bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12773: Ethnicity and Primary PCI for ST-Elevation Myocardial Infarction: Data From the First "Nationwide" Primary PCI Program
Authors: Gehani Abdorrazzak , Al Suwaidi Jassim , Tamimi Omer , Arafa Salah , Al Quhtani Awad , Arabi Abdulrahman , Rafie Ihsan , Nabti Abulrahman , Abujalala Salem , Elsousy Reem , Yacoub Magdi
Published: July 2021

Introduction:
The Middle East is posed to witness one of the highest rise in Coronary Artery Disease (CAD) in the world and at younger age. Multi-Ethnic society is a prominent feature in the Gulf. A nationwide 24/7 Primary PCI (PPCI) program was established for all for STEMI patients. This analysis compares the two most dominant ethnic groups in the gulf, namely Arabs and Asians.

Methods:
Primary PCI was performed in 496 patients with STEMI, 121 Arabs and 375 Asians. Asians were 6 years younger (48±8 vs 54±12 year, p<0.001), and had fewer females (2.6% vs 11%). Conversely, Arabs had more frequent Diabetes (42% vs 32% in Asians) and Smoking (37% vs 30% respectively). However, in-hospital mortality was similar (1.1 vs 1%).

Results:
The Door to Balloon Time (DBT) was similar, Asians (55.5 ±19) vs Arabs (56±25 min), p<0.13) and 93% achieved DBT<90min in both groups. Ejection fraction (EF) was also similar (44±8% vs 45.5%), but Asians with DBT>90min had lower EF (42%) than Arab counterparts (48%). This may indicate greater myocardial vulnerability with delay in Asians. Further total coronary Occlusion (TIMI-0) at presentation was seen more frequently in Asians (60%) than in Arabs (48%), p<0.01, but TIMI-III from TIMI-0 was achieved in similar proportion (85% vs 87%). However, in the range of TIMI flow (0-II), TIMI-III was achieved in fewer Asians (94%) compared to Arabs (97%). First ECG on arrival was normal in 5.6% Asians and 2.7% Arabs, however, TIMI-0 flow was found in 60% and 44% respectively. There was a trend towards longer Out of Hospital Delay (OHD, i.e. time from symptoms to arrival to hospital) in Asians (265min) vs 234min in Arabs, particularly in Asian females (409min) vs 330min in Arab females. Radial access was used similarly in Asians vs Arabs (48% vs 45%), and a fall of ≥2gr of Hemoglobin (13% in both). Length of stay was similar (2.7 vs 2.6 days respectively).

Conclusion:
The age of our STEMI patients is one of the youngest worldwide. It is even younger in Asians than Arabs. Despite greater risk profile and relatively older age in Arabs, in-hospital mortality in Primary PCI was similar. There was similar and excellent DBT in both, but Out of Hospital Delay was greater in Asians, especially females. Time delay appear to have greater adverse effect on the Ejection Fraction in Asians.
Abstract 12776: Outcomes and Survival With Home Intravenous Inotrope Therapy in Contemporary Heart Failure Management
Authors: Hashim Taimoor , Sanam Kumar , Revilla Martinez Marina I , Morgan Charity J , Tallaj Jose A , Pamboukian Salpy V , Loyaga-Rendon Renzo Y , George James F , Acharya Deepak
Published: July 2021

Introduction:
Inotrope use in decompensated congestive heart failure (CHF) is associated with improved hemodynamics, but did not improve outcomes in previous trials, with 50% 6-month mortality. However, many of these studies predated modern CHF therapies, including aldosterone antagonists, implantable cardioverter-defibrillators (ICDs), and resynchronization. We evaluated contemporary survival and outcomes on long-term inotropes in advanced CHF.

Methods:
We collected baseline and post-inotrope data on 197 consecutive patients discharged from our hospital between January 2007 and March 2013 on intravenous inotropes. Clinical, hemodynamic, catheterization, and survival data were collected. T-tests and Chi-square tests were used to compare outcomes, and Kaplan-Meier curves to evaluate survival.

Results:
Among the 197 patients, 25.8% were women, 40% had ischemic etiology and mean age was 54.4 years (standard deviation [SD] 14.6 years). Patients started on inotropes had CHF refractory to standard management, with mean baseline NYHA 3.7, cardiac index (CI) 1.7 L/min/m2, pulmonary capillary wedge pressure (PCWP) 25.6 mmHg, and left ventricular ejection fraction 17%. Milrinone was used in 85% and dobutamine in 15% of patients. Sixty-eight patients died, 24 were weaned off inotropes, 23 were transplanted, 32 received a LVAD, and 50 remained on inotropes. Mean NYHA class decreased from 3.7 to 2.7 (p <0.001), CI increased from 1.7 L/min/m2 to 2.2 L/min/m2 (p <0.001), and PCWP decreased from 25.6 mmHg to 21.1 mmHg (p <0.001) . During follow-up, fifty-six patients (28%) had an infection related to intravenous inotropes. Thirty-three patients (16.7%) had at least one ICD shock. For the entire cohort, median survival was 18.1 months (Interquartile range [IQR] 4.7-37.1 months) and mean survival was 19.2 months (SD 1.5 months). For patients who did not receive a LVAD or transplant, median survival time was 13.2 months (IQR 3.7-37.1 months) and mean survival was 17.7 months (SD 1.5 months).

Conclusions:
Survival on long term-inotropes in this study was improved compared to previous reports. Routine ICD use may mitigate some arrhythmic risks of inotropes. Inotropes may be used as a bridge to initiate standard CHF therapy and subsequently weaned in selected cases.
Abstract 12893: Left Atrial Appendage CT Contrast Defects Correlate With CHADS2 Score and is a Prognostic Indicator for Embolism in Subjects With Atrial Fibrillation or Flutter
Authors: Funabashi Nobusada , Takaoka Hiroyuki , Uehara Masae , Ozawa Koya , Kobayashi Yoshio
Published: July 2021

Introduction:
Early phase CT contrast defects in the left atriium (LA) and left atrial appendage (LAA) are often observed in atrial fibrillation (AF) or atrial flutter (AFL) despite absence of thrombi. However their clinical significance is unclear.

