bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17112: Acute Myocardial Infarction in a Young Man in the COVID-19 Era: A Case Report
Authors: Rashed Eman , Cagliostro Matthew , Kamran Mazullah
Published: November 2020

Introduction:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, as well as significant cardiovascular complications, such as acute myocardial infarction (AMI). There is controversy on the mechanism and management of AMI during the COVID-19 era. We describe a case of a 22 year old patient with no past medical history who presents with an acute myocardial infarction, who was found to be COVID-19 positive.

Investigations:
Patient’s vitals were: temperature 99.3F, blood pressure 136/99 mmHg, heart rate 80 bpm, respiratory rate 16 breaths/minute, SpO2 96% on room air. There were no abnormalities on pulmonary or cardiovascular exam. Initial laboratory testing showed elevated inflammatory markers such as ferritin, IL-6, C-reactive protein, lactate dehydrogenase, and an elevated white blood cell count with a neutrophilic predominance. LDL was normal. There was also an initial elevated troponin T. A chest radiograph was without abnormalities. EKG was notable for ST elevations in leads II, III, aVF, with depressions in leads V1, V2, V4, V5 accompanied by hyperacute T waves. Echocardiogram was notable for inferior and infero-lateral wall hypokinesis. COVID-19 PCR resulted positive.

Management:
Coronary angiography revealed one hundred percent stenosis of proximal left circumflex artery. The lesion was a total thrombotic occlusion with an organized thrombus. Aspiration thrombectomy was performed, and an Onyx 2.5x26 stent was placed and TIMI III flow achieved.

Discussion:
This is a very unique case of COVID-19 in a young patient with no co-morbidities who presented with an acute myocardial infarction. Plaque instability and rupture due to cytokine release in patients with existing atherosclerosis is a common hypothesis. It is also postulated that direct endothelial injury can occur via entry of the SARS-CoV-2 virus, with activation of the renin-angiotensin-aldosterone system causing widespread endothelial dysfunction and multiple organ injuries. This issue warrants further study, as well as discussion regarding post- intervention care in this population who are at significant thrombotic risk.
Abstract 17117: Prevalence of Systemic AV Valve Regurgitation in Patients With Congenitally Corrected Transposition of the Great Arteries: Anatomic versus Physiologic Repair
Authors: Bhimani Salima A , ZIA Aisha , Barrios Paola , Moses Anabila , Klein Jared , Karamlou Tara , Komarlu Rukmini R
Published: November 2020

Background:
Congenitally corrected transposition of the great arteries (ccTGA) is a rare anomaly with highly variable time of diagnosis. Depending on time of diagnosis and associated lesions, multiple therapies exist, directed towards surgical correction. Anatomic repair (AR) involving double switch or atrial switch/Rastelli and physiologic repair (PR) leaving the right ventricle as the systemic ventricle are the two main surgical options. A subset of patients without associated lesions exist who can be followed expectantly over time. Systemic atrioventricular valve (SAVV) function is a major anatomic variable, determining eligibility for double switch and durability of physiologic repair or expectant management (medical group). We therefore sought to assess the prevalence of AV valve regurgitation in the different subgroups and its determinants, hypothesizing that SAVV regurgitation (SAVVR) was reduced in the AR group.

Methods:
Retrospective record review coupled with prospective cross-sectional follow-up of 240 patients with ccTGA treated at our center was performed. Echocardiographic imaging review was conducted to assess SAVV function and systemic ventricular function among the 3 subgroups.

Results:
Of 240 patients with ccTGA, 162 met inclusion. Median follow up was 10 years (mean +/- SD 11+/- 9 years). In the AR group majority (85%) had none/mild SAVVR. Prior PA band did not influence the severity of SAVVR following double switch. In the PR group, 22% underwent SAVV repair/replacement, and 75% had none/mild SAVVR; as opposed to only 65% with none/mild SAVVR in the medical group. Only 14% of patients were free of systemic ventricle dysfunction in PR group as opposed to 72% in the AR group.

Conclusions:
SAVV function is preserved in the AR group. In contrast patients in the PR group had higher prevalence of more than mild SAVVR followed by patients who were managed expectantly.
Abstract 17118: Myocarditis in Multisystem Inflammatory Syndrome in Children (MIS-C) Temporally Related to COVID-19
Authors: Jain Supriya , fuisz anthon , Cowles Heather , Gewitz Michael H
Published: November 2020

Background:
Little is know about the pathophysiology of Multisystem Inflammatory syndrome in Children (MIS-C) temporally associated with COVID-19

Hypothesis:
Patients with MIS-C may present with myocarditis. Cardiac magnetic resonance (CMR) may help in its diagnosis.

Methods:
Nine children and adolescents were identified to have clinically suspected myocarditis based on their clinical presentation, abnormal cardiac enzymes and evidence of ventricular dysfunction on echocardiogram. 5 patients underwent CMR.

Results:
All patients had evidence of current/recent SARS-COV-2 infection. Five were PCR+, 7 were IgG+. On echocardiogram at presentation, all the patients had mild-severe left ventricular dysfunction (EF: 25%-53%). Three had left ventricular dilation, 7 had evidence of valvulitis presenting as mitral regurgitation, 4 had pericardial effusion with no evidence of tamponade and 3 patients had associated coronary dilation. Seven patients presented in cardiogenic shock requiring inotropic support. Out of the 5 patients who underwent CMR, 2 had evidence of early and late gadolinium enhancement. Small focal area of late gadolinium enhancement was noted in the inferolateral segment of the subepicardial region of the left ventricle. There was evidence of myocardial edema in the other 3 patients.

Conclusions:
Children with Multi system Inflammatory Syndrome in Children can present as myocarditis. Cardiac magnetic resonance has a role in its diagnosis, prognosis, better understanding of this disease and may be useful for the long term follow up of these children.

