 2021

Introduction:
Racial differences in atrial fibrillation (AF) prevalence and disparities in treatment are well established; however, racial differences in outcomes among patients hospitalized with AF are less clear. We assessed racial differences in complications related to AF in a representative sample of AF hospitalization in the United States.

Methods:
We identified adults (≥ 40 years) with a principal diagnosis of AF and length of stay (LOS) among survivors of 1-30 days using weighted national estimates from the Nationwide Inpatient Sample. We excluded patients undergoing cardiac surgery or with missing covariates. Annual AF hospitalization rates by race were calculated using the total US population obtained from the US Census Bureau. We used multivariable regression models (covariates listed in Table) to examine associations of race with heart failure and hospital mortality among patients admitted with AF.

Results:
2,244,036 AF hospitalizations (85% White, 6.7% Black, 5.0% Hispanic and 1.4% Asian/Pacific Islander) were analyzed from 2001-09. Hospitalization and outcome data by year are summarized in the table. Across all studied years, Blacks had lower AF hospitalization rates than Whites. Yet in all study years, mean LOS was longer for Blacks (range 4.2-4.6 days) than Whites (range 3.4-3.6 days). Blacks consistently had increased risk of in-hospital heart failure (Odds Ratio [OR] ranged from 1.5 [1.4, 1.7] to 1.7 [1.6, 1.9] across years) and death (OR, 1.5 [1.1, 2.1] to 2.3 [1.7, 3.0]) compared with Whites after adjustment for comorbidities.

Conclusions:
Although Blacks have lower incidence of hospitalizations for AF, they experience higher risk of heart failure, longer LOS, and greater mortality compared with Whites hospitalized with AF. Further public health investigation is warranted to examine the causes for disparities in outcomes among Blacks with AF and identify modifiable factors that may improve outcomes of Blacks with AF.
Abstract 12440: Does Low Diastolic Blood Pressure Contribute to the Risk of Recurrent Cardiovascular Disease Events? The Framingham Heart Study
Authors: Franklin Stanley S , Gokhale Sohum G , Chow Vincent H , Wong Nathan D , Levy Daniel , Larson Martin G , Vasan Ramachandran S , Mitchell Gary F
Published: July 2021

Background:
The clinical significance of low diastolic blood pressure (DBP) as a risk for recurrent cardiovascular disease (CVD) events in persons with isolated systolic hypertension (ISH) is controversial.

Methods:
We examined risk for recurrent CVD events in 791 individuals (age 75 years, 47% female, mean follow-up time: 8±6 years) with DBP<70 (N=225) versus 70-89 mmHg (N=566) following initial CVD events in the original and offspring cohorts of the Framingham Heart Study.

Results:
Recurrent CVD events occurred in 153 (68%) participants with lower DBP and 271 (48%) with higher DBP (p<0.0001). Risk of recurrent CVD events in risk factor-adjusted Cox regression was higher in those with DBP<70 mmHg versus DBP 70-89 mmHg in both treated [HR, 5.1 (95% CI: 3.8-6.9) p<0.0001] and untreated individuals [HR, 11.7 (6.5-21.1) p<0.0001] (treatment interaction: p=0.10). Individually, coronary heart disease, heart failure, and stroke recurrent events were more likely with DBP<70 mmHg versus 70-89 mmHg (p<0.0001). To judge the potential modifying effect of wide pulse pressure (PP) on excess risk associated with low DBP, we defined 4 binary groupings of median PP (≥ 68 verses <68 mmHg) and categorical DBP (<70 versus 70-89 mmHg), and found that CVD event rates were higher only in the group with wide PP and DBP<70 mmHg (Chi Square = 32.6, p<0.001, see Figure).

