bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3308: New Doppler Ultrasound Criteria for Renal Artery In-Stent Restenosis
Authors: Thornton Stanley N , Cardenas Gustavo A , Imsais Joseph K , Daniel Gary A , Afshar Hamid , Goldman Corey , Chi Yung-Wei , White Christopher J
Published: July 2021

Background:
Renal artery Doppler ultrasound (DUS) has been well established as an effective non-invasive screening tool for renal artery stenosis in native renal arteries. Stent placement alters the elastic properties of arteries and would be expected to decrease arterial compliance resulting in higher DUS velocities than non-stented arteries. To date, no criteria have been established for detecting in-stent restenosis (ISR) with DUS.

Purpose:
To establish the optimal DUS parameters to detect hemodynamically significant renal artery in-stent restenosis.

Methods:
We included consecutive patients (N=68) with clinically suspected renal artery ISR. Each patient underwent DUS and quantitative renal angiography that were blindly interpreted. Pearson’s correlation coefficients of 0.80 to 0.87 (P<0.0001) suggested strong agreement among observers. Significant ISR was defined as ≤ 70% reduction of in-stent luminal diameter when compared to the nearest normal reference segment. Angiographic criteria were compared to the renal artery peak systolic velocity (PSV) and the renal-aortic ratio (RAR) from corresponding DUS measurements. Receiver Operating Characteristic curves were constructed using PSV and RAR as continuous variables to determine the DUS parameters with the highest sensitivity and specificity for detecting ISR.

Results:
There was a statistically significant correlation for both PSV and RAR in detecting ISR as defined by quantitative angiography (P<0.0001). PSV>325 cm/sec and RAR>4.9 were most predictive of angiographically significant ISR, while a combination of the two criteria resulted in a greater sensitivity and specificity than either one alone.

Conclusion:
Renal artery Doppler ultrasound is an effective screening tool for renal artery in-stent restenosis. A PSV of 325 cm/sec and a RAR of 4.9 are most predictive of angiographic in-stent restenosis, with a combination of the two criteria offering the greatest sensitivity and specificity.

DUS DETECTION OF ≥70% RENAL ARTERY IN-STENT RESTENOSIS (ISR)
Abstract 3309: Repeated Thermal Therapy Mobilizes CD34+ Cells and Improves Peripheral Artery Disease
Authors: Shinsato Takuro , Miyata Masaaki , Kihara Takashi , Fukudome Tsuyoshi , Kubozono Takuro , Ikeda Yoshiyuki , Hamasaki Shuichi , Tei Chuwa
Published: July 2021

Background
: We developed a form of thermal therapy that differers from the traditional sauna. We reported that repeated thermal therapy upregulated eNOS protein and augmented ischemia-induced angiogenesis in a mouse model of hindlimb ishemia. Furthermore, we demonstrated that repeated thermal therapy improved limb ischemia in patients with peripheral artery disease (PAD). To investigate the underlying mechanism of thermal therapy for the treatment of PAD, we examined whether thermal therapy could mobilize blood-derived progenitor cells for local vascular regeneration.

Method
: We enrolled 6 patients with PAD and 4 patients with spinal canal stenosis (SCS) as a control. They were treated with a far infrared-ray dry sauna at 60 degrees centigrade for 15 minutes and then kept on bed rest with a blanket for 30 minutes, daily for 6 weeks. The leg pain was scored with a visual analogue scale (10: severest pain, 0: no pain). Ankle-brachial pressure index (ABI) and distance of 6-minute walking were measured before and 6 weeks after repeated thermal therapy. To detect the shift of circulating CD34+ progenitor cells in the periphery with higher sensitivity, we established the use of quantitative real-time polymerase chain reaction (PCR) for CD34 messenger RNA using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene as an internal control.

Results
: After 6 weeks of thermal therapy, the leg pain score, ABI, and distance of 6- minute walking were significantly improved in patients with PAD, while did not change in patients with SCS. Circulating CD34+ cell numbers were determined biweekly by quantitative real-time PCR before and after the initiation of repeated thermal therapy. In successfully treated patients with PAD, the number of cells increased 1.8-fold from 2.0 ± 1.5 (x10
−4
) before thermal therapy to 3.6 ± 2.3 (x10
−4
) after thermal therapy (p=0.018), while the number of cells in patients with SCS was 2.5 ± 0.6 (x10
−4
) before thermal therapy and 2.5 ± 0.7 (x10
−4
) after thermal therapy (no significant difference).

Conclusion
: Repeated thermal therapy mobilized circulating endothelial progenitor cells and improved limb ischemia in patients with PAD. This therapy is a novel, safe, and highly promising strategy for treating PAD.
Abstract 3315: Therapeutic Implications of Sympathetic Stimulus in Orthostatic Patients: Measured by Spectral Domain Analysis
Authors: Arora Rohit , Aysin Elif , Aysin Ben , Colombo Joe
Published: July 2021

