bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13499: A 34-year-old Man With Debilitating Polyneuropathy, Pericardial Effusion and Monoclonal Gammopathy Presents With Right Heart Failure
Authors: Nakamura Kenta , Zhang Mary H , Shin Jordan T
Published: July 2021

A 34-year-old man with debilitating polyneuropathy and monoclonal gammopathy presents with progressive lower extremity edema, pericardial effusion and dyspnea. Pulmonary edema, elevated jugular venous pressure and peripheral edema suggested right heart failure, and dyspnea responded initially to diuresis. Echocardiography revealed occult pericardal effusion, right heart dysfunction and estimated right ventricular systolic pressure of 54 mmHg. The differential diagnosis included pulmonary hypertension secondary to chronic pulmonary or left heart processes, pericardial constriction, restrictive myopathy or a syndromic condition capturing his neurologic and hematologic findings. Chest CT and VQ-scan were negative for acute and chronic pulmonary thromboembolic disease, respectively. Cardiac magnetic resonance imaging was most consistent with amyloidosis. Pericardial enhancement was normal, arguing against constriction. Amyloidosis was thought to be unlikely given preserved left ventricular size and function, increase in both serum free κ and λ light chains, and was ultimately excluded by fat pad biopsy. The paraneoplastic disease Crow-Fukase or POEMS syndrome, classically described as polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes explained the patient’s constellation of signs and symptoms. Pulmonary hypertension subsequent to cor pulmonale is common and reversible with treatment of the underlying gammopathy. Diagnosis of the POEMS syndrome was confirmed by the presence of sclerotic bone lesions and markedly elevated vascular endothelial growth factor (VEGF) level of 1028 pg/mL (ref. range 31-86 pg/mL). VEGF is highly induced in the POEMS syndrome and correlates closely with disease activity. VEGF-mediated microangiopathy, neovascularization, and vasopermeability likely underlie multiple clinical sequelae of extravascular volume overload such as pericardial effusion and peripheral edema. The patient responded to sildenafil for pulmonary arterial hypertension and immunomodulatory therapy for the monoclonal gammopathy. At six months of treatment, the patient has recovered substantial strength, heart failure has not reoccurred and repeat VEGF level reduced to 383 pg/mL.
Abstract 13520: Sex Differences in Clinical Characteristics and Outcomes of Patients with Heart Failure with Preserved Ejection Fraction -A Report from the CHART-2 Study
Authors: Tsuji Kanako , Sakata Yasuhiko , Miura Masanobu , Miyata Satoshi , Nochioka Kotaro , Tadaki Soichiro , Ushigome Ryoichi , Yamauchi Takeshi , Sato Kenjiro , Onose Takeo , Abe Ruri , Takahashi Jun , Shimokawa Hiroaki
Published: July 2021

Background:
Several studies have reported that the prognosis of patients with heart failure with preserved ejection fraction (HFpEF) was similar to that of patients with reduced ejection fraction. However, sex differences in clinical characteristics and mortality of HFpEF patients remains to be fully elucidated.

Methods:
Among the 10,219 patients registered in our Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study, we examined sex differences in clinical characteristics, treatment and long-term outcome of 3,124 patients with HFpEF in stage C/D (EF≥50%, mean age 69.4 years, 34.7% female). We constructed the Kaplan-Meier curves and Cox hazard models for all-cause death to evaluate sex difference in mortality.

Results:
Female patients, as compared with male patients, were characterized by higher age (71.6 vs. 68.3 years, P<0.001), higher prevalence of NYHA class III/IV (14.1 vs. 7.0%, P<0.001), higher left ventricular ejection fraction (67.2 vs. 64.5%, P<0.001), and higher brain natriuretic peptide levels (106 vs. 72.9pg/ml, P<0.001). Furthermore, less female patients received beta-blockers (37.8 vs. 43.9%, P=0.001) and renin-angiotensin system inhibitors (64.7 vs. 71.8%, P<0.001) compared with males. During the median 3.2-year follow-up, 392 patients (12.5%) died. Although Kaplan-Meier curves showed that the crude mortality was comparable between males and females (hazard ratio (HR) 1.18, P=0.11), the adjusted mortality risk was significantly lower in females (HR 0.72, P=0.009) (Figure). Female patients died due to cardiovascular causes more frequently than males (53.7 vs. 39.2%, P<0.01).

Conclusions:
Although female HFpEF patients had comparable all-cause mortality with males, they had severer HF and higher cardiovascular mortality than males.
Abstract 13585: Up Regulation of Autophagy in Hsp60 Mutant Heart is an Adaptive Response to Increased Oxidative Stress and Causes Cardiomyopathy
Authors: Enomoto Hirokazu , Makino Shinji , Mittal Nishant , Kimura Akinori , Arimura Takuro , Hayashi Takeharu , Inomata Takayuki , Fukuda Keiichi
Published: July 2021

Introduction:
Despite the recent advance of genetic studies, genetic causes of hereditary dilated cardiomyopathy (DCM) are still unknown in most cases. Heat shock protein 60 (Hsp60) is a well-known chaperonin, responsible for correct folding and transportation of cytoplasmic protein to mitochondria. This study is aimed to investigate whether dysfunction of Hsp60 leads to cardiomyopathy in a fish model.

Methods:
We previously developed a zebrafish mutant, nbl, which has a missense mutation in hsp60, leading to the loss of function. To evaluate the phenotype of cardiomyopathy in nbl, we performed RT-PCR, western blot and immunohistochemistry of the hearts.