Table 1: Patient characteristics, labs, imaging findingsAbbreviations:-BNP: Brain natriuretic peptide, CRP:C-reactive protein, LV EF: Left ventricular ejection fraction, CAs: Coronary abnormalities, Valvar R: valvar regurgitation, EGE: Early gadolinium enhancement, LGE: Late gadolinium enhancement
Abstract 17124: Severe Bradycardia in Critically Ill Patients With COVID-19
Authors: Larue Julie , De Jode Patrick , Timsit Jean-François , Franchineau Guillaume , Extramiana Fabrice , Algalarrondo Vincent
Published: November 2020

Cardiac manifestations of severe Covid19 infection are still poorly understood. From January to May 2020, 113 consecutive patients were admitted in intensive care units for severe Covid19 and 10 out of them presented an episode of bradycardia.

Patients had a median age of 63 years, 6/10 were men, 7/10 were under mechanical ventilation for severe acute respiratory distress syndrome and 4/10 received a veno-venous extracorporeal membrane oxygenation. All bradycardias were due to sinus node bradycardia with a median heart rate of 36 bpm (range 10 - 45 bpm). For 6 patients, bradycardia was persistent and 3 required continuous isoprenaline infusion (Figure, patient A). Bradycardia was sudden for 4 patients and required brief resuscitation maneuvers for one (Figure, patient B)
.
Patients had normal baseline ECG and echocardiography, except for two patients who were under beta-blockers. For those two patients beta blockers were interrupted several days before bradycardia. A comprehensive review of patient’s files ruled out bradycardia due to drug-drug interactions, myocarditis, hyperkalemia, hypoxia or vagal physical stimulation. Holter ECG was performed for 7 patients: 3 recordings evoked vagal hyperactivity (low mean heart rate and elevated pNN50 / RMSSD, Figure Patient A), 3 others cardiac dysautonomia (SDNN<100ms, Figure Patient B).

Amongst these 10 patients, 5 were discharged from ICU among which 2 returned home and five died from covid-19 associated multiple-organ failure. None of them required temporary or permanent cardiac pacing.

To conclude, sinus bradycardia occurred commonly in severe Covid19 infection. This highlights the need to monitor cardiac rhythm. Even if the pathophysiology remains unclear, cardiac dysautonomia and vagal hyperactivity could be hypothesized rather than an intrinsic sinus node disease.
Abstract 17131: Myocardial Fibrosis Measured by Magnetic Resonance Imaging in People Living With Human Immunodeficiency Virus and Ethnic Differences: Myocardial and Coronary Abnormalities in HIV Infection (MACHIN) Study
Authors: Reddy Pavan , Minasian Arazin , Javed Ahsan , Banayan April , Valencerina Samuel , Nayak Krishna , Dube Michael P , Bahrami Hossein
Published: November 2020

Introduction:
Recent studies have suggested that increased risk of cardiovascular disease (CVD) in people living with HIV (PLWH) extends beyond coronary artery disease to involve myocardial fibrosis. Cardiac MRI can accurately detect overt scar and diffuse fibrosis in this population.

Hypothesis:
Compared to controls, virologically-suppressed PLWH without known clinical CVD have increased risk of myocardial fibrosis and scar, as demonstrated by T1/ECV (extracellular volume) mapping and late gadolinium enhancement (LGE) respectively.

Methods:
Myocardial structure and function were assessed using CMR (GE 3.0T; acquisition: RT-Hawk, Heart Vista Inc; analysis: cvi42, Circle Inc, v5.10). Our protocol included cine, pre-contrast images, LGE and post contrast T1 mapping 12 minutes after infusion of 0.1mmol/kg of gadolinium (Multihance). 12-minute ECV maps were generated and ECV>32% was considered increased extracellular volume indicating diffuse fibrosis.

Results:
We studied 92 participants (54 PLWH and 38 HIV- controls, mean age 47±14 years, 28% female). There was no difference in LV systolic function and mass between groups. Clinically detectable LGE was observed in 5 PLWH (10%) and no controls (p :0.04). While there was no significant difference in pre-contrast T1 values in cases vs controls (1044±14 vs 1023±15 ms, p: 0.30), PLWH were more likely to have 12mECV values above the median of 25.5% (57% vs 41%, p: 0.23). In regression models, PLWH had higher ECV values (coefficient: 3.4%, p:0.04) and higher odds of increased ECV (OR: 3.9, 95%CI: 1.0-15.6, p:0.05) adjusted for age, gender, and ethnicity. In multivariable models, women had significantly lower ECV values (p: 0.04). African Americans (AAs) had significantly higher chance of having LGE (OR:12.6, p: 0.03). However, while non-black PLWH had a significantly higher odds of increased ECV (adjusted OR:6.0, p: 0.03), this association was not significant in AAs (p:0.9).

Conclusion:
Virologically suppressed PLWH are at higher risk of clinically detectable LGE in myocardium and diffuse myocardial fibrosis, independent of their demographics and cardiac function. HIV infection is associated with higher risk of LGE in AAs, while subclinical increased ECV is the more common finding in other ethnicities.
Abstract 17141: Pulmonary Artery Pulsatility Index is Associated With Greater Mortality Across a Broad Hospital-Based Cohort
Authors: Zern Emily K , Rambarat Paula , Paniagua Samantha , Liu Elizabeth , McNeill Jenna , Andrews Carl T , Pomerantsev Eugene V , Picard Michael , Ho Jennifer E
Published: November 2020

Introduction:
The pulmonary artery pulsatility index (PAPi), calculated from the ratio of pulmonary artery pulse pressure to right atrial pressure, was initially described as a novel predictor of right ventricular failure after inferior myocardial infarction or left ventricular assist device implantation. Whether PAPi is associated with adverse outcomes in broader samples is unknown.