Upon assuming an upright, head up posture, a sympathetic surge is expected. Sympathetic Withdrawal (SW) is abnormal and can differentiate Orthostasis. SW, with blood pressure (BP) and heart rate (HR), can fully define the continuum that is Orthostasis, including pre-clinical forms: Orthostatic Hypotension (OH-), Orthostatic Intolerance (OI), Orthostatic Hypertension (OH+), and Postural Orthostatic Tachycardia Syndrome (POTS). Our objective was to test the therapeutic implications of SW in Orthostatic patients. Autonomic profiling of 210 consecutive Orthostatic patients recruited from ambulatory clinics was performed using the ANX-3.0 Autonomic Monitoring System (Ansar, Inc., Philadelphia, PA). The cohort (age=58.9±11.6; 30 Diabetics; 132 Females, 28 Controls) was followed over a two year period. Autonomic profiling was based on patient responses to a standard clinical study that includes a resting baseline and periods of deep (relaxed) breathing, short Valsalva maneuvers, and quick stand immediately followed by quiet standing. The control group were patients with known diagnoses. The experimental group were prescribed 2.5 mg Midodrine once a day around dinner. Control patients were administered Flourinef, or support hose, or when possible were requested to modify their diets to add salt and build fluid volume. Patients with dysautonomia, with symptoms of elevated BP when supine were omitted from the study. In 89% of the experimental cases, SW was reversed in approximately 6 months and weaned from the medication. The remaining cases were reversed and weaned before the end of the two year follow up. In the control group, 46% of the patients on Flourinef, 4% of the support hose patients and 12% of the diet modification patients corrected SW within the two year period. The application of an alpha-adrenergic agonist seems to have greater efficacy than a mineralo-corticoid, mechanical intervention, or dietary modification in correcting SW associated with Orthostasis.
Abstract 3324: Assessment of Coronary Calcification by Optical Coherence Tomography in the Culprit Lesions: Comparison between Acute Coronary Syndrome and Stable Angina Pectoris
Authors: Mizukoshi Masato , Kubo Takashi , Takarada Shigeho , Kitabata Hironori , Tanimoto Takashi , Ueno Satoshi , Kuroi Akio , Arita Yuu , Ikejima Hideyuki , Ookouchi Keishi , Tsujioka Hiroto , Kashiwagi Manabu , Matsumoto Hiroki , Kataiwa Hideaki , Nakamura Nobuo , Tanaka Atsushi , Imanishi Toshio , Akasaka Takashi
Published: July 2021

[BACKGROUND] Calcification is an important phenomenon of atherosclerosis. Histopathological and intravascular ultrasound studies suggest that the characteristics of calcification might be associated with the pathogenesis of the vulnerable plaque. Optical coherence tomography (OCT) is a high-resolution imaging modality and allows us to analyse the plaque morphology in detail. In this study, we assessed the characteristics of calcification by OCT at the sites of culprit lesions in acute myocardial infarction (AMI), unstable angina pectoris (UAP), and stable angina pectoris (SAP).

[METHOD and RESULTS] We evaluated the characteristics of calcification in the 20-mm-long culprit lesion segment per patient by OCT in 56 patients (AMI : n=21, UAP : n=14, SAP : n=21). In each patient, the number of calcium deposits, the arc, the distance from the luminal surface to each calcification were measured. Each calcium deposit was categorized into one of two groups by the arc :

spotty calcification : a small calcium deposit with an arc of less than 90 degrees ;

large calcification : a calcific lesion with an arc of more than 90 degrees.

The average number of spotty calcification per patient in AMI and UAP was significantly greater than that in SAP (AMI 1.7+/−1.3, UAP 1.9+/−1.7, and SAP 0.6+/−0.8, p=0.012; AMI vs SAP, p=0.046, UAP vs SAP, p=0.030). The average number of large calcification per patient in AMI was significantly lower than that in SAP (AMI0.2+/−0.4, UAP 0.42+/−0.7, and SAP0.9+/−0.7; AMI vs SAP, p=0.005). Consequently, the percent of spotty calcification in each culprit lesion was higher in AMI and UAP than in SAP (AMI 87.5%, UAP 81.3%, and SAP40.1%, p<0.01). The distance between the luminal surface and the inner edge of each spotty calcification was significantly shorter in AMI and UAP than in SAP (AMI 0.18+/−0.11mm, UAP 0.15+/−0.1mm, SAP 0.30+/−0.13mm, p<0.001; AMI vs SAP, p=0.007, and UAP vs SAP, p=0.001), but that of each large calcification was not significantly different among AMI, UAP, and SAP.

[CONCLUSION] In the culprit lesions of AMI and UAP, calcium deposits more spotty in size and more close to the lumen would be observed frequently. These characteristics of the calcium deposition might play an important role in the pathogenesis of the plaque vulnerability.
Abstract 450: Phosphorylation Of Platelet αIIbβ3 Is Crucial For Arterial Thrombosis In Vivo And Microparticle Generation
Authors: Valiyaveettil Manojkumar , Feng Weiyi , Mahabaleshwar Ganapati , Phillips David , Byzova Tatiana , Podrez Eugene
Published: July 2021

Functional activity of platelet fibrinogen receptor αIIbβ3 is crucial for hemostasis and thrombosis. The process of αIIbβ3 activation in platelet aggregation is tightly regulated. It has been previously shown that β3 subunit of the complex undergo tyrosine phosphorylation, which, in turn, is believed to control recruitment of several intracellular adaptors. Mutations of Tyr747/ Tyr759 within the cytoplasmic domain of αIIbβ3 (DiYF substitution) were found to result in reversible platelet aggregation. To assess whether αIIbβ3 tyrosine phosphorylation is critical for arterial thrombosis, we utilized intravital microscopy to monitor thrombus formation in vivo in WT and DiYF mice. Compared to WT, DiYF mice exhibited delayed platelet adhesion and reduced rate of thrombus formation at the initial stages of thrombosis. Likewise, isolated DiYF platelets exhibited reduced adhesion to collagen under in vitro sheer conditions compared to WT. The progression phase of thrombosis in vivo was similar in WT and DiYF mice. The most dramatic difference was observed at the final phase of thrombus formation since it took 3-times longer for blood vessels in DiYF mice to occlude compared to WT. To specifically address the role if β3 phosphorylation in platelet αIIbβ3 vs αvβ3 on leukocytes and vascular cells, we transfused labeled WT and DiYF platelets into irradiated WT mice with low blood cells and platelet counts. It was found that transfusion of DiYF but not WT platelets resulted in reversal of the thrombotic phenotype and significantly prolonged blood vessel occlusion time in vivo. Similar differences were observed in tail bleeding test. Importantly, we have found that the lack of β3 phosphorylation impaired an ability of platelets to generate microparticles in response to activation, an event believed to be critical for the final stages of thrombosis. When stimulated with thrombin and PMA, DiYF platelets shed ~50% less Annexin V-positive microparticles as compared to WT platelets. Thus, β3 tyrosine phosphorylation of αIIbβ3 in platelets is crucial for the microparticles generation by activated platelets and the overall process of arterial thrombosis in vivo.
Abstract 451: Platelet Activation and Thrombosis by Antibodies against VEGF and CD40 Ligand: Extending the mechanism of HIT
Authors: Amirkhosravi Ali , Meyer Todd , Langer Florian , Robson Theresa , Robles Liza , Desai Hina , Davila Monica , Amaya Mildred , Francis John L
Published: July 2021

Introduction:
The vascular endothelial growth factor (VEGF) monoclonal antibody, bevaci-zumab (Avastin), has been associated with arterial thromboembolic events in some cancer patients. Another therapeutic antibody, hu5c8, which targets CD40L, also produced unexpected thrombosis in lupus clinical trials. Because platelets play a crucial role in arterial thrombosis, we hypothesized that antibodies against VEGF and CD40L may activate platelets via a mechanism similar to that responsible for thrombosis in Heparin-Induced Thrombocytopenia (HIT).

