bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4632: Left Atrial Size and Advancing Age Predict the Need to Restart Drug Therapy after AF Ablation to Maintain AF Control
Authors: Harding John , Zado Erica , Hutchinson Mathew , Riley Michael , Bala Rupa , Garcia Fermin , Lin David , Cooper Joshua , Dixit Sanjay , Verdino Ralph , Gerstenfeld Edward , Russo Andrea , Callans David , Marchlinski Francis
Published: July 2021

Background
: While many patients (pts) remain free of atrial fibrillation (AF) without anti-arrhythmic drug(AAD) therapy after ablation, some pts require re-initiation of medications to control AF long-term. Factors associated with need for reinstituting AAD have not been identified.

Methods:
A total of 578 pts who underwent AF ablation and demonstrated AF control for at least 12months were included in this study. The ablation included proximal pulmonary vein (PV) isolation with entry and exit block and elimination of non PV triggers. AAD were reinitiated if with ECG documented AF recurrence after the 2 month blanking period. Confirmation of AF control was based on symptoms and transtelephonic ECG monitoring at 6 mos, 12 mos, and with symptoms. Clinical variables were compared between each group by univariate analysis to determine if significant differences existed. Significant parameters were included in a multivariate analysis to determine interaction between variables.

Results:
Table 1

delineates clinical parameters included in the analysis, with unadjusted P values for each variable. Multivariate analysis with forward and backward regression identified larger LA size and advancing age as only factors which correlated with the need for AAD therapy after ablation to maintain AF control.

Conclusions:
Increased LA size and advancing age are clinical parameters which suggest progressive fibrosis of the LA. In our analysis, these two variables strongly predicted the need to restart AAD therapy after proximal PV ablation and elimination of non PV triggers in order to maintain long-term control of AF.

Table 1
Abstract 4651: Local Bipolar Electrogram-Based Criteria to Evaluate the Transmurality of the Atrial Ablation Lesion
Authors: Otomo Kiyoshi , Uno Kikuya , Iesaka Yoshito
Published: July 2021

It is important to recognize whether a transmural lesion (TL) was created by ablation in each ablation site during atrial ablation procedures. The local bipolar atrial electrogram (LBAE)-based criteria to diagnose TL formation, however, remain to be established. This study was performed to define LBAE-based criteria for local TL formation. In 13 anesthetized adult porcines, point-by-point radiofrequency energy applications (30W/55°C/30sec) were performed using a conventional 4-mm tip ablation catheter in the atria (right/left3150/91 sites) during sinus rhythm. After the ablation procedure, the hearts were extracted and the ablation lesions were macroscopically identified. The hearts were fixed with formalin, and each section (0.5 mm interval) was stained with Masson’s trichrome stain and examined under light microscopy. Histopathological examination revealed TLs in 111 and non-transmural lesions (NTLs) in the remaining 130 sites. The LBAEs recorded from the TLs exhibited predominant attenuation in the positive deflection with a morphological change to the QS, Qr or rS pattern, while those recorded from the NTLs exhibited the RS or QR pattern without an abbreviation of the positive deflection (ratio of the amplitude of the positive (Ap) and negative deflection (An) after ablation (=Ap/An) in the TL vs NTL: 0.2±0.3 vs 0.9±1.0; P<0.0001, the Ap after ablation in the TL vs NTL: 0.07±0.6 mV vs 0.5±0.4 mV; P <0.0001). The percent reduction in the Ap (Rp), An (Rn) and total amplitude (Rt) after ablation was significantly larger in the TLs than in the NTLs (Rp:94±6% vs 48±30%; P<0.0001, Rn: 25±48% vs 14±41%; P=0.04, Rt:65±24% vs 35±25%; P<0.0001). A cut-off value of Rp≥80% best discriminated the TL from the NTL with a sensitivity, specificity and positive and negative predictive values of 100%, 85%, 84% and 100%, respectively. The cut-off value of the Rp≥80% with the morphological change of the LBAE to the QS, Qr or rS pattern could discriminate the TLs from the NTLs with high accuracy. This criterion can be one of the practical endpoints for energy delivery at each ablation site during ablation procedures.
Abstract 4660: Death Due to Pacemaker or ICD Device Failure is Rare: Implications for the Management of Recalls
Authors: Hauser Robert G , Hayes David L , Cannom David S , Epstein Andrew E , Vlay Stephen C , Tyers G. Frank O , Song Susan L , Kallinen Linda
Published: July 2021

Knowledge of major adverse clinical events (MACE) associated with ICD and pacemaker (PM) pulse generator (PG) and lead performance may be important for managing patients who have these devices. The aim of our study was to assess MACE in our Multicenter Registry. Participating centers prospectively reported ICD and PM PG and lead failures, and PG replaced for normal battery depletion (NBD). Data included dates of implant and removal, failure signs including the elective replacement indicator (ERI), clinical consequences, and reason for removal. MACE were death, inappropriate shocks (IAS), syncope, heart failure, ischemia, sustained tachyarrhythmias, and replacement of a normally functioning PG or lead due to a manufacturers recall. Since 1998, 6,291 ICD and PM PG and leads were removed from service. Of 5,212 ICD and PM PGs, 4,562 (88%) were removed for NBD, 346 (7%) for a recall, and 304 (5%) for component defects. MACE are shown in the Table

