bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 150: Novel Mechanism for Regulation of Extracellular SOD Expression and Activity by Antioxidant-1
Authors: Ozumi Kiyoshi , Kim Ha Won , Itoh Shinichi , Mckinney Ronald , Folz Rodney , Yang Jay , Nakagawa Osamu , Ushio-Fukai Masuko , Fukai Tohru
Published: July 2021

Extracellular superoxide dismutase (ecSOD), a copper-containing secretory antioxidant enzyme, plays an important role in various oxidative stress-dependent cardiovascular diseases. Little is known regarding the mechanisms by which ecSOD expression and activity are regulated. We previously demonstrated that antioxidant-1 (Atox1) functions as a copper chaperone for ecSOD at transGolgi network (TGN) to regulate its activity. Unexpectedly, we also found that ecSOD mRNA is markedly decreased in Atox1-knockout (KO) fibroblasts. We thus hypothesize that Atox1 functions not only as copper chaperone but also as transcription factor to regulate both expression and activity of ecSOD. Here we show that in ApoE-KO mouse aorta, Atox1 was intensely stained in the nucleus at the intimal lesion of atherosclerosis where ecSOD was highly expressed. In cultured mouse fibroblast, copper treatment stimulated translocation of Atox1 from the cytosol to the nucleus. The ecSOD mRNA and its promoter activity were markedly decreased in Atox1 KO cells (82.5% and 85.7% decrease, respectively). Promoter deletion analysis identified Atox1-response element (Atox1-RE) at −314/−304 segment of ecSOD promoter. Gel shift and ChIP assays showed that Atox1 directly bound to the Atox1-RE including DNA segment in a copper dependent manner. To segregate a transcription factor and a copper chaperone function of Atox1, we generated adenovirus expressing wild-type, nucleus-targeted, and TGN-targeted Atox1 (Atox1-WT, Atox1-NLS, and Atox1-TGN). Re-expression of either Atox1-NLS or Atox1-WT, but not Atox1-TGN, in Atox1-KO cells increased ecSOD mRNA by 3.2-and 2.5-fold, respectively. Importantly, re-expression of either Atox1-WT only or both Atox1-NLS and Atox1-TGN in Atox1 KO cells increased ecSOD activity (2.1- and 2.7-fold, respectively), while either Atox1-NLS or Atox1-TGN alone had no effect. In summary, Atox1 functions as a novel copper dependent transcription factor to increase ecSOD expression, and modulates ecSOD activity through both copper chaperone and transcription factor function. Thus, not only ecSOD but also Atox1 are potential therapeutic targets for oxidant stress-dependent cardiovascular disease such as atherosclerosis.
Abstract 3170: Inferior Infarct Patching Reduces Mitral Regurgitation, Decreases Infarct Expansion, and Maintains Global and Remote-Zone Contractility: An Echo-MRI Study
Authors: Chaput Miguel , Hung Judy , Holmvang Fred , Guerrero J. L , Tournoux Francois , Sullivan Suzanne , Levine Robert A
Published: July 2021

Infarct (MI) patching has been shown to reduce mitral regurgitation (MR) in chronic MI models, but its local and global effects on the LV require further study. We tested the hypothesis that MI patching with papillary muscle (PM)repositioning not only reduces MR but also limits infarct expansion and progression of global LV dysfunction. Methods. Fourteen sheep with MIs created in a standard vascular territory as confirmed by first-pass gadolinium (Gd) MRI were studied at baseline, acutely post-MI and at 3 months by sonomicrometry, 3D echo and MRI. Animals were randomized to control versus treatment with an adjustable patch device to reposition the inferior PM (n=7 each). MI size was assessed by Gd-enhanced MRI and local wall motion by echo-derived tissue velocities. Results. MR was reduced chronically in all patch animals (vena contracta=0.08 vs 0.5 cm, p<0.001). At 3 months, despite end-diastolic dilatation in both groups (127±20 vs 128±16 mL, p=0.91, 1.4±0.1 x baseline), end-systolic volumes were smaller (71±9 vs 100±21 mL, p=0.05) and EF higher (43±11 vs 24±10%, p=0.02) in the treated group, with better maintained preload recruitable stroke work (41±5 vs 33±3, p=0.01). Infarct expansion at 3 months was reduced by patching (infarct/LV surface area=22±5 vs 41±6%, p=0.001; figure

). Remote zone contractile function was also improved by patching (strain=20±5 vs 11±4%, p=0.03; tissue velocity=3.5±0.7 vs 1.8±0.6 cm/s, p=0.05). Conclusion. Despite continued LV remodeling, inferior infarct patching leads to long-term decreased MR and better preserved global LV function, with both diminished expansion of the restrained infarct and preserved contractility of the remote myocardium.
Abstract 3175: Plasma Tansforming Growth Factor Beta as a Biochemical Marker to Predict the Recurrence of Atrial Fibrillation After Surgical Maze
Authors: On Young Keun , Shin Dae-Hee , Choi Jin-Oh , Park Yong Hwan , Lee Sang Yeub , Sung Ki-Ick , Park PyoWon , Sung Jidong , Jeon Eun-Seok , Kim June Soo , Park Jeong Euy
Published: July 2021

BACKGROUND
Atrial remodeling leads to perpetuation of atrial fibrillation (AF). Structural remodeling in the form of fibrosis alters the substrate. The surgical Maze procedure was developed as a surgical treatment of AF. Our purpose was to evaluate the role of plasma NT-proBNP, hsCRP, TIMP-1(Tissue inhibitors of MetalloProteinase-1), TGF-β, MMP-3(Matrix MetalloProteinase-3), and pro-MMP-1in predicting the recurrence of AF after surgical Maze procedure. And we also evaluated the association of expression of CTGF, TGF-β, BNP, ANP, collagen-1α, and collagen-3α in LA with the recurrence of AF after surgical Maze procedure.