Methods:
Immune complexes (ICs) were prepared by combining these monoclonal IgG antibodies with their antigens: M90 (or hu5c8) with CD40L (“M90+CD40L”), or bevacizumab with VEGF and heparin (“BVH”). VEGF binds heparin (as does platelet factor 4, the HIT antigen). We measured platelet activation by serotonin release assay, platelet aggregometry, and flow cytometry. We also evaluated IC-induced thrombosis in hFc mice, transgenic for the human IgG receptor, CD32.

Results:
Similar to HIT antibodies, these ICs potently induced platelet activation dependent on CD32, IC concentration (>10nM) and optimal stoichiometry. Intravenous injection of M90+CD40L or BVH into hFc, but not wild-type mice rapidly produced signs of thrombotic shock, thrombocytopenia and pulmonary thrombosis. However, wild-type control mice (lacking platelet CD32) were unaffected by IC injection. Similarly as with HIT antibodies, bevacizumab IC activity was reduced in the absence or excess of heparin both
in vitro
and
in vivo,
whilst M90+CD40L-induced platelet activation was abolished
in vitro
by blockade of the platelet CD40L receptor, CD40, demonstrating a requirement for Fab-dependent anchoring. Furthermore, VEGF
121
(which lacks the heparin-binding domain of VEGF
165
) and bevacizumab with or without heparin failed to activate platelets or cause thrombosis in hFc mice.

Conclusions:
Together, these findings demonstrate that Fab-dependent anchoring of anti-CD40L and anti-VEGF ICs is required for potent platelet activation and thrombosis, as is the case in HIT, suggesting common mechanistic elements. Clinical implications may apply in patients with cardiovascular comorbidity receiving immunotherapy.
Abstract 3330: Effect of Achieved Low-density Lipoprotein Cholesterol Level by Atorvastatin on Stabilization of Coronary Plaques - Results from TWINS study
Authors: Okada Katsuki , Ueda Yasunori , Saito Satoshi , Hirayama Atsushi , Kodama Kazuhisa
Published: July 2021

Background
We have previously reported the stabilization and regression of coronary plaque by atorvastatin using both angioscopy and IVUS. However, it has not been clarified if plaque stabilization is achieved through the reduction of cholesterol level or the direct effect of statin. Then, we analyzed the effect of achieved low-density lipoprotein (LDL) cholesterol level on the stabilization of coronary plaque.

Methods
Twenty-nine patients with hypercholesterolemia and coronary heart disease were studied. They received lipid-lowering therapy with atorvastatin (10 –20 mg/day) for 80 weeks and were divided into 2 groups by the achieved LDL cholesterol level at 80-week follow up (low LDL group: LDL cholesterol < median value, and high LDL group: LDL cholesterol ≥ median value). Angioscopic examination was performed before and after 80 weeks treatment with atorvastatin. Angioscopic findings of coronary yellow plaque characteristics were divided into six grades (grade 0 to 5) to evaluate vulnerability of plaques; and the mean grade of each patient was evaluated.

Results
In all 29 patients, LDL cholesterol level was reduced (146.2 to 87.9 mg/dl; p<0.001) and the mean yellow plaque grade was decreased (1.4 to 1.2; p=0.002) at 80-week follow up. LDL cholesterol level was reduced both in low LDL group (140.3 to 75.9 mg/dl; p<0.001) and in high LDL group (151.7 to 99.1 mg/dl; p<0.001). Angioscopic examination showed significant improvement of the grade in low LDL group (1.4 to 1.1; p=0.012) at 80-week follow up, but no significant difference in high LDL group (1.4 to 1.3; p=0.11).

Conclusions
Lipid-lowering therapy with atorvastatin stabilized coronary plaques, and this effect was larger in the patients LDL cholesterol was reduced more.
Abstract 3334: Comparison of Medical Treatment and Coronary Revascularization in Patients with Moderate Coronary Lesions and Borderline Fractional Flow Reserve Measurements
Authors: Courtis Javier , Bertrand Olivier F , Larose Eric , Nguyen Can M , Déry Jean-Pierre , Gleeton Onil , Roy Louis , Proulx Guy , Barbeau Gerald , Noël Bernard , DelaRochellière Robert , Rodés-Cabau Josep
Published: July 2021

Background.
There is little information available regarding deferral of revascularization in cases of fractional flow reserve (FFR) measurements in the borderline range (between 0.75 to 0.80). The objectives of this study were

to evaluate the clinical outcomes of patients with moderate coronary lesions and FFR measurements between 0.75 and 0.80, comparing those who underwent coronary revascularization (CR) to those who had medical treatment (MT), and

to determine the predictive factors of major adverse cardiac events (MACE) at follow-up.

Methods.
A total of 107 consecutive patients (mean age 62 ± 10 years) with at least one moderate coronary lesion (mean percent diameter stenosis 47 ± 12%) evaluated by coronary pressure wire with FFR measurement between 0.75 and 0.80 (mean 0.77 ± 0.02) were included in the study. Maximal hyperemia was obtained by intracoronary administration of adenosine (mean dose 215 ± 84 μg). MACE (coronary revascularization, myocardial infarction, cardiac death) and the presence of angina were evaluated at follow-up.

