bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 15688: Electrocardiographic Patterns Differentiating "Apical Ballooning" From Anterior Myocardial Infarction
Authors: Schneider Birke , Peters Kay , Desch Udo , Stein Jürgen 
Published: July 2021

Introduction:
Left ventricular apical ballooning (AB) mimics anterior myocardial infarction (AMI). This study assessed if the ECG can differentiate between these two syndromes with a similar clinical presentation.

Methods:
Among 2086 patients (pts) with an ACS, 33 (1.6%) with AB were identified (29 f, 4 m, median age 77 years) and compared to 28 consecutive age and sex matched AMI pts undergoing PCI of the LAD with similar findings on LV angiography.

Results:
AB pts arrived at the hospital later after symptom onset (median 21 vs 5 hours; p<0.001). On the admission ECG, the number of leads with ST-segment elevation (4 [3-6] vs 5 [5-7], p=0.005) and the magnitude of ST-segment elevation (0.7 [0.5-0.9] vs 0.9 [0.7-1.5] mV, p=0.002) were greater in AMI. Reciprocal ST-segment depression was similar (27% vs 54%, p=ns). A positive T wave in aVR was more frequent in AB (49% vs 7%, p<0.001).

During follow-up, AB pts had more leads with T-wave inversion (8 [8-9] vs 6 [5-8], p<0.001) and a larger magnitude of T-wave inversion (2.9 [2.2-4.6] vs 1.4 [0.9-2.3] mV, p<0.001). T-wave inversion was similar in I, aVL and V2-V5. AB pts, however, showed negative T-waves also in lead II (74% vs 22%, p<0.001), III (34% vs 4%, p=0.004), aVF (51% vs 11%, p=0.001) and a positive T wave in aVR (100% vs 70%, p=0.005). The QTc interval was longer in AB (515 [482-543] vs 458 [435-484] ms, p<0.001). An abnormal Q wave on admission was more frequent in AMI (21% vs 79%, p<0.001) and persisted but was absent in AB at discharge (0% vs 61%, p<0.001). Ventricular tachycardia was similar (2% vs 14%, p=ns) but atrial fibrillation occurred only in AB (21% vs 0%, p=0.013). The ECG normalized in all AB but in only 1 AMI pt (p<0.001).
Overall, despite a similar ejection fraction (54±15 vs 55±13 %) and lower troponin I values (7.5±6.9 vs 238±221 ng/ml, p<0.001), AB pts developed significantly more adverse events compared to AMI pts (52% vs 18%, p<0.008).

Conclusion:
ECG patterns in AB are significantly different from those in AMI. On admission, the extent of ST-segment elevation and the number of Q waves are greater in AMI. During follow-up, no Q wave, a longer QTc interval, a greater extent of T-wave inversion and a positive T wave in aVR are typical findings in AB. Adverse events are more frequent in AB than in AMI.
Abstract 15961: Syncytial Model of Type 2 Long QT Syndrome Derived From Human iPS Cells Can Be Paced and Responds to Ikr Block and Activation
Authors: Zhu Renjun , Joshi-Mukherjee Rosy , Blazeski Adriana , Boheler Kenneth R , Tomaselli Gordon F , Tung Leslie 
Published: July 2021