METHODS
Preoperative plasma NT-proBNP, hsCRP, TIMP, TGF-β, MMP-3, and pro-MMP-1 levels were measured in consecutive 86 patients (age 54±12 yrs) who underwent the open heart operation for valvular heart disease and surgical Maze procedure for AF. Moreover, we performed molecular examinations of CTGF, TGF-β, BNP, ANP, Collagen-1α, Collagen-3α in the resected left atrial tissues. Symptomatic AF documented by ECG or an episode of AF revealed at follow-up holter monitoring were considered atrial fibrillation recurrences.

RESULTS
At 1-year follow-up, 10 among 86 patients had persistence of AF. Patients with AF persistence had higher plasma TGF-β levels than the patients with sinus rhythm (0.44 ± 0.29 vs 0.32 ± 0.15 ng/ml) . Patients with AF persistence had higher messenger RNA expressions of Collagen-3α (0.21 ± 0.20 vs 0.12 ± 0.12, compared with internal standard GAPDH by RT-PCR) and lower messenger RNA expressions of ANP (0.31 ± 0.16 vs 0.60 ± 0.76, compared with internal standard GAPDH by RT-PCR ) in left atrial tissues. Multiple logistic regression analysis revealed that plasma TGF-β was independently associated with postoperative persistence of atrial fibrillation at 1 year follow-up after surgical Maze procedure.

CONCLUSIONS
Advanced atrial degenerative change might result in a decrease of atrial ANP secretion. Cardiac fibrosis might be a determinant of myocardial heterogeneity and the persistence of AF. Plasma TGF-β could predict the persistence of AF at 1 year follow-up after surgical Maze procedure.
Abstract 3184: Dynamics of Mitral Complex Geometry During Left Ventricular Pressure Overload: in Vivo Experimental Study by Real-time 3D Echocardiography
Authors: Yamada Ryotaro , Watanabe Nozomi , Kume Teruyoshi , Tsukiji Miwako , Obase Kikuko , Kawamoto Takahiro , Neishi Yoji , Hayashida Akihiro , Toyota Eiji , Okura Hiroyuki , Yoshida Kiyoshi
Published: July 2021

Background:
Functional mitral regurgitation (MR) occurs as a consequence of regional or global left ventricular (LV) dysfunction despite a structurally normal mitral valve (MV). Degree of MV coaptation should be an important parameter in the assessment of functional MR.

Purpose:
We sought to investigate the change of MV coaptation and to clarify relationship between MV coaptation and development of MR in LV pressure overload.

Methods:
Using a canine model, LV pressure overload was induced by staged aortic banding (60 to 120mmHg). Echocardiographic examinations were performed before and during the banding. Degree of MR was evaluated by tracing the color jet MR area (MR area). By using a novel software system (RealView
TM
) for 3D quantification, mitral annulus (MA) area, tenting volume, tenting length and 3D tenting surface area were analyzed. MA and surface of MV was manually traced both at the onset of MV closure [O] and at the maximum MV closure [M]. Coaptation index was calculated by the difference in 3D tenting surface area at O and at M devided by that at O.

Results:
MA area was gradually increased during banding (
p
< 0.01). Tenting length and tenting volume tended to increase during banding but they did not reach statistical significance (tenting length;
p
= 0.17, tenting volume;
p
= 0.12). MR area increased with decrease in coaptation index (Figure

). The best cutoff value of the coaptation index to predict presence of MR was calculated as 0.24, giving a sensitivity of 82 % and specificity of 86 %.

Conclusions:
During aortic banding, MA dilated and coaptation of the MV decreased with apparent leaflet tenting. Coptation index might be able to predict the appearance of functional MR.
Abstract 3190: Gender Differences in Long-term Prognosis of Patients with Known or Suspected CAD and Severe LV Dysfunction Undergoing Gated Myocardial Perfusion SPECT
Authors: Abidov Aiden , Hayes Sean W , Friedman John D , Kang Xingping , Thomson Louise E , Cohen Ishac , Miranda-Peats Romalisa , Slomka Piotr , Germano Guido , Berman Daniel S
Published: July 2021

Objective
: We aimed to assess the impact of gender on long-term prognosis in pts with known or suspected CAD and impaired vs. preserved left ventricular (LV) function assessed by means of gated myocardial perfusion SPECT (gSPECT).

Methods
. 575 consecutive pts (38% women, mean age 66±12 yrs;43% pharmacological stress) had rest/stress gSPECT and were then followed up for 11±1 yrs. 55 pts (9.6%) had severe LV dysfunction (post-stress LVEF≥35%). Follow-up end-point was all-cause death (ACD). Prognostic value of clinical and gSPECT variables in predicting ACD was assessed by multivariable Cox proportional hazards analysis. We also evaluated tested variables for presence of confounding and interactions.

Results
. During the follow-up, there were 143 ACD events (24.9%). Compared to men, women were younger, had less severe perfusion defects, higher LVEF, and smaller LV volumes. There was as a significant interaction between female gender and LV function; survival of women with LVEF≥35% was significantly worse compared to men with the same level of LV impairment, even after adjustment for all other significant predictors, such as age, perfusion defect extent/severity, abnormal ECG, rest HR, dyspnea, history of known CAD and diabetes. (Figure

; *p<0.001). No difference found among the male and female pts with LVEF>35%.

Conclusion
: In pts with severe LV dysfunction (within the so-called “AICD range”), female gender is associated with worse long term prognosis, independent of other prognostic markers and despite more favorable clinical profile. If confirmed in prospective studies, these findings may have important clinical implications in management of pts with severe LV impairment.
Abstract 3252: Thoracoscopic Epicardial Pulmonary Vein Isolation Is A Realistic Alternative For Endocardial Radiofrequency Ablation: Lower Risk Of Arterial Embolism And Shorter Procedure Times
Authors: Sauren Loes , la Meir Mark , Pison Laurent , De Roy Luc , van der Veen Erik , Mess Werner , Crijns Harry , Maessen Jos
Published: July 2021

Background
Pulmonary veins isolation (PVI) has become an established treatment for atrial fibrillation (AF). However, post-procedural complications by cerebroembolic events might occur. In order to evaluate the cause of these complications we compared the number of cerebral microemboli during two approaches of PVI; epicardial microwave ablation and percutaneous endocardial radiofrequency ablation in patients with AF.