Hypothesis:
A lower PAPi is associated with mortality in a broad population referred for right heart catheterization.

Methods:
We examined consecutive patients undergoing right heart catheterization between 2005-2016 in a hospital-based cohort. The following exclusion criteria were applied: shock or cardiac arrest within 24 hours of catheterization, presence of mechanical circulatory support, prior cardiac transplant, prior valvular surgery, or those with missing key clinical covariates. Multivariable Cox models were utilized to examine the association between PAPi and mortality. Analyses were adjusted for age, sex, BMI, hypertension, diabetes, prior myocardial infarction, and prior heart failure.

Results:
We studied 8559 patients with mean age 63 years and 40% women. We found that patients in the lowest quartile of PAPi were younger, with greater proportion of men, and higher BMI, yet similar NT-proBNP compared with other quartiles (
Table 1
). Over 12.5 years of follow-up, there were 2441 death events. Patients in the lowest PAPi quartile had a 31% greater risk of death compared with the highest quartile (multivariable adjusted HR 1.31, 95% CI 1.15-1.48, p<0.001), whereas no differences in survival were seen among individuals in quartile 2 or 3 (p>0.05 vs quartile 4 for both).

Conclusions:
Patients in the lowest PAPi quartile had a 31% increased risk of all-cause mortality in a broad population referred for right heart catheterization. These findings highlight a potential role for PAPi in identifying high-risk individuals across a spectrum of disease.
Abstract 17144: miR-146a-5p Induces Pulmonary Barrier Disruption via Macrophage-Derived TNFa
Authors: Huang Huang , Hu Jiang , Zhu Jing , Chao Wei , Zou Lin
Published: November 2020

Introduction:
Sepsis-induced acute lung injury (ALI) has substantial morbidity and mortality. Diffused alveolar damage as a result of increased endothelial cell (EC) permeability is a hallmark of ALI. We have previously demonstrated that certain uridine-rich extracellular (ex) miRNAs such as miR-146a activate innate immune response and possess a potent proinflammatory property, but their effect on EC function is largely unknown.

Hypothesis:
Pulmonary EC barrier function is impaired by miR-146a-5p.

Methods:
Conditioned media (CM) were collected from macrophages (Mφ) cultures treated with lipofectamine (lipo) or miR-146a-5p (50 nM) for 24 h. EC barrier function was analyzed in human pulmonary arterial endothelial cells (HPAECs) by transendothelial electric resistance (TER) using an electric cell-substrate impedance sensing system.

Results:
Direct miR-146a-5p treatment of HPAECs did not cause any change in TER even though it induced robust IL-6 and CXCL2 production in Mφ. To test whether miR-146a-5p affects EC function indirectly, we incubated HPAECs with miR146a-CM and observed a more than 50% reduction in TER (
Fig. A
). Lipo-CM had no such effect. This barrier effect was accompanied by VE-cadherin internalization and disrupted VE-cadherin lining following 8 hours of incubation (
Fig. B)
. To determine the potential mediators in the CM responsible for the EC barrier disruption, we performed a cytokine array analysis of 111 cytokines in the CM and identified 15 differentially expressed cytokines. Among them, we found that TNFα neutralizing Ab (1μg/ml), but not control IgG (1μg/ml), partially blocked the miR-146a-CM-induced EC barrier disruption with improved VE-Cadherin integrity (
Fig. B
).

Conclusion:
Our data demonstrated miR-146a-5p induces HPAEC barrier dysfunction via an indirect mechanism involving Mφ production of TNFα.
Abstract 17155: Is Aortic Annular Calcium Burden a Predictor of Post TAVR Right Ventricular Pacing?
Authors: Ranka Sagar , Dalia Tarun , Parimi Nikhil , APTE NACHIKET MADHAV , Shrestha Amit , Akhtar Tauseef , Dendi Raghuveer , Sheldon Seth , Reddy Madhu , Rosamond Thomas , Pimentel Rhea C
Published: November 2020

Background:
Preliminary reports have suggested the role of annular calcium in independently predicting pacemaker implantation after transcatheter aortic valve replacement (TAVR). Data regarding role of calcium in the aortic-valvular complex on pacemaker dependency is lacking.

Hypothesis:
Calcium volume and score in the aortic annular region predicts RV (right ventricle) pacing burden.

Methods:
We conducted a retrospective single-center study at our tertiary care center including patients who had new pacemaker implantation after TAVR procedure (n=47). Standard calcium scoring software was used to demarcate and quantify the calcium along the aortic cusps and subvalvular region and dichotomized into septal and non-septal based on proximity to the interventricular septum. Standard statistical tests were used for analysis with two-sided p-value <0.05 considered significant.

Results:
The mean age was 78.6 ± 10.3 years and females were 42.6%. At baseline, 44.7% had narrow QRS complex, with 31.9% had right bundle branch block (RBBB), 8.5% had left bundle branch block (LBBB). Median Pre-TAVR QRS duration was 112 ms. Median septal and non-septal calcium score were 646 and 474 with a volume of 441 mm
3
and 327.2 mm
3
, respectively. Patients with progression to complete heart block (CHB) during index admission had significantly higher non-septal volume (650 mm
3
vs 344 mm
3
;p=0.01) and score (892 vs 485;p=0.01) when compared to progression after discharge. Similarly, the high burden of RV pacing (>40%) was associated with lower septal calcium score (989 vs 552, p= 0.03) and volume (717 mm
3
vs 385 mm
3
, p=0.03) within 3 months of TAVR. No septal or non-septal parameters were predictive of pacing burden for mid-term (3-12 months) and long-term (>12 months) follow up. Septal calcium parameters were not predictive of RV pacing burden or progression to CHB.