Results:
Homozygous nbl embryos showed lower survival rate (65%), compared to 81% in wild-type (WT) embryos, when subjected to 33°C (stress condition). We observed pericardial edema in 92% of nbl homozygous mutants. Also, nbl homozygotes showed sudden death at around 8 months post fertilization (mpf), when grown in non-stress condition. At 8 mpf, nbl mutants showed dilated heart and high expression of reactive oxygen species (ROS). Both mRNA and protein levels of Hsp60 were similar in nbl homozygotes and WT, at 3 mpf but, much higher expression of Hsp60 in nbl homozygotes was observed at 6 mpf, beginning of death of nbl homozygous mutants. Electron microscopy analysis showed dark mitochondria, disrupted sarcomeric structure and higher number of autophagosomes in nbl homozygote hearts at 8 mpf. We, then, analyzed autophagy related genes and found that atg5, atg3 and gabarap mRNAs were increased in nbl homozygotes, suggesting the increased autophagy might underlie the pathogenesis of DCM. Furthermore, analysis of genetically unrelated patients with familial DCM, who had no mutations in the known DCM-causing genes, identified an hsp60 mutation in one DCM family in which two of four mutation prone individuals died suddenly. Over expression of nbl mutation or DCM-associated hsp60 mutation, but not normal hsp60, increased autophagosomes in Hela cells carrying GFP-LC3.

Conclusions:
Functional loss of Hsp60 increased oxidative stress in the heart, which leads to increased autophagy and confer the susceptibility to cardiomyopathy.
Abstract 13673: Aging Impairs Cardiac Akt Activity Leading to Myocardial Sarcopenia
Authors: Bando Yasuko K , Aoyama Morihko , Kawase Haruya , Monji Akio , Xiangwu Cheng , Kuzuya Masafumi , Murohara Toyoaki
Published: July 2021

Introduction:
Aging causes skeletal muscle atrophy (i.e. sarcopenia). In heart, aging is also known to cause cardiac dysfunction such as diastolic dysfunction; however, the impact of aging on myocardial cell growth remains uncertain.

Hypothesis:
Because of the pivotal role of protein kinase Akt in cellular aging and growth of cardiomyocytes, we hypothesized whether #1 aging may impairs cardiac Akt activation leading to myocardial atrophy in aged heart and #2 regular exercise may enhance cardiac Akt activity, leading to augmentation of cardiomyocyte growth that results in reversal of the aging-mediated cardiac atrophy.

Methods:
[cohort-1]: Male genetically senescence-accelerated [(SAM; senescence-accelerated prone (P10)] and senescence-resistant counterpart (R1) were allocated to EX [60-min running by treadmill/day for 6 months] and EX-free control (CON).

[cohort-2] Male aged (40 w/o) and young (14 w/o) C57BL6 mice were subjected to the EX (agedC57EX and agedC57CON).

Results:
At baseline, cardiac geometry of R1 revealed normal, whereas P10 exhibited LV wall thinning and diastolic dysfunction. Systolic function of both P10 and R1 was preserved. After EX, body and heart weight (HW/BW) of R1 were increased (BW; +6.7% and HW; +3.5% versus R1CON); however, EX had no influence on HW/BW of P10. EX promoted LV hypertrophy in R1EX with concomitant increase in cardiac capillary density through activation of Akt/eNOS pathway, which was absent in P10EX. EX had no influence on systolic function of R1EX, however, EX promoted systolic dysfunction in P10EX [EF(%) 68.9±1.5 for P10EX versus 74.3±1.2 for P10CON] with attenuation of phosphorylated Akt and phospholamban levels in myocardium. In youngC57EX, EX promoted myocardial hypertrophy with augmentation of cardiac Akt/mTOR/S6K axis, which was diminished in agedC57EX. Age- and gender-matched Akt knockout mice exhibited lack of the EX-induced cardiac hypertrophy.

Conclusions:
Aging promotes cardiac sarcopenia in mice, in which Akt plays an essential role. EX-induced adaptive cardiac hypertrophy requires Akt activation and aging heart lacks the EX-induced Akt activation.
Abstract 13678: HDL Cholesterol, Leptin and Interleukin-6 Are Independent Predictors of Coronary Atherosclerotic Burden and Plaque Composition Assessed by Coronary Ct Angiography in Patient With Stable Angina
Authors: Caselli Chiara , De Graaf Michiel , Lorenzoni Valentina , Rovai Daniele , Marinelli Martina , Del Ry Silvia , Giannessi Daniela , Neglia Danilo , Scholte Arthur
Published: July 2021

Introduction:
Coronary CT angiography (CTA) has been used to develop a novel CTA risk score for risk stratification of individual patients with stable angina. The new score integrates several features of coronary artery disease (CAD), i.e. plaque location, severity, and composition on coronary segments basis.

Hypothesis:
We hypothesized that circulating biomarkers related with metabolism and inflammation could be associated with the CTA risk score and its components.

Methods:
In 429 patients (60.3 ±0.4 years, 268 males) with chronic chest pain, enrolled in the European EVINCI study and submitted to quantitative CTA, a panel of 17 biomarkers was evaluated. The CTA risk score was calculated to assess overall atherosclerotic burden based on plaque extent, severity, composition, and location. Univariate and multivariate analysis was used to identify biomarkers associated with the CTA score.

Results:
Only three biomarkers [HDL cholesterol, Interleukin (IL)-6 and leptin] were independent predictors of the overall atherosclerotic burden expressed by the CTA risk score (HDL: Coefficient - 0.129 (SE 0.03), p < 0.0001; IL-6: 1.330 (0.42), p = 0.0017; leptin: - 0.166 (0.05), p = 0.0011), even after correction for clinical variables and medications. Lower HDL cholesterol levels and higher IL-6 were associated with non-calcified and mixed plaques, while lower leptin with mixed and calcified plaques (Fig. A).

Conclusions:
In patients with stable angina, circulating biomarkers, expressing abnormal cholesterol and lipid profiles as well as enhanced inflammatory process, are independently associated with the overall coronary atherosclerotic burden assessed by an integrated CTA risk score. HDL cholesterol and IL6 are markers of more vulnerable plaque types.
Abstract 13720: High Serum Levels of Thrombospondin-2 Correlate with Poor Prognosis of Patients with Heart Failure with Preserved Ejection Fraction
Authors: Kimura Yuichi , Izumiya Yasuhiro , Hanatani Shinsuke , Onoue Yoshiro , Araki Satoshi , Ogawa Hisao
Published: July 2021

Introduction:
Thrombospondin-2 (TSP-2) is highly expressed in hypertensive heart. Interstitial fibrosis is frequently observed in hypertensive heart, and it is a characteristic feature of heart failure with preserved ejection fraction (HFpEF).