Methods and Results
Eight patients underwent a right 3 port mono-lateral thoracoscopic epicardial microwave (MW) ablation on the beating heart of the 4 pulmonary veins and the posterior left atrium. Twelve patients underwent endocardial RF ablation of the 4 pulmonary veins. Transcranial Doppler was used in all patients to detect cerebral MES. There was no significant difference in total ablation time between the two groups. However, the total procedural time was significant longer in the percutaneous endocardial PVI approach. Stroke or CVA was not reported in any of the patients. The average of 4 (± 7) cerebral MES per patient during the epicardial ablation is highly significantly lower than the 2703 (± 1919) cerebral MES during percutaneous endocardial RF ablation.

Conclusion
Cerebral MES were almost absent during thoracoscopic epicardial microwave ablation for the treatment of AF. This finding is in sharp contrast with the abundant MES detected during percutaneous endocardial RF ablation. Due to a positive association between the number of MES and cerebral complications, the striking difference of the amount of MES and the absence of thrombus formation might indicate a comparatively low risk of cerebrovascular complications for the epicardial approach as compared to the percutaneous approach. Since the success rates of both PVI approaches is reported to be around 80%, the shorter procedural time and the absence of cerebral MES render the thorascopic epicardial microwave approach a realistic alternative for endocardial RF ablation.

Number of MES during both PVI approaches
Abstract 3261: Papillary Fibroelastomas in Hypertrophic Cardiomyopathy
Authors: Kumar Gautam , MacDonald Ryan J , Sorajja Paul , Edwards William D , Ommen Steve R , Klarich Kyle W
Published: July 2021

Introduction:
Papillary fibroelastomas (PFEs) are the 3rd most common primary cardiac tumors with a prevalence of around 0.01% in patients with echocardiograms. The pathogenesis is controversial but endocardial trauma has been implicated. We hypothesized that increased turbulence in hypertrophic cardiomyopathy (HCM) would be a risk factor for PFE development and characterized PFEs in HCM. Around 5% of HCM patients had neurologic events. We postulated that patients with both PFE and HCM had a higher risk of neurologic events.

Methods:
We reviewed pathology records from 1990 –2006 and identified 129 subjects with PFEs and 2479 patients with HCM. We then identified the subjects who had both HCM and PFE (n = 19). All subjects signed release for use of their medical records for research.

Results:
19 subjects (68.4% female) had both HCM and PFE. Mean age at diagnosis of HCM was 49 (range 21– 81) years. All had outflow tract obstruction with resting gradient >/=30 mm Hg except 2 who had resting gradients <30 mm Hg but elevated gradients on provocation. PFE diagnosis was after a mean of 9.7 years (SD 8.3) following HCM diagnosis. 5 subjects were diagnosed pre-operatively by transthoracic echocardiography, 2 subjects by transesophageal echocardiography and 12 subjects at surgery only. Most subjects had only 1 PFE (57.9%) but 1 subject had as many as 40 tumors. Most PFEs were on the aortic valve (47.4%) and the left ventricular side of the septum and left ventricular outflow tract (42.1%). Only 2 patients had right heart lesions that were presumably unrelated to HCM. 3 patients had previous septal myectomies and all 3 had PFEs near the previous resection. 5 of 19 subjects (26.3%) with PFE and HCM had neurologic events (either strokes or transient ischemic attacks) compared to 199 of 2261 subjects (8.8%) with HCM alone (OR = 4.1; 95% CI 1.4 –11.4, p < 0.05).

Conclusion:
Nearly 90% of PFEs in HCM are located in the septum, left ventricular outflow tract and aortic valve. This may be supportive of endocardial trauma as a risk factor for PFE development in HCM. About a quarter of patients with PFEs and HCM had neurologic events. This may indicate that these lesions are not innocuous and should perhaps be actively searched for in patients with HCM and unexplained neurologic events.
Abstract 3269: Association of Aortic Regurgitation with Cardiovascular Morbidity and Mortality in Hypertensive Patients with Left Ventricle Hypertrophy: The LIFE study
Authors: Li Zhibin , Wachtell Kristian , Kjeldsen Sverre E. , Julius Stevo , Olsen Michael H. , Gerdts Eva , Nieminen Markku S. , Jern Sverker , Okin Peter M. , Dahlöf Björn S , Devereux Richard B.
Published: July 2021

Background
: Whether aortic regurgitation (AI) is associated with higher cardiovascular (CV) morbidity and mortality in hypertension with electrocardiographic (ECG) left ventricular hypertrophy (LVH) is unknown.

Methods
: Hypertensive patients with ECG-LVH were randomized to losartan- or atenolol-based treatment and followed for 4.8 years in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. In the LIFE echo substudy, echocardiograms were used to detect AI. Baseline clinical, echocardiographic variables and cardiovascular endpoints data were used in current analyses.

Results:
The presence of AI was detected in 132 participants (68 women; 68.4 ± 7.3 years). AI was associated with older age (p < 0.001) but not gender. After adjustment for age, AI was associated with significantly increased LV mass indexed by body surface area (BSA) and height
2.7
(both p < 0.005), echocardiographic eccentric LVH (p < 0.05) but not concentric left ventricular (LV) geometry (p < 0.05). After adjusting for significant confounders including history of CV disease, Framingham risk score, randomized antihypertensive therapy, LV eccentric geometry, LV mass indexed by BSA and height
2.7
, multivariate Cox regression analyses showed that AI was independently associated with 2.83-fold more CV death (95% confidence interval [CI] 1.12 to 7.13), 2.24-fold more all-cause mortality (95% CI 1.17 to 4.28) (both p < 0.05).