. The deaths (n=2) were due to component defects causing an ICD PG to short-circuit and a PM PG to deliver high rate pacing. Thus, of the 304 component defects in our database, 2 resulted in death (0.7%). No deaths were associated with ICD or PM lead failure, but 2 deaths occurred following PM lead extraction. The ERI, signifying NBD, resulted in 48 MACE, primarily syncope (67%). Most MACE are due to replacement of normally functioning recalled devices. However, our experience suggests that death due to ICD and PM PG component or lead failure is rare; this finding may be important for managing patients who have recalled devices. Overall, MACE may be substantially reduced by improving high voltage lead reliability, and by providing physiologic ERIs.
Abstract 4666: Anatomic Substrate as Determinant of Dominant Frequency Dynamics During Human Ventricular Fibrillation
Authors: Umapathy Karthikeyan , Masse Stephane , Sevaptsidis Elias , Asta John , Farid Talha , Shokrollahi Elnaz , Nair Krishnakumar , Ross Heather , Yau Terry , Cusimano Robert , Krishnan Sridhar , Nanthakumar Kumaraswamy
Published: July 2021

Background: Dominant frequency (DF) analysis is a common way of quantitatively studying the spatio-temporal variation of frequency during VF. Areas of high frequencies (e.g. rotors) and low frequencies (e.g. blocks) have been associated with the occurrence and maintenance of VF. However, the relation of these high or low frequency areas to anatomical or physiological substrate remains unclear. Objective: We tested the hypothesis that the Max-Min DF locations in the epicardium during VF are due to anatomical substrate.

Methods and Results: We analyzed 33, 4 seconds VF episodes acquired from 6 isolated human hearts using a Langendorff setup. The hearts were received from the heart-transplanted patients with informed consent. Electrode array consisting 112 bipolar electrodes was used to acquire the surface unipolar and bipolar electrograms from the epicardium. DF was computed as the peak frequency of the VF segment from each of electrodes using Welch’s modified periodogram method. From the DF distribution, the regions of max and min frequencies were identified for LV and RV regions. Scar maps were computed for each of the 6 hearts using a previously published method by mapping the amplitude of bipolar electrograms (<0.5mv = scar) during the pacing protocol. The areas of max-min DF frequencies in each of the VF episode were compared to the corresponding spatial locations in the scar map. Table 1

shows the match between the max-min DF frequency locations and the scar locations. 50% of max-min DF frequencies locations match the scar locations and in 97% of the matched locations the max-min DF occur at the vicinity of the scar.

Conclusion: During human VF, DF dynamics are only partially explained by the anatomical substrate. This suggests that ion channel heterogeneity and dynamic physiological factors may play an important role in determining fibrillation dynamics.

Match Between Max-Min DF locations and Scar Locations
Abstract 4686: Noncontrast Three Dimensional Dark Blood Magnetic Resonance Imaging in Adult Congenital Heart Disease Patients After Transcatheter Intervention
Authors: Winner Marshall W , Raman Subha V , Simonetti Orlando P , Chung Yiu-Cho , Arnott Lindsay , Mihai Georgeta , Cook Stephen C
Published: July 2021

Background
: Adults with congenital heart disease (ACHD) often require transcatheter therapies as a result of residual lesions. CT is well-suited for evaluation of stents but exposes young adults to radiation. Gradient echo MRI suffers from artifact limiting assessment of stented segments. We investigate the use of a novel 3D turbo spin echo (TSE) MRI sequence in these patients.

Methods:
ACHD patients presenting for MRI with prior interventions underwent an additional T1-weighted 3D dark blood navigator respiratory gated TSE scan on a1.5 Tesla system. Type of CHD, prior CT, radiation dose, length of time between examinations, and luminal diameters on each study were obtained. Continuous variables analyzed using Student’s t-test and Bland-Altman plots.

Results:
Eleven patients underwent both MRI and CT. Diagnoses were coarctation of the aorta (n=6) and tetralogy of Fallot (n=5) with intervention in the aorta or pulmonary arteries respectively. Average radiation dose was 19.57mSv; average time between CT and MRI was 99 ± 160 days. Luminal diameters of stented vessels correlated closely between TSE MRI and CT (r
2
= .85) with a small bias toward overestimation with MRI (mean 22.4 +/− 4.3 mm and 20.9 +/− 3.7 mm, p< .01). There were no cases of in-stent stenosis demonstrated by CT.

Conclusion:
Metallic artifact is significantly reduced with 3D navigator respiratory gated TSE MRI allowing visualization of anatomy in the vicinity of stents, providing a potential method for assessment of complex anatomy without radiation exposure or use of contrast agents. Further studies of this technique are warranted, particularly in patients with in-stent stenosis.
Abstract 4688: The Impact of Marfan Syndrome on Arterial Stiffness and Endothelial Function: The Role of Matrix Metalloproteinases
Authors: Brilli Stella , Tousoulis Dimitris , Antoniades Charalambos , Hatzis George , Ioakeimidis Nikos , Vlachopoulos Charalambos , Papazoglou Georgia , Papageorgiou Nikos , Stefanadi Elli , Stefanadis Christodoulos
Published: July 2021

Background: Marfan syndrome is characterised by high risk of aortic dissections and increased cardiovascular risk. However, the impact of Marfan syndrome on endothelial function and arterial stiffness is unclear, while the role of matrix metalloproteinases is unknown. We examined the impact of Marfan syndrome on the elastic properties of the arterial tree, and vascular endothelial function, and we evaluated the potential role of matrix metalloproteinases in these effects.

Methods: The study population consisted of 17 subjects with Marfan syndrome, aged 26.6±2.3 years old, with BMI 20.5±1.03Kg/m2 and 22 healthy individuals matched for gender, age (26.4±0.78 years old, p=NS) and BMI (22.4±0.86 Kg/m2). Arterial stiffness was evaluated by measuring carotid-femoral pulse wave velocity (PWV), while augmentation pressure and augmentation index (AIx) were also determined, as measures of arterial wave reflections. Endothelial function was evaluated by determining flow mediated dilation (FMD) in the brachial artery while matrix metalloproteinase 9 (MMP-9) levels were determined by ELISA.