Conclusion:
Quantitative calcium in the non-septal and septal regions were predictive of early progression to CHB and a higher burden of RV pacing, respectively. Larger scale studies on calcium distribution and the burden should be performed to validate our findings.
Abstract 17157: The SGLT2 Inhibitor Empagliflozin Ameliorates Interstitial Myocardial Fibrosis and Aortic Stiffness in Non-Diabetic Patients With Heart Failure With Reduced Ejection Fraction: A Secondary Analysis of the EMPATROPISM Trial
Authors: Santosgallego Carlos G , Requena-Ibanez Juan Antonio , Vargas Ariana P , Garcia-Ropero Alvaro , Rodriguez-Cordero Anderly , MANCINI Donna M , Pinney Sean , Lala Anuradha , Contreras Johanna P , Moreno Pedro R , SANZ Javier , Fuster Valentin , Badimon Juan J
Published: November 2020

Background:
SGLT2 inhibitors (SGLT2i) improve prognosis in HFrEF patients. We recently demonstrated in a porcine model of non-diabetic HFrEF that empagliflozin (EMPA) ameliorates adverse cardiac remodeling and improves LV systolic function. However, the effect of EMPA on interstitial myocardial fibrosis (IMF) and aortic stiffness has not yet been studied

Hypothesis:
Empagliflozin ameliorates IMF and aortic stiffness in non-diabetic HFrEF patients

Methods:
The EMPATROPISM clinical trial (NCT 03485222) investigated the efficacy and safety of EMPA in non-diabetic HFrEF patients. 84 patients were randomized to EMPA 10mg daily for 6 months or placebo on top of optimal medical treatment, and were evaluated with cardiac magnetic resonance (CMR). IMF was assessed by CMR using extracellular volume (ECV) by T1 mapping. Aortic stiffness was quantified by pulse wave velocity (PWV) by CMR. The primary endpoint was change in LVEDV. Prespecified secondary endpoints were changes in ECV (ΔECV) and PWV (ΔPWV) at 6 months between both arms

Results:
80 patients completed the follow up period. There were no differences at baseline in LVEDV (220±75 vs 209±68mL for EMPA vs placebo, p=0.5) or LVEF (36±8 vs 37±8%, p=0.7). There were no differences at baseline in both groups in either ECV or PWV (Table). In the primary endpoint, EMPA-treated patients showed decrease in LVEDV and increase in LVEF (ΔLVEDV -25±25 vs -1±25mL, p<0.001; and ΔLVEF 6±4 vs 0±4%, p<0.001 for EMPA vs placebo). EMPA-treated patients exhibited a reduction in ECV (ΔECV -1.25±1.5 vs 0.3±1.4% for EMPA vs placebo, p<0.001), which demonstrates IMF regression with SGLT2i. EMPA-treated patients exhibited a reduction in PWV (ΔECV -0.6±1 vs 0.6±1.4 m/s for EMPA vs control, p<0.001), which indicates amelioration of aortic stiffness with SGLT2i

Conclusions:
In HFrEF patients without diabetes, treatment with empagliflozin ameliorates IMF and aortic stiffness. This may explain the benefits of SGLT2i in HFrEF even in the absence of diabetes
Abstract 17161: Type and Intensity of Strategies to Reduce Readmissions Under the Hospital Readmissions Reduction Were Not Associated With Improvements in Readmission Rates
Authors: Hammond J Gmerice , Yu Jonathan , Figueroa Jose , Joynt Maddox Karen E
Published: November 2020

Background:
Little is known about what strategies are associated with improvements in hospital readmissions under the Hospital Readmissions Reduction Program.

Objective:
To determine whether the type or intensity of readmission reduction strategies were associated with changes in readmission rates for heart failure, acute myocardial infarction, and pneumonia among acute care hospitals participating in the HRRP.

Methods:
We surveyed leaders of 1,600 U.S. acute care hospitals participating in the HRRP about their use of 13 specific strategies to reduce readmissions. Strategies were grouped into three domains: transitions of care (TOC, e.g. discharge checklist), quality improvement (QLT, e.g. medication reconciliation), and patient-centered (PC, e.g. patient engagement programs). Intensity of each domain was scored as high or low according to how many strategies were implemented. We calculated hospital-level readmission rates prior to (2011-12) and following (2014-15) HRRP implementation. We used linear regression to determine if there were associations between individual strategies, domains, or overall scope of strategies and a reduction in readmission rates.

Results:
Of the 1,600 hospitals surveyed, 926 participated (58% response rate). Hospitals reported using 6.1 (SD 2.5) strategies on average. TOC was the most commonly used domain: 69% of hospitals scored high intensity in TOC, compared to only 22% and 14% of hospitals scoring high intensity in QLT and PC domains, respectively. After adjusting for hospital size, type, teaching status, and location, there were no statistically significant associations between any individual strategy and changes in readmission rates, nor between domain intensity and changes in readmission rates. Nearly half of all hospitals, 49%, scored high in only one domain; only 22% scored high in two domains and 5% scored high in all three domains. In fully adjusted models, there was no association between scoring high in multiple domains and reducing readmission rates.

Conclusions:
Under the HRRP, hospitals focused most on transitions of care strategies. There was no evidence that any of the most commonly employed strategies for reducing readmissions were associated with differential changes in readmission rates.
Abstract 17162: Prediction of Functional Severity of Coronary Bifurcation Lesions by Means of Angiographically-Derived Score
Authors: Vassilev Dobirn , Mileva Niya , Nikolov Pavel , Dimitrov Georgi , Karamfiloff Kiril , Collet Carlos , Rigatelli Gianluca , Gil Robert , Serruys Patrick W
Published: November 2020

Background:
There is uncertainty about relation between clinical and angiographic characteristics and functional significance of bifurcation stenosis.