Conclusion
: In hypertensive patients with ECG-LVH, AI independently identifies patients at increased risk of CV and all-course mortality.
Abstract 3289: Vortex Formation Index in Heart Failure: Novel Non-invasive Assessment Of Fluid Dynamics using Transthoracic Echocardiography
Authors: Lee Li Ching , Tan Yee-Leng , Tan Huay Cheem , Omar Abdul Razakjr , Chai Ping , Yeo Tiong Cheng , Low Adrian Fatt Hoe , Yip James WL , Chia Boon Lock , Poh Kian Keong
Published: July 2021

Background:
In clinical heart failure (HF), inefficient propagation of blood through the left ventricle (LV) may result from suboptimal vortex formation (VF) ability of the LV during early diastole. We aim to

validate echocardiographic-derived VF index (VFI) in normal subjects and

examine its utility in both systolic and diastolic HF.

Method:
Echocardiography was performed in 100 normals and 155 pts admitted with HF (110, systolic and 45, isolated diastolic failure). In additon to biplane LV ejection fraction (EF) and conventional parameters, the Tei index and tissue Doppler (TD) indices were measured. VFI was obtained using: 4 X (1-β) / πX α
3
X LVEF where β is the fraction of total transmitral diastolic stroke volume contributed by atrial contraction (assessed by time velocity integral of the mitral E and A waves) and α is the biplane end diastolic volume (EDV)
1/3
divided by mitral annular diameter during early diastole.

Results:
Mean VFI was 2.75 ± 0.7 in control subjects; reduced in heart failure, diastolic, 2.21 ± 0.8; systolic, 1.24 ± 0.5 (P<0.001, Fig 1

). It correlated positively with TD early diastolic myocardial velocities (E, septal, r =0.58; lateral, r =0.58), inversely with LV filling pressure (E/E’ septal, r =−0.42; lateral, r =−0.41) and the Tei index (r =−0.57, curvilinear relation, Fig 2

); all Ps <0.001. In comparison with age, sex and LVEF-matched controls, only VFI, but not all other echo indices, remained significantly different (attenuated) in diastolic HF patients (2.01 ± 0.7 vs 2.74 ± 0.8, P=0.005).

Conclusion:
VFI, a novel, dimensionless index, incorporating LV geometry, systolic and diastolic contributions to fluid dynamics, may be useful in heart failure.
Abstract 3292: Cardiac Dysfunction Induced By Chronic Restrain Stress Is Mediated By Opioid Receptors
Authors: Gao Jinping , Chua Chu C , Yin Deling , Wang Hong , Hamdy Ronald C , Chua Balvin
Published: July 2021

Psychological and physical stressors are a major health problem in our society. The effect of chronic stress on myocardial function has not been assessed. Our hypothesis is that chronic stress induces cardiac dysfunction and that its effect is mediated by activation of opioid receptors (OPR). Six week-old male ICR mice were restrained for 12 h with no food and water. This was followed by 12 h of rest with food and water provided ad labium. Unstressed (control) mice were kept in the original cage and were not given food and water during the stress period of the experimental group. Left ventricular performance was analyzed in mice anesthetized with 2% isoflurane using an ARIA pressure-volume conductance system (Millar Instruments). Our studies demonstrated for the first time that cardiac function was significantly depressed in restrained mice, as evidenced by a significant decrease in body weight (9%), heart rate (21%), stroke volume (38%), cardiac output (52%), ejection fraction (27%) and preload recruitable stroke work (43%). Systolic function (control vs. stressed group) (P<0.05), was 88 ± 2.2 vs. 68 ± 2.8 mmHg for end-systolic pressure, 6.1 ± 0.15 vs. 7.6 ± 0.15 μl for end-systolic volume, and 11,471 ± 913 vs. 5,860 ± 761 mmHg/s for +dP/dt. Diastolic function (control vs. stressed group) (P<0.05), was 2.9 ± 0.3 vs. 5.0 ± 0.5 mmHg for end-diastolic pressure, 17.1 ± 0.4 vs. 14.4 ± 0.5 μl for end-diastolic volume, 7,678 ± 419 vs. 4,195 ± 358 mmHg/s for -dP/dt, and 7.1 ± 0.5 vs. 10.8 ± 1.1 ms for tau (time constant of isovolumic relaxation). Peripheral vascular resistance (Ea) increased from 7.7 ± 0.2 in the control group to 9.8 ± 0.7 mmHg/μ l in the stressed group (P<0.05). Administration of an opioid antagonist naltrexone (8 mg/kg, i.p.) during each cycle of stress completely restored the cardiac function of stressed mice. Naltrexone alone had no effect on cardiac function in unstressed mice. These intriguing data suggest that opioid receptors are involved in the chronic stress-induced cardiac dysfunction and that treatment with an opioid antagonist can prevent this cardiac dysfunction.
Abstract 3339: Effects of Atorvastatin 10 mg versus 40 mg in Eight Months Follow-up Coronary Flow Reserve and Clinical Events in Patients with Acute Myocardial Infarction
Authors: Hong Soon Jun , Choi Seung Cheol , Choi Jong Il , Joo Hyung Joon , Shin Seung Yong , Shim Wan Joo , Park Seong Mi , Lim Sang Yup , Lim Do-Sun
Published: July 2021

Background:
Circulating bone marrow-derived stem cells are capable of homing to sites of myocardial infarction and endothelial disruption, thereby restoring myocardial function and microvascular integrity after acute myocardial infarction. We compared the effects of atorvastatin 10 mg versus 40 mg in follow-up clinical events and in restoring coronary flow reserve (CFR) during the 8 months follow-up in patients with acute myocardial infarction.

Methods:
CFR, which is reflective of the integrity of coronary microvasculature, was measured by using intracoronary Doppler wire in 102 consecutive patients with acute myocardial infarction 5 days after the successful primary coronary intervention with sirolimus-eluting stents. Stented patients were randomly assigned to either atorvastatin 10 mg (ATOR10, n=52) or atorvastatin 40 mg (ATOR40, n=50). All patients received aspirin and clopidogrel. Clinical events such as death, myocardial infarction, and target lesion revascularization (TLR) were compared during the 8-month follow-up.