Conclusions:
Persons with ISH and initial CVD events have increased risk for recurrent CVD events in the presence of DBP<70 mmHg versus DBP 70-89 mmHg, supporting wide PP as an important risk modifier of the adverse effect of low DBP; we postulate increased CVD risk is related to the pernicious effects of faulty microvascular function resulting from increased elastic artery stiffness in combination with low diastolic perfusion pressure.
Abstract 12492: Multimodality Intravascular Imaging Assessment of Plaque Erosion vs Plaque Rupture in Patients With Acute Coronary Syndrome
Authors: Kim Sang-Wook , Won Hoyoun , Mintz Gary S , Hong Young Joon , Lee Sung Yun , Kim Ki Seok , Hahn Joo Yong , Lee Wang Soo , Hyeon Seong Hyeop , Kwon Jee Eun , Shin Seung Yong , Lee Kwang Je , Kim Tae Ho , Kim Chee Jeong
Published: July 2021

We used optical coherent tomography (OCT) and virtual histology intravascular ultrasound (VH-IVUS) to assess culprit lesions in 146 Korean pts with acute coronary syndrome (ACS).

Methods:
Culprit lesion plaque rupture (PR) or plaque erosion (PE) was diagnosed with OCT; and IVUS was used to determine arterial remodeling. PE (n=56) was the presence of intracoronary thrombus attached to the luminal surface with no detectable signs of fibrous cap rupture that was seen in 90 ACS pts with PR. Positive remodeling was a remodeling index (lesion/reference EEM [external elastic membrane] area) >1.05.

Results:
Pt age was 60±12 yrs in PR and 62±11 yrs in PE; 19% of PR vs 18% of PE were females. Overall, 25% (14/56) of PE had non-ST elevation myocardial infarction (NSTEMI) and 34% (19/56) had STEMI; conversely, 14.4% (13/90) of PR had NSTEMI and 71% (64/90) had STEMI (p<0.0001). Vessel size, minimal lumen area, and lumen area at the PR or PE site were similar; however, lesion length was longer in PR. Plaque area was smaller with negative remodeling in PE while PR showed positive remodeling with a larger necrotic core area by VH-IVUS (Table). By OCT, PE were fibrotic in 50% (28/56), fibrocalcific in 16% (9/56), and lipidic in 32.1% (18/56, all but one of which was a thick cap fibroatheroma).

Conclusion:
Multimodality intravascular imaging with OCT and VH-IVUS showed fundamentally different pathoanatomic substrates underlying plaque rupture and erosion in Asian pts.
Abstract 12495: Fibrin-Thrombin Patch for Endothelial Cell Differentiation and Cardiac-Tissue Patch Manufacturing Using Human Induced-Pluripotent Stem Cells
Authors: Zhang Sophia , Dutton James , Su Liping , Zhang Jianyi , Ye Lei
Published: July 2021

Aim:
To explore the feasibility using fibrin-thrombin patch for endothelial cell differentiation and cardiac scaffold manufacturing using cardiac cells derived from human induced-pluripotent stem cells (hiPSCs).

Method and Result:
hiPSCs were dissociated into single cells and seeded into three-dimensional (3D) fibrin-thrombin patches and undergo a two-stage differentiation protocol. With this protocol, up to 45% of the differentiated hiPSCs assumed an EC phenotype, and after purification, greater than 95% of the cells displayed the EC phenotype (based on CD31 expression). The hiPSC-ECs continued to display EC characteristics for 4 weeks in vitro. Gene and protein expression levels of CD31, CD144 and von Willebrand factor-8 (vWF-8) were significantly up-regulated in differentiated hiPSC-ECs. hiPSC-ECs also have biological function to up-take Dil-conjugated acetylated LDL (Dil-ac-LDL) and form tubular structures on Matrigel. A human cardiac-tissue patch (hiCP) was developed by seeding the hiPSC-ECs with hiPSC-derived cardiomyocytes (hiPSC-CMs) and smooth muscle cells (hiPSC-SMCs) into a 3D fibrin scaffold. The hiCP began to contract 3 days after synthesis, 4 days earlier than patches that were created identically but without hiPSC-ECs, and continued to beat regularly (100-120 beats/min) for at least 4 weeks in vitro.