Hypothesis:
In order to investigate this correlation we compared CT, transesophageal echocardiology (TEE), CHADS2 score, and occurrence of embolism (including cerebral infarction).

Methods:
A total of 32 AF or AFL subjects who underwent CT and TEE within 3 months were enrolled. 5 subjects with LAA thrombi by TEE were excluded. A total of 27 subjects were retrospectively analyzed (persistent AFL 10, persistent AF 9, chronic AF 3, paroxysmal AF 3, permanent atrial standstill 2, 22 male, 61±11 years, occurrence of embolism 26%, median CHADS2 score 1). We measured velocity in the LAA by TEE. We also measured CT attenuations in the LAA and LA, and calculated LAA/LA ratios.

Results:
CT LAA/LA ratios were significantly lower in subjects with embolism than without (0.44±0.30 vs 0.74±0.24). CT LAA/LA ratios were smaller when CHADS2 score was ≥2 (0.57±0.31 vs 0.75±0.24). CT LAA/LA ratios correlated with TEE LAA velocity (R=0.44). According to receiver operating characteristic (ROC) curves, at a best cutoff of 24.3m/sec (TEE LAA velocity), sensitivity and specificity for occurrence of embolism were 70% and 86%, respectively (Area under the curve (AUC) 0.69). Another ROC curve, at a best cutoff of 0.41 (CT LAA/LA ratio), produced a sensitivity and specificity for occurrence of embolism of 90% and 71%, respectively (AUC 0.78). In logistic regression models using LA diameter, left ventricular ejection fraction, presence of moderate to severe mitral valve stenosis or regurgitation measured by TEE, the odds ratio for CT LAA/LA ratios was 0.017 (P=0.043) for prediction of embolism.

Conclusion:
CT LAA/LA ratio correlates with TEE LA velocity and is a prognostic indicator for the occurrence of embolism in AF or AFL subjects without LAA thrombosis.
Abstract 12951: Human C-Type Natriuretic Peptide-53: A Distinct Molecular Form With in vitro and in vivo Biological Actions Through cGMP Generation
Authors: Sangaralingham S. J , Huntley Brenda K , Ichiki Tomoko , Sandberg Sharon M , Burnett John C
Published: July 2021

Introduction:
ANP and BNP are cardiac hormones that have a natriuretic and diuretic role in heart failure (HF) through guanylyl cyclase receptor A (GC-A) and cGMP generation. C-type natriuretic peptide (CNP) is part of this hormone family and is produced in the heart and endothelium. The biologically active form, CNP-22, is known to have potent anti-remodeling properties through the activation of GC-B and cGMP, but lacks natriuretic actions. Recently we have identified that another larger CNP form, CNP-53, is elevated in the plasma of acute decompensated HF patients, however it unclear if CNP-53 possesses biological actions.

Hypothesis:
We hypothesized that CNP-53 would be biologically active in vivo and in vitro, and would stimulate GC-B specific cGMP production.

Methods:
HEK 293 cells over-expressing GC-A and GC-B and human cardiac fibroblasts (hCFs), in which GC-B are in abundance, were stimulated with CNP-53 for 10 minutes at a dose of (10-8M). Two groups of anesthetized rats (n=8) received a 75-minute infusion of normal saline vehicle (V) or CNP-53 (1 ug/kg/min) and then mean arterial pressure (MAP), sodium excretion and urinary and plasma cGMP were assessed.

Results:
CNP-53 significantly activated cGMP in GC-B HEK cells (75±9 vs. 0.4±0.1 pmol/well, p<0.05) and in hCFs (0.17±0.03 vs. 0.00±0.00 pmol/well, p<0.05) compared to no treatment. In contrast CNP-53 failed to generate cGMP in GC-A HEK cells. In vivo, CNP-53 decreased MAP compared to vehicle (V: 101±2, CNP-53: 94±2 mmHg, p<0.05). CNP-53 had a greater natriuretic effect compared vehicle (V: 0.86±0.11, CNP-53: 1.39±0.21 uEq/min, p<0.05). Urinary cGMP excretion (V: 33±6, CNP-53: 177±28 pmol/min, p<0.05) and plasma cGMP generation was also significantly higher with CNP-53 compared to vehicle (V: 9±2, CNP-53: 91±3 pmol/ml, p<0.05).

Conclusions:
CNP-53, a higher molecular form of CNP that was reported to be increased human HF plasma, is bioactive with GC-B specific cGMP generation in vitro. Moreover, infusion of CNP-53 generates significant urinary and plasma cGMP and has natriuretic actions with minimal hypotensive effects in vivo. This study advances our understanding of CNP biology and provides new insights into potential CNP therapeutic opportunities targeting the progression of HF.
Abstract 13000: Trends in Incidence, Invasive Management and Outcomes of Cardiogenic Shock Complicating Non ST-Segment Elevation Myocardial Infarction
Authors: Gupta Navdeep , Aggarwal Saurabh , Guo Yu , Bangalore Sripal
Published: July 2021

Background:
Cardiogenic shock complicating Acute Myocardial Infarction (AMI) is usually described in the setting of a ST-segment elevation MI (STEMI). However, the trend in incidence, invasive management and outcomes of cardiogenic shock complicating NSTEMI, are not well defined.

Methods:
We analyzed patients in the Nationwide Inpatient Sample (NIS) between 2002-2011 with primary discharge diagnosis of Acute Myocardial Infarction (AMI) and secondary diagnosis of cardiogenic shock. Primary outcome was trend in cardiogenic shock complicating NSTEMI. Secondary outcome was trends in in-hospital mortality.