Results:
CFR increased significantly in both groups during the 8 months follow-up (1.9 ± 0.6 at baseline vs. 2.6 ± 0.7 at follow-up in the ATOR10, p<0.05; 1.9 ± 0.7 at baseline vs. 2.9 ± 0.8 at follow-up in the ATOR40, p<0.05). The changes from baseline in CFR was greater in the ATOR40 Group compared with the ATOR10 Group (1.0 ± 0.8 vs. 0.7 ± 0.6, p<0.05, respectively). The numbers of CD34+ and CXCR4+ cells were significantly greater in the ATOR40 Group compared with the ATOR10 Group (13 ± 10 vs. 6 ± 6, p<0.05, respectively for CD34 cells and 15 ± 14 vs. 10 ± 9, p<0.05, respectively for CXCR4+ cells per 1uL). Clinical events such as death (0 patient in the ATOR10 vs. 2 patients in the ATOR40, p=0.247), myocardial infarction (2 patients in the ATOR10 vs. 1 patient in the ATOR40, p=0.557), and TLR (2 patients in the ATOR10 vs. 2 patients in the ATOR40, p=0.692) demonstrated no significant differences during the follow-up.

Conclusion:
The increases from baseline in CFR, CD34+ cells and CXCR4+ cells were significantly greater in the ATOR40 Group compared with the ATOR10 Group. However, the improvement in left ventricular systolic function and the rate of clinical events revealed no significant differences between the 2 groups.
Abstract 3415: Cardiovascular Magnetic Resonance Accurately Detects Myocardial Hemorrhage in Reperfusion Injury
Authors: Kumar Andreas , Green Jordin D , Mitchell Andrea J , Sykes Jane M , Wisenberg Gerald , Friedrich Matthias G
Published: July 2021

Introduction Hemorrhage can complicate reperfusion injury in myocardial infarction, but no in vivo imaging method exists. We hypothesized that a T2*-weighted cardiovascular magnetic resonance imaging (CMR) sequence accurately detects myocardial hemorrhage in vivo.

Methods Reperfused myocardial infarcts were generated in 14 dogs by ligation of the LAD for 3– 6 hours. At day 3, a CMR study was performed using established sequences for quantification of function, microvascular obstruction and myocardial infarction in short axis slices covering the entire myocardium. For hemorrhage, a T2*-weighted multi-echo gradient-echo sequence was applied (TE=35msec, TR=1 RR, FOV 380x280mm, matrix 256 x 192). A segmental analysis was performed using 6 segments per slice: T2*-segments were considered hemorrhagic when signal intensity was >2 standard deviations below the mean of remote myocardium. The contrast-to-noise ratio of hemorrhagic segments over normal segments was assessed. Post-mortem TTC staining was performed with infarcted and hemorrhagic areas analyzed with the same segmental approach. In vivo/ ex vivo correlation statistics were performed.

Results In 14 dogs, 378 segments were assessed. Of the T2* CMR segments, 10.2% were excluded due to artifacts; 27 segments yielded a signal drop consistent with hemorrhage (see figure

). The correlation with ex vivo TTC staining was R=0.79 and contrast-to-noise ratio was 9.2±3.4. Sensitivity to detect a hemorrhagic segment was 77%, specificity 99%.

Conclusion T2*-weighted CMR accurately detects reperfusion hemorrhage in vivo. The method may be applied in patients to study hemorrhage as a complication of reperfusion injury.
Abstract 3430: Ethnic Differences in the Prevalence and Treatment of Cardiovascular Risk Factors in Outpatients with Peripheral Arterial Disease: Insights from the REACH Registry
Authors: Meadows Telly A , Bhatt Deepak L , Hirsch Alan T , Creager Mark A , Califf Robert M , Ohman E. M , Cannon Chris P , Eagle Kim A , Alberts Mark , Goto Shinya , Wilson Peter W , Steg Ph. G
Published: July 2021

Background
: In the United States, African Americans have been reported to have an increased prevalence of peripheral arterial disease (PAD) with poorer outcomes as compared to whites. Whether this can be attributed to differences in the presence and treatment of traditional coronary artery disease (CAD) risk factors versus other factors specifically related to ethnicity is unknown.

Methods
: We identified 2,235 patients from the United States with documented PAD with and without concomitant CAD and cerebrovascular disease (CVD) at one year enrolled in the REduction of Atherothrombosis for Continued Health (REACH) Registry. We compared the baseline demographics, risk factor profiles, medication use, and one-year outcomes between the 236 African Americans and 1,810 non-Hispanic whites.

Results
: Among the traditional atherosclerotic risk factors, African Americans were more likely than whites to have diabetes (64.0% vs. 48.6%, p<0.0001), hypertension (95.3% vs. 86.5%, p=0.0001), obesity (45.9% vs. 34.3%, p=0.0002), and isolated PAD (44.9% vs. 28.7%, p<0.0001). In comparison to whites, African Americans were less likely to be on aspirin (62.0% vs. 72.4%, p=0.0009) and lipid-lowering therapy (76.1% vs. 83.2%, p=0.0071), and more likely to have an elevated blood pressure (BP ≥140/90 mmHg: 54.9% vs. 38.1%, p<0.0001) and fasting cholesterol (>200 mg/dL: 41.7% vs. 24.9%, p<0.0001) at baseline. Overall, there were no significant difference in all-cause mortality (4.70% vs. 5.32%, p=0.97) or CV death, MI, or stroke (4.92% vs. 6.20%, p=0.79) between African Americans and whites in this cohort (data adjusted for age and sex).