Results: Patients with Marfan syndrome had significantly lower pulse pressure in the radial artery (41.0±1.07mmHg) compared to controls (51.3±4.4mmHg). In addition, patients had higher AIx (17.6±2.4%) and augmentation pressure (5.44±0.65mmHg) compared to controls (7.72±3.43% and 2.41±1.14mmHg respectively, p<0.05 for both). However, the difference in PWV between patients and controls did not reach statistical significance (6.33±0.33 vs 5.96±0.23m/s respectively, p=NS). Patients with Marfan syndrome had lower FMD (2.05±1.13%) and higher plasma MMP-9 (827±70ng/ml) compared to controls (6.8±2.3% p<0.05 and 326±50ng/ml, p<0.01).

Conclusions: Marfan syndrome is associated with increased MMP-9 levels, as well as with elevated augmentation index and augmentation pressure compared to healthy individuals, matched for age, gender and body mass index. Moreover, flow-mediated dilation is also impaired in these subjects. These findings suggest that Marfan syndrome directly affects the elastic properties and endothelial function of the arterial tree, with matrix metalloproteinases being important mediators in the pathophysiology of this syndrome.
Abstract 4693: Osteoporosis Treatment Associated with Decreased Progression of Aortic Stenosis
Authors: Skolnick Adam H , Osranek Martin , Formica Phillip , Kronzon Itzhak
Published: July 2021

A decline in bone mineral density has been reported to be associated with progression of aortic stenosis (AS). We hypothesized that osteoporosis treatment (OT) is associated with decreased progression of AS. We performed a retrospective chart review of patients with mild and moderate aortic stenosis from our echocardiographic database comparing 18 patients on OT (bisphosphonates, calcitonin or estrogen receptor modulators) to 37 patients not on OT. All patients had serial echocardiograms. Patients with mitral stenosis, aortic valve replacement, renal failure, calcium disorders, or LVEF<40% were excluded. Aortic valve area (AVA) was calculated using the continuity equation. There was no significant difference in age (mean of 82 years), gender (76% female), renal function, hypertension, statin use, diabetes or calcium level between the two groups. The mean baseline aortic valve area was 1.33 cm
2
and was not significantly different between the two groups. After a mean of 2.4 ± 1.0 years, the mean annual change in AVA was −0.10 ± 0.18 cm
2
in patients receiving OT and −0.22 ± 0.22 cm
2
in those not on OT (p=0.025). There was a graded association between AS progression rate and OT (Figure

). Age, gender, hypertension, renal function and statin use were not significantly associated with change in AVA. In a relatively small population of patients, osteoporosis treatment is strongly associated with decreased progression of aortic stenosis. This association warrants investigation in a larger, prospective study.
Abstract 4700: Changes in Left Ventricular Myocardial Strain after Aortic Valve Replacement: Comprehensive 2-Dimensional Speckle Tracking Strain Imaging Assessment
Authors: Delgado Victoria , Tops Laurens F , van Bommel Rutger J , van der Kley Frank , Klautz Robert J , Holman Eduard R , van der Wall Ernst E , Schalij Martin J , Bax Jeroen J
Published: July 2021

Background:
In patients with severe aortic stenosis and preserved left ventricular (LV) ejection fraction (EF), the presence of subtle left ventricular (LV) dysfunction may be misdiagnosed by the standard methods. Two-dimensional speckle tracking strain imaging enables multidirectional assessment of LV myocardial strain.

Objectives:
To evaluate the presence of subtle LV dysfunction in patients with severe aortic stenosis by using 2-dimensional speckle tracking imaging and the recovery of myocardial function after aortic valve replacement (AVR).

Methods:
Changes in radial, circumferential and longitudinal strain/strain rate of the LV were evaluated by using 2-dimensional speckle tracking imaging in 100 severe aortic stenosis patients after AVR. Radial and circumferential strain/strain rate were assessed at mid ventricular short axis level of the LV. Longitudinal strain/strain rate were evaluated at the conventional 2-, 4-chambers and long-axis apical views of the LV. These LV functional parameters were compared to conventional LVEF.

Results:
After AVR (median follow-up 5.3 months), the aortic valve area significantly increased (from 0.8 ± 0.2 cm
2
to 1.6 ± 0.5 cm
2
, p<0.001) together with a significant decrease in the maximal transaortic pressure gradient (from 72 ± 21 mmHg to 22 ± 9 mmHg, p<0.001). In addition, a significant regression of LV mass index was observed (from 154 ± 48 g/m
2
to 132 ± 44 g/m
2
, p<0.001). The LVEF remained unchanged at follow-up whereas a significant improvement of LV longitudinal and circumferential shortening was observed (Table

).

Conclusions:
In severe aortic stenosis patients, impaired LV longitudinal and circumferential shortening exist although preserved LVEF. After AVR, myocardial strain improves significantly in these two directions. Two-dimensional speckle tracking strain imaging enables an early detection of these subtle changes in LV performance.