Type 2 long QT (LQT2) syndrome is a cardiac disorder associated with hERG channel mutation that may lead to tachyarrhythmia and sudden death. We developed a syncytial model of cardiomyocytes (CMs) differentiated from iPS cells derived from an LQT2 patient harboring an A422T mutation. The A422T mutation has been shown to cause a marked decrease in IKr current mainly due to a trafficking defect in the hERG channel. Immunostaining of cTnI revealed that CMs were isotropically distributed with well-formed sarcomeres. Both wild type (WT) and LQT2 monolayers were stable in culture for at least 60 days with spontaneous activity, and could be paced at cycle lengths (CL) from 2000 down to 300 ms. After staining the monolayers with di-4-ANEPPS, optical mapping showed that all monolayers formed a functional syncytium that supported propagating action potentials. LQT2 monolayers had longer APD80s than WT monolayers (332±43 ms, n=6, vs. 267±46 ms, n=18, mean±SD, CL = 700 ms, p<0.005), showing the delayed repolarization expected of the LQT2 phenotype. Reentrant spiral waves were observed in LQT2 (n=2), but not WT monolayers.
Application of 0.2μM E-4031 (IKr blocker) slowed repolarization and prolonged APD80 in both WT and LQT2 monolayers, and slowed conduction velocity in WT monolayers (4.7±1.0 cm/s, n=6 vs. 10.4±1.4 cm/s, n=11 control, CL = 1000 ms). The slowing effect may reflect a role of IKr in setting the maximum diastolic potential in these CMs where IK1 is weakly expressed, as has been recently suggested. Application of 10μM ML-T531 (IKr activator) shortened APD80 in LQT2 monolayers (313±36 ms vs. 162±19 ms, n=4, p<0.0001), showing successful reversal of the LQT phenotype. ML-T531 also shortened APD80 in WT monolayers (202±43 ms vs. 154±26 ms, n=4, p<0.04). These results indicate that syncytial models of heritable cardiac disease are feasible and may be useful for studying drug effects that affect electrophysiology and arrhythmogenesis.
Abstract 16030: Heterogeneity of Electrocardiographic Findings in Cardiac Transthyretin (ATTR) Amyloidosis and Impact on Survival
Authors: Patel Ketna S , Fontana Marianna , Sachchithanantham Sajitha , Sayed Rabya , Wechalekar Ashutosh D , Lachmann Helen J , Hawkins Philip N , Whelan Carol J , Gillmore Julian D 
Published: July 2021

Introduction:
Cardiac transthyretin (ATTR) amyloidosis is an increasingly diagnosed cause of heart failure. Wild-type ATTR amyloidosis (ATTRwt) is a disease of older Caucasian men. Hereditary (mutant) cardiac ATTR amyloidosis (ATTRm) is most commonly associated with the V122I transthyretin (TTR) variant carried by 3-4% of African Americans or the T60A TTR variant in patients of Irish ancestry, the latter presenting with a mixed cardiac and neurologic phenotype. Most published data consider electrocardiographic (ECG) findings in ATTR amyloidosis as a single entity. Prognostic factors for survival in cardiac ATTR amyloidosis are poorly defined.

Methods and Results:
We analysed ECGs from 158 patients with cardiac ATTR amyloidosis (ATTRwt=75; V122I=49; T60A=34) in a longitudinal retrospective study.

Results are shown in Table 1.
63 patients died; 29 ATTRwt, 24 V122I, 10 T60A, during follow-up of 22.7±14.6, 23.8±12.8, and 31.3±20.4 months respectively. Overall median survival: ATTRwt 3.1yr (95%CI:2.2-4.0); V122I 2.6 yr (95%CI:2.2-3.0); T60A not reached. In ATTRwt, broad QRS (≥120ms) was associated with worse survival (1.6yr; 95%CI:1.3-1.9 vs not reached). No other ECG parameter in ATTRwt, and none in either ATTRm group affected survival. On univariate analysis of the ATTRwt cohort, broad QRS, age, systolic BP, TropT and NTproBNP were significant variables at the <1% level, and eGFR at the 5% level; LVEF, septal S’ TDI and global longitudinal strain were not significant. On multivariate analysis only broad QRS (HR: 3.0, CI 1.2-7.5; P=0.024) and NTproBNP (HR: 3.0, CI 1.1-7.4; P=0.026) predicted mortality. Among ATTRwt patients, there were no significant differences of other characteristics between those with narrow and those with broad QRS complexes.

Conclusions:
The ECG in cardiac ATTR amyloidosis is heterogeneous, greater awareness of which might help prevent diagnostic delays. Broad QRS complexes and NTproBNP are independent predictors of mortality in ATTRwt.
Abstract 17128: Pathophysiology of Coronary Artery Disease in Hiv-infected Patients: Dissociation Between Anatomy and Function
Authors: Mancone Massimo , Cinque Alessandra , Bruno Noemi , Armato Alessandra , Salvi Nicolò , Ceccacci Andrea , Bruno Pasqualina , Sardella Gennaro , d’Ettorre Gabriella , Vullo Vincenzo , Fedele Francesco 
Published: July 2021

Introduction:
Numerous reports suggest, among HIV+ patients (pts), an increased rate of acute coronary syndrome and cardiac death. Several data suggest that endothelial dysfunction is a major mechanisms in the development of coronary atherosclerosis in non-HIV infected patients.