Hypothesis:
High TSP-2 serum levels reflect disease severity and can predict poor prognosis of patients with HFpEF.

Methods:
Serum TSP-2 levels were measured by ELISA in 150 patients with HFpEF. HFpEF was defined as clinical signs or symptom of HF, left ventricular ejection fraction >50%, B-type natriuretic peptide (BNP) >100 pg/ml or E/e’ >15. The endpoints of this study were mortality rate, HF-related hospitalization, stroke and non-fatal myocardial infarction.

Results:
The median serum TSP-2 level was 19.2 (14.4-26.0) ng/ml in all study participants. Serum TSP-2 levels correlated with the New York Heart Association (NYHA) functional class. Then the patients were divided into high and low TSP-2 groups based on the median value. Pulmonary capillary wedge pressure, and circulating levels of BNP and high-sensitivity cardiac troponin T were significantly higher in the high TSP-2 group than low TSP-2 group. Whereas, cardiac index was significantly lower in the high TSP-2 group. Kaplan-Meier survival curve showed high risk of adverse cardiovascular events in the high TSP-2 group, and that the combination of high TSP-2 and high BNP (>100 pg/ml) was associated with the worst event-free survival rate. Univariate Cox proportional hazard analysis showed that high levels of TSP-2, NYHA functional class, presence of atrial fibrillation, high levels of BNP, left atrium dilatation were associated with future adverse events. Stepwise multivariate Cox proportional hazard analysis identified BNP (ln(BNP)) (hazard ratio [HR]: 1.98; confidence interval [CI]: 1.26-3.10, p=0.003) and TSP-2 (HR: 2.59; CI: 1.09-6.14, p=0.031) as independent predictors of risk of death and cardiovascular events.

Conclusions:
Circulating TSP-2 correlates with disease severity in patients with HFpEF. TSP-2 is a potentially useful predictor of future adverse cardiovascular events in patients with HFpEF.
Abstract 13765: Impact of Atrial Fibrillation on Clinical Outcomes After Transcatheter Aortic Valve Implantation. Study From the FRANCE 2 Registry
Authors: Chopard Romain , Meneveau Nicolas , Chocron Sidney , Gilard Martine , Laskar Marc , Eltchaninoff Helene , Iung Bernard , Leprince Pascal , Teiger Emmanuel , Chevreul Karine , Prat Alain , Lievre Michel , Leguerrier Alain , Donzeau-Gouge Patrick , Fajadet Jean , Schiele Francois
Published: July 2021

Introduction:
Atrial fibrillation (AF) is well-known to be associated with mortality and morbidity after conventional cardiac surgery. In the present sub-analysis of the FRANCE 2 registry, we investigated the impact of AF on VARC-defined outcomes in patients with severe aortic stenosis undergoing transcatether aortic valve implantation (TAVI).

Methods:
The FRANCE 2 registry included all TAVI performed in France between January 2010 and December 2011. Analyses were performed at 2 different time points: (1) AF vs no AF, before valve implantation, and (2) AF vs no AF, after the procedure, among the survivors at day 2. Comparisons of clinical outcomes at 30 days and 1 year, between patients with and without AF, were adjusted for baseline (all analysis) and procedural (analysis 2) characteristics by multivariate analysis.

Results:
In total, 3875 patients whose pre-TAVI ECG was reported were included (25.8% with AF) (study population for analysis 1). Procedural success was 94% in the non-AF group and 94.5% in the AF group. Three hundred thirteen patients (8.1%) died during the first 24 hours (non-AF: 7.8%, AF: 9.2%; P=0.13); 3377 were alive at day 2 with an ECG (study population for analysis 2); 827 (24.5%) were in AF, including 164 patients with new onset AF (4.8%). The main findings concerning the clinical outcomes of the study populations are displayed in the table. The higher rate of VARC-defined combined efficacy endpoint observed in patients with AF vs those without, in both analysis, is driven by cardiovascular deaths, worsening congestive heart failure and NYHA functional status class III or IV.

Conclusion:
AF, before and after TAVI, is associated with a higher rate of one-year mortality and morbidity.
Abstract 13783: Paradigms to Predict Cardiometabolic Disease in African Descent Populations Should Focus on HDL-Cholesterol Rather than Triglyceride
Authors: Sumner Anne E , Thoreson Caroline K , Ricks Madia , Chung Stephanie T
Published: July 2021