Conclusion:
These data demonstrate that this new 3D differentiation protocol can efficiently generate stable ECs from hiPSCs and, furthermore, that the differentiated hiPSC-ECs can be combined with hiPSC-CMs and -SMCs to construct an hiCP with improved contractile activity. Our observations also suggest that interactions between the cardiac endothelium and myocytes may contribute to the optimized beating of hiCPs.
Abstract 12518: Ventricular Arrhythmias and Mortality After Left Ventricular Assist Devices Implantation: A Meta-Analysis
Authors: Makki Nader , Mesubi Olurotimi , Steyers Curtis , Olshansky Brian
Published: July 2021

Background:
Ventricular arrhythmias (VAs) are among the most commonly reported adverse effects associated with left ventricular assist devices (LVADs). However, prevalence of VAs post-LVAD implantation, and their relation to all-cause mortality, remains to be elucidated. We conducted a meta-analysis and systematic review of observational studies with the primary objective of evaluating the risk of VAs after LVAD implantation and the risk of all-cause mortality in patients with LVADs who had VAs.

Methods:
We searched Medline, Embase and Cochrane Central from 2001 to 2014. Two reviewers independently searched,selected and assessed quality of included studies with differences resolved by consensus. Data were collected and analyzed using random and fixed-effect model, as appropriate, with inverse variance weighting.

Results:
Of 2,393 studies identified, 15 observational studies were eligible including 1,517 patients with a mean follow up of 201 days. An LVAD was associated with an increased risk of VA after implantation (OR = 2.21, 95% confidence interval [CI] 1.37-3.59, p<0.001).There was an increased risk of all-cause mortality in LVAD patients who had post-LVAD VA (OR = 1.91, 95% CI 1.18-3.11, p<0.001). Using meta-regression and sensitivity analyses to account for risk factors such as etiology of cardiomyopathy, duration of follow-up, destination LVAD versus bridge therapy and presence of an implantable cardioverter defibrillator at time of LVAD implantation did not change the results of our main analysis.

Conclusions:
LVADs are associated with an increased risk of VA and presence of VAs post LVAD implantation is associated with increased risk of all-cause mortality.
Abstract 12523: Crucial Role of SmgGDS in the Inhibitory Effects of Statins on Cardiac Hypertrophy and Fibrosis in Mice
Authors: Kudo Shun , Satoh Kimio , Tanaka Shinichi , Minami Tatsuro , Kikuchi Nobuhiro , Omura Junichi , Suzuki Kota , Ikeda Shohei , Shimokawa Hiroaki
Published: July 2021

Introduction:
We have previously demonstrated that small GTP-binding protein dissociation stimulator (SmgGDS) plays a crucial role in the pleiotropic effects of HMG-CoA reductase inhibitors (statins) in mice and humans. In the present study, we tested our hypothesis that SmgGDS plays a crucial role in the inhibitory effects of statins on the development of cardiac hypertrophy and fibrosis.

Methods & Results:
We administered angiotensin II (AngII, 2 mg/kg/day, 2 weeks) to SmgGDS-deficient (
SmgGDS
+/-
) mice and littermate controls (
SmgGDS
+/+
), which were orally treated with either statins (atorvastatin 10 mg/kg/day or pravastatin 50 mg/kg/day, n=10 each group) or vehicle. AngII equally elevated systolic blood pressure and promoted cardiac hypertrophy and fibrosis in
SmgGDS
+/+
and
SmgGDS
+/-
. Both statins significantly reduced LV wall thickness, cardiac myocyte cross-sectional area, and fibrotic area in AngII-infused
SmgGDS
+/+
mice (all P<0.01). In contrast, the inhibitory effects of statins were absent in AngII-infused
SmgGDS
+/-
mice. Additionally, statins significantly improved LV diastolic function (E/A) in
SmgGDS
+/+
mice (P<0.01) but not in
SmgGDS
+/-
mice. Interestingly, immunostaining revealed that SmgGDS was highly expressed in cardiac fibroblasts (CFs) in the heart of AngII-infused
SmgGDS
+/+
mice. Then, we harvested CFs from
SmgGDS
+/+
and
SmgGDS
+/-
mice and stimulated them with AngII with or without statins. At baseline,
SmgGDS
+/-
CFs showed significant increase in Rac1 expression (1.8-fold), ERK1/2 activity (4.0-fold), Rho-kinase activity (phospho-MYPT/total-MYPT, 1.4-fold) compared to
SmgGDS
+/+
CFs, whereas Akt activity was significantly less in
SmgGDS
+/-
CFs compared to
SmgGDS
+/+
CFs (n=4, all P<0.05). Statin treatment significantly reduced Rac1 expression in
SmgGDS
+/+
CFs (-30%, n=4, P<0.05), which was not observed in
SmgGDS
+/-
CFs, suggesting that SmgGDS mediates the inhibitory effects of statins on Rac1 signaling.