Results:
We identified 6,667,087 patients with AMI among which 4,032,193(60.5% of AMI) had NSTEMI and 2,634,894(39.5%) had STEMI. Cardiogenic shock complicated , 92,654(2.3%) patients with NSTEMI and 204,389(7.8%) patients with STEMI. Among patients with cardiogenic shock, there was a steady increase in proportion of patients with NSTEMI (vs. STEMI) (23.6% to 38.0% from 2002 to 2011, p<0.001). While an increasing percentage of NSTEMI shock patients underwent invasive management (55.1% to 67.3% from 2002 to 2011, p<0.001) this was significant lower when compared with STEMI shock (68.0% to 84.0% from 2002 to 2011, p<0.001) patients. Mortality in NSTEMI and STEMI shock patients were similar and continued to account for high in-hospital mortality (36.6% vs. 38.9%, P<0.001).

Conclusions:
Among patients with cardiogenic shock complicating AMI, there are an increasing proportion of patients with shock complicating NSTEMI. While the percentage of patients with NSTEMI shock undergoing invasive management has increased it continues to be lower as compared to STEMI shock despite similarly high in-hospital mortality.
Abstract 13252: The Effects of Pre-LVAD Diabetes on Post-LVAD Outcomes
Authors: Mohamedali Burhan , Yost Gardner , Bhat Geetha
Published: July 2021

Introduction:
Diabetes Mellitus (DM) is a major risk factor for adverse cardiovascular (CV) outcomes. In this study, we investigated the effects of DM on post HeartMate II left ventricular assist device (LVAD) outcomes.

Methods:
In this retrospective study, 244 patients (Pts) were enrolled. Pts were stratified based on the presence or absence of pre-LVAD DM. DM was defined as a pre-existing history of DM requiring insulin or oral hypoglycemic medications or a new diagnosis of DM based on HgbA1C> 7mg/DL. Baseline information and post adverse outcomes were tabulated.

Results:
The cohort comprised of 108 diabetics and 136 non-diabetics. DM pts had a slightly worse baseline medical profile than non-DM. DM pts were more likely to be obese, had worse creatinine, and higher systolic and mean arterial blood pressure. DM pts also had a higher prevalence of atrial fibrillation, obstructive sleep apnea, and renal insufficiency. HgbAIC profiles revealed sub-optimal diabetic control at baseline (Table1). Post-LVAD, other than a higher incidence of hemolysis in the diabetic pts (12% vs 4%; p= 0.03), there were no differences between the two groups. Post LVAD HgbA1C was statistically significantly better (7.2 vs 6.1 P-value <0.001).

Conclusions:
Although DM is a poor risk factor for many adverse CV outcomes, there are no differences in adverse events in our pts post-LVAD placement compared to non-diabetic pts. This may be a result of improved access to care for diabetics, improvement in hemodynamics and biochemical derangements after normalization of cardiac output, or increased pancreatic blood flow. Our results indicate that diabetic pts who receive LVAD therapy are overall not at higher risk for adverse outcomes compared to non-diabetics. Further larger prospective studies are needed to validate our findings.
Abstract 13320: Effect of Cardiovascular Comorbidities on the Mortality Risk Associated with Serum Potassium
Authors: Pitt Bertram , Collins Allan J , Reaven Nancy , Funk Susan , Bakris George L , Bushinsky David A
Published: July 2021

Introduction:
Both hypokalemia and hyperkalemia are known to be associated with an increased mortality risk. The serum potassium (K
+
) levels associated with these risks and the relationships to comorbidity, however, are not well defined. We therefore evaluated the odds of death in patients with and without comorbid conditions, stratified by K
+
level.

Methods:
De-identified medical records (2007-2012) from a large U.S. population of persons ≥ 5 years of age with at least 2 K
+
readings were evaluated. Patients 45-64 years of age with comorbidities defined as CKD stages 3-5, heart failure, diabetes, hypertension, and cardiovascular disease (n=231,070) were identified from demographic data, ICD-9 codes and biochemical data, excluding those with acute kidney injury or end stage renal disease, and compared with controls having none of these conditions (n=146,645). A separate analysis of patients ≥ 65 years of age was performed. Index K
+
value was defined as the last reported value prior to pre-determined cut-off date. Mortality was evaluated through hospital discharge records and Social Security registry information.

Results:
Among patients aged 45-64 with comorbid conditions, index K
+
levels below 4.1 mEq/L and above 4.6 mEq/L demonstrate a significant increase in mortality (Figure). This finding was similar in patients ≥ 65 years of age. The general pattern remained after adjustments for demographic characteristics (sex, race) and subgroup analyses controlling for comorbidities associated with the propensity to develop hypo- and hyperkalemia.

Conclusions:
These results indicate that the level of potassium and the risk of mortality in patients with hypokalemia or hyperkalemia is highly associated with underlying disease; is significantly greater in patients with comorbid conditions; and is independent of demographic characteristics. The increased mortality in patients with comorbidity occurs even at K
+
levels within the usual normal laboratory range.
Abstract 13480: Utility of Combined Assessment of Exercise Oscillatory Breathing and Global Circumferential Strain to Predict Cardiac Events in Heart Failure Patients
Authors: Tanaka Hidekazu , Tsuboi Yasunori , Matsumoto Kensuke , Dokuni Kuniko , Hatani Yutaka , Matsuzoe Hiroki , Hatazawa Keiko , Toki Hiromi , Shimoura HIroyuki , Ooka Junichi , Sano Hiroyuki , Sawa Takuma , Motoji Yoshiki , Mochizuki Yasuhide , Tatsumi Kazuhiro , Sakai Yoshitada , Hirata Ken-ichi
Published: July 2021

Background:
The occurrence of cardiopulmonary exercise testing-derived exercise oscillatory breathing (EOB) is a predictor of survival in heart failure (HF) patients. Whereas, it was recently reported that global circumferential strain (GCS) as assessed by two-dimensional speckle-tracking imaging reflects intrinsic left ventricular (LV) myocardial function and is a powerful predictor of cardiovascular events, and thus appears to be a better predictive parameter than global LV function, including LV ejection fraction (EF). The objectives of our study were to test the hypothesis that a combined assessment of EOB and GCS can further enhance the ability of the method to predict cardiac events in HF patients.