Results.
A total of 63 patients (59%) underwent CR and 44 patients (41%) had MT, with no clinical differences between groups. At a mean follow-up of 13 ± 7 months, MACE related to the coronary lesion evaluated by FFR were higher in the MT group compared to CR group (23% vs 5%, difference 18%, 95% CI 5%–30%, p=0.005). FFR measurement in an artery supplying a territory with previous myocardial infarction was the only predictive factor of MACE in the MT group (odds ratio 14.1, 95% CI 1.3–39, p=0.03). The presence of angina at follow-up was more frequent in the MT group compared to the CR group (41% vs 9%, difference 32%, 95% CI 11%–49%, p<0.001).

Conclusions.
In patients with moderate coronary lesions and FFR measurements in the “grey zone” range deferral of revascularization was associated with a higher rate of cardiac events and a higher prevalence of angina at follow-up, especially in those with previous myocardial infarction in the territory evaluated by FFR. These results suggest that a FFR cut-off point of 0.80 rather than 0.75 might be more appropriate for deferring coronary revascularization in these cases.
Abstract 3341: Human Coronary Collaterals Inversely Correlate with Indices of Ischemic Left Ventricular Diastolic Dysfunction during Coronary Balloon Occlusion.
Authors: Hoole Stephen P , White Paul A , Heck Patrick M , O’Sullivan Michael , Clarke Sarah C , Shapiro Leonard M , Schofield Peter M , Dutka David P
Published: July 2021

Background:
Coronary collaterals are thought to reduce myocardial ischemia during coronary artery occlusion. Coronary collaterals, defined angiographically, reduce end diastolic LV dilatation during coronary occlusion. However, counter to a role in reducing ischemia, they appear to be associated with an increase in LV end diastolic pressure. These changes may be explained if coronary collaterals act as an external LV scaffold. We aimed to re-evaluate this relationship by simultaneously measuring coronary collaterals and LV contractility quantitatively.

Methods:
Ten patients with normal LV function and single vessel coronary disease awaiting PCI were recruited. Collateral flow index, derived by pressure-wire measurement (CFI
p
= [P
distal (occluded)
− P
venous
] / [P
aorta
− P
venous
]) and change in LV end-diastolic pressure (LVEDP), volume (LVEDV) and Tau, measured by an LV cavity conductance catheter, were recorded simultaneously after 1 minute coronary balloon occlusion. A mean of 5 cardiac cycles was analyzed. Measurements were repeated after a recovery period of 30 minutes.

Results:
Percentage change in LVEDP and Tau inversely correlated with CFI
p
(ΔLVEDP vs. CFI
p
: y = −216.6x +63.4, r = 0.57, p=0.01; ΔTau vs. CFI
p
: y = −64.1x + 27.8, r = 0.47, p<0.05) (Figure

). There was also an inverse relationship between ΔLVEDV vs. CFI
p
(y = −8.4x + 1.5, r = 0.35, p = 0.15).

Conclusion:
Coronary collaterals inversely correlate with LV end diastolic stiffness and dilatation after 1 minute of coronary artery occlusion. This reflects a role in reducing ischemic LV diastolic dysfunction, by providing an alternative blood supply to the LV myocardium, rather than acting as an LV scaffold.
Abstract 3351: The Coronary Suction Wave in Humans Is Not Diminished by Ischemia Induced Left Ventricular Diastolic Dysfunction.
Authors: Hoole Stephen P , White Paul A , Heck Patrick M , Khan Sadia N , O’Sullivan Michael , Clarke Sarah C , Shapiro Leonard M , Schofield Peter M , Dutka David P
Published: July 2021

Background: A dominant suction wave due to ventricular relaxation has been postulated to contribute to normal coronary artery flow. We hypothesised that this wave would:

be present in diseased coronary arteries,

occur at the appropriate time in the cardiac cycle and

be diminished following coronary artery balloon occlusion due to ischemia induced diastolic LV dysfunction.

Methods: Simultaneous coronary pressure - velocity and LV pressure - volume were invasively recorded at baseline and after 1 minute coronary balloon occlusion, in 10 patients with single vessel coronary disease and normal LV function. Net coronary wave intensity (WI) = (dP/dt).(dU/dt) was calculated using MatLab software.

Results: A dominant forward pushing wave and a backward suction wave (figure

- shaded wave) were demonstrated in diseased coronary arteries. The suction wave occurred early in diastole, during active ventricular relaxation. Ischemia induced LV diastolic dysfunction was demonstrated after coronary artery occlusion (mean % Δ from baseline (SD): LV dP/dt min = −14.8 (13.8), p=0.008, LV Tau = +19.1(14.9), p = 0.011) but there was no significant change in suction WI (mean (SD): baseline = −1.35 (0.20) m
−2
s
−2
x10
5
, post-balloon occlusion −1.49(0.59) m
−2
s
−2
x10
5
, p =0.67).

Conclusion: The coronary suction wave occurs in diseased coronary arteries at the appropriate time in the cardiac cycle but is not diminished by ischemia induced diastolic left ventricular dysfunction.
Abstract 3366: Imaging of Peroxidase Activity in Injured Myocardium
Authors: Nahrendorf Matthias , Sosnovik David E , Chen John , Figueiredo Jose-Luis , Panizzi Peter , Aikawa Elena , Weissleder Ralph
Published: July 2021