Paradigms for the early detection of cardiometabolic disease usually incorporate both elevated triglyceride (TG) and low high density lipoprotein -cholesterol (HDL-C). However, African-Americans with cardiometabolic disease usually have normal TG levels. The HDL-C pattern of African-Americans with cardiometabolic disease is uncertain. The TG and HDL-C pattern in Africans with cardiometabolic disease is unknown. To clarify the TG and HDL-C pattern in African descent populations with cardiometabolic disease, 377 blacks (167 African-Americans, 210 African immigrants, 59% male, age 36±9y, mean±SD, range 20-64y, BMI 29.0±6.3 kg/m2, range 18.5-54.7) had glucose tolerance status determined by OGTT, lipid profiles and insulin resistance determined by the insulin sensitivity index (SI). Insulin resistance was defined as the lowest quartile of SI (<2.18 L/mU - 1min- 1). Metabolic triad was defined as hyperinsulinemia (fasting insulin≥3.7 μU/mL), hyperapolipoproteinB (≥64 mg/dL) and sdLDL(≥21.5 nm) based on the median values of the group with normal BMI. Cardiometabolic disease was defined as one or more of the following: pre-diabetes, diabetes, insulin resistance or metabolic triad. The frequency with which hypertriglyceridemia (TG≥150 mg/dL) or low HDL-C (<40 mg/dL in men or <50 mg/dL in women) occurred in the presence of cardiometabolic disease was determined. The prevalence of cardiometabolic disease did not differ in African-Americans and African immigrants (63% vs. 60%, P=0.51). TG and HDL-C levels in blacks with cardiometabolic disease did not differ by African ancestry. In the presence of cardiometabolic disease, TG levels were 80±40 vs. 87±43, P=0.24, resp. while HDL-C levels in men were: 45±11 vs. 44±12, P=0.63, and in women: 48±10 vs. 49±10, P=0.86). Less than 10% of people with cardiometabolic disease had TG≥150 mg/dL. However, 42% of people with cardiometabolic disease had low HDL-C. If HDL-C levels were low, the odds of having cardiometabolic disease was 2.84 (95% CI 1.76, 4.59. P<0.001). Overall, more than 40% of people with cardiometabolic disease had low HDL while <10% had elevated TG levels. Therefore, paradigms to detect cardiometabolic disease in African descent populations should focus on HDL-C rather than TG.
Abstract 13799: Electrical Pacing Inhibits Gap Junction-Mediated Cardiac Cell -Cell Communication by Promoting Cx43-Acetylation
Authors: Azzimato Valerio , Meraviglia Viviana , Colussi Claudia , Florio Maria Cristina , Panariti Alice , Qanud Khaled , Gaetano Carlo , Pramstaller Peter P , Capogrossi Maurizio C , Pompilio Giulio , Recchia Fabio A , Rivolta Ilaria , Rossini Alessandra
Published: July 2021

Background:
Communication among cardiomyocytes depends upon Gap Junction (GJ) protein expression and conductance. Previous studies demonstrated that electrical stimulation can induce GJ remodeling and evidences from neurons also indicate that electrical pacing modifies Lysine acetylase (KAT) and deacetylases (KDAC) activities.

Objectives:
Aim of the present work was to establish whether electrical stimulation modulates GJ-mediated cardiac cell-cell communication by acetylation dependent mechanisms.

Methods and Results:
Neonatal rat cardiomyocytes (NRCM; n=3) and in HL-1 atrial cells (n=20) were exposed to electrical field stimulation for 24 hours (Ionoptix C-Pace®; 0.5 Hz, 20 V, 0.5 msec pulses). Connexin 43 (Cx43) expression decreased almost 50% in NRCM and 40 % in HL-1; in contrast Cx40 and Cx45 expression was unchanged. Further, confocal microscopy revealed that electrical stimulation induced Cx43 accumulation in the cytoplasm of HL-1 cells. Electrical stimulation significatly down-regulated KDAC activity up to the 30% (n=3), whereas KAT activity was not modified; the net effect was a general increase of cell protein acetylation, confirmed by western blot analysis. Specifically, the pacing-dependent acetylation of Cx43 was proven by immunoprecipitation assay (n=5). Interestingly, our model mimicked the action of the KDAC pan-inhibitors TSA and SAHA on Cx43 expression and intracellular distribution, although we did not observe Cx43 mRNA significant reduction in electrically stimulated cells. In agreement, MG132 proteasome inhibitor (10 μM) restored Cx43 expression level. Finally, also the treatment of paced cells with the KAT inhibitor Anacardic Acid (0.5 μM) was able to rescue Cx43 level (n=4). Intriguingly, preliminary results also indicate lateralization and increased acetylation of Cx43 in the left ventricles of dogs with pacing-induced dilated cardiomyopathy (n=2).

Conclusions:
In vitro electrical stimulation of cardiac cells promotes Cx43 acetylation, which results in Cx43 down-modulation and intracellular relocalization. These findings suggest that electrical activity-dependent increase in acetylation may represent a novel mechanism for the regulation of cardiomyocyte communication.
Abstract 13804: Correlation between Electrocardiographic Features and Local Activation Pattern in Arrhythmogenic Right Ventricular Dysplasia
Authors: Tanawuttiwat Tanyanan , Te Riele Anneline S , Philips Binu , James Cynthia A , Murray Brittney , Tichnell Crystal , Sawant Abhishek C , Calkins Hugh , Tandri Harikrishna
Published: July 2021

Background:
Depolarization abnormalities in the terminal portion of the QRS are frequently seen in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C). The purpose of this study was to correlate the electroanatomic activation pattern of the RV endocardium and epicardium to the surface ECG.

Methods:
Thirty consecutive ARVD/C patients (Mean age 33.1 +/- 11.2 years, 16 (53%) men) underwent detailed endocardial and epicardial electroanatomical mapping (EAM). Local sinus rhythm activation was annotated at the sharpest intrinsic deflection of the bipolar electrogram, including late potentials. ECG features were classified into 5 major patterns; 1. Normal QRS (12 patients) 2. Epsilon wave (5 patients) 3. Incomplete RBBB (5 patients) 4. Atypical complete RBBB (6 patients) and 5. Prolonged terminal activation duration (TAD) (2 patients)

Results:
The earliest endocardial and epicardial RV activation occurred on the mid anteroseptal wall on all ECG patterns. Figure 1 represented activation area (purple) after the QRS or during the delayed depolarization phase. Nearly all endocardial and epicardial RV was activated well within the QRS duration in patients with normal QRS but was activated during R’ in patients with CRBBB. The delayed activation during Epsilon wave consistently occurred in basal anterior wall and basal angle of RV. In patients with TAD, the activation of RVOT and basal angle RV represented slurred S wave.

Conclusion:
ECG features in ARVD/C are correlated with late activation in specific regions of RV and total endocardial activation time. The delay activation of basal anterior wall and basal angle of RV represents the Epsilon wave in the right precordial ECG.
Abstract 13818: Effect of Gender on Hospital Discharge Survival After an Out-of-hospital Cardiac Arrest - a Systematic Review and Meta-analysis
Authors: Bougouin Wulfran , Mustafic Hazrije , Marijon Eloi , Murad Hassan , Dumas Florence , Barbouttis Anna , Jabre Patricia , Beganton Frankie , Empana Jean-Philippe , Cariou Alain , Jouven Xavier
Published: July 2021

Introduction:
Conflicting results exist regarding the impact of gender on survival after Sudden Cardiac Arrest (SCA).