Methods:
A total of 86 HF patients with LVEF of 44±11% underwent cardiopulmonary exercise testing and echocardiography. GCS was determined as the peak global speckle-tracking strain from mid-LV short-axis view, and GCS of <10.7% was predefined as significant LV myocardial dysfunction for HF patients. EOB definition was based on the criteria as previously reported. Long-term unfavorable outcome events were pre-specified as primary end points of hospitalization for deteriorating HF over 2.0 years.

Results:
Overall, patients with EOB (n=35) were associates with unfavorable clinical events compared with those without EOB (n=49) (2% vs. 18%, p=0.04). Of 35 patients with EOB, there were 10 patients with EOB and GCS10.7%. The prevalence of unfavorable clinical events of patients with EOB and GCS10.7% (70% vs. 4%, p<0.001).

Conclusions:
The combined approach of EOB and GCS leads to more accurate prediction of unfavorable cardiac events than using individual parameters in HF patients. The study presented here offers new insights into management of HF patients.
Abstract 13533: 1-Year Results of Paclitaxel-Coating Nitinol Stent Placement for Chronic Total Occlusion in the Femoropopliteal Artey
Authors: Murata Naotaka , Soga Yoshimitu , Tomoi Yusuke , Hiramori Seiichi , Kobayashi Yohei , Ichihashi Kei
Published: July 2021

Introduction:
The mid-term outcomes of paclitaxel-coating nitinol stent (Zilver PTx) placement for chronic total occlusion (CTO) in the femoropopliteal artery have not been assessed.

Hypothesis:
Zilver PTx placement for CTO in the femoropopliteal artey is reliable.

Methods:
All patients enrolled in this prospective, single center study underwent Zilver PTx placement for de novo or restenotic CTO and non-CTO in the superficial femoral and/or popliteal artery. Baseline and follow-up Rutherford classification and Ankle-brachial index (ABI) measurements were obtained. Follow-up was completed at 3, 6, 12 months.

Results:
There were 61 of CTO and 58 of non-CTO treated. Mean age was 74 ± 8 years and male was 82 % in overall. Patients characteristics and degree of lesion calcification was not different significantly between two groups. CTO group had a longer mean lesion length than non-CTO group (209 mm ± 93 mm vs 131 mm ± 87 mm, P < .0001). Procedural success in both treatments was over 98 %. The operative complications were 3 cases in CTO group and 2 cases in non-CTO group. The primary patency of CTO group was significantly lower than non-CTO group in Kaplan-Meier estimate curves at 12 months (75 % vs 82 %, Log-rank P < 0.05). There were no significant differences in event-free survival or freedom from target lesion revascularization in Kaplan-Meier estimate curves at 12 months (68 % vs 70 %; Log-rank P = 0.82, 63 % vs 65 %; Log-rank P = 0.47, respectively). Both groups experienced a significant improvement in Rutherford classification and ABI after treatment, and these improvements were sustained to 12-months follow-up. Based on multivariate analysis, CTO was the negative predictor for primary patency at 12 months (HR 2.37, 95 % CI 1.02 to 5.9, adjusted P < 0.05).

Conclusions:
CTO influences negatively the primary patency of Zilver PTx placed in the femoropopliteal artery. However, Improvement of Rutherford classification and ABI at 12-months after CTO- intervention is sustained.
Abstract 13728: Changes in Myocardial Function Following 8 to 12-hour Rebreathing Cold Water Dives
Authors: Chopard Romain , Barrot Loic , Belon Francois , Brocq Francois-Xavier , Blanchard Jean-Christophe , Blatteau Jean-Eric , Peny Christophe , Regnard Jacques , Castagna Olivier
Published: July 2021

Aim:
This study assessed hemodynamic changes and myocardial function after prolonged dynamic cold water immersions with hyperbaric hyperoxic exposure.

Methods:
Trained military divers were studied during 8-hour (6 subjects) and 12-hour (6 subjects) dives in a hyperbaric chamber (1.7 and 3 bar) in 18°C water. Subjects were breathing hyperoxic gas (100% oxygen or up to 1.7 bar PO2) and performed bouts of physical exercise. Conventional and speckle tracking transthoracic echocardiography (TTE) were performed before, immediately after, and 15 hours after dives.

Results:
We observed a decrease in left and right ventricular preloads, and lowered stroke volume immediately after dives. These parameters remained below baseline values 15h after dive termination. These changes were not significantly different between 8h and 12h dives. Speckle tracking analysis showed altered function of the left and right ventricles reflected by a transient decrease in ventricular parameters as measured by echography in the hour immediately after the end of immersion (table).

Conclusion:
Hemodynamic changes and transient alterations in strain and strain rate myocardial parameters were assessed immediately after 8 to 12 h dives. Immersion-linked changes in blood volume were likely involved in lowering cardiac preload and stroke volume. Altered ventricular strain and strain rates could be the result of lowered blood volume, hyperoxic breathing and increased cardiac pre- and after-load.
Abstract 14026: Atrial Fibrillation is Associated with Altered Left Atrial 3D Hemodynamics and Increased Stasis
Authors: Lee Daniel C , Markl Michael , Ng Jason , Carr Maria , Benefield Brandon C , Carr James C , Goldberger Jeffrey J
Published: July 2021

Introduction:
Clinical scores used for stroke risk estimation in atrial fibrillation (AF) have limited predictive accuracy. 4D Flow MRI can acquire blood flow in a volume data set encompassing the entire left atrium (LA) with quantification of blood velocity in 3 orthogonal directions for every voxel at multiple time points throughout the cardiac cycle (4D = 3D coverage + time).

Hypothesis:
4D Flow MRI can assess 3D LA flow abnormalities in AF patients, which may potentially be linked to stroke.

Methods:
We performed 4D flow MRI in 30 volunteers (10 young, 20 older) and 70 patients with a history of AF: 40 in sinus rhythm (AF-sinus) and 30 in AF during MRI scan (AF-afib). The typical LA contained 3000 voxels and 18 phases per voxel. LA flow velocity histograms for each patient were quantified by mean LA velocity, median LA velocity, and the percentage of LA velocities < 0.2 m/s (%stasis). CHA2DS2-VASc scores were calculated for each patient.