Ischemic myocardial injury causes timed recruitment of neutrophils and monocyte/macrophages, which produce significant amounts of myeloperoxidase (MPO). MPO leads to the formation of reactive chlorinating species capable of oxidizing proteins. We developed a small molecule based MPO substrate for MRI, Gd-bis-5-HT-DPTA, which is first radicalized, and then oligomerized and covalently bound to matrix proteins, all leading to enhanced R1-relaxivity and delayed wash out kinetics. Mice were subjected to coronary artery ligation and injected with 0.3mmol/kg Gd-bis-5-HT-DPTA (or Gd-DTPA as control). We performed T1-weighted cardio-respiratory gated MRI 10–120min later, followed by immunoreactive staining for MPO. 3 mice each were studied at day 1, 2, 4, 8, and >1 month after MI. Subsequently, MPO tissue activity was determined with the guaiacol method. MPO activity peaked 2 days after MI (contrast-to-noise-ratio (CNR) day 1, 26+/−4; day 2, 39+/−10; day 4, 29+/−3), and tissue levels of MPO over time correlated well with probe activity in vivo (r2=0.65, p<0.01). CNR following Gd-DTPA peaked ten minutes after injection (10.5+/−0.2), and returned to pre-injection values at 60min. In contradistinction, following injection Gd-bis-5-HT-DPTA, CNR was higher and peaked later (p<0.05 vs. Gd-DTPA, arrows depict MI in figure

). Immunoreactive staining for MPO correlated well with enhancement (r2=0.92, p<0.05). Gd-bis-5-HT-DPTA facilitates in-vivo assessment of MPO activity in injured myocardium. This approach allows non-invasive probing of the inflammatory response to ischemia and has the potential to guide the development and application of novel cardioprotective therapies.
Abstract 3383: Assessment Of The Left Ventricular Long-axis And Short-axis Function Using Strain Rate Imaging In Chronic Severe Mitral Regurgitation: A Comparative Echocardiography-catheterization Study
Authors: Kim Min-Seok , Kim Dae-Hee , Kim Hyung-Kwan , Chun Hong-Gu , Suh Jung-Won , Park Jin-Shik , Chung Woo-Young , Oh Seil , Choi Dong-Ju , Sohn Dae-Won , Oh Byung-Hee , Park Young-Bae , Choi Yun-Shik , Kim Yong-Jin
Published: July 2021

Background
Assessment of the left ventricular (LV) contractile function is critical for deciding optimal timing of surgery in patients with chronic severe mitral regurgitation (MR). We investigated the LV long-axis and short-axis function in MR.

Methods
We studied 30 patients (16 men, age: 51 ± 14 years) who had 3+ or 4+ MR with LV ejection fraction (EF) greater than 50%. Comprehensive 2D and Doppler echocardiography was performed. Peak systolic radial (SR
R
), circumferential (SR
C
), and longitudinal strain rate (SR
L
) were measured using speckle tracking imaging. In all patients, peak dP/dt was measured using micromanometer-tipped catheter.

Results
Mean LVEF was 63.1% and regurgitation fraction was 61.8%. LV end-systolic volume was 78.3 ml. Peak dP/dt ranged from 1019 to 2049 mmHg/sec with the mean value of 1583 mmHg/sec. 16 patients (53.3%) showed latent systolic dysfunction defined by peak dP/dt less than 1300 mmHg/s. SR
R
and SR
C
correlated well with peak dP/dt (Fig. A

, r=0.74, p< 0.01, r=− 0.54, p<0.01, respectively). However, SR
L
did not correlate with peak dP/dt (r=− 0.58, p=0.76). SR
R
> 1.94 S
−1
showed a sensitivity of 86 % and a specificity of 75 % for predicting latent LV systolic function (Fig. B

, AUC=0.87, CI=0.732– 0.991). SR
R
also correlated with LV end-diastolic and end-systolic sphericity index (r=− 0.54, p<0.01, r=− 0.66, p< 0.01, respectively).

Conclusion
SR
R
and SR
C
, not SR
L
, correlated well with peak LV dP/dt. These results imply the importance of short-axis function in the presence of chronic severe MR, probably due to the geometrical change in response to chronic volume overload.
Abstract 3390: Marginal Overlap between Electrocardiographic Abnormalities in Patients with Hypertrophic Cardiomyopathy and Trained Athletes: Implications for Preparticipation Screening
Authors: Melacini Paola , Cianfrocca Cinzia , Calore Chiara , Bovolato Francesca , Di Paolo Fernando , Quattrini Filippo , Pelliccia Francesco , Sharma Sanjay , McKenna William J , Maron Barry J , Pelliccia Antonio , Corrado Domenico
Published: July 2021

Background: Hypertrophic cardiomyopathy (HCM) is usually associated with ECG abnormalities such as left ventricular hypertrophy (LVH), repolarization changes, and pathologic Q waves; instead, physiologic hypertrophy in trained athletes manifests as an isolated increase of QRS amplitude. We assessed whether the ECG pattern of pathologic hypertrophy of HCM overlaps with that of physiologic hypertrophy of athlete’s heart, particularly by evaluating what proportion of individuals from both groups had pure QRS voltage criteria (Sokolow-Lyon) for LVH.

Methods: Using accepted diagnostic criteria, we examined and compared the ECG tracings of 260 consecutive patients with clinical and echocardiographic diagnosis of HCM and those of 1005 trained athletes undergoing preparticipation cardiovascular evaluation, including ECG and echocardiography.

Results: An abnormal ECG was found in 246 of 260 (94.6%) patients with HCM and in 817 of 1005 athletes (81.3%). The majority of patients with HCM had one or more of the following ECG changes: repolarization ST/T abnormalities in 209 (80%), pathologic Q waves (Q waves ≥0.04 s in duration or ≥25% of the height of the ensuing R wave) in 103 (39.6%); left atrial enlargement in 75 (28.8%), intraventricular conduction abnormalities (QRS duration ≥90 ms) in 71 (27.3%) and left axis deviation in 9 (3.5%). ECG tracings showed isolated increase of QRS voltages in 5 HCM patients (1.9%) and were completely normal in 14 (5.4%). Compared with patients with HCM, trained athletes significantly more often had isolated voltage criteria for LVH (403, 40%; p<0.0001), but less often showed negative T waves (27, 2.7%; p<0.0001), pathologic Q waves (17, 1.7%; p<0.0001), and nonvoltage criteria of LVH (13, 1.3%; p<0.0001). No athletes with isolated voltage criteria had echocardiographic evidence of HCM.