Hypothesis:
Assess association between female gender and survival after SCA

Methods:
An electronic search of Embase, Ovid MEDLINE In-Process & Non-Indexed Citations and EBM Reviews - Cochrane Register of Controlled Trials, EBM Reviews - Cochrane Database of Systematic Reviews and Google was conducted (January 1948 to January 2014) for studies of any study design and language, examining the gender effect on survival at hospital discharge after a SCA.

Two independent reviewers selected studies and extracted data.

The inter-rater agreements kappa were measured at the first and second selection steps.

Moreover, the pooled OR and 95% CI, concerning women vs. men survival at hospital discharge after an OHCA were calculated with a random effect model.

Subgroups analyses were performed, according to the cardiac origin of OHCAs and according to the study quality. Study quality criteria were based on the New Castle Ottawa Scale.

Results:
After a detailed screening of 556 citations, 12 studies were identified involving 404 621 patients.

The inter-rater agreements kappa was high for the 2 study selection steps (0.91 and 1).

In most studies, women were older and had less favorable baseline characteristics including a lower prevalence of witnessed-OHCA, OHCA in a public location, bystander cardio-pulmonary resuscitation and shockable rhythms compared to men. However and after adjustment for these differences, women were more likely to survive at hospital discharge (N=12; OR: 1.11 [1.02-1.21]; p=0.013). This result remains in studies analyzing OHCA of presumed cardiac origin (N=7; OR: 1.17 [1.03-1.34]; p=0.017) and in studies of high quality (N=7; OR: 1.11 [1.02-1.21]; p=0.017).

Conclusion:
Despite less favorable baseline characteristics, women are more likely to survive at hospital discharge after an OHCA. Further studies are needed to explain this paradox.
Abstract 13879: Ischemic Postconditioning Confers Cardioprotection through Adiponectin-dependent Mitochondrial STAT3 Activation in Mice
Authors: Li Haobo , Irwin Michael G , Xia Zhengyuan
Published: July 2021

Introduction:
Signal transducer and activator of transcription 3 (STAT3) plays a key role in postconditioning (IPo) mediated protection against myocardial ischemia reperfusion injury, but the mechanism by which IPo activates STAT3 is unknown. Adiponectin (APN), a protein with anti-ischemic properties, activates STAT3. We hypothesized that IPo activates mitochondrial STAT3 (MitoSTAT3) via APN signaling.

Methods and Results:
Wild type (WT) and APN knockout (KO) mice were either sham operated or subjected to 30 min of coronary artery occlusion followed by 2 hours of reperfusion with or without IPo (3 cycles of 10 seconds reperfusion and 10 seconds reocclusion; n=8/group). At the end of reperfusion, KO mice exhibited more severe myocardial injury evidenced as increased infarct size (% of area at risk) 49.2±2.0
vs
WT 39.4±3.5,
P
<0.01; plasma troponin I (ng/ml): KO 72.8±7.6
vs
WT 45.7±4.0,
P
<0.01; worse cardiac function (lower dP/dt
max
and end-systolic pressure-volume relation,
P
<0.05); more severely impaired mitochondrial function (reductions in complex IV and complex V protein expression) and more severe reduction of MitoSTAT3 phosphorylation (activation) at site Ser727,
P
<0.01. IPo significantly attenuated post-ischemic cardiac injury and dysfunction with a concomitant increase in phosphorylated MitoSTAT3 and attenuation of mitochondrial dysfunction in WT (all
P
<0.05) but not in KO mice.

In cultured cardiac H9C2 cells, hypoxic postconditioning (HPo, 3 cycles of 5 min hypoxia and 5 min reoxygenation) significantly attenuated hypoxia/reoxygenation (HR, 3 hours hypoxia/3 hours reoxygenation) induced cell injury (increased apoptotic cell death as % of HR): HR 100.2±0.4 vs HPo 78.2±4.8,
P
<0.05) and reduced mitochondrial transmembrane potential (% total cells, HR 37.2±4.9 vs HPo 23.5±3.7,
P
<0.01). APN, adiponectin receptor 1 (AdipoR1), or STAT3 gene knockdown but not AdipoR2 gene knockdown, respectively, abolished HPo cellular protection (all
P
<0.05
vs.
HPo). APN supplementation (10μg/ml) restored HPo protection in cells with APN knockdown but not in cells with AdipoR1or STAT3 gene knockdown.

Conclusion:
Adiponectin and AdipoR1 signaling are required for IPo to activate myocardial mitochondrial STAT3 to confer cardioprotection.
Abstract 13882: Impact of Ischemic Mitral Regurgitation on Long-Term Prognosis in Patients With Acute Myocardial Infarction After Primary Percutaneous Coronary Intervention
Authors: Kim Kitae , Kaji Shuichiro , Kitai Takeshi , Kobori Atsushi , Ehara Natsuhiko , Kinoshita Makoto , Tani Tomoko , Furukawa Yutaka
Published: July 2021

Introduction:
Ischemic mitral regurgitation (IMR) portends a poor prognosis during long-term follow-up and has been identified as an independent predictor of heart failure (HF) and reduced long-term survival. Despite the poor prognosis with chronic IMR, few studies report the impact of IMR on long-term prognosis in patients with acute myocardial infarction (AMI) who underwent primary percutaneous coronary intervention (PCI).

Methods:
We studied 674 consecutive patients with AMI from 2000 to 2006 who underwent emergent coronary angiography and primary PCI, and who were assessed by transthoracic echocardiography during index hospitalization. Primary outcomes were cardiac death and the development of HF during follow-up.

