bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16087: A Propensity Matched Comparison of a Hybrid Approach of Percutaneous Coronary Intervention Followed by Minimally Invasive Valve Surgery versus Conventional Median Sternotomy Coronary Artery Bypass Graft Plus Valve Surgery
Authors: Pineda Andres M , Mihos Christos G , Yang Solomon C , Santana Orlando , Lamelas Joseph , Beohar Nirat
Published: July 2021

Introduction:
A hybrid approach of PCI followed by minimally invasive valve surgery (MIVS) has been recently introduced as an alternative for patients with concomitant coronary artery and valvular heart disease.

Hypothesis:
A hybrid approach might be better than the conventional median sternotomy CABG plus valve surgery for such patients.

Methods:
We retrospectively evaluated 525 consecutive patients with concomitant coronary artery and valvular heart disease who underwent surgical intervention at our institution between January 2009 and April 2014. A propensity score matching was performed to adjust for differences between the hybrid and the conventional groups.

Results:
A total of 63 patients who underwent a hybrid approach were propensity score-matched with a cohort of 63 conventional approach patients. There were no differences in the baseline characteristics (Table). Most patients in the hybrid group had drug-eluting stents (83%) placed for single (44.4%) or dual (50.8%) vessel disease, and within a median of 40 days, underwent single (87%) or double (13%) valve surgery. There was no difference in the type of valve surgery between the groups. Post-operatively, patients in the hybrid group had significantly shorter intensive care unit length of stay, fewer packed red blood cell units transfused, and a decreased incidence of re-intubation, prolonged ventilation, and acute kidney injury. There was no difference between the groups in other post-operative complications, including cerebrovascular accidents, re-operation for bleeding, atrial fibrillation, and 30-day mortality. At long-term follow-up (mean 29 months) the overall all-cause mortality was 9.5%, and the Kaplan-Meier estimated 5-year survival rates were similar (85 vs 90%,
p
=0.45).

Conclusions:
A hybrid approach of PCI followed by MIVS is associated with a decreased morbidity, and similar short and long-term survival when compared with conventional median sternotomy CABG plus valve surgery.
Abstract 16091: Cardioprotective Actions of the N-Terminal-Derived Annexin-A1 Peptide, Ac2-26, Against Myocardial Infarction in vivo
Authors: Ritchie Rebecca H , Qin Chengxue , Li Renming , Bourke Jane E , Kiriazis Helen , Rosli Sarah , Cao Nga , DeBlasio Miles , Yang Yuan , Du Xiao-Jun , Gao Xiaoming
Published: July 2021

Myocardial infarction (MI) is the major cause of heart failure and death in the Western world. Annexin-A1 is an endogenous, glucocorticoid-regulated anti-inflammatory protein. We have previously shown that this protein plays an important protective role in preserving left ventricular (LV) viability and function in vitro, actions that are reproduced by treatment with its N-terminal-derived peptide, Ac2-26. Little is known however about its cardioprotective actions in vivo, particularly beyond its early anti-necrotic actions in the first few hours of reperfusion. We now test the hypothesis that exogenous Ac2-26 limits multiple aspects of MI injury, over both the short and longer-term in vivo. In the first study, adult C57BL/6 mice were subjected to ischemia-reperfusion (left arterial descending coronary artery ligation, with 1-7 days reperfusion), and Ac2-26 was administered at 1mg/kg i.v. every 24h commencing 5mins before reperfusion. In the second study, mice were subjected to permanent coronary artery occlusion, with Ac2-26 administered 1mg/kg/day i.p. via osmotic pump inserted at time of surgery. As shown in the Table, Ac2-26 reduced cardiac necrosis after 24h reperfusion (infarct size, plasma troponin I levels), systemic and cardiac inflammation after 48h reperfusion (neutrophil and macrophage infiltration) and cardiac fibrosis after 7 days reperfusion. These protective actions at the level of cardiac morphology were associated with preservation of LV function 4wks after permanent occlusion, as determined on fractional shortening and velocity of circumferential fiber shortening. Taken together, our data is the first evidence of Ac2-26 cardioprotection beyond the first few hours of reperfusion in vivo, and importantly, the first to report Ac2-26-induced preservation of LV function in the heart post MI in vivo.
Abstract 16182: Diabetics With Acute Chest Pain Have Similar Length of ED Stay From Early CCTA Compared to Standard Evaluation but More Downstream Testing and Radiation Exposure: The ROMICAT II Trial
Authors: Truong Quynh , Schulman-Marcus Joshua , Zakroysky Pearl , Chou Eric T , Nagurney John T , Wiviott Stephen D , Fleg Jerome L , Schoenfeld David A , Udelson James E , Hoffman Udo , Woodard Pamela K
Published: July 2021

Objective:
In the evaluation of acute chest pain (ACP), early cardiac computed tomographic angiography reduces emergency department (ED) length of stay (LOS) compared with standard evaluation. It is unknown whether patients with diabetes mellitus (DM) have similar benefits.

Methods:
In the ROMICAT II multicenter trial, we randomized 1000 patients (17.3% DM) 40-74 years old with symptoms suggestive of acute coronary syndrome (ACS) but without ischemic ECG changes or initial positive troponin to early CCTA or standard ED evaluation. In this pre-specified analysis, we compared differences between the two strategies for the primary endpoint of LOS in DM and non-DM patients. Secondary endpoints were examined in Table 1.