Conclusions: ECG in HCM overlaps marginally with ECG findings in trained athletes. An isolated increase of QRS voltage is an unusual pattern (1.9%) of LVH in patients with HCM, while is frequently observed in trained athletes. Systematic echocardiographic evaluation of athletes fulfilling isolated QRS voltage criteria at preparticipation screening is not justified, resulting in a considerable cost savings.
Abstract 3398: Comparison of Once Versus Twice a Day Valsartan Dosing in Heart Failure -Results of the DESTINY Trial
Authors: Anand Inder S , Deswal Anita , Kereiakes Dean J , Steljes Alan , Zappe Dion H , Daley William L
Published: July 2021

Background.
Valsartan causes a sustained 24-hour reduction in blood pressure (BP) in hypertensive patients, when given once a day (q.d.). Because many CHF patients have low baseline BP and concomitant chronic kidney disease, valsartan was prescribed twice a day (b.i.d.) in Val-HeFT (Valsartan in Heart Failure Trial) to avoid any possible adverse effects like symptomatic hypotension and worsening renal dysfunction with the q.d. dosing.

Methods and Results.
DESTINY-HF (
D
iovan
E
valuation of
S
afety
T
w
I
ce vs o
N
ce dail
Y
study in
H
eart
F
ailure) was a 10-week double blind randomized trial designed to test the safety of q.d. (n=55) vs b.i.d. (n=60) dosing of valsartan in patients with NYHA class II–III heart failure receiving diuretics (87%), ACE-I (98%), beta-blockers (92%), aldosterone antagonists (25%) and digoxin (32%) over a 12-week period. Valsartan was started in the dose of 40 mg b.i.d. vs 80 mg q.d. and titrated to a maximum of 320 mg per day by doubling the dose every 2 weeks. Clinical and biochemical measurements were made at 2, 4, 6, and 10 weeks. The baseline characteristics of the two groups were similar. The average dose of valsartan at the end of study was 245 mg vs 256 mg in the bid vs qd dose groups (p=NS). The % of patients who tolerated the up-titration regimen at week 2, 4 and 6 and at the end of study were not significantly different between the dose groups (b.i.d. vs q.d., 75 vs 75, 74 vs 85, 77 vs 78, and 67 vs 68; p=NS). There was no difference in the reduction of systolic or diastolic BP, or in the incidence of hypotension, renal impairment, orthostatic dizziness or syncope between the groups at any time point. Changes in serum K
+
, creatinine, cystatin-C, and estimated GFR were also not different between the groups at any time point. Brain natriuretic peptide decreased, and by the same amount in both groups at all time points.

Conclusions.
These data demonstrate that the use of valsartan in q.d. dosing has the same safety profile as b.i.d. dosing in patients with moderate to severe heart failure.
Abstract 3406: Plaque Characterization Using Different X-ray Energy By Dual Source CT And Its Comparison With Histology
Authors: Komatsu Sei , Kuhlmann Alexander , Campean Valentine , Ropers Dieter , Ropers Ulrike , Wechsel Martin , Daniel Werner G , Amann Kerstin U , Achenbach Stephan
Published: July 2021

Background In addition to high spatial (0.4 mm) and temporal resolution (83 ms), Dual Source CT (DSCT) allows simultaneous imaging with two different x-ray energies. This may be beneficial for tissue characterization.

Objectives. To determine the accuracy of ex vivo atherosclerotic plaque characterization with DSCT and to assess the CT attenuation of various plaque components depending on X-ray energy.

Materials and Methods. 18 atherosclerotic vessels of coronary, carotid and iliac arteries obatined from autopsy were analyzed by DSCT. Each lumen of the vessels was filled with contrast media (30X Imeron 350). The collimation was 2X64X0.6 mm, rotation time was 330 msec., temporal resolution was 83 msec. Data sets were obtained using a tube voltage of 80, 100, 120, and 140 kV. The x.-ray attenuation of lipid-rich plaque, fibrous plaque, calcified plaque and contrast-enhanced lumen were determined for all x-ray energies by comparison to histology at 25 sites. In addition, cross-sectional images were reconstructed with 0.75 mm slice thickness and 0.4 mm increment. 26 slices at 10 mm interval were analyzed by comprehensive color-coding according to CT number.

Results. There were significant differences among CT attenuations of lipid-rich, fibrous and calcified plaque using 80, 100, 120, and 140 kV (Table

, p<0.01), respectively. The averaged ratio of CT attenuation of lipid-rich, fibrous plaque, and calcified plaque to the Contrast-enhanced lumen for 80kV and 140kV were −16%, 11%, 14%, respectively (p<0.05). Lipid-rich plaque was well-differentiated with lumen attenuation in all energies.

Conclusions. The relationships between lumen enhancement and each plaque component were different as changing the x-ray energy level. Using of varying x-ray energy, DSCT may able to detect atherosclerotic plaque and characterization of plaque components.

The Attenuation on Different Energy
Abstract 3412: Prognostic Value of Non-Obstructive CT low-dense Coronary Artery Plaques Detected by Multislice Computed Tomography
Authors: Kunimasa Taeko , Sato Yuichi , Matsumoto Naoya , Nakano Yoshimochi , Yoda Shunichi , Kanai Takashi , Tani Shigemasa , Kunimoto Satoshi , Saito Satoshi , Hirayama Atsushi
Published: July 2021

Background:
The prognostic value of non-obstructive, CT low-dense plaques (CTLDP) on multislice computed tomography (MSCT) for the prediction of nonfatal acute myocardial infarction (AMI), unstable angina and cardiac death has not yet been defined.

Methods and Results:
We identified 760 patients who underwent MSCT and had non-obstructive coronary artery disease were followed up for the occurrence of AMI, unstable angina and cardiac death. Non-obstructive CTLDP were defined as plaques with the CT density <68 Hounsfield unit, which accompanied by mild to moderate coronary artery stenosis (25–75%). Patients were followed-up for the occurrence of

acute coronary syndrome (ACS) including nonfatal AMI and unstable angina, and

cardiac death for 1060 ± 539 days. CTLDP were detected in 189 patients (24.9 %).