Results:
The mean age of the study patients was 65±12 years and 534 patients (79%) were men. Sixty patients (9%) had moderate or severe MR before hospital discharge. Patients with moderate or severe MR were older, more frequently non-smoker, and more likely to have Killip class ≥2, lower ejection fraction, larger left ventricular end-diastolic volume, compared with patients with no or mild MR. During the mean follow-up period of 5.7±3.6 years, 35 cardiac deaths and 53 episodes of HF occurred. Kaplan-Meier analysis revealed that patients with moderate or severe MR had significantly increased risk for cardiac death (P<0.001), and HF (P<0.001), compared with patients with no or mild MR. Multivariate analysis revealed that moderate or severe MR was the significant predictor of the development of cardiac death (P<0.001), and the development of HF (P=0.006), independently of age, gender, history of MI, Killip class ≥2, initial TIMI flow≤1, peak CPK level, ejection fraction.

Conclusions:
Moderate or severe IMR detected early after AMI was independently associated with adverse cardiac events during long-term follow-up in patients with AMI after primary PCI.
Abstract 13892: Fragmented QRS Activity Representing Inhomogeneous Left Ventricular Conduction on Magnetocardiography Predicts Adverse Outcomes in Patients With LBBB and Left Ventricular Dysfunction
Authors: Oguchi Yasutaka , Takaki Hiroshi , Hashimoto Shuji , Wada Mitsuru , Nakajima Ikutaro , Ishibashi Kohei , Miyamoto Koji , Okamura Hideo , Noda Takashi , Aiba Takeshi , Kusano Kengo , Yasuda Satoshi , Kamakura Shiro , Sugimachi Masaru
Published: July 2021

Background:
Left bundle branch block (LBBB) is known to be a risk factor in patients with heart failure or structural heart diseases. We have already reported that the fragmented QRS (fQRS) activity on QRS vector magnitude waveform (VMW) derived from high-resolution multi-channel magnetocardiography (MCG) represents heterogeneous left ventricular (LV) activation sequences due to myocardial scar and can predict adverse outcomes in patients with dilated and hypertrophic cardiomyopathy. Therefore, we investigated whether MCG also can predict the outcome of patients with LBBB noninvasively using fQRS.

Methods:
64-ch MCG was recorded in 58 patients with LV dysfunction (LVEF<45%) and LBBB (QRS interval ≥120ms). Clinical characteristics, electrocardiographic parameters, and clinical outcomes were compared between patients with and without fQRS on the QRS VMW, which was constructed from 64 superimposed signals during sinus rhythm. The fQRS on MCG was defined as the presence of ≥1 discrete component larger than 20% of the maximum amplitude within QRS complex.

Results:
The fQRS was identified on MCG in 29 patients (Group-A), but not in the rest of 29 patients (Group-B). Age, Sex, presence of structural heart disease, QRS or QTc interval, fQRS (≥8 spikes in leads I, aVL, V5 and V6) on 12-lead ECG, history of arrhythmias, LVEF, and medications were not different between 2 groups. During the follow-up of 30 ± 23 months, cardiac events (sudden cardiac death, heart failure, hospitalization, and life-threatening arrhythmia) occurred more frequently in the Group-A (17/29, 58.6%) than in the Group-B (3/29, 10.3%; p < 0.0002), although patients with fQRS on ECG showed the similar event rate to those without. Multivariate analysis revealed that the presence of fQRS on MCG was only an independent predictor of poor outcome (p=0.0137).

Conclusions:
The prognosis of LBBB patients with fQRS on MCG was poor. The fQRS on MCG, which indicates the presence of inhomogeneous LV conduction, can be a reliable marker for predicting adverse outcomes in patients not only with cardiomyopathy but also with LBBB.
Abstract 13901: Elevated Cardiovascular Risk Factors among Appalachian Women with a History of Pregnancy Complications
Authors: Dekker Rebecca L , Ashford Kristin B , Lennie Terry A , Chung Misook L , Biddle Martha , Mudd-Martin Gia , Bailey Alison L , Moser Debra K
Published: July 2021

Introduction:
A growing body of evidence links complications of pregnancy (gestational diabetes, preeclampsia, and pregnancy-induced hypertension) with double the risk of future cardiovascular disease (CVD) related death in affected women. However, little is known about which CVD risk factors are more prominent among women who have experienced pregnancy complications.

Purpose:
Compare the presence of modifiable CVD risk factors among women with and without a self-reported history of pregnancy complications living in Appalachian Kentucky- an area with the highest rate of CVD mortality in the U.S.

Methods:
Rural Kentucky Appalachian women (n = 122, 97% Caucasian, 42 ± 12 years) engaged in a comprehensive measurement of CVD risk factors including body mass index (BMI), waist circumference, blood pressure, A1C, lipid profile (total cholesterol, triglycerides, HDL, and LDL), tobacco smoke exposure (objectively measured with urine cotinine), depression (Patient Health Questionnaire-9), and anxiety (Brief Symptom Inventory). We used independent t-tests and chi-square analysis to compare risk factors between women with and without a history of pregnancy complications.

Results:
One-fourth of the sample had one or more pregnancy complications: gestational diabetes (8.2%), preeclampsia (6.6%) and pregnancy-induced hypertension (15.6%). Women with at least one pregnancy complication had a higher average BMI (33.4 vs. 30.4,
p
= .014), larger waist circumference (42.8 vs. 39.1 cm, p = .006), and a higher proportion with moderate to severe symptoms of depression (27.6% vs. 15.9%, p = .02) compared to women without a history of pregnancy complications. There were no differences between groups in systolic or diastolic blood pressure, A1C levels, lipid profiles, tobacco smoke exposure, or anxiety.

Conclusions:
Women with a history of pregnancy complications have several modifiable risk factors- higher BMI, higher waist circumference, and higher levels of depression- that could constitute a link between past pregnancy complications and their risk of future CVD death. Pinpointing which modifiable risk factors are elevated in these women will help us develop self-management interventions to prevent the development of CVD in this high-risk population.
Abstract 13903: When an Octopus Acts Like a Chameleon: a Case of Takotsubo’s Cardiomyopathy with Concurrent Severe Coronary Disease
Authors: Leo Troy , Damp Julie , Mendes Lisa
Published: July 2021

Introduction:
Takotsubo’s cardiomyopathy, or stress induced cardiomyopathy, is characterized by transient wall-motion abnormalities involving the left ventricular apex and mid-ventricle in the absence of obstructive epicardial coronary disease. It is seen more commonly in post-menopausal women and is usually preceded by an acute medical illness or intense emotional or physical stress. While the Mayo Criteria for the classification of Takotsubo’s cardiomyopathy involves the absence of epicardial coronary disease, up to 10% of patients have been found to have concurrent significant coronary artery disease.