Results:
ACS rate was similar between DM and non-DM (both 7.5%, p=1.0). DM (70% on oral hypoglycemics, 25% insulin) were older (57 vs 54 years) with more cardiac risk factors, though more frequently female (56%) and on cardiac medications than non-DM (all p<0.001). Table 1 shows the effects of early CCTA versus standard evaluation in DM and non-DM groups. LOS was unaffected by CCTA strategy in DM, whereas LOS was significantly reduced in non-DM. Early CCTA was associated with higher rates of direct ED discharge in both groups, but hospital admissions were significantly reduced with CCTA only in non-DM. Although both groups had more downstream testing and higher radiation dose with CCTA, these differences were accentuated in DM (all p-interaction≤0.04). There was no missed ACS. More DM had abnormal CCTA than non-DM (68% vs 50%, p=0.003), but among DM with no CAD or non-obstructive CAD (69%) by CCTA, LOS was similar compared to non-DM patients (p=NS).

Conclusions:
An early CCTA strategy in the ED was associated with shorter LOS in non-DM but not in the DM group. The higher prevalence of CAD in DM and direct visualization of atherosclerosis by CCTA may explain the increased testing and radiation exposure with CCTA that were accentuated in DM.
Abstract 16235: The Impact of Atrial Fibrillation on Heart Failure With Preserved versus Reduced Ejection Fraction in the Middle East Region: Insights From the Gulf aCute heArt failuRe rEgistry (Gulf CARE)
Authors: Asaad Nidal A , Sulaiman Kadhim , Mohsen Mohammed K , Al-Suwaidi Jassim , Alsheikh-Ali Alawi , Darbar Dawood , Singh Rajvir , AlHabib Khalid F , AlFaleh Husam , Elasfar Abdelfatah , Al-Motarreb Ahmed , Panduranga Prashanth , Almahmeed Wael , Bazargani Nooshin , Ridha Mustafa , Bulbanat Bassam , Al-Jarallah Mohammed , Amin Haitham , Bollensdorff Christian , Salam Amar M , Yacoub Magdi
Published: July 2021

Background:
Atrial Fibrillation (AF) and heart failure (HF) are two common prevalent conditions that may present independent of each other or coexist. The impact of AF on mortality in patients with HF and reduced (HFrEF) or preserved ejection fraction (HFpEF) is unclear with conflicting results.

Methods:
We analyzed data from the Gulf acute HF registry, a prospective, multinational registry of patients admitted with acute HF in 47 hospitals in 7 Middle Eastern Arab Gulf countries (recruited between February 13, 2012 and November 13, 2012). We compared the 12-month mortality in patients with AF versus sinus rhythm (SR) in both types of HF (HFrEF and HFpEF).

Results:
Among 5005 patients admitted with HF, 835 patients (16.7%) had AF and 3964 (79.2 %) had no history of AF and were in SR. Remaining percentage included patients with rhythms other than AF or SR (e.g. junctional rhythm). After excluding patients with no available echocardiography and those with other rhythms, the number of patients in our study population was 4394 patients where 770 patients (17.5 %) were in the AF group ( 10.2% with HFrEF and 7.3% with HFpEF) and 3624 patients (82.5 %) were in the SR group (56.2% with HFrEF and 26.3% with HFpEF). The mortality at 12 month was significantly higher in the AF compared to SR group (21.1% vs. 16.3%; P = 0.001), even after covariate adjustment (odds ratio [OR] = 1.23, 95% C.I 1.01-1.5; P = 0.04). Furthermore, subgroup analysis revealed that AF was associated with a higher risk of 12 month mortality in patients with HFrEF (23.7% vs. 16.6%; P = 0.001) but not among patients with HFpEF (17.5% vs. 15.8%; P = 0.48), even after covariate adjustment (adjusted OR among patients with HFrEF = 1.40, 95% C.I. 1.10-1.80; P=0.009 while adjusted OR among patients with HFpEF = 0.93. 95% C.I.:0.65 - 1.32; P=0.67).

Conclusion:
AF is associated with significantly higher 12-month mortality among patients with HFrEF, but not among those with HFpEF, suggesting a stronger impact of AF in patients with systolic HF.
Abstract 16289: Can We Personalize CPR? Challenges With Hemodynamics, Monitoring, and Pharmacology
Authors: Lampe Joshua W , Yin Tai , Bratinov George , Weiland Theodore , Kaufman Christopher L , Becker Lance B
Published: July 2021

Introduction:
Coronary perfusion pressure (CPP) guided CPR improves survival over guideline CPR. EtCO2 has also been used to guide CPR. These efforts reflect that one-size-fits-all CPR is sub-optimal, but assume that CPP and EtCO2 guidance will result in similar definitions of “high quality” chest compressions (CC). A mechanistic study of the interaction between CC, blood flow, CPP, and EtCO2 has not been done.

Methods:
CPR was performed on 21 domestic swine (~30 Kg) using standard physiological monitoring. Flow was measured in the abdominal aorta, the inferior vena cava (IVC), the right renal artery and vein, the right common carotid and external jugular. Ventricular fibrillation (VF) was electrically induced. Mechanical CC were started after ten minutes of VF. CC waveforms varied so that sternal release occurred over 100 ms, 200 ms, or 300 ms. CC were delivered at a rate of 100 per minute and at a depth of 1.25” (n=9), 1.9” (n=8), or 1.9” with vasopressor use (n=4) for a total of 54 min. CC release times changed every 2 min and were randomized.

Results:
In the first 18 min of CPR, EtCO2 was optimized by a 100 ms release (27.2±2.5 mmHg) vs. a 200 ms (24.7±2.5 mmHg; p = .005) or 300 ms release (25.1±2.5 mmHg; p= 0.03). CPP was optimized by a 200 ms release (6.7±1.0 mmHg) vs. a 100 ms (5.7±1.0 mmHg; p = 0.03) or 300 ms (4.9±1.0 mmHg; p < 0.01) release. Deeper CC increased blood flow in the IVC (1.5±0.2 vs. 0.12±0.2 mL/comp: p<0.001) and carotid artery (0.4±0.03 vs. 0.2±0.03 mL/comp: p<0.001) and changed the distribution of blood flow. In prolonged CPR, CC efficacy decayed with time, particularly with 1.25” CC, and resulted in distinct periods of to and fro flow (sloshing). Vasopressor effects appeared to be time dependent, but trended towards improved CPP at the expense of significantly reduced carotid blood flow.