Conclusions:
These results indicate that SmgGDS plays a crucial role in the inhibitory effects of statins on cardiac hypertrophy and fibrosis, partly through inhibition of Rac1, Rho-kinase, and ERK1/2 pathways.
Abstract 12539: Physical Activity, Uric Acid and Risk of Hypertension
Authors: Mos Lucio , Saladini Francesca , Fania Claudio , Garavelli Guido , Ruscio Maurizio , Martina Stefano , Casiglia Edoardo , Palatini Paolo
Published: July 2021

Introduction:
The association of uric acid with risk of hypertension is controversial and may be modulated by other risk factors. We did a prospective study to investigate whether uric acid was an independent predictor of risk of hypertension in the young and whether an unhealthy lifestyle could favour this association.

Design and methods:
The study was conducted in a cohort of 1060 young to middle age subjects screened for stage 1 hypertension and followed for a median of 11 years. In multivariable Cox analyses, data were adjusted for age, gender, body mass index (BMI), parental hypertension, 24-hour systolic and diastolic blood pressure, serum creatinine, lifestyle factors and metabolic data.

Results:
At baseline uric acid showed an independent positive association with male gender, BMI, creatinine and metabolic data and a negative association with age and smoking. The uric acid level was 5.03 mg/dL in the sedentary subjects (n=659) and 5.00 mg/dL in the active subjects (p=n.s.). At follow-up end, 677 subjects developed hypertension needing treatment. In the whole group, uric acid was an independent predictor of future hypertension (p=0.004). Participants with uric acid > 5.60 mg/dL (lower limit of the top tertile) had a 31% increase in risk compared to those of the bottom tertile. However, the risk of hypertension related to uric acid was increased only among the sedentary subjects (p=0.0017) with a hazard ratio of 1.43 (95%CI, 1.10-1.88) for the subjects of the top uric acid tertile compared to those of the bottom tertile. In contrast, among the active subjects no association was found between uric acid and risk of hypertension (p=0.56). The association between uric acid and future hypertension remained virtually unchanged when baseline serum glucose, cholesterol and triglycerides were included in the regression models.

Conclusions:
Uric acid is an independent predictor of hypertension in young to middle age subjects. However, regular physical activity prevents the development of hypertension related to hyperuricemia. These data suggest that exercise can counteract the pathophysiological mechanisms involved in the association between hyperuricemia and development of hypertension.
Abstract 12547: Time-Course Influence of Brain Death on Cardiac Function and Its Impact on Posttransplant Graft Function
Authors: Li Shiliang , Korkmaz Sevil , Loganathan Sivakkanan , Radovits Tamás , Hegedüs Peter , Karck Matthias , Szabó Gábor
Published: July 2021

Introduction:
Heart transplantation became the most effective treatment for end-stage heart failure. Donors after brain death are currently the only reliable source for cardiac transplants. However, hemodynamic instability and cardiac dysfunction have been demonstrated in brain-dead donors and this could therefore also affect posttransplant graft function.

Hypothesis:
Our aims were to evaluate in rats the time-course cardiac influence of brain death and we tested the hypothesis that brain death impairs graft left ventricular function.

Methods:
Lewis rats were either maintained brain death for 5h by inflation of a subdurally placed balloon catheter (n=7) or subjected to sham-operation (control group, n=9). We continuously assessed cardiac function during 5 h. Then, hearts were excised, stored in cold preservation solution for 1 h, and heterotopically transplanted. We evaluated graft function 1.5 h after transplantation.