Methods:
We analysed patients from FIESTA registry (ClinicalTrials.gov:NCT01724957). Subjects (>18 years) with stable angina, bifurcation lesions with diameter ≥2.5mm and ≤4.5 mm, SB diameter≥2.0 mm were included. We excluded patients with ST-segment elevation myocardial infarction, left main disease, hemodynamic instability. Provisional stenting was the default strategy in all patients. Fractional flow reserve(FFR) was performed using the PrimeWire or PrimeWire Prestige(Volcano Corp., USA). Bifurcation lesion with FFR above 0.80 were deferred from PCI.

Results:
A total of 171 patients, mean age 67±10 years, 66% males were included in the analysis. Of them 78(46%) had functionally significant bifurcation lesion (FSL) versus 93(54%) with non-significant lesion (nFSL). There were no differences (FSLvs.nFSL) in baseline characteristics: dyslipidemia(88%vs96%), diabetes(44%vs.32%), smoking (52%vs40%), past MI (24%vs15%), previous PCI(54%vs49%), atrial fibrillation (17%vs29%), peripheral artery disease (10%vs9%), renal failure(29%vs31%) –all p>0.05. On logistic-regression analysis independent predictors of functional significance were: SYNTAX score≥11 (OR=5.523,CI:1.666-18.311,p=.005), lesion length≥25mm (OR=21.737,CI:4.963-95.202,p<.001),MV%DS≥55%(OR=9.535,CI:2.508-34.883,p=.001) and MB%DS≥65% (OR=12.927,CI:3.015-55.418,p=.001). We created score for prediction of functional significance of bifurcation lesion with the following parameters: SYNTAX ≥11 gives 1 point, SB BARI≥12%- 1 point, MV%DS ≥55%- 1.5 point, MB%DS≥65%- 2 points, lesion length ≥25 mm – 3 points. The overall performance of the score was excellent with AUC=.960, p<.001. With a cut-off value ≥4.5 points it has sensitivity of 90%, specificity 91%, accuracy 90%, p<.001.

Conclusion:
Different degree of stenosis in proximal main vessel and distal side branch, lesion length, SB myocardium territory and SYNTAX score are significant predictors of functional severity of bifurcation lesion. A score based on those parameters was developed with excellent discriminatory ability.
Abstract 17168: Myocardial Natriuretic Peptide Expression in Heart Failure With Preserved Ejection Fraction
Authors: Hahn Virginia S , Knutsdottir Hildur , Bedi Kenneth C , Margulies Kenneth B , Haldar Saptarsi M , Stolina Marina , Bader Joel S , Kass David A , Sharma Kavita
Published: November 2020

Introduction:
Serum natriuretic peptides (NP) are reduced in heart failure with preserved ejection fraction (HFpEF) compared to HFrEF; however, myocardial NP expression in HFpEF is unknown. We analyzed serum NTproBNP and myocardial RNAseq data to test the hypothesis that 1) lower myocardial NP expression in HFpEF drives the difference in serum levels, and 2) HFpEF with higher NP expression have transcriptomic signatures more similar to HFrEF.

Methods:
HFpEF patients (n=41) with clinical HF, LVEF≥50%, and meeting current consensus criteria for HFpEF underwent right heart catheterization and right ventricular (RV) endomyocardial biopsy. We performed differential gene expression analysis of RV septal tissue from HFpEF and compared to explanted HFrEF (n=30) and unused donor hearts (n=24, Control).

Results:
Myocardial
NPPB
expression was 5-fold higher in HFrEF vs Control (p<0.001) and unchanged in HFpEF vs Control, while
NPPA
expression was 9-fold higher in HFrEF and 5-fold higher in HFpEF vs Control (p<0.0001 for both comparisons). After adjustment for renal function and BMI, myocardial
NPPB
expression was significantly associated with serum NTproBNP in HFpEF (R
2
0.68; p<0.0001 for renal function,
NPPB
expression; p=0.03 for BMI). Pulmonary artery (PA) systolic pressure and PA wedge pressure correlated with myocardial
NPPB
expression (PASP R
2
0.45, p<0.0001; PAWP R
2
0.25, p=0.01), even after adjustment for comorbidities. HFpEF patients with high (≥ median
NPPB
expression in HFpEF) vs low
NPPB
expression had transcriptomic signatures more similar to HFrEF using ~13,000 genes in a Principal Component Analysis (Figure), quantified by vector distance from HFrEF (p=0.017).

Conclusions:
HFpEF patients have reduced serum NTproBNP due to lower myocardial
NPPB
gene expression. HFpEF patients with higher
NPPB
expression have transcriptomic signatures more similar to HFrEF, highlighting a HFpEF subgroup that may benefit from targeted therapies.
Abstract 17172: Pre Ablation Voltage Mapping Can Alter VT Inducibility
Authors: Al Aboud Asad A , Richardson Travis , Adeola Oluwaseun G , HOLMES Benjamin B , Julia McHugh , Nakajima Ikutaro , Michaud Gregory , Stevenson William G , KANAGASUNDRAM Arvindh
Published: November 2020

Introduction:
VT inducibility is often used to assess the efficacy of VT ablation. Sinus rhythm voltage maps (VMs) are used to guide ablation of VT substrate, but catheter manipulation may mechanically traumatize critical sites, altering VT inducibility. We prospectively evaluated the effect of VM on VT inducibility.

Methods:
Twenty-nine patients (mean age 62, 70% ischemic cardiomyopathy) with planned VT ablation underwent initial programmed electric stimulation (PES). Fifteen patients then underwent VM followed by repeat PES and 14 patients underwent a waiting period with ICE imaging and transseptal puncture but no VM (imaging group) before repeat PES. Responses to repeat PES were categorized as type I if the same VT was induced, type II if a different VT was induced, and type III if no VT was inducible.