Conclusions:
CPP and EtCO2 provide insight into two distinct aspects of CC generated blood flow, and consequently cannot be simultaneously optimized. CC generated blood flow transitions from forward blood flow to sloshing as a function of time and CC depth. Pressure measurements are insufficient to titrate vasopressor use, as tissue perfusion can collapse while maintaining the CPP. We currently lack the monitoring and the physiological understanding required to personalize CPR.
Abstract 16320: The Practical Use of the Latest Standards of Electrocardiography (PULSE) Trial: Nursing-Focused Intervention Improves Nurses’ Knowledge and Quality of ECG Monitoring
Authors: Funk Marjorie , Fennie Kristopher P , Stephens Kimberly , May Jeanine L , Winkler Catherine , Chang Pei-Shiun , Feder Shelli , Knudson Krista , Rose Bovino Leonie , Turkman Yasemin , Drew Barbara J ,   PULSE Site Investigators
Published: July 2021

Objectives:
To evaluate the effect of implementing AHA practice standards for ECG monitoring on nurses’ knowledge (NK), quality of care (QoC), and patient outcomes (PO). We hypothesized that our intervention would increase NK, which would enhance QoC, which would lead to improved PO.

Methods:
The PULSE Trial was a 6-year multi-site randomized clinical trial with crossover that took place in 65 cardiac units in 17 hospitals. We randomized hospitals to the Experimental (Exp) or Control group after obtaining baseline data at T1. We collected data at 2 additional time points: T2 after the intervention in the Exp group and T3 after the intervention in the Control group. The 2-part intervention consisted of an interactive online ECG monitoring education program and strategies to implement and sustain change in practice, led by nurse champions on each unit. We measured NK by a validated 20-item online test. We assessed QoC over 5 consecutive days by observing monitors and electrode placement, reviewing current medical records, and comparing arrhythmias stored in the monitor with nurses’ documentation. For PO, we used administrative and lab data to identify a subset of medical records for review to determine mortality and in-hospital MI. To account for covariates and intra-hospital and unit correlations, we used linear mixed models for NK, generalized linear mixed models for QoC, and generalized estimating equations for PO.

The intervention was significantly associated with better NK and improved markers of QoC. NK was not sustained at T3 in the Exp group, but was significantly better than at T1 (p<.0001). For several QoC variables, at T2 the Exp group was better than at T1 (p<.05), and better than the Control group (p<.05); at T3, the Control group improved (p<.05) and improvement was sustained in the Exp group. The intervention was not associated with change in PO.

Conclusions:
Online education and strategies to change practice can result in improved NK and QoC related to ECG monitoring.
Abstract 16343: Normal Values and Age Related Changes of Left and Right Atrial Phasic Functions by Speckle Tracking Echocardiography
Authors: Rimbas Roxana Cristina G , Calin Simona Ionela , Enescu Oana Aurelia , Mihaila Sorina , Vinereanu Dragos
Published: July 2021

Introduction:
Limited data are reported about age related changes of LA and RA functions, and interatrial relationship.

Methods:
131 normal subjects (19-78 yrs, 89 women), divided in 4 age groups, were studied by conventional and speckle tracking echo (STE). LA and RA volumes were measured: pre atrial contraction (Vp), minimal (Vmin), and maximal (Vmax), and computed to define atrial ejection fractions: active EF = (Vp-Vmin)/Vp; expansion index EI = (Vmax-Vmin)/Vmin; passive EF = (Vmax-Vp)/Vmax. Active function was assessed from negative strain at atrial contraction (GSA-) and time from P onset to peak (TGSA-), and late diastolic strain rate (GSRL); passive function from positive global strain (GSA+) and time from R to peak (TGSA+), and from early negative diastolic SR (GSRE); reservoir function from the sum of GSA- and GSA+ (SUMGSA), positive global SR at the beginning of ventricular systole (GSR+) and derived time from P onset (TGSR+). We defined for LA a maximal difference (DIF) of all derived times, as a measurement of LA synchrony, and also a difference between RA times and maximal correspondent LA times, as an interatrial synchrony.

Results:
All LAEFs, Vmin, and Vp decreased over 50 yrs, and Vmax over 60 yrs. RA reservoir function decreased over 60 yrs, while passive RA function over 50 yrs. Active LA function (GSRL) decreased over 60 yrs. LA reservoir and conduit function decreased over 50 yrs. All derived times were increased over 40 yrs. LA and also interatrial contraction and relaxation synchrony were altered only after 60 yrs (all p<0.001) (Tables). Correspondent RA and LA functions are significantly correlated, irrespective of age (r=0.6, p<0.001).

Conclusion:
Although LA and RA functions are strongly correlated, they have different age related changes. RA volumes, EFs, and active function were not affected by age, whereas LAEFs, volumes, passive and reservoir LA and RA functions decreased over 50 yrs. LA and also interatrial synchrony were altered after 60 yrs.
Abstract 16396: Phosphodiesterase-5 Expression and Activity is Increased in Children With Single Ventricle Heart Failure
Authors: Miyamoto Shelley D , Nelson Penny , Sobus Rebecca , Nunley Karin , Peterson Valencia , Stauffer Brian L , Sucharov Carmen C
Published: July 2021

Introduction:
Single ventricle congenital heart disease (SV) is the leading cause of cardiovascular death and indication for heart transplantation in infancy. There are no proven therapies for SV heart failure (HF). Human and animal models of HF demonstrate that myocardial phosphodiesterase-5 (PDE5) is increased with cardiac stress and treatment with a PDE5 inhibitor (PDE5i) results in enhanced cardiac function and prevents remodeling. Sildenafil, a PDE5i, is increasingly utilized for the treatment of patients suffering from failing SV. The objective of this study was to determine myocardial PDE5 expression and activity in children transplanted for failing SV.