Changes in LV mechanics after AVR
Abstract 4776: Prophylactic Intravenous Magnesium Sulphate in Addition to Oral Beta Blockade does not Prevent Atrial Arrhythmias after Cardiac Surgery
Authors: Cook Richard C , Humphries Karin H , Gin Ken , Janusz Michael T , Bernstein Victoria , Tholin Mats , Slavick Richard , Ansley David , Lee May K
Published: July 2021

Background
Atrial arrhythmias (AA) affect up to 40% of patients following cardiac surgery. The best strategy for prevention of AA remains undetermined, however, beta blocker (BB) administration is the standard of care at many centers (including ours). Although there is now compelling evidence demonstrating the utility of magnesium sulphate (MgSO4) for treatment of AA, the effectiveness of MgSO4 for prophylaxis of AA remains controversial. This study is the largest randomized, placebo-controlled trial of intravenous (IV) MgSO4 for the prevention of AA following cardiac surgery.

Methods Eligible patients requiring either coronary artery bypass graft surgery (CABG), or valve surgery ± CABG, were randomized to receive either 5g IV MgSO4, or placebo upon removal of the crossclamp, followed by daily infusions of IV MgSO4 or placebo over 4 hours, from the day of surgery until post-operative day 4. All patients were treated according to an established protocol with oral BB (atenolol). Patients were monitored by continuous telemetry for the first 5 post-operative days. The primary endpoint was an AA lasting ≥ 30 minutes, or requiring treatment because of hemodynamic compromise.

Results Table 1

summarizes the results. There was no difference in the incidence of AA between patients who received IV MgSO4 or those who received placebo.

Conclusions In patients proactively treated with atenolol using an established protocol, the addition of daily IV MgSO4 infusions for 5 days post-operatively did not reduce the incidence of clinically important AA following cardiac surgery.

Results For Primary Outcome (Post-Operative AA)
Abstract 4830: The Effects of Stem Cells on C-Kit Up-Regulation and Cell-Cycle Reentry of Neonatal Cardiomyocytes are Mediated by IGF-1 Receptor Activation
Authors: Yu Xi-Yong , Geng Yong-Jian , Li Xiao-Hong , Deng Chun-Yu , Lin Shu-Guang , Yang Tong , Song Yao-Hua , Li Yangxin
Published: July 2021

Mesenchymal stem cells (MSCs) contribute myocardial regeneration, and the beneficial effects may be mediated by paracrine factors produced by MSCs. C-kit positive neonatal cardiomyocytes (NCMs) contribute to myocardial regeneration, but they do not give a robust regenerative response since low expression of c-kit. Cell-cycle reentry of NCMs and insulin-like growth factor (IGF-1) improve myocardial function in infarcted hearts. MSCs and NCMs were prepared from Lewis rats, and cocultured in two chambers which allowed the diffusion of secreted factors from upper chamber to lower chamber, but prevented cell contacts. MSCs secreted significant amount of IGF-1 (159.6 ± 34.4 pg/ug DNA at 24 h, 285.3 ± 28.5 pg/ug DNA at 48 h, and 358.3 ± 39.9 pg/ug DNA at 72 h), whereas the amount of IGF-1 in conditioned medium from NCMs was undetectable assessed by IGF-1 ELISA. Using flow cytometry, we found that the secreted factors by MSCs increased c-kit protein expression, which was attenuated by IGF-1 receptor neutralizing antibody (IGF-1R Ab) and phosphatidylinositol 3 (PI3) kinase inhibitor LY 294002 (NCM vs MSC/NCM vs MSC/NCM+IGF-1R Ab vs MSC/NCM+ LY294002= 1.5 ± 0.6 % vs 5.5 ± 0.3 % vs 1.9 ± 0.6% vs 2.1 ± 0.5%) assessed by flow cytometry. The cytokinesis of NCMs was increased when cocultured with MSC analyzed by calcein fluorescence intensity (3.1 ± 0.5 fold increase, p<0.02). As determined by BrdU assay, the DNA synthesis of NCMs was significantly increased when cocultured with MSC compared to NCM alone (1.8 ± 0.3 fold increase at 48 h, 2.6 ± 0.2 fold increae at 72 h), which was attenuated by IGF-1R Ab and by PI3 kinase inhibitor. To confirm the paracrine effects of MSCs are mediated by IGF-1 signaling and PI3/Akt pathway, we performed in vitro Akt kinase assay using GSK-3 fusion protein as substrate, and found that co-culture system increased the activity of Akt kinase in NCMs, and the IGF-1R Ab and PI3 kinase inhibitor dose-dependent blocked the ability of co-culture system to increase Akt kinase activity. Our results demonstrate that the paracrine effects of MSC on c-kit up-regulation and cell-cycle reentry of NCM are mediated by IGF-1R activation through PI3 kinase/Akt - mediated pathway. These findings provide a new paradigm for the biological effects of IGF-1 on myocardial regeneration.

This research has received full or partial funding support from the American Heart Association, AHA South Central Affiliate (Arkansas, New Mexico, Oklahoma & Texas).
Abstract 4840: Tako-Tsubo Cardiomyopathy without Apical Ballooning - Results of the German Tako-Tsubo Registry
Authors: Athanasiadis Anastasios , Schneider Birke , Schwab Johannes , Gottwald Uta , Hoffmann Ellen , Hauber Juergen , Mackes Karl Giso , Stellbrink Chrisoph , von Scheidt Wolfgang , Sechtem Udo
Published: July 2021

Background

: The German tako-tsubo cardiomyopathy (TTC) registry has been initiated to further evaluate this syndrome in a western population. We aimed to assess different patterns of left ventricular involvement in TTC.

Methods

: Inclusion criteria were: 1) acute chest symptoms, 2) reversible ECG changes (ST-segment elevation±T-wave inversion), 3) reversible left ventricular dysfunction with a wall motion abnormality not corresponding to a single coronary artery territory, 4) no significant coronary artery stenoses.