Results:
Mean LA velocity, median LA velocity, and %stasis were significantly different between groups: young volunteers (0.26±0.02 m/s, 0.23±0.02 m/s, 37.3±7.6%), older volunteers (0.21±0.03 m/s, 0.20±0.03 m/s, 52.2±16.0%), AF-sinus (0.18±0.03 m/s, 0.17±0.03 m/s, 67.5±16.9%), and AF-afib (0.16±0.01 m/s, 0.14±0.03 m/s, 78.2±12.9%), p < 0.0125 for all comparisons. CHA2DS2-VASc had moderate but significant correlations with mean LA velocity (R
2
=0.27, p<0.001), median LA velocity (R
2
=0.23, p<0.001), and stasis% (R
2
=0.26, p<0.001). LA flow indices also correlated significantly with age, LA volume, and left ventricular ejection fraction (LVEF) as seen in the Table.

Conclusions:
Left atrial 4D flow MRI is a novel approach to identify patients with reduced LA blood velocities and increased LA stasis. Further study is needed to determine whether these measures can improve upon the CHA2DS2-VASc score for stroke risk prediction and enhance individual decisions on anticoagulation in patients with AF.
Abstract 14935: Impact of Paravalvular Regurgitation after Surgical Aortic Valve Replacement for Severe Aortic Stenosis: An Intraoperative Transesophageal Echocardiography Study
Authors: Mihara Hirotsugu , Berdejo Javier , Itabashi Yuji , Utsunomiya Hiroto , De Robertis Michele A , Trento Alfredo , Shiota Takahiro
Published: July 2021

Introduction:
Greater than mild paravalvular regurgitation (PVR) is reported to worsen late mortality after transcatheter aortic valve replacement (TAVR). However the impact of PVR on the prognosis after surgical aortic valve replacement (SAVR) is not determined. The purpose of this study was to investigate the impact of PVR on the prognosis after SAVR in patients with aortic stenosis (AS) using intraoperative transesophageal echocardiography (iTEE).

Hypothesis:
We hypothesized that the prognosis of mild PVR after SAVR in patients with AS is benign.

Methods:
We retrospectively reviewed 304 consecutive patients with severe AS who underwent isolated SAVR using bioprosthesis and who had color Doppler iTEE images after SAVR. Severity of PVR was determined by the sum of the cross-sectional area of the vena contracta (VCA) using 2D color Doppler just after SAVR. Grading of PVR was determined using the following VCA cutoffs: trivial 0-4 mm2; mild 5-9 mm2; moderate 10-29 mm2; severe ≥ 30 mm2. We investigated the clinical course after SAVR including death, re-hospitalization due to heart failure exacerbation, and reoperation.

Results:
The patients were 76 ± 10 years old, and 57% were male. PVR was trivial in 28 patients (9%), mild in 18 (6%), moderate in 9 (3%), severe in 0. During the follow-up period of 1111 ± 582 days (median 1071 days), there were significant differences in survival between moderate and none/trivial or mild PVR group (p < 0.001 and 0.004, respectively). There was no significant differences in survival between mild and none/trivial PVR group (p = 0.69). Of 35 patients with ≥ mild PVR, only 3 patients with moderate PAR re-hospitalized for heart failure exacerbation and 1 of them resulted in successful percutaneous paravalvular leak closure. There was no other patient for reoperation except this patient.

Conclusions:
Although infrequent, moderate PVR showed worse survival following SAVR for severe AS, while the prognosis of mild PVR was benign.
Abstract 15318: Association of Single-Nucleotide Polymorphisms with Left Atrial Scar in Patients with Atrial Fibrillation
Authors: Mohanty Sanghamitra , Hall Amelia W , Mohanty Prasant , Trivedi Chintan , Di Biase Luigi , Bai Rong , Al-Ahmad Amin , Horton Rodney , Burkhardt John D , Sanchez Javier , Zagrodzky Jason , Bailey Shane , Gallinghouse Joseph G , Hranitzky Patrick , Iyer Vishwanath R , Natale Andrea
Published: July 2021

Introduction:
Earlier studies have demonstrated that some AF patients develop spontaneous atrial scarring that leads to genesis and perpetuation of the arrhythmia. However, it is still unclear why it happens in some and not in others. Therefore, we hypothesized that the atrial scar phenotype is associated with certain specific genetic variants and examined the relationship between AF-related single-nucleotide polymorphisms (SNP) and left atrial scar.

Methods:
Four hundred AF patients (67% male, 62±12 year, left atrial size 45.3±7 mm, 64% non-paroxysmal) undergoing catheter ablation were prospectively enrolled at our center. DNA extraction and genotyping for 16 AF-associated SNPS identified by GWAS study were performed from the collected blood samples using Qiagen QiaAMP 96 well blood kit and TaqMan assay respectively. Three hundred seventy-two DNA samples were available for genotyping. The Hardy-Weinberg equilibrium was assessed using Chi-square analyses. Multivariable logistic model was utilized to identify predictors of LA scar after adjusting for age, gender, LA size, hypertension and diabetes mellitus and odds ratio (OR) and 95% confidence intervals were computed.

Results:
Of all 16 SNPs, rs3807989 showed a strong inverse association with LA scar at univariate analysis (0.54 [0.348-0.89] p= 0.014) in the overall population. After adjustment for covariates, the association became highly significant indicating a 50% reduction in scar risk (OR 0.50 (0.30-0.83) p=0.007). When stratified by type of AF, rs3807989 genotype predicted a substantially stronger 69% risk-reduction in the non-PAF population (OR 0.31 (0.15-0.62) p=0.0009).