Methods:
At the time of cardiac transplantation, explanted pediatric hearts were immediately cooled in ice cold oxygenated Tyrodes in the operating room. The tissue is rapidly dissected, flash frozen and stored at -80
0
C until further use. RNA, protein and cytosolic fractions were isolated from explanted right ventricle (RV) tissue from SV and non-failing (NF) donors. RTqPCR for PDE5, Western blot (normalized to calnexin loading control) for PDE5 and PDE5 activity assays were performed. For PDE 5 activity, cGMP hydrolysis was measured using [
3
H]cGMP as the substrate. Sildenafil was added to measure PDE5 specific activity, and activity was calculated using nonlinear regression.

Results:
All patients used in the SV analysis had a failing morphologic RV and were selected from a cohort of 17 SV (median age 0.5, range 0.05-10 yrs) and 8 NF controls (median age 7, range 1.3-13 yrs). PDE5 gene expression was higher in SV myocardium compared to NF (1.9±0.7, n=17 SV vs 1.1±0.5 ct fold change, n=8 NF, p=0.02). There was a trend towards higher PDE5 protein expression in SV myocardium compared to NF (1.5±0.7, n=4 SV vs 1.0±0.4 protein expression normalized to NF, n=3 NF; p=ns). There was increased PDE5 activity in SV compared to NF (22.3±1.2, n=3 SV vs 11.9±4.2 pmol/mg/min, n=2 NF; p=0.02).

Conclusions:
There is increasing evidence that PDE5i has beneficial direct myocardial effects. There is increased PDE5 gene expression and activity in failing SV myocardium compared to NF control suggesting that PDE5 may represent a promising therapeutic target in this challenging population.
Abstract 16445: Reference Echocardiographic Measurements in Free-Living Adults: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)
Authors: Foppa Murilo , Santos Angela B , Freire Claudia M , Fernandes Luciana P , Vasconcellos-Silva Paulo R , Sharovsky Rodolfo , El Aouar Lilia M , Pires Julio C , Bessel Marina , Mill Jose G , Lotufo Paulo A , Duncan Bruce B
Published: July 2021

Background:
Current normal reference values for echocardiography are derived from North American or European populations, and it is not known if these are applicable to the multiethnic constitution of Brazilian and South American populations.

Objective:
We aimed to describe reference values for echocardiographic measurements in a contemporary cohort of middle-aged and elderly free-living Brazilians.

Methods:
Echocardiographic studies from 3234 participants (33% of those for whom echocardiography was available) were read in the ELSA Echocardiography Reading Center. Their demographic characteristics did not differ substantially from remaining participants of similar age in the ELSA-Brasil cohort - a study of Brazilian public servants aged 35 to 74 years. Among these, we identified a reference normal sample of 950 (29%) participants (56±10 years; 40% men) after excluding those with prevalent hypertension (51%), diabetes (27%), metabolic syndrome (45%), self-reported cardiovascular disease (13%), or echocardiographically determined myocardiopathy or significant valvular disease (13%).

Results:
The Table describes sex-specific mean±SD values from the reference normal sample. Mean values for structural measurements were larger for men, but systolic function and mitral annular tissue Doppler measurements were similar. The majority of measurements were within the normal range of other populations.

Conclusion:
Although results in this sample, which we believe to be the largest drawn to date from an apparently normal Latin American population, are mostly similar to those of other international reference samples, particularities exist that may relate to its multi-ethnic nature or to other regional characteristics. We believe that these results are suitable for use as regional normative values and for international comparisons.
Abstract 16483: Marital Status and Long-Term Mortality of Male Patients Presenting With Acute Myocardial Infarction
Authors: Yokoyama Hiroaki , Higuma Takumi , Nishizaki Fumie , Izumiyama Kei , Shibutani Shuji , Yamada Masahiro , Tomita Hirofumi , Abe Naoki , Osanai Tomohiro , Okumura Ken
Published: July 2021

Background:
Although unmarried has been associated with an increased risk of acute coronary syndrome, little is known about the relationship between marital status and long-term mortality after acute myocardial infarction (AMI).

Methods and Results:
To elucidate the clinical characteristics and outcomes of AMI patients who have never married, the consecutive 364 male AMI patients (mean age; 63±13 years) admitted to our hospital were studied. Mean follow-up period was 1.7 years.

The patients were divided into 2 groups by their marital status: those who had married at least one time (Married Group (MG), n=328) and those who had never married (Unmarried Group (UG), n=36 (9.9%)). UG patients were younger (54±11 vs 65±12 years, p<0.0001) and had a higher level of body mass index (BMI) (26.5±4.5 vs 24.1±3.5 kg/m2, p=0.0002) than MG. None of coronary risk factors including hypertension, dyslipidemia, diabetes mellitus and smoking habit, Killip classification, culprit lesion of AMI nor maximal creatine phosphokinase-MB (CPK-MB) level was different between 2 groups. The time from the symptom onset to admission was significantly longer in UG (6.1 (2.6-14.3) vs 3.8 (2.3-8.3) hours, p=0.033). Left ventricular ejection fraction (LVEF) assessed at the acute phase of AMI was not different between 2 groups. Kaplan-Meier Curve showed no significant difference of all-cause mortality between 2 groups (20% in UG vs 12% in MG, p=0.27 by Log-rank test). When the analysis is done in patients with the ages >50 years (272 patients in MG and 19 in UG), all-cause mortality tended to be higher in UG than in MG (38% vs 15%, p=0.098 by Log-rank test). After adjustment for age, Killip IV and LVEF at the acute phase, unmarried status was independently associated with all-cause long-term mortality after AMI (hazard ratio (HR); 3.84, 95% confidence interval (CI); 1.22-10.2, p=0.024).