Results:
In the VM group, the same VT was inducible in 3 patients, a different VT in 9, and no VT in 3 patients (figure). In contrast, those in the imaging group had the same VT induced in 10 patients, a different VT in 3 and no VT in 1 patient. There was no difference in the number of extrastimuli needed to induce VT between the two PES in either group. VT cycle length in the VM group was shorter after mapping (295 vs 331ms), although this was not statistically significant. There was no difference between the groups in anesthesia method, time between initial and second PES, type of cardiomyopathy, or ejection fraction.

Conclusions:
The mechanical effects of VM can alter inducibility of VT independent of ablation. This may contribute to late recurrences of VT by preventing mapping of clinically relevant VT circuits, or falsely indicating effective ablation when PES is repeated only after ablation.
Abstract 17173: Association of Acute Gout Flares and Colchicine Use With Clinical Outcomes During Admission for Acute Decompensated Heart Failure
Authors: Chinn Melissa E , Roth Mary E , Dunn Steven P , Bilchick Kenneth C , Mazimba Sula
Published: November 2020

Introduction:
Gout is a common comorbidity in heart failure (HF) patients, and is often exacerbated by diuretic use. The impact of gout or the treatment of gout on HF outcomes is unknown. The purpose of this study was to assess clinical outcomes in patients being treated for an acute HF exacerbation and receiving colchicine for an acute gout flare.

Methods:
This was a single center, retrospective cohort study of patients treated for an acute HF exacerbation from March 2011 to February 2020. The gout group included patients receiving colchicine for an acute gout flare during admission. The control group included those who did not receive colchicine for an acute gout flare. The primary outcome was 30-day readmission rate. Secondary outcomes included in-hospital mortality and length of stay.

Results:
In the cohort of 1,047 patients (68.8 +/- 13.7 years, 38% female), 237 patients received colchicine for acute gout during admission. Length of stay was significantly greater (9.93 days vs. 7.96 days, p < 0.0001) and in-hospital mortality was significantly lower (2.2% vs. 6.6%, p = 0.009) in patients with versus without gout. In a multivariate logistic regression model, in-hospital colchicine given for a gout flare was significantly associated with reduced in-hospital mortality (OR 0.322, 95% CI 0.105-0.779, p = 0.02) after adjustment for home beta blocker use, inotrope use, age, and diabetes mellitus (p < 0.05 for all in the model). The association between colchicine and survival to hospital discharge was only observed in patients who received colchicine during the hospitalization, as opposed to home use only. There was no significant difference in 30-day readmission rate based on gout status for patients surviving to hospital discharge (21.5% vs. 19.5%, p = 0.495).

Conclusions:
Among patients with an acute HF exacerbation, patients treated for an acute gout flare with colchicine had a greater length of stay and lower in-hospital mortality compared with those not having gout. Future analyses are warranted to identify the relationship between colchicine use and HF outcomes.
Abstract 17176: Burden and Prognostic Importance of Heart Failure Signs and Symptoms - Differences in Heart Failure With Preserved versus Reduced Ejection Fraction
Authors: Jering Karola , Claggett Brian , Pfeffer Marc A , Desai Akshay S , Mc Causland Finnian R , Lefkowitz Marty , Packer Milton , Rouleau Jean L , SHI Victor , Swedberg Karl B , Zile Michael R , McMurray John J , Solomon Scott
Published: November 2020

Introduction:
In patients with heart failure (HF), worsening of HF signs and symptoms is associated with increased cardiovascular (CV) risk. Differences in burden of HF signs and symptoms and their prognostic value in HF with preserved (HFpEF) versus reduced ejection fraction (HFrEF) are poorly understood.

Hypothesis:
High burden of HF signs and symptoms is associated with adverse CV events, and is of greater prognostic value in patients with HFrEF.

Methods:
Using combined data from PARADIGM-HF (LVEF eligibility ≤40%) and PARAGON-HF (LVEF eligibility ≥45%), Cox models were fit to assess the relationship between burden of HF signs and symptoms (≤2 or ≥3) and first HHF or CV death in patients with HFrEF (n=8385) and HFpEF (n=4709) with available signs and symptoms at screening (rest dyspnea, exertional dyspnea, paroxysmal nocturnal dyspnea, orthopnea, fatigue, edema, jugular venous distension, rales, third heart sound).

Results:
High burden of HF signs and symptoms (≥3) was more common among patients with HFpEF (48%) than HFrEF (42%, p<0.001). In both HF types, patients with high burden of signs and symptoms were more commonly female, had higher NYHA functional class and NT-proBNP and were more frequently prescribed diuretics (all p<0.001). Patients with HFrEF and high burden of signs and symptoms more commonly had atrial fibrillation (AF) than those with low burden (32 vs 41%, p<0.001) while prevalence of AF was similar regardless of sign and symptom burden in HFpEF (32 vs 32%, p = 0.98). High burden of signs and symptoms was associated with greater risk of HHF or CV death in patients with HFrEF (HR 1.47; 95% CI, 1.35-1.61) than in those with HFpEF (HR 1.28; 95% CI, 1.13-1.44; p
interaction
= 0.03) (Figure).