Hypothesis:
The aim of our study is to assess coronary microvascular function using Doppler-flow wire in HIV+ patients in therapy with HAART.

Methods:
Thirteen HIV-infected patients were enrolled from the Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences of the “Sapienza” University of Rome (Italy).

The main inclusion criteria were: Framingham risk score <10%, absence of metabolic syndrome (according to the definition of Adult Treatment Panel III e ATPIII12), negative echocardiographic and ECG stress-test and negative for anti-HCV antibodies.
Diagnostic coronary angiography was performed via percutaneous radial approach. Microvascular function was assessed by measuring coronary flow velocity reserve (CFR). Intracoronary functional tests were performed to evaluate both endothelium-dependent microvascular function [via intracoronary (IC) infusion of acetylcholine (2.5[[Unable to Display Character: &#8211;]]10 μg)] and non-endothelium-dependent microvascular function [via IC infusion of adenosine (5 μg) ].

Results:
All the patients presented a Framingham risk score <10%. The medium age was 53.3±4.1 years. The mean duration of highly active antiretroviral therapy was 12.9±2.4 years. Thirteen patients presented 23 coronary atherosclerotic plaques; while endothelium and non endothelium-dependent microvascular function was quite normal in our population (CFR after adenosine 2.37±0.4; CFR after Achetylcholine 2.43±0.4).

Conclusion:
Microvascular function is not compromised in HIV + pts who presented coronary atherosclerotic plaque. Microvascular dysfunction, involved in pathophysiology of coronary artery disease in general population, seems to be not implicated in coronary atherosclerosis in HIV + pts. These data suggest a peculiar pathophysiological mechanisms for HIV related atherosclerosis.
Abstract 17620: Does Doppler E/e’ Ratio Reliably Estimate Diastolic Filling Pressures in Stress Cardiomyopathy?: A Validation Study in Apical and non-Apical Phenotypes
Authors: Iskandar Aline , Aurigemma Gerard P , Fitzgibbons Timothy P , Ahmed Mohammed , Tighe Dennis 
Published: July 2021

BACKGROUND:
We have recently shown that mean LV end diastolic pressure (LVEDP) is commonly elevated in apical ("Tako-tsubo") stress cardiomyopathy (SCM) and likely contributes to heart failure in this syndrome. The assessment of diastolic filling pressures by use of E/e’ ratio (early diastolic transmitral E to tissue Doppler e') has been applied to many forms of heart disease, but has not been validated in SCM, and has not been studied in the apical sparing variant.

METHODS:
We identified 62 patients with SCM, 43 patients with apical/Tako-tsubo SCM and 19 patients with apical sparing (basal and midventricular) variant of SCM, who underwent measurement of E/e', using the average of lateral and septal e’ (cm/s), within 48 hours of direct invasive measurement of LVEDP (mm Hg).

RESULTS:
LVEDP was significantly higher in apical sparing SCM compared to apical SCM (28 ± 6 mmHg vs. 22 ± 7 mmHg, p<0.002). LVEDP directly correlated with E/e’ ratio in apical SCM (r = 0.64, p < 0.0001, Figure 1). When individual data were examined, we found that of the apical SCM group, 3 pts had normal LVEDP and were correctly identified with normal E/e’ ratio (< 8). All apical SCM patients with elevated LVEDP (16 mm Hg or greater) had E/e’ > 8, and fifteen of these had E/e’ ratio > 15.

By contrast, all apical sparing SCM had elevated LVEDP. In this group, E/e’ did not predict LVEDP: the overall correlation between E/e’ and LVEDP (r = 0.27, p = 0.26, Figure 2) was poor. When individual data were examined, 5 patients with elevated LVEDP had normal E/e’ and, of the remaining 14 patients with elevated LVEDP, only 1 patient had E/e’ >15.