Conclusions:
Unmarried status is independently associated with significantly increased all-cause long-term mortality in the male AMI patients with the ages >50 years.
Abstract 16485: The Nitroxyl Donor 1-Nitrosocyclohexyl Acetate Limits Cardiac Superoxide Upregulation and Diastolic Dysfunction in a Mouse Model of Diabetic Cardiomyopathy
Authors: Ritchie Rebecca H , Cao Nga , Wong Yung George , Rosli Sarah , Kiriazis Helen , Huynh Karina , Qin Chengxue , Du Xiao-Jun , Kemp-Harper Barbara K
Published: July 2021

Nitroxyl (HNO), a redox congener of NO•, is a novel regulator of cardiovascular function combining vasodilator and positive inotropic properties. Our previous studies have demonstrated these properties occur concomitantly in the intact heart; HNO moreover also exhibits antihypertrophic and superoxide-suppressing actions. HNO donors may thus offer favorable actions in heart failure. The impact of chronic HNO donor administration has however yet to be reported in this context. We tested the hypothesis that the HNO donor 1-nitrosocyclohexyl acetate (1-NCA) limits cardiomyocyte hypertrophy and left ventricular (LV) diastolic dysfunction in a mouse model of diabetic cardiomyopathy in vivo. Male 6 week-old FVB/N mice received either streptozotocin (55 mg/kg/day i.p. for 5 days, n=17), to induce type 1 diabetes, or citrate vehicle (n=16). After 4 weeks of hyperglycemia, mice were allocated to 1-NCA therapy (83mg/kg/day i.p.) or vehicle, and followed for a further 4 weeks. As shown in the table, blood glucose was unaffected by 1-NCA. LV diastolic dysfunction was evident in diabetic mice, measured as echocardiography-derived A wave velocity, deceleration time and E:A ratio; LV systolic function was preserved. Diabetes-induced diastolic dysfunction was accompanied by increased LV cardiomyocyte size, hypertrophic and pro-fibrotic gene expression, and upregulation of LV superoxide. These characteristics of diabetic cardiomyopathy were largely prevented by 1-NCA treatment. Selectivity of 1-NCA as a donor of HNO versus NO• was demonstrated by the sensitivity of the coronary vasodilation response of 1-NCA to the HNO scavenger L-cysteine (4mM), but not to the NO• scavenger hydroxocobalamin (50μM), in the normal rat heart ex vivo (n=3-7). Collectively, our studies provide the first evidence that HNO donors may represent a promising new strategy for the treatment of diabetic cardiomyopathy, and implies their therapeutic efficacy in settings of chronic heart failure.
Abstract 16515: Differential Functions of HCN1 and HCN4 Pacemaker Channels Within the Sinoatrial Node for the Stable and Precise Beating of the Heart
Authors: Fenske Stefanie , Marks Vanessa , Koenigsbauer Stefanie , Hassan Sami I , Ziegler Tilman , Kupatt Christian , Martin Biel , Wahl-Schott Christian A
Published: July 2021

The heart beat is initiated by the generation of spontaneous action potentials in pacemaker cells of the sinoatrial node (SAN) region. The maintenance of a stable heart beat requires mechanisms which protect the SAN pacemaker cells from potential perturbing influences which arise from inside and outside the sinoatrial network. Our previous work suggests that the hyperpolarization-activated cyclic nucleotide gated channel subtype 1 (HCN1) protects against such perturbations and thereby increases the stability, the precision and the safety of the sinoatrial network. Here, we investigate the role of HCN4 channels within this context. Using genetic mouse models deficient for HCN channels as well as mouse models expressing engineered HCN channels, we performed a detailed functional characterization of pacemaker mechanisms in single isolated sinoatrial node cells, explanted beating sinoatrial node preparations, with telemetric in vivo electrocardiography, echocardiography, and in vivo electrophysiology. We provide evidence that HCN4 has a critical role in counteracting and balancing potentially destabilizing effects of the autonomic nervous system on the regulation of the heart rate. Specifically, HCN4 channels smooth the transition of the heart rate to a new equilibrium. Furthermore, we provide evidence that the cAMP- dependent fine tuning of HCN4 channel activity could provide the exact dosage of current to balance and counteract overshooting responses of the heart rate to autonomic regulation. In the absence of such a protecting effect, mice display a brady- tachy syndrome.
Abstract 16595: Airway Ciliary Dysfunction and Increased Postoperative Respiratory Complications in Broad Spectrum of Congenital Heart Disease Patients
Authors: Stewart Eileen , Zahid Maliha , Khalifa Omar , Munoz Ricardo , Feingold Brian , Wearden Peter , Devine William , Leatherbury Linda , Lo Cecilia W
Published: July 2021

Introduction:
Congenital heart disease (CHD) patients with heterotaxy (HTX) have high prevalence of airway ciliary dysfunction (CD). This is associated with higher postoperative morbidity and more respiratory complications. As a high prevalence of airway CD is also observed in CHD patients without HTX, we hypothesize patients with broad spectrum of CHD may have increased postoperative morbidity associated with airway CD.

Methods:
CHD patients <1 yr undergoing cardiac surgery were recruited. CD testing was conducted with two tests used for primary ciliary dyskinesia (PCD) diagnosis: nasal nitric oxide (nNO) was measured, typically low with PCD, and nasal scrape was obtained for ciliary motion (CM) analysis with videomicroscopy. Data on post-operative outcome parameters were collected.

Results:
We recruited 55 CHD patients with 76 surgical events; 38% had airway CD (low nNO/ abnormal CM). Demographics and surgical complexity scores were similar between patients with or without CD. In CHD patients with CD, there was significant increase in continuous positive airway pressure ventilation (CPAP) (p = 0.008) and trend for more reintubation (11% non-CD vs. 27% CD patients) (Table 1). There was significant increase in beta-agonist use in CD patients (p = 0.006) and five-fold increase in respiratory medication use (Table 1). No difference was observed in length of stay, ventilator days, overall supportive ventilation (CPAP, high flow nasal cannula, nasal cannula), use of pulmonary vasodilators, chest tube days, effusion, or need for extracorporeal membrane oxygenation (ECMO).