Conclusions:
We present a case of a patient who presented with seizures and was found to have ST elevations, elevated cardiac enzymes and a new cardiomyopathy. While it was discovered that she had severe coronary disease of her LAD and RCA, the true nature of her cardiomyopathy and presentation was a stress-induced cardiomyopathy in the setting of seizure. The accuracy of this diagnosis affected the prognosis and treatment options for our patient. Cardiac MRI, and specifically the presence or absence of late gadolinium enhancement, helped differentiate the etiology of her cardiomyopathy. With the increasing prevalence of coronary disease, we will likely see more cases such as these in the future and should continue to evolve our definition and tools for the diagnosis of an increasing and interesting phenomenon.
Abstract 13915: Atrial Fibrillation Begets Atrial Fibrillation in Cryptogenic Stroke Patients: Results from the Crystal-AF Trial
Authors: Passman Rod S , Koehler Jodi L , Ziegler Paul D
Published: July 2021

Introduction:
Initial episodes of atrial fibrillation (AF) detected following a cryptogenic stroke (CS) may be brief in duration and the clinical relevance of such episodes is uncertain.

Hypothesis:
We investigated whether an initial brief episode of AF was predictive of subsequent long duration AF episodes in CS patients (pts) with an insertable cardiac monitor (ICM).

Methods:
CS pts (n=208, age 61.6±11.3 years, 66% male) randomized to the ICM arm of the CRYSTAL-AF study and inserted with a device (Reveal® XT) were followed for 21±9 months. AF episodes (>30 seconds) were independently adjudicated and the first adjudicated AF episode was classified as brief (<1 hour) or long (≥1 hour). The incidence of subsequent long duration AF episodes among pts with an initially brief episode was computed. The impact of episode duration on prescription of oral anticoagulation (OAC) therapy was also assessed.

Results:
Among 36 pts with an adjudicated AF episode for which duration information was available, the initial episode was classified as brief in 18 (50%) pts and long in 18 (50%) pts. Among those with initially brief episodes, 10 (56%) experienced only subsequent brief episodes while 8 (44%) went on to experience at least one long AF episode. The median time between the initial brief episode and first long AF episode was 75 days [interquartile range: 27-624 days]. OAC was prescribed in 7/10 pts (70%) with only brief AF episodes compared to 26/26 pts (100%) with at least one long episode of AF (p=0.017).
Conclusion:
Initial AF episodes in pts with CS are equally likely to be of short or long duration. However, nearly half of CS pts with initially brief episodes of AF subsequently have long duration episodes detected much later via prolonged monitoring with ICMs. Therefore, early detection of brief AF episodes may merit more rigorous monitoring of AF with ICMs since physicians were significantly more likely to prescribe OAC for secondary stroke prevention in response to longer duration episodes.
Abstract 13941: Combined Assessment of Right Ventricular Function and Reverse Remodeling as Prognostic Marker after Administration of Medical Treatment for Pulmonary Hypertension
Authors: Sano Hiroyuki , Tanaka Hidekazu , Motoji Yoshiki , Fukuda Yuko , Dokuni Kumiko , Hatani Yutaka , Hatazawa Keiko , Matsuzoe Hiroki , Toki Hiromi , Shimoura Hiroyuki , Ooka Junichi , Sawa Takuma , Mochizuki Yasuhide , Tatsumi Kazuhiro , Matsumoto Kensuke , Emoto Noriaki , Hirata Ken-ichi
Published: July 2021

Background:
Right ventricular (RV) dysfunction plays an important role in disease progression and prognosis of patients with pulmonary hypertension (PH). However, the association of RV reverse remodeling with long-term outcomes remains unclear. Our objective was thus to test the hypothesis that mid-term RV reverse remodeling after adding PH-specific drugs was linked to long-term outcomes in patients with PH.

Methods:
We studied 45 PH patients with resting mean pulmonary artery pressure (mPAP) of 35±10mmHg. PH patients with chronic thromboembolic pulmonary hypertension and left-sided heart failure including pulmonary capillary wedge pressure of >15mmHg were excluded. Echocardiography was performed at enrollment and mid-term of 5.7±4.1 months after adding PH-specific drugs. RV function was calculated by averaging the three regional peak speckle-tracking longitudinal strains from RV free-wall (RV-free). RV remodeling was assessed in terms of the RV area, which was traced planimetrically at the end-systole (RVESA) from RV-focused apical 4-chamber views. Mid-term RV reverse remodeling was defined as a relative decrease in RVESA of at least 15%. Long-term event-free survival was then tracked for 5 years.

Results:
Patients with mid-term RV reverse remodeling experienced favorable long-term outcomes than those without mid-term RV reverse remodeling (log-rank p<0.01). The incremental benefit using sequential Cox models in the prediction of long-term outcomes showed that a model based on clinical variables including mPAP and pulmonary vascular resistance (PVR) was improved by addition of RV-free (p=0.03), and further improved by addition of the parameter of mid-term RV reverse-remodeling (p=0.01).

Conclusion:
Mid-term RV reverse remodeling after adding PH-specific drugs was associated with long-term outcomes, and this combined approach may well have clinical implications for better management of PH patients.
Abstract 13943: Hypertrophic Cardiomyopathy with Left Ventricular Apical Aneurysm Represents a High-Risk Subgroup Necessitating Aggressive Preventive Therapy: A Long-term Follow-Up Study
Authors: Rowin Ethan J , Maron Barry J , Haas Tammy S , Lesser John R , Link Mark S , Maron Martin S
Published: July 2021

Background:
Increasing penetration of high spatial resolution cardiovascular magnetic resonance (CMR) imaging into routine cardiovascular practice has resulted in more frequent identification of a subset of hypertrophic cardiomyopathy (HCM) patients with thin-walled, scarred left ventricular (LV) apical aneurysms. Prior experience involved relatively small numbers of patients with short follow-up and therefore the risk associated with this subgroup remains incompletely defined. Therefore, we assembled a large HCM cohort with LV apical aneurysms and long-term follow-up in order to clarify clinical course and prognosis.