CONCLUSION:
Our results demonstrate:

1.
Elevated LVEDP is found among 95% of SCM, regardless of the phenotype.

2.
Unexpectedly, apical sparing SCM appears to have worse impairment of diastolic function and higher LVEDP than apical variant SCM

3.
E/e’ ratio reliably predicts LVEDP in pts with apical variant SCM; by contrast, this index underestimates LVEDP among patients with apical sparing SCM.
Abstract 18412: Long Non-coding RNA Meg3 Regulates Senescence-associated Genes and Controls Endothelial Cell Function
Authors: Boon Reinier , Hofmann Patrick , Michalik Katharina , Knau Andrea , Ponomareva Yuliya , Zeiher Andreas , Uchida Shizuka , Dimmeler Stefanie 
Published: July 2021

The majority of transcribed RNAs does not encode proteins, but function as regulatory RNAs. Non-protein-coding RNA are classified in short (<200 nt) and long (>200 nt) non-coding RNAs (lncRNAs). lncRNAs have been described to play an important role in many biological processes, including epigenetic regulation of gene expression.
To determine the expression and functional role of lncRNAs in endothelial cells, we performed RNA deep sequencing of human umbilical venous endothelial cells (ECs). Among the highest expressed lncRNAs, we identified Maternally Expressed 3 (Meg3, 35.3±0.6 RPKM), which has been correlated to VEGF expression. In HUVECs, Meg3 localizes to the nucleus and is induced by hypoxia (4.08±0.78-fold, p<0.05). Interestingly, Meg3 was also found to be induced in the intima of aged mice and correlates with age in human hearts (p=0.016). Meg3 levels are also induced in replicative senescent HUVECs in vitro (passage 16/17 vs 2/3, 2.9±0.99-fold).Conversely, silencing of Meg3 using LNA-GapmeRs induced angiogenic sprouting of endothelial cells in vitro (1.4±0.14-fold, P<0.05) but did not affect caspase-3 activation. Mechanistically, RNA immunoprecipations showed that Meg3 associates specifically to H3K27me3, a silencing chromatin mark. Silencing of Meg3 in HUVECs induces a robust repression of global gene expression, as measured by exon array analysis, with a highly significant repression of the anti-senescent HMGA2.
In summary these results demonstrate, that the lncRNA Meg3 is highly expressed in endothelial cells and is up-regulated by hypoxia and aging. Functionally, Meg3 inhibits sprouting angiogenesis in vitro. Meg3 depletion leads to a general repression of gene expression and the senescence marker HMGA2 likely by inducing the recruitment of silencing H3K27me3 marks to the promoters Therefore, modulating Meg3 may be a potential strategy to reduce endothelial senescence or increase regenerative angiogenesis.
Abstract P155: Weight Gain and Insulin Sensitivity in Adults With and Without Type 1 Diabetes
Authors: Duca Lindsey M , Schauer Irene E , Snell-Bergeon Janet K 
Published: July 2021

People with type 1 diabetes mellitus (T1D) have reduced insulin sensitivity (IS), which partially explains their increased risk of cardiovascular disease. However, there is limited data on how weight gain alters IS in T1D, and so this study aimed to analyze the effect of weight change on IS components in T1D and non-diabetic (non-DM) adults.
This study included 1133 adults (T1D=528 and non-DM n=605) with a mean ± SD age of 38 ± 9 years from the Coronary Artery Calcification in Type 1 Diabetes cohort, examined at baseline and after 6.2±0.6 years. Weight change was categorized as follows: weight loss (WL), lost > 2%), weight stable (WS), within 2% of baseline, and weight gain (WG), > 2%. Estimated IS (eIS) was calculated by a model derived from a clamp study (Table) at each visit. Multiple age and sex adjusted least squares means were calculated by weight change group and diabetes status, and progression of coronary artery calcium (CAC) was examined by logistic regression.
There was a significant improvement in eIS in the T1D WL group, along with a greater reduction in triglycerides and insulin dose and increase in adiponectin compared to the other weight change groups (Table). There was significant increase in eIS among the non-DM WL group, along with a reduction in triglycerides, fasting glucose, HbA1c and DBP and an increase in adiponectin. For each 2% increase in weight, the odds ratio (OR) for progression of CAC was 1.23 (95% CI 1.1-1.4, p=0.002), after adjusting for age, sex, diabetes status, and baseline BMI and CAC. The odds of CAC progression were decreased by 40% (OR 0.6, 95% CI 0.5-0.8, p=0.0007) for each SD increase in eIS, adjusting for the same variables.
In conclusion, over 6 years of follow-up, weight loss increased eIS and related factors in both people with and without T1D, but was not associated with improved Hba1c in T1D. Additionally, weight gain was associated with a greater risk and eIS with a lower risk for CAC progression, demonstrating the importance of avoiding weight gain in prevention of subclinical cardiovascular disease.
Abstract 199: Vasospastic Angina In A School Child Long After Kawasaki Disease
Authors: Kudo Yoshiyuki , Suda Kenji , Kishimoto Shintaro , Yoshimoto Hironaga , Matsuishi Toyojiro , Nishihara Shigetaka 
Published: July 2021