Results:
Brain death was associated with decreased left ventricular contractility (ejection fraction: 37±6% vs. 57±5%; dP/dt
max
: 4770±197 mmHg/s vs. 7604 ±348 mmHg/s; dP/dt
max
-EDV: 60±7 mmHg/s vs. 74±2 mmHg/s; E
max
: 2.4±0.1 mmHg/μl vs. 4.4±0.3 mmHg/μl; PRSW: 47±9 mmHg vs. 78±3 mmHg; p<0.05) and relaxation (dP/dt
min:
-6638±722 mmHg/s vs. -11285±539 mmHg/s; Tau: 12.6±0.7 ms vs.10.5±0.4 ms; EDPVR: 0.33±0.14 mmHg/μl vs. 0.09±0.03 mmHg/μl, p<0.05) 45 min after its initiation and for the rest of 5 h compared to controls. Moreover, after transplantation, graft systolic and diastolic functions were impaired in the brain-dead group compared to controls (reflected by decreased left ventricular systolic and developed pressures, dP/dt
max
and dP/dt
min
, and prolonged Tau).

Conclusions:
In conclusion, we have a well detailed characterized in vivo rat model to examine the influence of brain death on ventricular dysfunction using a microconductance catheter technology via pressure-volume analysis. These results demonstrate that brain death increases the susceptibility of donor heart to ischemia/reperfusion injury after transplantation.
Abstract 12563: Variation in Referral for Specialist Follow-Up and 30-Day Mortality in Patients Hospitalized With Heart Failure in England and Wales
Authors: Rahimi Kazem , Emdin Connor A , Cleland John G , Dargie Henry , Korshidi Reza , Hardman Suzanna , Woodward Mark , MacMahon Stephen , Mitchell Polly , McDonagh Theresa
Published: July 2021

Introduction:
Current US and European guidelines recommend that patients hospitalized with heart failure (HF) are followed up after discharge, but do not specify whether or not this should be with HF specialist services. We investigated referral patterns to specialist services amongst hospitals in England and Wales and assessed whether these differences were associated with 30-day mortality.

Methods:
We used data from the National Heart Failure Audit, which included 84647 HF patients from 176 hospitals. Vital status was obtained from the UK national death registry. Using hierarchical statistical models and instrumental variable analysis, we estimated whether different types of follow-up (cardiologist, HF nurse or geriatrician) were associated with 30-day mortality, adjusting for case mix.

Results:
At the hospital level, rates of referral to cardiologists for follow up varied from 4% to 94%, to HF nurses from 0% to 97% and to geriatricians from 0% to 65%. When heart failure patients were referred for follow-up to a heart failure nurse, to a geriatrician, or to a cardiologist, they were 15%, 15% and 47% less likely to die than patients who were not referred to these specialists (odds ratio [OR] = 0.85, p<0.001; OR = 0.85, p<0.001; OR = 0.53, p<0.001). A patient admitted to one randomly selected UK hospital would have, on average, 2.1-fold odds of receiving referral to a cardiologist for follow up than a second similar patient admitted to another randomly selected hospital (95% confidence interval [CI]: 1.9, 2.3) Use of quintile of hospital preference as an instrumental variable for cardiology referral resulted in a consistent estimate for the effect of cardiology referral on 30-day mortality (OR=0.65, CI: 0.40, 0.90, p=0.005).

Conclusion:
Referral at discharge to cardiology services for follow-up varies considerably amongst UK hospitals. At both an individual patient and at a hospital level, referral to cardiology for follow-up is a major determinant of 30-day mortality.
Abstract 12575: Right Ventricular Dysfunction Plays an Important Role in Predicting Non-Response to Tolvaptan Treatment in Patients With Heart Failure With Reduced Ejection Fraction With Chronic Kidney Disease
Authors: Iwahashi Noriaki , Gohbara Masaomi , Kataoka Shunsuke , Akiyama Eiichi , Maejima Nobuhiko , Tsukahara Kengo , Hibi Kiyoshi , Kosuge Masami , Ebina Toshiaki , Umemura Satoshi , Kimura Kazuo
Published: July 2021

Background:
Tolvaptan (TLV), a newly-developed vasopressin type 2 receptor antagonist, has a unique feature of diuresis, but the response to this drug can be unpredictable especially in patients with heart failure(HF) with renal dysfunction. This retrospective study used a novel speckle tracking echocardiography to examine the predictability of TLV effectiveness in patients with HF. RV function was estimated by TAPSE and RV strain in this study.