The annual event rate of AMI, unstable angina, ACS and cardiac death was 0.94 %, 1.13 %, 2.08 % and 0.37 %, respectively in patients with CTLDP and 0.05 %, 0.64%, 0.70 % and 0.23 %, respectively in patients without CTLDP. The event rate of ACS was significantly higher in patients with CTLDP than in those without CTLDP (p=0.002). Univariate Cox regression analysis disclosed that the presence of CTLDP is an independent predictor of the occurrence of ACS.

Conclusion:
Non-obstructive CTLDP detected by MSCT yield prognostic information toward the identification of ACS.

Figure:

Kaplan-Meyer curves for the ACS-free survival
Abstract 3418: Infarct-Related Myocardial Edema Detected by Diffusion-Weighted Imaging; Comparison with T2-Weighted imaging
Authors: Okayama Satoshi , Uemura Shiro , Onoue Kenji , Takemoto Yasuhiro , Somekawa Satoshi , Ishigami Ken-ichi , Takeda Yukiji , Kawata Hiroyuki , Horii Manabu , Nakajima Tamio , Saito Yoshihiko
Published: July 2021

Background:
Cardiac MRI permits diagnosis with acute myocardial infarction (AMI) by detection of infarct-related myocardial edema (IRME) on black-blood T2-weighted images (T2WIs), and myocardial scar on delayed-enhanced images (DEs). Diffusion-weighted image (DWI) is an established method for detection of cerebral infarction edema, but few reports are available on detection of IRME.

Objective:
To detect IRME using DWIs, and compare the contrast-to-noise ratio (CNR) with T2WIs.

Methods:
Cardiac MRI was performed on a 1.5T scanner (SIEMENS Avanto, Erlangen, Germany) in 12 AMI patients within 14 days after successful reperfusion. T2WIs were acquired using a double inversion-recovery fast-spin echo sequence. DWIs were acquired using combined cardiac and respiratory gated single-shot echo-planar sequence with a b-value of 50 s/mm
2
. DEs were acquired using an inversion-recovery segmented gradient-echo sequence, fifteen minutes after administering 0.15 mmol/kg gadolinium-DTPA. CNR was calculated in the T2WIs and DWIs using the following formula: CNR = (signal intensity[ME]-signal intensity[M]) / SD(B), where ME = myocardial edema, M = myocardium, and SD(B) =standard deviation of background signal intensity.

Results:
IRME was detected on T2WIs, and myocardial scar on DEs in all patients. DWIs revealed an area of significantly increased signal intensity in the same region identified as IRME on T2WIs in all patients. The CNR of DWIs (78.9 ± 44.5) was significantly higher than those of T2WIs (31.5 ± 23.3) (p = 0.0001).

Conclusion:
Our findings indicate that low b-value DWI provides better contrast in infarct-related myocardial edema than T2WIs.
Abstract 3429: Amlodipine Improves Endothelial Function and Metabolic Parameters in Patients with Hypertension
Authors: Koh Kwang K , Quon Michael J , Han Seung H , Chung Wook-Jin
Published: July 2021

Background

: Reciprocal relationships between endothelial dysfunction and insulin resistance imply that improvement in endothelial dysfunction will have beneficial metabolic consequences. We hypothesized that amlodipine therapy will improve endothelial dysfunction and metabolic parameters in hypertensive subjects.

Methods

: Amlodipine (10 mg daily for 8 weeks) or placebo was given to each 45 patients with mild to moderate hypertension in a randomized, double-blind, placebo-controlled, and paralleled study. Age, sex, and body mass index were matched.

Results

: Amlodipine therapy significantly reduced systolic and diastolic blood pressure and increased HDL-cholesterol to greater extent than placebo therapy (all
P<
0.001). Amlodipine therapy significantly improved flow-mediated dilator response to hyperemia and reduced plasma malondialdehyde levels to greater extent than placebo therapy (
P<
0.001 and
P
=0.035). Amlodipine therapy significantly increased plasma adiponectin levels (
P
=0.009) and decreased plasma leptin and resistin levels (
P<
0.001 and
P
=0.025, respectively) to greater extent than placebo therapy. Correlations were noted between percent changes in adiponectin levels and percent changes in HDL-cholesterol (
r
=0.348,
P
=0.019) and QUICKI (
r
=0.326,
P
=0.029) following amlodipine therapy. Only changes in HDL-cholesterol (β = 0.469,
P
= 0.019) and QUICKI (β = 1.786,
P
= 0.069) were independent predictors of changes in adiponectin levels (multivariate regression analysis). We also observed inverse correlations between percent changes in leptin levels and percent changes in QUICKI (
r
= −0.569,
P<
0.001) following amlodipine therapy with changes in QUICKI (β = 1.810,
P <
0.001) as an independent predictor of changes in leptin levels.

Conclusions

: Amlodipine therapy improves blood pressure, endothelial function, and metabolic parameters in patients with hypertension.
Abstract 3434: Novel Predictors of Functional Capacity in Peripheral Arterial Disease
Authors: Anderson Justin D , Epstein Frederick H , Meyer Craig H , Hagspiel Klaus D , Wang Hongkun , Berr Stuart S , Harthun Nancy L , Weltman Arthur L , Isbell David C , Norton Patrick T , Kramer Christopher M
Published: July 2021

Introduction
The relationship between limb hemodynamics and walking capacity in PAD is inconsistent. More precise predictive measures of functional capacity in PAD are needed.

Methods
Sixty-two patients with mild-to-moderate symptomatic PAD (35 M, mean age ± SD 65 ± 11 years, ABI 0.68 ± 0.13) underwent a Skinner-Gardner exercise treadmill test. Total treadmill time (TTT), time to claudication (TTC) and VO2max were measured. Six minute walk distance (6WD) was recorded. A runoff contrast-enhanced magnetic resonance angiogram was segmentally scored (MRAi) by number and degree of arterial stenoses distal to the aorta. Black blood MRI of the superficial femoral artery measured % plaque volume (%PV) as the ratio of plaque volume to total vessel volume. Calf muscle perfusion index (PI) was measured at peak exercise using an MRI-compatible pedal ergometer and first pass gadolinium-enhanced MRI and defined as the ratio of slopes of calf muscle perfusion to arterial input.
31
Phosphorus MR spectroscopy measured calf muscle phosphocreatine recovery time constant (PCr) immediately after exercise. Pearson correlation coefficients were measured between imaging and functional parameters. The bivariate relationship between them were tested using F-tests and stepwise linear regression models.