Methods and Results:
Of 2,400 HCM patients, 60 (2.5%) were identified by CMR with LV apical aneurysm, 24 to 86 years of age, including 19 (32%) <45 years old; 70% male, and followed for 5.6 ± 3.5 years. Over the follow-up period, 24 patients experienced 31 adverse disease-related complications including: appropriate implantable cardioverter-defibrillator discharge for VT/VF (n=11), received or listed for heart transplant (n=6), heart failure death (n=5), nonfatal thromboembolic events (n=4), resuscitated out-of-hospital cardiac arrest (n=3), and sudden death (n=2). In addition, an intracavitary thrombus was identified in the apical aneurysm in 9 patients without a thromboembolic history. Combined HCM-related death and aborted life threatening event rate was 8.6% per year, nearly 6-fold greater than the 1.5% annual mortality rate reported in the general HCM population.

Conclusions:
Patients with LV apical aneurysms represent a high-risk subgroup within the diverse HCM spectrum, associated with substantial increased risk for disease-related morbidity and mortality, including advanced heart failure, thromboembolic stroke and sudden death. Identification of this unique HCM phenotype should prompt consideration for primary prevention ICD, and anticoagulation for stroke prophylaxis.
Abstract 14029: New Findings in Women and Men Regarding Symptoms and Delay Times in Stemi
Authors: Swahn Eva
Published: July 2021

Introduction:
Myocardial infarction patients report higher prevalence of atypical symptoms in women, contributing to a less probability of a correct diagnosis. Studies exploring only the STEMI group where a prompt diagnosis is mandatory is lacking. We hypothesised that chest pain is equally common in women and men in a STEMI population. We further hypothesised that women have more associated symptoms than men in a STEMI population and thus a longer delay time.

Methods:
SymTime is a multicentre observational study where patients with a diagnosis of STEMI, admitted to CCUs where included. Within 24 h from admission they filled in a validated Swedish questionnaire, developed to measure how patients with MI describe their symptoms and actions in the pre-hospital phase.

Results:
126 women and 406 men were included, mean age 70 and 64 (SD11) years respectively. After age adjustment, men had 5 times higher odds of having chest pain. Women had more symptoms in other typical locations. (Table) Only general feelings of illness (25 vs 13%, p = .001), fearfulness (31 vs 17 %, p.= 001) and nausea (49 vs 29 %, p < .001) were more common in women. Women had longer delay times from symptom onset to first medical contact, median time 1:30 hours: minutes vs 1:05 in men (p = 0.03).

Conclusion:
Women had significantly less chest pain, one reason for longer delay times in women. The prevalence of other typical MI symptoms such as pain in the chin/teeth, throat, shoulders, arms or back was higher in women. These findings should be communicated to the health care system as well as the community in order to get a prompt and correct diagnosis of STEMI in both genders.

Table.
Main symptom(s) in women and men with STEMI
Abstract 14048: Snf1-related Kinase Improves Cardiac Metabolic Efficiency through a Decrease in Mitochondrial Uncoupling
Authors: Rines Amy K , Wu Rongxue , Khechaduri Arineh , Burke Michael A , Sato Tatsuya , Abdelwahid Eltyeb , Rawlings Tenley A , Lopaschuk Gary D , Schumacker Paul T , Abel E. Dale , Ardehali Hossein
Published: July 2021

Introduction:
Snf1-related Kinase (SNRK) is a serine/threonine kinase with sequence similarity to AMP-activated protein kinase, but its function is unknown. We found that SNRK is increased in hearts from patients with ischemic cardiomyopathy, and our gene array data suggested that SNRK alters metabolic genes. Here, we assessed the hypothesis that SNRK regulates cardiac metabolic efficiency.

Results:
Transgenic (TG) mice with cardiac-specific overexpression of SNRK were generated, and displayed decreased glycolysis (1267.66 vs. 1925.60 nmol/min/g, n=6), glucose oxidation (441.73 vs. 602.68 nmol/min/g), and palmitate oxidation (262.39 vs. 385.07 nmol/min/g) compared to wild type littermate controls in perfused working hearts. However, cardiac power, contractility, ATP, and triglyceride and glycogen stores were maintained, while oxygen consumption was reduced, suggesting that SNRK TG mice have increased metabolic efficiency. The hearts also exhibited decreased uncoupling protein 3 (UCP3) expression, mitochondrial uncoupling, and peroxisome proliferator-activated receptor α (PPARα) expression. SNRK homozygous knockout (KO) was embryonic lethal, but hearts from heterozygous SNRK KO mice had increased glucose and fatty acid oxidation and increased expression of UCP3 and PPARα. SNRK knockdown in cardiac cells also increased UCP3, mitochondrial depolarization, and substrate flux, which were all reversed with UCP3 knockdown. The SNRK-mediated changes in UCP3 were PPARα-dependent. To determine the mechanism of PPARα and UCP3 regulation by SNRK, we performed a yeast two hybrid screen and identified Tribbles homolog 3 (Trib3) as a binding partner of SNRK. SNRK transgenic mice had increased Trib3 expression, and Trib3 overexpression reversed the upregulation of PPARα and UCP3 by SNRK knockdown. Finally, SNRK overexpression in mice reduced infarct size compared to area-at-risk (53.01% vs. 37.95%, n=6) in response to myocardial ischemia/reperfusion.

Conclusions:
Our results demonstrate that SNRK increases cardiac metabolic efficiency and protects against ischemic damage through binding and upregulation of Trib3, leading to PPARα-driven UCP3 downregulation and improved mitochondrial coupling.