Conclusion:
Patients with HFpEF have slightly higher burden of HF signs and symptoms than those with HFrEF. High burden of HF signs and symptoms identifies patients at high risk foradverse CV events, and may have greater prognostic importance in patients with HFrEF than HFpEF.
Abstract 17197: Donor Circumstance and Mechanism of Death: Evolving Effects on Heart Transplant Recipient Survival
Authors: Smood Benjamin , Magruder J. Trent , Iyengar Amit , Patrick William L. , Han Jason J. , Helmers Mark , Kelly John J. , Desai Nimesh , Cevasco Marisa
Published: November 2020

Introduction:
Since 2000, suicide rates have dramatically increased, while deaths from motor vehicle accidents (MVAs) have declined. Poisoning has surpassed MVAs as the leading cause of preventable death, largely due to the opioid epidemic. Analyses regarding the forensic pathology of donor death and heart transplant recipient outcomes are lacking. We sought to determine how donor mechanisms (e.g. drug intoxication, asphyxiation) and circumstances (e.g. suicide, MVA) of death have affected heart transplant outcomes over the last 20 years.

Methods:
The UNOS database was queried for all first-time isolated heart transplants occurring between January 2000 through March 2019. First-time recipients were included. Donor, recipient, and procurement variables were screened by univariable logistic analysis to identify potential independent predictors of survival with freedom from transplantation at 1 year after heart transplant. A final parsimonious multivariable regression model was created, including all causes, mechanisms and circumstances of donor death. The primary endpoint of analysis was survival with freedom from retransplantation at last follow-up. Analyses were conducted for 2000-19, and stratified by decade (2000-09 and 2010-19).

Results:
34,373 patients met inclusion criteria. Median follow-up was 4.3 (IQR1.3-8.9) years. From 2000-19, death by suicide has had worse overall survival (HR 1.27; CI 1.1-1.5). A similar association is seen prior to 2010 (HR1.36; CI1.06-1.74). Since 2010, death by asphyxiation has been associated with improved survival (HR0.7; CI0.5-0.9). Death by MVA has become associated with early (i.e. 30-day) mortality (HR1.7; CI1.1-2.7), and worse survival among patients surviving 1-year after transplant. Donor death from drug intoxication has had no significant effect on recipient outcomes in the past 20 years.

Conclusions:
Since 2010, donors who died by MVA have worse early survival in heart transplant. Death by asphyxiation now appears to have a protective effect on overall survival. Suicide is no longer associated with poorer outcomes. Further study into how public health initiatives, policy, and epidemics effect transplant outcomes may improve donor selection and organ allocation in heart transplantation.
Abstract 17215: Differences in Anatomy, Physiology and Outcomes Between Blacks and Whites With Hypertrophic Cardiomyopathy
Authors: Arabadjian Milla E , Yu Gary , Sherrid Mark , Dickson Victoria V
Published: November 2020

Introduction:
Hypertrophic cardiomyopathy (HCM) in Black populations remains underexplored even though this inherited disorder can affect more than 220,000 Blacks in the US alone. Existing data suggest that Blacks with HCM are less likely to have obstructive physiology, but uncommon phenotypes, such as mid-ventricular obstruction have not been reported. Mortality outcomes have been reported as similar between groups.

Objective:
To evaluate structural HCM features and outcomes in Blacks and Whites with HCM

Methods:
The study design was a retrospective analysis of a prospective longitudinal observational study of a referred patient population with confirmed HCM and self-identifying as Black/African American and White/Caucasian.

Results:
We studied 434 individuals, 57 (13.1%) were Black. Males were 52.6% of the Black cohort and 59% of the White cohort. Blacks were younger, mean (SD) 54.6 (13.4) vs 62.6 (14.8) years, p<0.001. Ejection fraction and left ventricular hypertrophy (LVH) magnitude were similar between groups but LVH distribution differed with Blacks having more sub-basal LVH, which includes apical, apical-mid and mid LVH, 22 (38.6%) vs 56 (14.9%), p<0.001, and diffuse LVH, 6 (10.5%) vs 15 (4.0%), p=0.017, than Whites. Blacks also had more mid-ventricular obstruction, 7 (12.3%) vs 21 (5.5%), p=0.025. Of those who had a cardiac MRI, Blacks had more significant fibrosis (≥15% of LV mass), 10 (30.3%) vs 20 (9.5%), p<0.001. Mortality was low overall and both groups had similar proportion of ICD insertion for primary prevention of sudden death. However, Blacks had more appropriate ICD interventions, 5 (38.5%) vs 5 (6.8%), p=0.001.

Conclusions:
Blacks with HCM have more sub-basal LVH and mid-ventricular obstruction than Whites with HCM, phenotypes associated with worse disease progression. They are more likely to have significant myocardial fibrosis which has a pro-arrhythmic effect. They also had more aborted sudden death events. Precise evaluation of HCM structural and physiologic characteristics can improve targeted treatment and outcomes in this population.
Abstract 17227: Tobacco Use Prevalence and Transitions Among Adults With a History of Cardiovascular Disease
Authors: Zamora Cristian , Reynolds Lindsay M , Lee Un Jung , Stokes Andrew , Emelia J Benjamin , Bhatnagar Aruni , Payne Thomas , Rodriguez Carlos J
Published: November 2020

Introduction:
Although tobacco product transitions have been characterized in the general population, few studies have examined use in individuals with established cardiovascular disease (CVD).

Methods:
We examined tobacco use prevalence, and longitudinal patterns of tobacco product transitions in adult respondents (≥18 years) of the 2013-2014 (Wave 1) through 2016-2018 (Wave 4) Population Assessment of Tobacco and Health Study. Analysis was restricted to adults with prevalent CVD. Prevalent CVD was defined based on self-report at Wave 1 to the question from a health professional if she/he had: 1) a heart attack, 2) heart failure, 3) a stroke, or 4) some other heart condition. Factors associated with tobacco use (cigarette, e-cigarette, cigar, pipe tobacco, hookah, smokeless, dissolvable, or snus) and tobacco product transitions were investigated using logistic regression.