Results

: A total of 258 patients (pts) from 33 centers were included with a mean age of 68±12 years. Left ventriculography revealed the typical pattern of apical ballooning in 170 pts (66%) and an atypical mid-ventricular ballooning with normal wall motion of the apical and basal segments in 88 pts (34%). Mean age (68±11 vs 67±13 years) and gender distribution (150 women/20 men vs 80 women/8 men) were similar in both groups. Triggering events were present in 78% of the pts with apical ballooning (35% emotional, 34 physical and 9% combination) and in 75% of the pts with mid-ventricular ballooning (39% emotional, 25% physical and 11% combination). As assessed by left ventriculography, ejection fraction was significantly lower in pts with mid-ventricular ballooning (50±15% vs 45±13%, p=0.006). There was no difference in right ventricular involvement. Creatine kinase and troponin I were comparable in both groups. The ECG on admission showed ST-segment elevation in 87% of pts with apical ballooning and in 78% of pts with mid-ventricular ballooning. T-wave inversion was seen in 70% of the pts irrespective of the TTC variant. A Q-wave was significantly less present in pts with mid-ventricular ballooning (30% vs 16%, p=0.04). The QTc interval during the first 3 days was not different among both groups.

Conclusion

: A variant form with mid-ventricular ballooning was observed in one third of the pts with TTC. Left ventricular ejection fraction was significantly lower in these pts, although they revealed significantly less Q-waves on the admission ECG. All other parameters were similar and confirm the concept that apical and mid-ventricular ballooning represent two different manifestations of the same syndrome.
Abstract 4869: Pulmonary Vasoconstriction Occurs out of Proportion to Increases in Pulmonary Capillary Wedge Pressure During Exercise in Heart Failure
Authors: Lewis Gregory D , Shah Ravi V , Martinovic Maryann , Bloch Kenneth D , Semigran Marc J
Published: July 2021

Secondary pulmonary hypertension (PH) is an important prognostic indicator in patients with systolic heart failure (HF), but the pattern of increase in pulmonary arterial pressure (PAP) during exercise and its relationship to exercise capacity and pulmonary capillary wedge pressure (PCWP) have not been comprehensively investigated. We hypothesized that HF patients would develop an increase in PAP out of proportion to the increase in PCWP during exercise and that the rate of PAP increase during exercise would predict exercise capacity in HF. Thirty-three patients with systolic HF (mean±SD, age 58 ± 7 years, left ventricular ejection fraction 0.27 ± 0.05, peak oxygen uptake 11.2 ± 3.2 ml/kg/min) and 10 normal subjects (age 53±9, sex, VO2) underwent cardiopulmonary exercise testing with simultaneous hemodynamic monitoring. There was a linear relationship between PAP and work rate in watts (R>0.85 for all subjects) whereas no consistent relationship between PCWP and work rate was present (R=0.02– 0.93). HF patients had a 3-fold greater rate of increase in PAP per watt than normals (slope=0.23±0.02 vs. 0.07±0.002 mmHg/W respectively, p<0.0001). In HF patients, PAP increased out of proportion to PCWP, as indicated by the slope of the gradient between PAP and PCWP (0.11±0.005 mmHg/W in HF vs. 0.01±0.005 mmHg/W in normals, p<0.0001). In HF patients, PAP slope, but not PCWP slope, inversely correlated with exercise capacity as measured by peak VO
2
(R=−0.41, p=0.04 and R=−0.12, p=0.56, respectively). Fifteen of the HF subjects underwent repeated exercise testing after 12-weeks of treatment with the pulmonary vasodilator sildenafil, with a resultant decrease in slope of the PAP-PCWP gradient from 0.11±0.02 to 0.07±0.01 mmHg, P<0.05. In patients with systolic HF there is a linear increase in PAP/watt that is out of proportion to the increase in PCWP/watt and inversely correlated with exercise capacity. Abnormal pulmonary vasoconstriction in response to physical activity in HF may represent a target for therapeutic intervention in HF.

This research has received full or partial funding support from the American Heart Association, AHA National Center.
Abstract 4890: Myocardial Fibrosis and Diastolic Dysfunction Following Calcium-Channel Blockers or Angiotensin II Receptor Blockers in Hypertensive Patients
Authors: Yoshida Chikako , Tsujino Takeshi , Goda Akiko , Matsumoto Mika , Naito Yoshiro , Nakao Shinji , Ezumi Akira , Lee-Kawabata Masaaki , Masuyama Tohru
Published: July 2021

Objectives
: Myocardial fibrosis develops in the hypertensive heart, and brings about LV diastolic dysfunction. Myocardial fibrosis is regulated by collagen production and degradation. Collagen degradation is regulated by matrix metalloproteinases (MMPs), a family of zinc-dependent interstitial enzymes, and their tissue inhibitors (TIMPs). We investigated how long-term administration of calcium-channel blockers (CCB) or Angiotensin II receptor blockers (ARB) affects collagen production/degradation and LV diastolic dysfunction.

Methods
: Study population consisted of 44 untreated hypertensive patients (31 females, 13 males, mean age:57±11 years). They were randomly assigned to one of the 2 groups: CCB group in which Amlodipine of 5–10mg was given daily (n=22) and ARB group in which Losartan of 50–100mg was given daily (n=22). LV mass index (LVMI) and tissue Doppler early diastolic mitral annular velocity (E′) were echocardiographically assessed before and 6 and 12 months after treatment. Procollagen type I C-terminal propeptide (PICP) was determined with enzyme immunoassay as a serum marker of collagen production, while MMP-2 and TIMP-1 were determined with ELISA as makers of collagen degradation.