Conclusions:
CHD patients with airway CD have increased postoperative morbidity, including increased need for CPAP, more use of albuterol and respiratory medications, and more reintubations. These results suggest CHD patients may benefit from presurgical screening for airway CD, with those identified with CD given perioperative respiratory therapy to reduce postoperative morbidity.
Abstract 16606: Cardiac Fibroblast-Restricted Enhancement of G
q
Signaling Prolongs Calcium Transients and Increases Spontaneous Activity in Biomimetic Cardiac Microtissues
Authors: Kofron Celinda M , Kim Tae Yun , King Michelle E , Park Elizabeth M , Choi Bum-Rak , Mende Ulrike
Published: July 2021

Introduction:
Enhanced G
q
signaling in response to hemodynamic stress and injury is well known to induce remodeling in both cardiac myocytes (CMs) and fibroblasts (CFs). However, the effect of CF activation and fibrosis on CMs and integrated myocardial function cannot be easily discerned from concomitant effects on CMs.

Hypothesis:
Enhanced G
q
signaling in CFs influences CM function in a 3D microtissue model previously developed in our lab, in which neonatal rat ventricular CMs and CFs are highly interspersed as seen in the myocardium.

Methods:
CFs infected in suspension (2 hrs, 10 MOI) with empty adenovirus (Ad-Ctr) or Ad encoding wild-type (WT) or constitutively active (Q209L or QL) Gα
q
were co-seeded with uninfected CMs (CM:CF 1:1) into non-adhesive hydrogels at ~1200 cells per recess (400/800 μm wide/deep). After 2-4 days, we assessed tissue size by microscopy, G
q
and extracellular matrix proteins proteins by Western Blot analysis, and Ca
2+
transients ([Ca
2+
]
i
) with Rhod 2/AM.

Results:
Overexpression of Gα
q
in CFs was associated with a 3-fold (WT) and 7-fold (QL) increase in total inositolphosphate formation, indicating enhanced basal phospholipase β activity. After 4 days, CM:CF
QL
tissues were larger in size by 30-40% and expressed more laminin and fibronectin. After 3 days, CM:CF
CTR
paced at 1 Hz had [Ca
2+
]
i
duration of 218±3 ms, decay of 141±2 ms, and rise time of 35±4 ms (n=55-69). In CM:CF
QL
, duration and decay were prolonged by 160 ms and 21 ms, resp., and rise time was decreased by 5 ms (n=10-27). In CM:CF
WT
with less G
q
signaling, [Ca
2+
]
i
duration and decay were also prolonged but only by 30 ms and 7 ms, resp. (n=46-51). These effects were similar but less pronounced after 2 days and/or at 2 Hz. Spontaneous [Ca
2+
]
i
activity was seen in 50% of CM:CF
QL
, 11% of CM:CF
WT
, but only 2% of CM:CF
CTR
microtissues. The gap junction inhibitor carbenoxolone (100 μM) decreased this activity in CM:CF
QL
by 80% and in CM:CF
WT
by 15%.

Conclusion:
We show that enhanced CF-restricted G
q
signaling in biomimetic cardiac microtissues increases tissue size, prolongs [Ca
2+
]
i
duration and decay, and increases spontaneous Ca
2+
activity. Our findings suggest that depending on the CF activation state, CFs can greatly modulate CM calcium handling and potentially influence arrhythmogenesis.
Abstract 16642: Distinctive Characteristics of Left Atrial Remodeling in Heart Failure With Preserved or Reduced Ejection Faction
Authors: Melenovsky Vojtech , Zakeri Rosita , Redfield Margaret M , Borlaug Barry A
Published: July 2021

Introduction:
Left atrial structure and function (LA) is affected by the presence of heart failure (HF), but the specific impact of HF subtype is poorly characterized.

Hypothesis:
HF-induced LA remodeling differs between patients with preserved (pEF) or reduced ejection fraction (rEF).

Methods:
198 consecutive HF patients referred to Mayo Clinic (51% HFpEF, NYHA 3.1±0.7, 66±13 years, 39% females) and 40 HF-free controls of similar age and gender underwent right heart catheterization (LA pressures), echocardiography (LA volumes) and follow-up.

Results:
Compared with controls, HF patients had larger atria and more impaired LA reservoir and contractile function (total and active LAEF, all p<0.001). At identical mean LA pressure (20 vs 20 mmHg, p=0.9), HFrEF patients had larger LA volumes (LAVI 50 vs 41 ml/m
2
p<0.001), but HFpEF patients had higher LA peak (V-wave) and lower LA minimal pressures, with higher LA stiffness (0.79 vs 0.48 mmHg.ml
-1
, p<0.001, Fig-A) and LA pressure pulsatility (19 vs 13 mmHg, p<0.001). Despite smaller LA size, better LA function (total LAEF 39 vs 35 %, p=0.04, active LAEF 30 vs 22 %, p<0.001) and less mitral regurgitation (grade 1.8 vs 2.5, p<0.001), HFpEF patients had more atrial fibrillation (42 vs 26%, p=0.02). After a median follow-up 350 days, 31 HFpEF and 28 HFrEF patients died. LA function was associated with mortality in HFpEF, but not in HFrEF (Fig-B).