Results:
At Wave 1, 28.8% reported tobacco use among adults with CVD, the most commonly product was cigarettes (82.8%), followed by use of any type of cigar (49%) and e-cigarette use (23.2%), including 5.4% reporting dual use of cigarettes and e-cigarettes. E-cigarette use without concurrent cigarette use was uncommon (1.1%). Young male with lower level of education and lack of knowledge about the association between smoking and heart disease, were associated with tobacco use. Transition rates reported between Waves 1 and 4 demonstrate decreased cigarette use over time, with increased use of e-cigarette but less dual use. Male with prevalent CVD were less likely to use e-cigarettes compared to female (OR = 0.5, 95% CI: 0.4 - 0.8).

Conclusions:
Despite known harmful cardiovascular effects, almost a quarter of adults with prevalent CVD smoke cigarettes and few are quitting smoking.
Abstract 17233: Clock Modulating Small Molecule SR9011 Enhances Cell Cycle Arrest in Pulmonary Arterial Hypertension
Authors: Grobs Yann , Lampron Marie-Claude , Vitry Geraldine , Orcholski Mark , Provencher Steeve , BOUCHERAT Olivier , Bonnet Sebastien , Paulin Roxane
Published: November 2020

Background:
Pulmonary arterial hypertension (PAH) is a rapidly progressing disease of the lung vasculature, characterized by the remodeling of small pulmonary arteries in which pulmonary arterial smooth muscle cells (PASMCs) exhibit a cancer-like phenotype, with uncontrolled replication, self-sustaining growth signals, evasion of growth suppressors and resistance to apoptosis. In healthy cells, cell division is controlled by the circadian clock resulting in timed mitosis and rhythmic DNA replication. This suggests that impaired circadian clock might be involved in the cell cycle disorders seen in PAH. Especially, impaired function of the nuclear receptor Rev-Erbα (a core clock protein) has been associated with circadian clock impairment and cell cycle disorders in cancer.

Hypothesis:
Rev-Erbα impairment is involved in PAH pathogenesis.

Methods & Results:
We synchronized (Zeitgeber method using 50% horse serum for 2 hours) human PASMCs isolated from 4 PAH patients and 4 controls, and demonstrated a reduced (p=0.0192) (immunoblot) expression of Rev-Erbα 12 hours post synchronization in PAH-PASMCs compared to controls, associated with increased proliferation (Ki67 assay) and resistance to apoptosis (annexin V assay) (p<0.05), which were reversed by the Rev-Erbα agonist SR9011 (10μM for 24h). RNAseq (n=4/group) demonstrated that most of the downregulated (2-fold cut-off) genes following SR9011 treatments were involved in cytokinesis, meiosis, mitotic processes, cell cycle progression, chromosome segregation and recombination (p<0.05).
In vivo
, Rev-Erbα was also significantly decreased in male and female monocrotaline rats. SR9011 treatments (n=15/group) for 2 weeks (50mg/kg, i.p.) improved PA hemodynamics (
RVSP:47.80mmHg vs 75.29mmHg
\mPAP:26.69mmHg vs 44.36mmHg, p<0.0001); vascular remodeling, decreased proliferation(p=0.0001), increased apoptosis(p=0.0002)) and decreased RV hypertrophy (Fulton Index:0.3869 vs 0.5093 p=0.0006) compare to vehicle treated rats. These results were also repeated in the Fawn Hooded rats model.

Conclusion:
Our results suggest the involvement of Clock pathways in PAH etiology and thus open new avenue of investigation in PAH and new therapeutic options using clock-modulating small molecules.
Abstract 17236: Coronary Artery Calcification Scoring Stratifies Risk of Sudden Cardiac Death: The CAC Consortium
Authors: Uddin S M Iftekhar , Osei Albert D , Dardari Zeina , Dzaye Omar , Obisesan Olufunmilayo , Miedema Michael , Rumberger John A , Shaw Leslee J , Berman Daniel , Rozanski Alan , Budoff Matthew J , Cainzos Achirica Miguel , Nasir Khurram , Blaha Michael J
Published: November 2020

Introduction:
Sudden cardiac death (SCD) commonly presents as the initial manifestation of coronary heart disease in the general population. Coronary artery calcium (CAC), a sub-clinical marker of atherosclerosis, is a strong predictor of cardiovascular events. We assessed the ability of CAC to stratify risk of SCD.

Methods:
We studied 66,636 adults from the CAC Consortium, a large multi-center cohort of asymptomatic patients free of clinical CVD at baseline. We categorized participants into 4 CAC score groups—CAC=0, CAC 1-99, CAC 100-399, and CAC≥400. The primary outcome was defined by identifying accepted International Classification of Diseases codes for SCD on official death certificates obtained for all deaths from the National Death Index. Predictive value of CAC for SCD was assessed using Cox proportional hazards regression models adjusted for age, sex and traditional risk factors. We performed standard area under receiver operating curve (AUC) analyses from fully adjusted logistic regression models, with and without CAC. All analyses were also repeated among participants aged 45-75 years.

Results:
Mean age of the study population was 54.4 years, and 33% were females and 89% were Whites. Over a mean follow up of 12.3±3.9 years, there were 211 SCD events. Participants with CAC=0 had lower absolute SCD rates compared to those with CAC≥400 (0.05 vs 1.28 per 1000 person-years, respectively). Increasing CAC scores (reference CAC=0) were associated with increasing SCD risk [CAC 100-399: HR (95% CI) 2.8(1.6-5.0), CAC≥400: 4.3(2.4-7.7)]. Addition of CAC to the fully adjusted model (vs without CAC) improved AUC for SCD among the whole study population (0.88 vs 0.86,
P
<0.001) and more so among 45-75 year-olds (0.82 vs 0.76,
P
<0.001).

Conclusions:
We demonstrate the predictive value of CAC for SCD. CAC could be a cost-effective risk-stratification tool that can be used to help identify individuals at high risk of SCD who could undergo additional screening and management.