Conclusion:
The SNP, rs3807989 on chromosome 7p31, was demonstrated to be associated with reduced risk of left atrial scar formation in AF patients. This genetic variant is located in close proximity to the caveolin-1 gene which is known to have an anti-fibrotic role by inhibiting transforming growth factor-β1, a key mediator in the fibrosis process. Therefore, it can be postulated that by some unknown mechanism the candidate chromosomal variant potentially upregulates caveolin-1 function resulting in attenuation of fibrosis and scar formation.
Abstract 15322: Trifecta vs. Mitroflow: Superior Hemodynamics Despite Similar Design
Authors: Diab Mahmoud , Faerber Gloria , Tsanava Ivliane , Breuer Martin , Walther Mario , Amorim Paulo A , Doenst Torsten
Published: July 2021

Purpose:
Hemodynamic results of stented tissue valves are influenced by both valve design and sizing strategy. The Mitroflow and the Trifecta have an innovative design where the pericardium is wrapped around the stent. The goal of this study was to compare both valves giving special consideration to the suggested sizing strategies.

Methods:
We obtained pressure gradients from discharge echocardiograms from all patients having received an isolated Trifecta (n=104) or Mitroflow (n=246) between 01/2007 and 01/2014. We compared the results by size label and by the most likely selected size according to the suggested sizing strategy. This is important because the prostheses, despite having a similar design, have different diameters for the same size label and different sizing strategies.

Results:
The majority of implanted valves were size labels 21 and 23 (82.7% of the Trifecta and 74.8% of the Mitroflow). Mean pressure radients were lowest with Trifecta (Trifecta vs. Mitroflow, label-21: 11.4±4.65 vs 13.6±5.23 mmHg, label-23: 9.23±3.38 vs. 11.8±4.42 mmHg, p< 0.05, and label-25: 11.2±4.97 vs 12.0±4.46 mmHg, n.s.). The sizers for the Trifecta are metric, while those for the Mitroflow are 2-3 mm larger than the corresponding size label. It is therefore likely that for a patient with a 23 mm aortic annulus, a 23 Trifecta but often only a 21 Mitroflow is selected. Thus, comparing the Trifecta to the Mitroflow not by size label but by selected valve (e.g., 23 vs. 21) would therefore only increase the difference.

Conclusion:
The Trifecta shows a hemodynamic advantage over the Mitroflow which is not likely associated with the applied

sizing strategy.
Abstract 15396: Maintenance of Endothelial NO Release after Inhibition of NADPH Oxidase 4
Authors: Eickholt Claudia , Brunssen Coy , Langbein Heike , Brux Melanie , Hofmann Anja , Goettsch Claudia , Goettsch Winfried , Morawietz Henning
Published: July 2021

The NADPH oxidase isoform NOX4 mainly produces H
2
O
2
. Previously we could show, that NOX4 is the major endothelial NOX isoform and constitutively active. Regulation of NOX4 and formation of reactive oxygen species are involved in NO release. The transcription factor NRF2 is a key mediator of cellular adaptation to redox stress. Therefore, regulation of NOX4 on the transcriptional level by NRF2 might be directly linked to NO release and endothelial function. Besides endothelial nitric oxide synthase (eNOS), a role of neuronal nitric oxide synthase (nNOS) in endothelial NO and H
2
O
2
release has been proposed. In this study, endothelial cells (HUVEC) were constantly exposed to high laminar shear stress (24 h, 30 dyn/cm
2
). Application of shear stress stimulated NO formation and induced elongation of endothelial cells in the direction of flow. Lentiviral overexpression of NOX4 strongly increased endothelial H
2
O
2
release, while downregulation using shNOX4 decreased H
2
O
2
release. Furthermore, application of shear stress caused downregulation of NOX4 as well as upregulation of eNOS and antioxidative response via NRF2 and its target genes NQO-1 and HMOX-1. H
2
O
2
can affect NO release by eNOS. We could show that downregulation of NOX4 leads to upregulation of eNOS mRNA and protein expression accompanied by attenuation of NRF2 pathway under flow conditions. Determination of NO release confirmed these results. This supports a compensatory mechanism maintaining a stable NO release after NOX4 inhibition in response to flow. Attenuation of NRF2 by shNRF2 inhibited shear stress-dependent induction of NRF2 mRNA and protein expression and its target genes. In addition, shNRF2 enhanced the shear stress-dependent downregulation of NOX4. Finally, we detected a stable mRNA and protein expression of nNOS in endothelial cells, which was unaffected by flow. Interestingly, downregulation of NOX4 resulted in induction of nNOS expression.

In conclusion, our data suggest an important role of H
2
O
2
production by NADPH oxidase 4 in maintaining NO release and endothelial function in response to flow. Inactivation of NADPH oxidase 4 attenuates NRF2 pathway and increases neuronal nitric oxide synthase as compensatory mechanisms.
Abstract 15555: Administration of c-Kit+ Cardiac Stem Cells (CSCs) Results in Increased Proliferation and Cardiac Content of CSCs 1 Year Later
Authors: Li Qianhong , Chen Ning , Luo Li , Ou Qinghui , Xie Wei , Hunt Gregory N , Tang Xian-Liang , Rokosh Gregg D , Bolli Roberto
Published: July 2021

Background:
We have previously shown in rats that the beneficial effects of c-kit
+
CSCs on LV function and remodeling post-myocardial infarction persist for at least 1 year after CSC administration. However, in that study the retention of transplanted Y-chromosome
+
cells in the risk region (RR) of female rat hearts at 1 year was low (<10% of total nuclei) and not sufficient to account for the functional improvement, suggesting that other mechanisms must be at work.

Methods and Results:
To address this issue, rats received intracoronary vehicle or 1x10
6
syngeneic CSCs 4 h after a 90-min coronary occlusion; 11 months later, BrdU treatment was given for 1 month. CSCs, which are c-kit
+
/CD45
−
, were distinguished from c-kit
+
hematopoietic stem cells/mast cells, which are CD45
+
. At 1 year after CSC administration, the total number of c-kit
+
or c-kit
+
/BrdU
+
cells in the heart (the sum of c-kit
+
/CD45
−
and c-kit
+
/CD45
+
cells) did not differ between CSC and control groups (Figs. H and I). However, CSC transplantation resulted in increased numbers of CSCs (c-kit
+
/CD45
−
cells) in the RR (i.e., the infarct zone plus border zone)(47.6±7.0% of total c-kit
+
cells vs. 27.9±4.1% in vehicle group; n=5,
P
<0.05; Fig. J). Among CSCs (c-kit
+
/CD45
−
cells), the fraction that was newly formed (c-kit
+
/CD45
−
/BrdU
+
) was dramatically increased in the RR of the CSC group (+ 2.6-fold vs. vehicle group; n=4,
P
<0.05; Fig. M), indicating increased CSC proliferation and turnover.