Conclusion
: Among U.S. outpatients with PAD, African Americans are more likely than whites to have risk factors for cardiovascular disease, but less likely to receive aspirin or lipid-lowering therapy. In this registry, one-year event rates are relatively high, but similar in both groups.
Abstract 3431: Pulse Pressure Is Inversely Related to Aortic Root Diameter: Implications for the Pathogenesis of Systolic Hypertension
Authors: Farasat S. Morteza , Morrell Christopher H , Scuteri Angelo , Ting Chih-Tai , Yin Frank C , Spurgeon Harold A , Chen Chen-Huan , Lakatta Edward G , Najjar Samer S
Published: July 2021

Background:

The age-associated increase in central arterial stiffness manifests as a rise in pulse pressure, which leads to a marked increase in the prevalence of systolic hypertension among older individuals. Aortic root diameter (AoD) also increases with advancing age. According to the prevailing views, hypertension contributes to a further increase in AoD. Conversely, it has been suggested that the age-associated increase in AoD may partially compensate for the increased arterial stiffness. We tested the hypothesis that AoD is inversely associated with pulse pressure.

Methods:

The study population comprised 1256 individuals, aged 30 –79 years (48% women, 48% hypertensive), none of whom were on antihypertensive medications. Brachial pulse pressure (bPP) was calculated as the difference between sphygmomanometric systolic and diastolic blood pressures. Central pulse pressure (cPP) was derived from calibrated carotid artery pressure waveforms. AoD was measured by echocardiography at the level of the Sinuses of Valsalva. The relationships of AoD with bPP and cPP were evaluated with multiple regression analyses.

Results:

bPP was 54 ± 18 mmHg in women and 50 ± 14 mmHg in men, and AoD was 28.9 ± 3.5 mm in women and 31.9 ± 3.5 mm in men. After adjusting for age, age
2
, height, weight, and mean arterial pressure, bPP was
inversely
associated with AoD in both sexes. This inverse association persisted even after adjusting for aortic pulse wave velocity, carotid intima-media thickness, reflected waves, and left ventricular end-diastolic diameter and wall thickness. In the fully adjusted models predicting bPP, the regression coefficients for AoD were −0.48 in men (p = 0.0003, model R
2
=0.51) and −0.40 in women (p = 0.01, model R
2
= 0.61). Similarly, cPP was inversely associated with AoD in both men (coefficient = −0.45, p = 0.0007, model R
2
=0.50) and women (coefficient = −0.40, p = 0.01 model R
2
= 0.61). Thus, each 1 mm increase in AoD was associated with a 0.4 – 0.5 mmHg decrease in bPP and cPP in both sexes.

Conclusions:

Contrary to the prevailing views, AoD is independently and inversely associated with both bPP and cPP. These findings suggest that a small AoD may contribute to the pathogenesis of systolic hypertension. Longitudinal studies are needed to examine this possibility.
Abstract 3458: Dietary Arachidonic Acid, 5-Lipoxygenase and Myocardial Infarction
Authors: Campos Hannia , Ana Baylin , Hartiala Janna , Allayee Hooman
Published: July 2021

Five-lipoxygenase (5-LO), the rate-limiting enzyme in the biosynthesis of leukotrienes from arachidonic acid, has been associated with the development of atherosclerosis in mouse models, and a 5-LO promoter repeat polymorphism has been implicated in atherosclerosis in humans. To test the effect of the 5-LO polymorphism on risk of MI and whether dietary arachidonic acid modified the observed results, we studied 1,885 cases of myocardial infarction (MI) and 1,885 controls matched for age, sex, and area of residence, all living in Costa Rica. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95%CI). Dietary intake was assessed by a validated food frequency questionnaire. No case-control differences in the frequency of deletion (DD/WD) or addition (AA/WA) alleles were identified: DD/WD=28.7% and 29.7%; AA/WA=2.35% and 3.1%, respectively. However, a significant gene-diet interaction was found between the 5-LO polymorphism, arachidonic acid intake, and MI (P=0.014). Compared to the wildtype (WW), the D allele was associated with increased MI in the high (>0.25 g/d) dietary arachidonic acid group (OR=1.23, 95%CI 0.99 –1.53) and with decreased MI in the low (≤ 0.25) arachidonic acid group (OR=0.79 95%CI 0.63– 0.98). The A allele was inversely associated with MI in both diet groups, although this association was not statistically significant perhaps due to its low frequency. To examine if functional differences between alleles explain the observed results, we measured relative amounts of RNA from the D allele compared to the W allele in 66 heterozygous individuals from the same population using allele specific quantitation with Pyrosequencing technology. As a control, DNA from the same heterozygote individuals for each respective allele was used. Consistent with the results above, the D allele had a ~50% increased expression relative to the W allele. Thus, carriers of the 5-LO D allele are more susceptible to the effects of arachidonic acid on risk of MI. The finding of increased expression of 5-LO from the D allele is consistent with the observation that this allele is associated with increased atherosclerosis and risk of MI, at least in the context of a diet high in arachidonic acid.
Abstract 3466: Hypertension Treatment and Control Among Patients Hospitalized with Heart Failure: An Analysis of Get With The Guidelines Heart Failure
Authors: Lackland Daniel T , Cannon Christopher P , Egan Brent M , Fonarow Gregg , Yu Yanglin , Hernandez Adrian F , Robertson Rose Marie , Jones Daniel W
Published: July 2021

Background: Hypertension is a major factor associated with heart failure (HF).While effective blood pressure (BP) control is recommended in patients with HF, little is known regarding treatment and control rates in these patients.

Methods: The analyses assessed HF patients from 195 hospitals participating in the GWTG-HF quality improvement program from January 2005 through September 2006. Patients with hypertension were assessed for number and type of hypertension treatment as well as BP control rates. Analyses were stratified by race-sex groups with multivariate logistic regression models using the generalized estimating equations methods assessed the factors associated with multiple treatment, type of therapy, and BP control levels.