Results
(table

): E′ increased in the ARB group but not in the CCB group while reductions in blood pressure (BP) and LVMI were comparable between the group. PICP did not change after treatment in either group, but MMP-2 increased only in the ARB group. TIMP-1 did not change in either group.

Conclusions
: In spite of similar reduction of SBP and LVMI, ARB provided larger benefits on LV diastolic function than CCB. Collagen production was constant in both groups, but ARB facilitated more collagen degradation than CCB, and the difference should have contributed to the impact on LV diastolic function.
Abstract 4921: Differential Healing in Paclitaxel and Sirolimus-Eluting Stents in Combination with Oral PPAR Gamma Agents: The Role of Drug Interaction in Delayed Healing
Authors: Finn Aloke , John Michael C , Nakazawa Gaku , Raghunathan Chitra , Ezell Tucker , Lajoie Scott , Xu Xin , Cheng Qi , Kolodgie Frank , Virmani Renu , Gold Herman K
Published: July 2021

Drug eluting stents (DES) contain different pharmacologic agents, yet the clinical relevance of this is unknown. Overlap exists between the molecular targets of sirolimus (SRL) (i.e. PI3K/mTOR) and many agents used to treat diabetes (DM). Because paclitaxel (PAC) works through other mechanisms, it might avoid this issue. The impact of interactions between eluted drug and commonly used DM meds on healing remains unknown. In rabbits receiving bare (BMS), PAC, and SRL DES, we investigated the effect of oral PPAR gamma agents, rosiglitazone (RSG) and pioglitazone (Pio), on stent endothelialization (ENDO). Rabbits were randomized to SRL, PAC or BMS and to placebo (PLC) versus RSG(3mg/kg/day) or Pio(10mg/kg/day). Animals were sacrificed at 28 days and arteries evaluated by scanning electron microscopy (SEM). 14day organ culture (OC) was also conducted. Cell culture experiments used human aortic endothelial cells (HAEC). RSG significantly reduced ENDO of the stent by SEM in animals receiving SRL vs. PLC, but no differences were seen in animals receiving PAC or BMS (table

). OC studies revealed significantly reduced VEGF levels in animals received SRL +RSG versus SRL +PLC, whereas animals receiving BMS and PAC demonstrated increased VEGF versus PLC. Similar results were seen in animals randomized to Pio vs. PLC. RSG +SRL additively inhibited p70s6k and SRL significantly blocked phosphorylation of Akt by RSG in HAEC. QRT-PCR revealed that SRL inhibited transcriptional upregulation of VEGF and heme oxygenase, a PPAR target gene, by RSG and suggests that in addition translational regulation, sirolimus may inhibit PPAR activity. RSG +SRL inhibits endothelialization because of significant drug interaction. No effect of PPAR gamma agonists is seen in animals receiving BMS or PAC. Our data suggest that SRL DES should be avoided in DM receiving PPAR gamma agonists and that investigation of other DM agents in combination with SRL is needed.

28 Day Endothelialization by SEM
Abstract 5576: Obstructive Sleep Apnea and Myocardial Infarction: Evidence of a Clinical Association
Authors: Fumagalli Stefano , Cipriani Chiara , Rinaldi Marta Casaloni , Francini Sara , Makhanian Yasmine , Tarantini Francesca , Marchionni Niccolò
Published: July 2021

Background
. Obstructive sleep apnea (OSA) is frequently associated with hypertension, chronic heart failure and atrial fibrillation; a correlation with ischemic heart disease is less defined. Aim of this study was to assess the prevalence of OSA and its clinical predictors after a recent myocardial infarction (MI).

Methods
. We studied all consecutive patients (pts) with MI, evaluated by our out-patient Clinic at 1-month follow up (exclusion criteria: atrial fibrillation and permanent pacemaker). For detection of OSA we used a validated tool (Lifescreen, Spacelabs/ESAOTE) which determines the mean Apnea-Hypopnea Index (AHI) by processing the electrocardiographic data of the sleep period. According to AHI, pts were classified as normal (≤5), borderline (5.1–15) or diseased (>15).

Results
. Between March 2007 and February 2008, we studied 107 pts (age: 62±13 years; men: 83.2%; weight: 78±12 Kg). Left ventricular ejection fraction was 49±12%. The prevalence of STEMI and anterior MI was 68.4 and 37.7%, respectively; primary PCI was performed in 76.5% of pts. Mean sleep period was 8:04±1.20 hours; AHI was 14.3±12.0; 80/107 pts (74.1%) scored >5, with 43 pts (39.8%) >15. In univariate analysis, women had lower AHI values than men (7.0±6.6 vs 15.7±12.4, p<0.001). AHI correlated directly with body weight (p=0.013), creatinine and uric acid concentrations (p=0.046 and p=0.030, respectively), and with the presence of aortic insufficiency (24.3±8.4 vs 13.8±12.1, p=0.020). AHI increased with CK MB and troponin I concentrations (p<0.001 and p=0.033) and was higher in pts treated with primary PCI of the left coronary artery (p=0.044) and in pts with complex ventricular arrhythmias (16.8±12.2 vs 12.2±10.3, p=0.049). At multivariate analysis, complex ventricular arrhythmias, body weight, creatinine concentration, and the presence of aortic insufficiency significantly correlated with AHI values, with complex ventricular arrhythmias being the best predictor of the presence of OSA (p=0.009).