Conclusions:
These data reveal, for the first time, that a single intracoronary infusion of CSCs is followed by an increase in both the proliferation and the total number of c-kit
+
CSCs in the myocardium that persists, surprisingly, for at least 1 year after cell delivery. Since transplanted cells do not differentiate into adult myocytes, these data suggest that the long-term salubrious effects of CSCs on cardiac function are mediated by sustained activation of the CSC pool in the heart.
Abstract 15572: Trans Fat Consumption is Adversely Linked to Memory in Working-Age Adults
Authors: Golomb Beatrice A , Bui Alexis K
Published: July 2021

Background:
Dietary industrial trans fatty acids (
dTFA
) have
pro
oxidant and cell energy
harms
. Food with
anti
oxidant and cell energy
benefits
has been favorably linked to word memory in younger adults, prior to major age-induced variance.

Goal:
We assessed the cross-sectional relation of dTFA to word-memory.

Participants:
1018 adult men age ≥20 and post-menopausal women without CAD, with LDL 115-190mg/dL, fasting glucose ≤142mg/dL, assessed in 1999-2004 (before dTFA regulation). Primary analyses focused on men, as only men (N=694) were represented in younger adult ages.

Measurements:
“Recurrent words” (
RecWd
) assessed word memory. A Food Frequency Questionnaire (
FFQ
) estimated TFA (gms/day). An age-by-dTFA interaction was assessed. Regression, stratified at age 45, assessed the relation between RecWd and dTFA across models adjusting for potential confounders (see Table). Potential mediators were examined.

Results:
An age-by-dTFA interaction was significant (P=0.025), supporting stratification. dTFA adversely predicted memory in age <45 (only), robust to adjustment model (Table). Findings were replicated in the full sample, including women (not shown). Each gm/day dTFA was associated with an estimated 0.76 fewer words recalled (full model), P=0.006 - yielding an estimated 11 fewer words at the highest dTFA intake vs none - from a mean of 86. Adjustment for SBP, waist and BMI (but not lipid or glycemic variables) attenuated the relationship, consistent with mediation by factors involving, relating to, or concurrently influencing, these factors.

Conclusion:
Greater dTFA was significantly associated with worse word memory in adults aged 20-45 years, often critical years for career building. dTFA findings remain relevant because US regulations do not extend worldwide, and presumed dTFA mechanisms have relevance to other exposures. Prooxidant and energetic detriments of dTFA and triangulation with other evidence offer prospects for causality.
Abstract 15720: Synergistic Effect of Acetylation and Methylation Modifiers in Attenuating Lung Vascular Hyperpermeability in Endotoxemia-Induced Inflammatory Lung Injury
Authors: Rajasingh Johnson , Thangavel Jayakumar , Rajasingh Sheeja , Xuan Yu-Ting , Dawn Buddhadeb
Published: July 2021

Background:
Migration of fluid and inflammatory cells across vascular endothelial barrier is crucial in pathogenesis of acute lung injury (ALI) in sepsis. Currently no treatment can effectively improve the profound dysregulation of lung endothelial barrier in ALI.

Hypothesis:
We hypothesized that combinatorial treatment with DNA methyl transferase inhibitor 5-Aza 2-deoxycytidine (Aza) and histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) would synergistically preserve lung microvascular endothelial barrier function.

Methods and Results:
The trans-endothelial electrical resistance (TER) and capillary filtration coefficient (K
fc
) data show that in LPS-exposed endothelial cells and mice, therapy with Aza+TSA leads to a significant decrease in lung microvascular permeability as compared with either alone. The ChiP data show that the VE-cadherin promoter region was more acetylated at histone 3 in LPS-induced lung ECs treated with Aza+TSA than either alone. In an ALI mouse model, post-injury treatment with a single dose of Aza+TSA prevented lung injury and afforded a significantly higher survival rate (80%) as compared with mice treated with either Aza or TSA alone. These effects were mediated by a significant attenuation of adverse lung histopathological changes and preservation of endothelial barrier integrity. Aza+TSA also significantly reduced neutrophil infiltration in the ALI model. The RT-PCR array data revealed that 42 inflammation-related miRNAs were differentially expressed in LPS-induced endothelial cells, among which miRNA-92a, 125b, 133a, 146, 214, 222, and 424 were strongly upregulated. Importantly, Aza+TSA treatment significantly reduced the expression of these miRNAs. The protection was ascribed to inhibition of the
eNOS-Cav1-MLC2
signaling pathway and enhanced acetylation of histone markers on the VE-cadherin promoter.

Conclusions:
These data for the first time show the efficacy of synergistic effect of Aza+TSA therapy in preventing ALI in LPS-induced endotoxemia, and raise the possibility of an essential role of DNMT and HDAC in pathogenesis of ALI. This novel combinatorial regimen may improve and prolong the lives of people with ALI.
Abstract 15813: Loss-of-Function Mutation in Toll-Like Receptor 4 Partially Protects Against Peripheral and Cardiac Insulin Resistance During a Long-Term High-Fat Diet
Authors: Jackson Ellen , Rendina-Ruedy Elizabeth , Priest Matt , Smith Brenda , Lacombe Veronique
Published: July 2021