Conclusions:
HFrEF is characterized by greater eccentric LA remodeling, but HFpEF is associated with increased LA stiffening and greater LA pressure pulsatility which may contribute to greater burden of atrial fibrillation. The observation that LA function is more closely linked to outcome in HFpEF supports the goal to maintain or improve LA function in HFpEF.
Abstract 16663: Patient and Cell Characteristics Associated With Clinical Outcomes in the CCTRN LateTIME Trial
Authors: Bhatnagar Aruni , Johnston Brian H , Traverse Jay H , Henry Timothy D , Pepine Carl J , Willerson James T , Perin Emerson C , Eillis Stephen G , Zhao David X , Lai Dejian , Cooke John P , Schutt Robert C , Trachtenberg Barry H , Resende Micheline , Ebert Ray F , Sayre Shelly L , Cohen Michelle , Cohen Michelle , Simari Robert D , Moye' Lem , Cogle Christopher R , Taylor Doris A
Published: July 2021

Background and Hypothesis:
In the CCTRN LateTIME trial, there was no improvement versus placebo in cardiac function 6 months after intracoronary infusion of autologous bone marrow mononuclear cells (BMC), 2-3 weeks post-MI. We hypothesized that clinical outcomes are associated with patient demographics and BMC populations that contribute to the efficacy of the intervention.

Methods:
Left ventricular (LV) function was evaluated at baseline and at 6 months. BMC study product data associated with phenotype and colony formation capability were collected at baseline. Principal components analysis was used to define a composite variable, LV dysfunction, encompassing both LV volume and wall motion data. Case control analysis was then conducted comparing those with improved LV dysfunction (cases) with those without (controls).

Results:
Hypertension, diabetes, and obesity were associated with lower levels of endothelial progenitor cells; whereas hyperlipidemia was inversely associated with CD11b+ cells, and obesity with CD3+ cells. Adjusted multivariate analysis indicated that CD11b+ cells were negatively associated with LV function; both globally (P<0.02) and regionally (P<0.01 and P<0.001, border and infarct zone wall motion, respectively). Global LV function was positively associated with MSC colonies formed (P<0.02) and regional LV function (border zone wall motion) and with cell viability (P<0.03). Case control analysis revealed a significant association of CD133+, CD34+/CD31+, and CXCR4dim cells with cases. Increased LV dysfunction was associated with CD11b+cells.

Conclusions:
These results suggest that CVD risk factors significantly affect BMC and that baseline BMC characteristics of individual patients may be important determinants of clinical improvement. Higher frequencies or better function of specific cell populations with endothelial, mesenchymal and migratory phenotype may predispose patients to clinical improvements, whereas higher level of CD11b+ in the BM may contribute to impaired LV function. Product selection or treatment to modify bone marrow constituents, such as negative selection of CD11b+ cells prior to BMC injection, may be a potential strategy to improve outcomes of future clinical trials.
Abstract 16683: Reduced Lung Function is Associated With Decreased Ejection Fraction and Decreased Left Ventricular Size in Patients in a Tertiary Care Center
Authors: Burroughs Pena Melissa S , Durheim Michael , Schulte Phillip , Kussin Peter , Checkley William , Velazquez Eric J
Published: July 2021

Background:
Pulmonary disease has been associated with poor cardiovascular outcomes including heart failure; yet, the relationship between measures of obstructive and restrictive lung disease as defined on pulmonary function testing (PFT) and left ventricular size and function remains unknown. The objective of this study is to determine the correlation between forced expiratory volume/1 sec (FEV1), forced vital capacity (FVC) and FEV1/FVC with left ventricular ejection fraction (LVEF), internal diastolic diameter (LVIDD), and internal systolic dimension (LVISD) as measured by transthoracic echocardiography (TTE).

Methods:
We selected patients who underwent both TTE and PFT within 7 days from January 2012 to April 2013. We examined for bivariate relationships by using Pearson’s correlation coefficient to determine associations between pre-bronchodilator FEV1, FVC and FEV1/FVC and the following TTE measures: LVEF,LVIDD, and LVISD. Multivariable regression analysis was used to adjust for age and sex.

Results:
We identified 2238 patients who had TTE and PFT within 7 days. After adjusting for age and sex, FEV1, FVC, and FEV1/FVC were positively correlated with LVEF and LVIDD. Every 100 cc reduction in FVC or 90 cc reduction in FEV1 was associated with a 5% decrease in LVEF (95% CI 0.079- 0.128, 0.068- 0.109). Moreover, a 200 cc reduction in FEV1 or 220 cc reduction in FVC was associated with a 1 cm decrease in LVIDD (95% CI 0.152- 0.247, 0.165- 0.282,). These correlations remained significant when percent predicted instead of absolute FEV1 and FVC were evaluated.

Conclusion:
Abnormal lung function is associated with reduced LV function without corresponding increases in ventricular size. These findings suggest that the association between pulmonary disease and heart failure may not depend on adverse ventricular remodeling and requires further study.
Abstract 16722: Changes in Carotid Wall Morphology and Plaque Composition in Patients With Established Vascular Disease and Treated With Intensive Lipid Therapy in the AIM-HIGH Study
Authors: Zhao Xue-Qiao , Hatsukami Thomas , Hippe Daniel , Isquith Daniel , Sun Jie , Balu Niranjan , Neradilek Moni B , Yamada Kiyofumi , Canton Gador , Crouse John R , Anderson Todd J , Huston John , Polissar Nayak , O’Brien Kevin D , Yuan Chun
Published: July 2021

Objective:
Changes in carotid wall morphology (MORPH) and plaque composition (COMP) over 2 years (yrs) of intensive lipid therapy by plaque types were investigated in AIM-HIGH.

Methods:
Qualified baseline and 2-yr follow-up scans were obtained in 156 AIM-HIGH subjects. MR images were analyzed by independent Core Lab reviewers using published criteria for quantifications of MORPH and COMP. MORPH included volumes of total vessel (TVV), lumen (LV), wall (WV=TVV-LV) and fibrous tissue (FTV) in mm3 and %WV was calculated using the formula: (WV/TVV) X 100% in all available slices. COMP focused on percentages of lipid-rich necrotic core (%LRNC), FT (%FT) and calcium (%CA) calculated using the formula: (LRNC, FT or CA V/WV) x 100% using the slices containing LRNC. Of 156, 89 were in statin+placebo for extended-release niacin (ERN) and 67 in statin+ERN groups. Changes in MORPH and COMP were compared between the 2 treatment groups and between plaque types: w/o LRNC (n=76), w/ LRNC but w/o intraplaque hemorrhage (IPH) (n=62), w/ LRNC & IPH (n=18).