Conclusions
. OSA is a common clinical condition in pts with a recent MI and correlates with the presence of complex ventricular arrhythmias. OSA evaluation might be particularly important in pts with MI to plan interventions such as CPAP therapy or ICD implantation.
Abstract 5583: Clinical Characteristics and Outcomes of Acute Myocardial Infarction Patients with Previous Cerebrovascular Diseases
Authors: Li Yong Jian , Rha Seung Woon , Chen Kang Yin , Poddar Kanhaiya L , Park Jae Hyoung , Na Jin Oh , Choi Cheol Ung , Lim Hong Euy , Kim Jin Won , Kim EungJu , Park Chang Gyu , Seo Hong Seog , Oh DongJoo , Jeong Myung Ho , Ahn Youngkeun
Published: July 2021

Background:
Cerebrovascular disease (CVD) can be an important future cardiovascular event. The impact of previous cerebrovascular disease (CVD) on the clinical characteristics and midterm outcomes of patients (pts) with acute myocardial infarction (AMI) has not been well described in Asian population.

Methods:
Data were analyzed from 8151 pts with AMI (either STEMI or NSTEMI) enrolled in Korea Acute Myocardial Infarction Registry (KAMIR) from 2005 to 2007.

Results:
Of 8151 pts, 552 pts (6.8%) had previous CVD. The pts with CVD were older (68.95 ± 10.11 vs 62.83 ± 12.74,
P
<0.001), more incidence in women (70.4% vs 62.7%,
P
<0.001), showed higher incidence of hypertension and diabetes than the pts without CVD. The pts with previous CVD presented more often with NSTEMI and higher Killip class than the pts without CVD. Further, pts with CVD received less percutaneous coronary intervention (PCI) or thrombolysis compared with the pts without CVD. Intensive medical therapy was equally maintained in both groups. Pts with CVD showed higher incidences of cardiac death [13.6% vs 5.1%, adjusted odd ratio (OR) 2.11, 95% confidence interval (CI) 1.60 –2.79,
P
<0.001], total death (15.9% vs 5.9%, adjusted OR 2.15; 95% CI 1.65–2.80,
P
<0.001) and total major adverse cardiac events (MACE, 23.0% vs 11.6%, adjusted OR 1.45; 95% CI 1.14 –1.85,
P
=0.003) at 8 months. The incidences of recurrent MI and repeat revascularization at 8 months were similar between the two groups.

Conclusions:
Pts with CVD showed more severe and worse clinical characteristics on admission and was associated with lower rates of PCI or thrombolysis. When we consider the poorer midterm clinical outcomes including higher mortality and MACE, in pts with prior CVD, more intensive and aggressive management for this particular subset of pts should be emphasized for better long-term clinical outcomes.
Abstract 5584: Heart Failure Eliminates the Risk Gradient Defined by TIMI Risk Score in Non-st-segment Elevation Acute Coronary Syndromes
Authors: Gonçalves Sara S , Amador Pedro , Mendes Lígia , Seixo Filipe , Santos José F
Published: July 2021

The TIMI Risk Score is a simple and effective tool for risk stratification in patients (pts) with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). The presence of heart failure (HF) or a low ejection fraction (EF) has also been associated with a worse outcome. We sought to evaluate the interaction of heart failure on the risk gradient defined by the TIMI Risk Score in a NSTE-ACS population. We studied 9980 pts with NSTE-ACS included in a prospective nationwide clinical registry since 2002. Pts were stratified by TIMI Risk Score in low (0 to 2), intermediate (3 and 4) and high risk (5 to 7) groups. The population was divided in two groups according to the presence or absence of HF. HF was defined as the presence of a Killip class >1 or a systolic EF <30%. In-hospital mortality or re-infarction was assessed in both groups during the index hospitalization and according to TIMI Risk Score Stratification.

Results: In-hospital mortality or re-infarction was 1,9% in low risk, 3,7% in intermediate and 6,3% in high risk pts (Qui-square trend p<0,001). The risk gradient defined by the TIMI risk score was not observed in patients without HF (Qui-Square for trend=ns). In pts with HF, the TIMI risk score maintains its predictor value (Qui-square trend=0,014), but the presence of HF identifies a higher risk subgroup. In this population, HF was a strong independent predictor for in-hospital mortality and re-infarction (OR 10,01). In NSTE-ACS pts, the presence of HF identifies the patients with higher risk for in-hospital risk and re-infarction within each TIMI Risk Score subgroup. There was no risk gradient assessed by the TIMI risk score in the absence of HF.
Abstract 5588: Paramedic Activated Cath Lab For STEMI Patients At Community Hospital Meets EMS Arrival-to-Intervention Guidelines With Low False-Positive Activation Rate
Authors: Vartanian Levon , Avendano Amilcar , Grieco Gustavo , Bober Steve , Bissell Catherine , Traynor Kevin , Kirk Terry , Egan Pam , Deloza Javier , Robbins Nick , Hicks Loretta , Shanks Molly
Published: July 2021

Background: Recent ACC/AHA STEMI guidelines state “STEMI patients presenting to a hospital with PCI capability should be treated with primary PCI within 90 minutes of first medical contact.” To address this Houston Northwest Medical Center developed a STEMI protocol in 2006 with Cypress Creek EMS, its primary paramedic service, initially to decrease hospital door-to-intervention (DTI) times. System evaluation post implementation indicated that EMS arrival-to-intervention (ETI) times better reflect overall combined performance. ETI is defined as time of EMS arrival on scene to reperfusion treatment. The purpose of this study is to see if a paramedic activated cath lab for STEMI patients met guideline recommendations while maintaining a low false-positive activation rate.