Results: Of 37,318 HF patients, 62.3% (23,257) had diagnosed hypertension. The majority (67.3%) of these high-risk individuals were treated with 3 or more hypertension drugs, which was significantly varied by race-sex groups. The use of ACEI (64.6%), beta blockers (79.9%), angiotensin receptor blockers (18.5%), diuretics (62.4%), loop diuretic (73.8%), and calcium channel blockers (13.3%) significantly varied by race-sex groups. BP control rates (< 140/90 mm Hg) at discharge significantly varied by race-sex group (total 70.8%; white males (WM) 76.3%; white females (WF) 71.1%; black males (BM) 63.0%; and black females (BF) 62.9%). Significant factors associated with BP control at discharge included age, race-sex (WF vs. BF, WM vs. BF), atrial fibrillation, hyperlipidemia, coronary heart disease, ICD, pacemaker, history of MI, and not having one or more of the following co-morbid conditions: diabetes, peripheral vascular disease, CVA and renal disease. Control rates considering BP < 130/80 mm Hg (52.3%) showed similar significant variation by race-sex group (WM 57.4%; WF 53.7%; BM 42.3%.; and BF 44.4%).

Conclusions: The less than optimal blood pressure control levels and the gender/racial disparities support continued emphasis on hypertension treatment and control among patients with heart failure.
Abstract 3468: Perioperative Betablockers Reduce Cardiovascular events in Patients Undergoing High Risk Non-cardiac Surgery-A Meta-analysis
Authors: Mapakshi Nandana , Swaminathan Paari D , Kodumuri Vamsi , Bhargava Sandeep , Reddy Namratha , Khosla Sandeep
Published: July 2021

Introduction:
ACC/AHA 2006 guidelines recommend perioperative beta blockers(BB) for high risk cardiac patients (class IIa), intermediate and low cardiac risk patients (class IIb) undergoing non-cardiac surgery. Meta-analysis of trials on perioperative blockers up to April 2003 found insufficient evidence for reduction of major cardiovascular events. We analysed the current evidence on effects of perioperative beta-blockers in patients not on BB and undergoing non-cardiac surgery.

Materials and Methods:
We did a literature search for randomized placebo controlled clinical trials of perioperative beta blockers in patients undergoing high risk non-cardiac surgery. End points were 30 day total mortality, cardiovascular mortality, perioperative cardiovascular outcomes, non-fatal MI, unstable angina, ventricular tachycardia, congestive heart failure, non-fatal stroke,non-fatal cardiac arrest,hypotension, bradycardia, bronchospasm. Data was extracted on an intention-to-treat basis. Heterogeneity of the studies was analyzed by Cochran’s Q statistics. The Mantel-Haenszel fixed-effect model was used to calculate combined relative risks for outcomes.

Results:
24 studies with 3454 patients were included. Perioperative BB showed statistically significant benefit in reducing perioperative cardiovascular events and non-fatal MI and a nominally statistically significant benefit for cardiovascular mortality. The other end points were not significantly different between the two treatment groups. The results are summarized in the table

below.

Conclusion:
Perioperative beta blockers reduce cardiovascular events and their use is recommended in all patients without contraindications and undergoing non-cardiac surgery.
Abstract 3474: Bleeding Complications Associated with Dual Antiplatelet Therapy plus Anticoagulant in Patients Who Underwent Percutaneous Coronary Intervention with Drug-eluting Stents
Authors: Uchida Yoshie , Tsurumi Yukio , Takahashi Atsushi , Higasitani Michiaki , Kameyama Kinichi , Nagashima Michitaka , Mori Fumiaki , Takagi Atsushi , Shiga Tsuyoshi , Hagiwara Nobuhisa , Kasanuki Hiroshi
Published: July 2021

Backgrounds:
Combinations of dual antiplatelet therapy (aspirin with thienopyridine derivatives) plus warfarin sodium are often used in various cardiac conditions. The purpose of this study was to evaluate bleeding complications associated with combinations of dual antiplatelet plus anticoagulant therapy in patients who underwent percutaneous coronary intervention (PCI) with drug eluting stents (DES).

Methods and Results
: We reviewed 563 PCI cases with DES between August 2004 and March 2007 in our hospital either in the setting of elective situation or acute coronary syndrome. On discharge, 515 patients (91.5%) were prescribed dual antiplatelet therapy alone, while 48 patients (8.5%) were discharged receiving dual antiplatelet plus anticoagulant therapy. Major and minor bleeding complications were observed in 90 patients (17.8%). Rates of bleeding complications were significantly higher among patients receiving triple therapy compared to those with dual antiplatelet alone (37.5% vs. 13.9%, P<0.05). Moreover, incidence of major bleeding was remarkably higher in patients receiving the triple therapy compared to those with dual antiplatelet alone (16.7% vs. 1.9%, P<0.01). Multivariate analysis revealed that chronic kidney disease (CKD) is a strongest predictor of both major and minor bleeding.

Conclusions
: Triple therapy, dual antiplatelet plus anticoagulant combination, was associated with significant increase in bleeding risk for patients who underwent PCI with DES. Our results also suggest that caution should be paid especially in those patients with CKD, that is a strongest predictor of major bleeding when the triple antithrombotic regimen was prescribed.
Abstract 3500: Cardiovascular Risk in Women with Non-Specific Chest Pain: Women’s Health Initiative Hormone Trials
Authors: Robinson Jennifer G , Wallace Robert , Limacher Marian , Ren Hong , Cochrane Barbara , Wassertheil-Smoller Sylvia , Ockene Judth K , Ockene Judth K , Blanchette Patricia , Ko Marcia
Published: July 2021

Context:
Women discharged with a diagnosis of nonspecific chest pain (NSCP) may have an increased risk of subsequent coronary heart disease (CHD) events. The influence of hormone therapy on NSCP is unknown.

Methods:
The WHI enrolled postmenopausal women aged 50 –79 years. After excluding women with prior cardiovascular disease, 9427 women in the estrogen alone (E-Alone) trial and 15,105 women in the estrogen plus progestin (E + P) trial were included in this analysis. NSCP, defined as having a primary hospital discharge diagnosis of NSCP by ICD-9 code, was reported in 322 E-Alone and 249 E + P women. Risks of subsequent CHD events were estimated using intent-to-treat Cox proportional hazard ratio (HR) models stratified by clinic and adjusted for age and other risk factors.