Though it has been already reported that the endothelial function was impaired in patients with a history of Kawasaki disease (KD) and coronary artery aneurysms, vasospastic angina has been rarely reported, especially in school child.
A 13-year-old school child referred to us because of repeated chest pain on exercise and reverse redistribution in myocardial perfusion scan. His past history included KD at 2 years of age that was complicated by resistance to initial immunoglobulin treatment and he was left with coronary aneurysms; left main trunk (LMT) of 6.1mm, left anterior descending artery (LAD) of 6.0mm, and right coronary artery (RCA) of 6.0mm. He received oral warfarin treatment in addition to aspirin for 2 years and since then aspirin alone. Coronary angiogram at 7 years old showed LMT aneurysm of 6.1mm starting from orifice extending to bifurcation and regression of RCA aneurysm. He joined baseball club since 8 years old and has been doing well without any symptoms. In this summer, he started complain chest pain after 10 minutes of running 2-3 times a week that lasts for about 30 minutes. Though exercise stress test using treadmill did not show any abnormal electrocardiographic finding, stress myocardial perfusion scan using Thallous chloride-201Tl showed an area of reverse redistribution in the LAD territory. Baseline coronary angiogram at this time showed basically the same finding as that in the last study, intact RCA without stenosis and LMT aneurysm without any stenosis. However, provocative study using intra-coronary administration of 100 ug of acetylcholine, showed diffuse coronary artery spasm in all LCA branches and he indeed complained the same chest pain as that felt in exercise. In addition, intra-coronary administration of nitroglycerine completely reversed coronary spasm and chest pain.

Conclusion:
Vasospastic angina with chest pain can occurred in the school child with coronary artery aneurysms without coronary stenosis long after KD.
Abstract 11427: Calcium Mobilization From Endoplasmic Reticulum Involves Calmodulin-mediated NADPH Oxidase-derived Reactive Oxygen Species Production in Porcine Aortic Endothelial Cells
Authors: Odagiri Keiichi , Hakamata Akio , Watanabe Hiroshi 
Published: July 2021

Introduction:
Previous studies indicate that calcium/calmodulin (Ca
2+
/CaM) mediates the phosphorylation and activation of NADPH oxidase (NOX). In endothelial cells, elevation of intracellular Ca
2+
concentration ([Ca
2+
]
i
) level consists of two components, mobilization of Ca
2+
from intracellular stores and subsequent store-operated Ca
2+
entry (SOCE). However, little is known which component is required to regulate NOX-derived ROS production via Ca
2+
/CaM dependent pathway in endothelial cells.

Hypothesis:
We hypothesized that Ca
2+
mobilization from endoplasmic reticulum (ER), but not SOCE, is required to regulate NOX-derived ROS via Ca
2+
/CaM dependent pathway in porcine aortic endothelial cells (PAECs).

Methods:
We evaluated the association between Ca
2+
/CaM mediated NOX-derived ROS production and Ca
2+
mobilization from ER. We measured [Ca
2+
]
i
by fura-2/AM a production of ROS by C-DCDHF-DA and in primary cultured PAECs with a fluorescence imaging and analysis system.