Results
Mean TTT was 517 ± 362s, TTC 130 ± 50s, VO2max 12.6 ± 4.2, 6WD 1028 ± 391ft. See Table

. By stepwise linear regression, independent predictors of TTT were ABI (r
2
=0.12, p<0.01) and PCr (r
2
=0.09, p<0.03). Independent predictors of V02max were %PV (r
2
=0.24, p=0.0001), MRAi (r
2
=0.20, p<0.001), and ABI (r
2
=0.11, p<0.02).

Conclusions
The ABI, MRAi, %PV, and PCr correlate with TTT while all but PCr correlate with V02. No measured parameter correlates with 6WD. TTT is predicted by both ABI and calf muscle metabolism, whereas V02max is predicted by ABI and plaque burden. Thus, functional capacity in PAD is determined in part by flow, but metabolism and plaque burden play a significant role.

Correlations Between Imaging and Functional Parameters
Abstract 3435: GeneChip Analyses Identify Bone Marrow Cells as a Rich Source of Paracrine Factors: Insight From the BOOST Study Program
Authors: Korf-Klingebiel Mortimer , Sauer Thomas , Kempf Tibor , Drexler Helmut , Wollert Kai C
Published: July 2021

It has been hypothesized that the improvement of left ventricular function observed after intracoronary bone marrow cell (BMC) transfer in patients with STEMI is related in part to paracrine effects. RNA was prepared from BMC that were obtained from patients with STEMI (n=3) included in the ongoing multicenter BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST)-2 trial. Peripheral blood leukocyte (PBL) RNA was obtained from the same 3 patients. GeneChip analyses (Affymetrix HG-U133 Plus 2.0, ca. 47000 probe sets) were performed to characterize the transcriptome in BMC vs. PBL. Using GeneSpring software 7.2, we identified 56 secreted factors that were more strongly expressed (>2-fold) in BMC as compared to PBL. In a second microarray (RNA from n=3 additional patients), 41 of these factors were confirmed. Twelve of these 41 factors were chosen for independent validation by real-time PCR using RNA from 6 additional patients; overexpression in BMC vs. PBL was confirmed for each of these 12 factors. Several factors overexpressed in BMC represented putative cardioprotective cytokines (e.g., BMP-2, CT-1, IGF-1, SDF-1α, VEGF-A). BMC from 7 additional patients were cultured for 24h in serum-free DMEM medium. Conditioned supernatants (SN) were filtered and pooled. BMC-SN (10μL/mL) reduced apoptotic cell death in neonatal rat ventricular cardiomyocytes exposed to simulated ischemia (3h) and reperfusion (1h), as shown by TUNEL (62 ± 7% vs. control, i.e. treatment with unconditioned DMEM medium; n=7; P<0.05) and histone-ELISA (69 ± 12% vs. control; n=5; P<0.05). Moreover, BMC-SN stimulated human umbilical vein endothelial cell (HUVEC) migration (transwell chambers; 293 ± 55% vs. control; n=5; P<0.01) and in-matrigel tube formation (tubular length, 275 ± 35% vs. control; n=5; P<0.05; tube/branch point ratio, 156 ± 10% vs. control; n=5; P<0.05). Finally, BMC-SN promoted enhanced endothelial cell sprouting in the mouse aortic ring assay ex vivo. In conclusion, BMC obtained from patients with STEMI are a rich source of secreted factors. Conditioned BMC supernatants protect cardiomyocytes from I/R-induced apoptosis, and promote pro-angiogenic effects in vitro. Our data tend to support the paracrine hypothesis.
Abstract 3447: Prevalence of PAD Varies Significantly Depending on the Method of Calculating Ankle Brachial Index: Results from the National Health and Nutrition Examination Survey (1999–2004)
Authors: Reed James , Eid Sherrine , Parks Allison , Edris Bree , Sumner Andrew D
Published: July 2021

Background:
Peripheral artery disease (PAD), a marker of subclinical coronary artery disease, is associated with increased morbidity and mortality. PAD is diagnosed by calculating the ankle brachial index (ABI). There exist different methods of calculating the ABI. The effects of various methods of calculating ABI on PAD prevalence is unknown.

Methods:
We analyzed data from three National Health and Nutrition Examination Surveys (NHANES) between the years 1999 –2004. The prevalence of PAD using three different methods of calculating ABI was determined in 5,376 participants, age 40 years and older with no prior history of cardiovascular disease . ABI, defined as an ankle-brachial index <0.9, was determined using the NHANES method, HAP method, and LAP method (TABLE 1

). Statistical analysis was performed using SPSS V15.0.

Results:
The prevalence of PAD among asymptomatic adults without CVD increased significantly during the six year time period 1999 –2004 regardless of the method used to determine ABI (TABLE 1

). Across the 3 NHANES assessments, the ABI method used significantly affected calculated PAD prevalence (TABLE 1

). The resulting differences in calculated PAD prevalence corresponds to approximately 2.2 million persons who would be reclassified as having or not having PAD based on type of ABI method.

Conclusions: This study demonstrates that the calculated prevalence of asymptomatic PAD in a nationally representative sample of the United States population varies significantly by the ABI method. Further study is required to determine the most accurate method of performing ABI.

TABLE 1:

NHANES Method: ABI of right or left side =mean SBP (mm Hg) of the right or left ankle/ mean of the two brachial SBP (mm Hg). HAP Method: ABI of right or left side =higher of the right or left ankle SBP (mm Hg)/ higher of the two brachial SBP (mmHg). LAP Method: ABI of right or left side =lower of the right or left ankle SBP (mm Hg)/ higher of the two brachial SBP (mm Hg).