Diabetes mellitus is an epidemic disease characterized by alterations in glucose transport, which is tightly regulated by a family of specialized proteins called the glucose transporters (GLUTs). Although diabetic cardiomyopathy is a common complication in diabetic patients, its pathogenesis is still not well understood. Toll-like receptor (TLR) 4, which plays a central role in pathogen recognition by the innate immune system, may also play a critical role in linking inflammation and metabolic disease. We hypothesized that TLR4 activation triggers cardiac insulin resistance. We used mice with a loss-of function mutation in TLR4 (C3H/HeJ) and age-matched wild-type (WT, C57BL/6N) mice (n=8/group) to investigate how feeding a high-fat diet (HFD, 60% kcal from fat) for 16 weeks affected whole-body and cardiac glucose metabolism. After 16 weeks, WT mice fed a HFD were obese and developed hyperglycemia and insulin resistance compared to WT mice on a control diet (10% kcal from fat). The C3H/HeJ mice were partially protected against HFD-induced obesity and insulin resistance. In the heart, WT mice fed a HFD had a 30% decrease (P<0.05) in GLUT4 protein content as measured by Western Blot of cardiac crude membrane protein extracts. In contrast, the loss-of-function point mutation in TLR4 partially rescued cardiac GLUT4 content in the face of a HFD. Interestingly, there was a 40% increase (P<0.05) in the novel GLUT isoform, GLUT8, in the heart when mice of either genotype were fed a HFD. Additionally, GLUT4 protein content was negatively (P<0.05) correlated with GLUT8 content in the myocardium, suggesting that GLUT8 may act as a compensatory mechanism in the face of HFD-induced GLUT4 downregulation. Phosphorylated Akt, a key protein of the insulin signaling pathway, was positively (P<0.05) correlated with GLUT4 content, while the basal/inactive form was negatively correlated. In conclusion, these data suggest that activation of TLR4 activation during diabetes and obesity alters glucose transport by an Akt mechanism, and as such is a pathogenic factor during peripheral and cardiac insulin resistance. Overall, TLR4 appears to be a key modulator in the cross-talk between inflammatory and metabolic pathways, as well as a potential therapeutic target for diabetes.
Abstract 15891: Age-Related Changes of Right Atrial and Right Ventricular Functions Assessed 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 the RA phasic functions, assessed by speckle tracking echocardiography (STE), and their correlation with the RV function.

Methods:
131 normal subjects (19-78 yrs, 89 women), divided in 4 age groups, were studied by conventional, tissue Doppler, and STE. Active RA function was assessed from negative global strain at atrial contraction (GSA-) and derived time from P onset (TGSA-), and late diastolic SR (GSRL); passive function from positive global strain at TVO (GSA+) and time from R to peak (TGSA+), and from early negative diastolic global strain rate (GSRE); reservoir function from the sum of GSA- and GSA+ (SUMGSA), positive global SR at the beginning of RV systole (GSR+) and derived time from P onset (TGSR+). RA volumes were measured. RV systolic function was assessed from TAPSE, FAC, S’, global systolic strain (GS) and strain rate (RVSRs); diastolic function from early and late global SR (RVSRe and RVSRl).

Results:
Active RA function was not affected by age, but RA contraction time was longer over 50 yrs. Reservoir function decreased starting from 50 yrs (GRS+), but especially over 60 yrs (SUMGSA, TGRS+). Passive function also decreased over 50 yrs (GSA+, TGSA+, GSRE). RV systolic function was not affected by age, whereas RVSRe decreased, and RVSRl increased over 50 yrs (Table). Global RV function (TAPSE, FAC) did not correlate with any of the RA functions. However, longitudinal RV systolic function (RVSRs, GS, S’) correlated inversely with active function (GSA-, GSRL). RVSRe had positive correlation with RA reservoir (SUMGSA, GSR+), and also with passive function (GSA+, GSRE) (r=0.4, p<0.001). Atrial volumes were not affected by age.

Conclusion:
Active RA function is not affected by age. Passive and reservoir RA functions, and diastolic RV function decreased over 50 yrs. Longitudinal systolic RV correlates with active RA function, and diastolic RV function with passive and reservoir RA functions.
Abstract 15997: Pooled Cohort Risk Equations: A Comparison of Their Predictions With Five Other Cardiovascular Risk Scores in Five Peruvian Sites
Authors: Bazo-Alvarez Juan , Peralta-Alvarez Frank , Quispe Renato , Poterico Julio , Valle Giancarlo , Burroughs Melissa , Pillay Timesh , Gilman Robert , Checkley William , Malaga German , Smeeth Liam , Bernabé-Ortiz Antonio , Miranda Jaime
Published: July 2021

Introduction:
Cardiovascular disease (CVD) risk scores are used to estimate an individual’s risk of developing a disease or death from a cardiovascular event. Recently, the American College of Cardiology/American Heart Association (ACC/AHA) introduced the Pooled Cohort risk equations (ACC/AHA model). It is important to know how comparable CVD risk predictions are in low-middle income countries (LMIC).

Hypothesis:
ACC/AHA model has a poor concordance with any other CVD risk score.

Methods:
We used secondary data from two Peruvian, age and sex-matched, population-based studies across five geographical sites. The ACC/AHA model was compared to five other CVD risk prediction tools: two versions of the Framingham Risk Score (FRS-Lipids and FRS-BMI), Reynolds Risk Score (RRS), four versions of the Systematic Coronary Risk Evaluation (SCORE 1-4), World Health Organization risk chart (WHO), and Lancet Chronic Disease risk chart (LCD). We calculated predicted risk as a continuous variable and used Lin’s concordance correlation coefficient (CCC). We also compared the high predicted risk prevalence between all the scores using the cut-off levels suggested by each score’s guidelines.

Results:
We included 2183 subjects in the risk scores age range of 45-65 years (mean age 54.3 (SD±5.6) years). CCC agreement values found in this study were generally poor. The highest concordance was observed between the ACC/AHA model and the risk scores derived from the Framingham Study (40% with FRS-BMI and 44% with FRS-Lipids). ACC/AHA model depicted the highest proportion of people with predicted high-risk of 10-year CVD, at 29.0% (95%CI 26.9-31.0%) and the same tendency was observed in all study sites.

Conclusions:
In Peruvian population-based samples, agreement between ACC/AHA model and five other CVD risk scores was generally poor. There is an urgent need to use an appropriate risk score for CVD in LMIC. In an ideal scenario, it would be significant to have a proper CVD risk score for LMIC.