Results:
(1) In the presence of 1mM extracellular Ca
2+
([Ca
2+
]
o
), BK induced a rapid increase [Ca
2+
]
i
and followed by a sustained increase. However, in the absence of [Ca
2+
]
o
(0mM with EGTA 1mM), BK caused only a small and transient increase [Ca
2+
]
i
which was cause by Ca
2+
mobilization from ER.

(2) BK (1μM) rapidly increased fluorescence intensity of C-DCDHF-DA compared with control. (150.2±51.3% and 107.2±5.6% of the baseline, respectively, p<0.05).
(3) BK-induced ROS production was inhibited by an inhibitor of NOX (VAS2870: 50μM) (125.5±9.9% of the baseline, respectively, p<0.05).

(4) When cells were exposed to BK with or without [Ca
2+
]
o
, there was no difference in BK-induced ROS production.

(5) In the absence of [Ca
2+
]
o
, BK-induced ROS production is inhibited by an inhibitor of calmodulin (W-7: 100μM) (121.3±13.1% of the baseline, p<0.05). Thapsigargin (an inhibitor of ER calcium ATPase: 1μM) and BAPTA/AM (100μM) eliminated BK-induced ROS production (110.0±5.1% and 115.7±9.5% of the baseline, respectively, p<0.05 vs 1mM [Ca
2+
]
o
).

Conclusions:
The NOX-derived ROS production by BK is mediated via Ca
2+
/CaM dependent pathway. This was strictly regulated by Ca
2+
mobilization from ER.
Abstract 15370: Genetic Study Identifies Common Variation in PHACTR1 to Associate With Fibromuscular Dysplasia
(Best of Basic Science Abstract)
Authors: Kiando Soto Romuald , Tucker Nathan , Katz Alexander , Tréard Cyrielle , D’Escamard Valentina , Castro-Vega Luis J , Ye Zi , Smith Carin Y , Austin Erin , Barlasina Cristina , Cusi Daniele , Galan Pilar , Empana Jean-Philippe , Jouven Xavier , Brunval Patrick , Olin Jeffrey W , Gornik Heather , Plouin Pierre-François , Kullo Iftikhar J , Milan David J , Ganesh Santhi K , Boutouyrie Pierre , Kovacic Jason , Jeunemaitre Xavier , Bouatia-Naji Nabila 
Published: July 2021

Fibromuscular dysplasia (FMD) is a nonatherosclerotic vascular disease leading to arterial stenosis, aneurysm and dissection, mainly in renal and carotid arteries. FMD has higher prevalence in females (80-90%) and is associated with hypertension and stroke. The pathophysiology of FMD is unclear and a genetic origin is suspected.
We performed a genetic association study in European ancestry individuals. The discovery included 249 cases and 689 controls, in which we analyzed ∼26K common variants (MAF>0.05) using an exome-chip array. We followed up 13 loci (P<10-4) in 393 cases and 2537 controls and replicated a signal on Chr6. Three additional studies (combined Ncases=512, Ncontrols=669) confirmed this association, with an overall OR of 1.39, (P=7.4х10e-10 , All Ncases=1154, All Ncontrols=3895).
The FMD risk variant is intronic to the phosphatase and actin regulator 1 gene (PHACTR1), involved in angiogenesis and cell migration. PHACTR1 is a risk locus for coronary artery disease, migraine, and cervical artery dissection, which may occur in FMD. We found a significant association between the risk allele and higher central pulse pressure (P=0.0009), increased intima media thickness (P=0.001) and wall cross-sectional area (P=0.003) of carotids assessed by echotracking in 3800 population-based individuals. The correlation of genotypes with the expression of PHACTR1 in primary cultured human fibroblasts showed higher expression in FMD risk allele carriers, compared to non carriers (N=57, P=0.02). Finally, Phactr1 knockdown of zebrafish showed significantly dilated vessels (P=0.003) indicating impaired vascular development.
In conclusion, we report the first risk locus for FMD with the largest genetic association study conducted so far. Our data reveal a common genetic variant at PHACTR1 providing indices of shared pathophysiology between FMD and other cardiovascular and neurovascular diseases.