Results:
In the 76 subjects w/o LRNC, there were significant increases in TVV (24±52 mm3/yr, p<0.001), LV (14±40 mm3/yr, p<0.01), WV (10±26 mm3/yr, p=0.002) and FTV (10±26 mm3/yr, p=0.002) while %WV was relatively stable (0.04±1.0%, p=0.48) over 2yrs. In the 62 w/ LRNC but w/o IPH, the slices containing LRNC showed a significant decrease in %LRNC (1.05±2.6%/yr, p=0.001) and significant increases in %FT (0.85±2.7%/yr, p=0.01) and %CA (0.20±0.63%/yr, p=0.002), although corresponding MORPH did not change significantly. By contrast, LRNC plaques w/ IPH tended to increase in %LRNC (1.4±3.2/yr) and decrease in %FT (1.4±3.0%/yr). These rates were significantly different from those of the LRNC plaques w/o IPH (p=0.008 and 0.012, respectively). These MORPH and COMP measures did not differ significantly between statin+placebo and statin+ERN groups.

Conclusions:
Intensive lipid therapy with statin or statin plus ERN significantly associated with positive MORPH remodeling in plaques w/o LRNC. Plaques w/ LRNC experienced COMP improvement without significant MORPH changes. However, the COMP improvement was not seen in plaques w/ IPH. These results indicate that plaques in different disease stages respond to lipid therapy differently.
Abstract 16732: Urinary 11-Dehydro-Thromboxane B2 is Associated With Vascular and Non-Vascular Events in Atrial Fibrillation Patients
Authors: Pastori Daniele , Pignatelli Pasquale , Cangemi Roberto , Hiatt William , Farcomeni Alessio , Bartimoccia Simona , Vicario Tommasa , Bucci Tommaso , Carnevale Roberto , Lip Gregory , Violi Francesco
Published: July 2021

Introduction:
Non-Valvular Atrial Fibrillation (AF) patients show high residual cardiovascular risk despite oral anticoagulants. Urinary 11-dehydro-thromboxane B2 (TxB2) is associated with an increased risk of cardiovascular events, but its predictive value in anticoagulated AF patients is unknown.

Hypothesis:
Aim of this was to assess whether urinary 11-dehydro-TxB2 is a predictor of cardiovascular events in anticoagulated patients with AF.

Methods:
Prospective single-center cohort study, including 864 consecutive AF patients. Mean time of follow-up was 30.0 months yielding 2062 person-years of observation. Urinary 11-dehydro-TxB2 was measured at baseline. The primary end-point was the composite of myocardial infarction, ischemic stroke, cardiac revascularization, cardiovascular death and deaths from any cause.

Results:
Cardiovascular events occurred in 98 (11.3%), whilst 81 patients died (9.4%), including 55 from cardiovascular and 26 from non-cardiovascular causes. At baseline, urinary 11-dehydro-TxB2 levels were higher in patients who experienced a cardiovascular event (p<0.001). An increased rate of cardiovascular events, cardiovascular death and all-cause death was observed across tertiles of 11-dehydro-TxB2 (p<0.001). On Cox proportional hazards analysis, CHA2DS2-VASc score, second and third tertile of 11-dehydro-TxB2, compared to the first tertile, were significant predictors of vascular and non-vascular events. On a logistic regression analysis, 11-dehydro-TxB2 levels progressively increase with increasing CHA2DS2-VASc scores.

Conclusions:
Urinary 11-dehydro-TxB2 predicts residual risk of cardiovascular events in anticoagulated atrial fibrillation patients. Urinary 11-dehydro-TxB2 progressively increases with increasing CHA2DS2-VASc score suggesting that anticoagulated patients with high CHA2DS2-VASc score may need additional antithrombotic strategies.
Abstract 16797: Mechanisms That Repress BMP2 in Mesenchymal Cells
Authors: Rogers Melissa , Fotinos Anastasios , Shah Tapan
Published: July 2021

BMP2 is an essential protein. A short burst of BMP2 promotes repair after vascular injury. However, excessive BMP2 levels in the vasculature and heart valves promote pathological calcification. A sequence within the 3’UTR of the mRNA termed the “ultra-conserved sequence” (UCS) has been largely unchanged since fishes and mammals diverged. Cre-lox mediated deletion of the UCS in a mouse reporter transgene revealed that one role of the UCS is to repress BMP2 synthesis in heart valves and vascular cells. We are now testing the hypothesis that normal heart morphology requires UCS-mediated restraint of BMP2 synthesis. We used homologous recombination to generate a Bmp2 allele with the endogenous Bmp2 UCS flanked by loxP sites. We bred this strain to strains that express Cre-recombinase thus deleting the UCS. The survival of pups with homozygous loss of the UCS was significantly reduced. We are now assessing embryonic heart morphology in these strains. We also postulate that the regulatory proteins and microRNAs that mediate UCS-mediated repression may be exploited to pharmacologically reawaken BMP2 repression in tissues undergoing pathological pathologies. Specific miRNAs inhibit UCS-bearing reporters and mutations of miRNA binding sites activate these reporters. Interestingly, an A+U rich element (ARE) known to bind HuR (generally an activator) and AUF1 (a repressor) is embedded in a conserved miRNA binding site. Selective mutations of the ARE and the miRNA seed indicate that repressive molecules bind this site in mesenchymal cells where the UCS functions as a repressor.