Results:
In the fully adjusted models of the combined trials, women with NSCP had a 2-fold greater risk of subsequent nonfatal CHD events including nonfatal myocardial infarction [2.3% vs 1.7%, HR 2.10 (1.11–3.98)], revascularization [3.5% vs 2.6%, HR 1.99 (1.20 –3.30)], and hospitalized angina [3.7% vs 2.3%, HR 2.39 (1.46 –3.92)]. Hormone therapy did not have a significant effect on either the incidence of NSCP hospitalizations [HRs (95% CIs): E-Alone 1.04 (0.81–1.32); E + P 0.78 (0.59 –1.02)] or on the risk of a subsequent CHD event over 7.1 or 5.6 years of follow-up, respectively.

Conclusion:
A NSCP hospitalization doubles the risk of a subsequent CHD event in postmenopausal women over the next 5 to 7 years. Further research is needed to identify appropriate diagnosis and treatment strategies for women with NSCP.
Abstract 3551: Waist Circumference, Body Mass Index, and Their Association with Cardiometabolic and Global Risk Among Whites and Racial/Ethnic Minorities
Authors: Christian Allison H , Mosca Lori
Published: July 2021

Purpose
: To determine if waist circumference (WC) or body mass index (BMI) is more strongly associated with cardiometabolic risk factors among family members of patients hospitalized for cardiac disease, overall and by race/ethnicity.

Methods
: Participants in the NHLBI
F
amily
I
ntervention
T
rial for
Heart
Health (
F.I.T. Heart
) were included in this analysis (n=472; mean age 48±14 years, 67% female, 36% non-white). Height, weight, WC, BMI, blood pressure, high density lipoprotein (HDL)-cholesterol, triglycerides, fasting glucose, and c-reactive protein (hs-CRP) were systematically measured in all participants. Global risk was calculated using the Framingham function.

Results
: The prevalence of cardiometabolic risk factors and their association with WC and BMI is shown in Table 1

. The most common correlate of increased WC and BMI was elevated hs-CRP. Overall, increased WC was the strongest correlate of glucose≥100 and hs-CRP≥3.0. BMI≥25 was the strongest predictor of blood pressure≥140/90, low HDL, triglycerides≥150, and global risk≥10%. Among non-whites, increased WC did not identify those with blood pressure≥140/90, glucose≥100 or global risk≥10% and BMI≥25 did not identify those with low HDL or glucose≥100. There was a significant interaction between race/ethnicity and increased BMI in predicting low HDL (p<0.01), with a stronger correlation in whites than non-whites.

Conclusions
: The prevalence of cardiometabolic risk factors and their correlation with WC and BMI varies by race/ethnicity. Our data support inclusion of both WC and BMI in screening guidelines for diverse populations to identify individuals at increased cardiometabolic and global risk.

Table 1.

Prevalence of and Association between Indices of Obesity and Cardiometabolic Risk
Abstract 3591: Group X sPLA2 Deficiency Increases Adiposity and Adipose Tissue Inflammation in Mice
Authors: Webb Nancy R , Li Xia , Forrest Kathy , Bailey William , Boyanovsky Boris B , Shridas Preetha , de Beer Frederick C
Published: July 2021

Introduction:
Of the 10 secretory phospholipase A
2
(sPLA
2
) enzymes expressed in humans, Group X (GX) sPLA
2
is the most potent in hydrolyzing phospholipids on cell membranes. In addition to its lipolytic activity, GX sPLA
2
is also a high affinity ligand for the M-type sPLA
2
receptor. Although numerous studies have implicated GX sPLA
2
in important biological processes
in vitro
, data from studies
in vivo
are lacking. To elucidate the physiological functions of this enzyme we recently developed C57BL/6 mice with targeted deletion of the GX sPLA
2
gene.

Results
: Analysis by real time RT-PCR showed that GX sPLA
2
mRNA is widely distributed in mouse tissues, with highest expression in intestine, testes, brain, thymus, spleen, fat, lung, and heart. Unlike some of the other members of the sPLA
2
family, tissue expression of GX sPLA
2
was not highly upregulated in mice injected with lipopolysaccharide. However, GX sPLA
2
was induced almost 5-fold in retroperitoneal fat of mice fed a high-fat (60 kcal%) diet for 17 weeks.Targeted disruption of GX sPLA
2
resulted in increased body weight in 1.5 year-old mice fed a normal laboratory diet (male GX sPLA
2
+/+
mice: 35.8±0.4 g; male GX sPLA
2
−/−
mice: 45.033.2 g; p<0.05). The increase in body weight was associated with significantly increased percent body fat (GX sPLA
2
+/+
mice: 16.0±1.0%; GX sPLA
2
−/−
mice: 19.6±1%; p<0.05), increased adipocyte size (GX sPLA
2
+/+
mice: 1300±26 um
2
GX sPLA
2
−/−
mice: 2700±78 um
2
; p<0.001), and decreased fasting plasma triglyceride levels (GX sPLA
2
+/+
mice: 46.3±4.9 mg/dl; GX sPLA
2
−/−
mice: 33.8±2.9 mg/dl; p<0.05) at 3 months of age. Food consumption, fasting blood glucose, and plasma total cholesterol levels were not significantly different between GX sPLA
2
−/−
and GX sPLA
2
+/+
mice. Compared to 3 month old GX sPLA
2
+/+
mice, the relative expression of IL-6 and F4/80 mRNAs in adipose tissue of age-matched GX sPLA
2
−/−
mice was increased 9- and 4-fold, respectively, suggesting that the increased adiposity in GX sPLA
2
−/−
mice was associated with an increase in the inflammatory profile of adipose tissue

Conclusions:
Our data points to a previously unrecognized role for Group X sPLA
2
in the development of obesity and associated adipose tissue inflammation.