Methods:
In total, 56 consecutive patients admitted for acute decompensated HF were enrolled (Age72±14 years, 29male). Their ejection fractions were uniformly reduced (HFrEF, LVEF <35%) and CKD stage 3B, 4, 5 (GFR <45ml/min/1.73m2). They were administered TLV at 7.5-15 mg/day for one week. Non-response to TLV was defined as no evidence of a 1 kg decrease in body weight (BW) during the week following TLV treatment. Blood sampling and echocardiography, including strain imaging, were performed just prior to starting TLV. Vivid q and Echo PAC PC (GE, Norway) were used for echocardiographic analyses including strain. We analyzed LV function by lobal longitudinal strain (GLS) and RV systolic function by 2D speckle strain from the 4ch view.

Results:
Although 46 patients decreased their BW by more than 1kg (Responders; ΔBW= 5.1±0.7kg), 10 patients were non-responders (ΔBW=0.5±0.4kg). Responders achieved the improvements of the symptoms (edema/ congestion). Logistic regression analysis showed that RV dysfunction (RV strain, TAPSE) was the significant predictor for non-responders. On the other hand, eGFR was not significant predictor for non-response to TLV in this population.

Conclusions:
RV dysfunction may be an important predictor of the effectiveness of TLV in patients with HFrEF with CKD. In particular, RV strain was useful was the useful predictor.
Abstract 12589: Quantitative Assessment of Mid-Systolic Deceleration and Notching in the Right Ventricular Ejection Doppler Envelope is Useful in Predicting Hemodynamics and Patient Outcomes in Pulmonary Arterial Hypertension
Authors: Takahama Hiroko , Kane Garvan C
Published: July 2021

Background:
Increased reflective wave from pulmonary artery (PA) causes mid-systolic deceleration (MSD) and notching in Doppler flow velocity envelope of RV ejection flow. Our aim is to test whether profile of MSD and notching provides insight into hemodynamics and patient outcomes in pulmonary artery hypertension (PAH), using quantitative measurements. We hypothesized that the deceleration time of the MSD slope (DTMSD), meaning the steepness of the slope, reflects interaction between RV ejection and reflective wave, and that peak velocity of post-notching flow (Vpost) reflects RV function.

Methods:
We reviewed RV ejection flow envelope recordings by pulsed wave Doppler for 157 consecutive patients with PAH between 1/2008 and 3/2013 (age 57 ± 14) with an estimated RV systolic pressure of 79 ± 23 mmHg. DTMSD was measured as the time between the first peak acceleration wave and MSD slope extrapolated to zero line. We also reviewed right heart catheterization performed within one month from echocardiography in 78 of the 157 patients.

Results:
We identified MSD and notching in 148 patients. On multivariate regression analyses, PA capacitance was the key determinant of DTMSD (beta = -0.49, p <0.0001). Vpost was determined by cardiac index (beta = -0.36, p = 0.0014). During a median follow-up period of 30 months, there were 47 deaths from all causes and 7 lung transplantations. On Cox hazard analyses, shorter DTMSD and smaller Vpost are significant predictors of higher mortality independently of each other (HR 0.92 / 10ms, p = 0.045 and HR 0.97, p = 0.028, respectively).

Conclusion:
Mid-systolic deceleration of RV ejection flow became steeper in the setting of lower PA compliance causing a greater reflectance wave. Reduced peak velocity of post-notching flow reflected impaired RV with reduced cardiac output. Quantitative assessment of profile of mid-systolic deceleration and notching in RV ejection flow envelope is useful in predicting hemodynamics and patient outcomes in PAH.