Methods: The initial protocol planning team determined greatest DTI reduction could be achieved through transfer of authority for cath lab activation to field paramedics. After obtaining a 12-lead ECG, paramedics notify the emergency department of a possible STEMI and the cath lab team is activated. Upon arrival, the emergency department physician obtains the ECG for interpretation and upon STEMI confirmation, the patient bypasses the emergency department and is transported directly to the cath lab. Data for protocol development was collected from a historical control group using retrospective chart review. Since protocol initiation in June 2006, ETI data is collected prospectively.

Results: Between June 2006 and December 2007, 113 patients were transported utilizing the STEMI protocol. Mean hospital DTI time decreased from 121 minutes (control group) to 53 minutes (p<0.01, two-tailed t-Test). Mean ETI time is 87 minutes; Historical ETI data was not collected. 15 (13.3%) false-positive STEMI activations occurred in the study period. Diagnostic accuracy was confirmed angiographically. Mortality rate comparison did not meet statistical significance - 5.4% historical, 5.3% protocol.

Conclusions: A paramedic activated cath lab for STEMI decreased DTI and ETI times to meet current guidelines. STEMI diagnostic accuracy was maintained with a low false-positive activation rate. Mortality data is insufficient for statistical significance.
Abstract 5598: Angiographic Evidence of Early Coronary Artery Disease and Inceased Risk of Mortality in Smokers with Non-ST-Segment Elevation Acute Coronary Syndromes: An Analysis of the ACUITY Trial
Authors: Robertson Jason O , Ebrahimi Ramin , Lansky Alexandra J , Mehran Roxana , Stone Gregg W , Lincoff A M
Published: July 2021

To determine the relationship between smoking and outcomes in a contemporary population of patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). Smoking has been associated with the “paradox” of reduced mortality following acute MI. This is thought to be due to favorable baseline characteristics and less diffuse CAD of smokers. In the ACUITY trial, 13,819 patients (29.1% smokers) with moderate- to high-risk NSTE-ACS underwent angiography and, if indicated, revascularization. Smokers were significantly younger and had fewer co-morbidities than nonsmokers. Incidence of death and MI were comparable at 30-days, although smokers had significantly reduced risks of 30-day major bleeding (HR=0.80, 95% CI=0.67– 0.96, p=0.016) and 1-year mortality (HR=0.797, 95% CI=0.65– 0.97, p=0.027). After multivariate correction for baseline and clinical differences, however, smoking status was no longer predictive of major bleeding (OR=1.06, 95% CI=0.85–1.32,
p
=0.59) and was associated with higher 1-year mortality (HR=1.38, 95% CI=1.07–1.78,
p
=0.013). This pattern of reversed risk following multivariable correction held true, as well, for those smokers requiring PCI. Core laboratory angiographic analysis showed that smokers and nonsmokers were comparable in terms of the extent of coronary artery disease, TIMI flow, myocardial blush and the presence of thrombi, but smokers had significantly less coronary artery calcification and fewer collaterals. In contrast to the paradox previously described in STEMI, our analysis finds smoking to be an independent predictor of higher 1-year mortality in patients presenting with NSTE-ACS, and our angiographic study demonstrates CAD disease in smokers that is comparable to nonsmokers but evident approximately one decade earlier.
Abstract 5600: Coronary Artery Distensibility and Plaque Composition Determined by Virtual Histology-IVUS - Comparison between Stable Angina Pectoris and Acute Myocardial Infarction
Authors: Sasaki Osamu , Nishioka Toshihiko , Isshiki Ami , Inoue Yoshiro , Kaneda Aki , Toyama Kentarou , Ando Toshiyuki , Yuhara Mikio , Sato Shunichi , Masaki Nobuyuki , Kamiyama Tetsuo , Kirimura Masato , Tsukada Shunichi , Ito Hiroyuki , Maruyama Yoshiaki , Yoshimoto Nobuo
Published: July 2021

The purpose of this study was to assess the difference in coronary artery distensibility and plaque composition determined by Virtual Histology-IVUS between non-culprit lesions of stable angina pectoris (SAP) and those of acute myocardial infarction (AMI). One-hundred thirty cross sectional areas (CSA) of 12 non-culprit de novo coronary artery lesions from 8 SAP patients and 128 CSAs of 12 non-culprit de novo coronary artery lesions from 10 AMI patients were imaged by IVUS (Volcano Therapeutics) with simultaneous intracoronary pressure (ICP) recording. Systolic and diastolic lumen areas (LA), vessel areas (VA), and plaque areas (PA) were measured. Lumen diameters (LD) were calculated with an assumption that the cross section was circular. Plaque burden; (PA/VA) X100, coronary compliance; {(LA change/diastolic LA)/(ICP change)} × 10
3
and stiffness index β (SI-β); {ln (systolic ICP/diastolic ICP)}/(LD change/diastolic LD) were calculated at each site. Color tissue maps were reconstructed from radio frequency data using IVUS-Virtual Histology software. Coronary compliance, SI-β and 4 tissue composition areas (Fibrous, Fibro-fatty, Dense-calcium and Necrotic core) were compared between SAP group and AMI group. LA, VA and PA were significantly larger in AMI group than in SAP group (7.88mm
2
vs 6.45 mm
2
, p<0.0001, 16.77 mm
2
vs 14.18 mm
2
, p<0.0001 and 8.88 mm
2
vs 7.73 mm
2
, p<0.0001). However, plaque burden showed no significant difference between AMI and SAP groups (53.4%vs 54.0%, p=0.60). Coronary compliance was significantly lower and SI-β was significantly higher in AMI group than in SAP group (0.82±0.75vs1.85±1.28, p<0.0001, 34.8±25.1vs 20.1±17.2, p<0.0001). Fibrous and Fibro-fatty areas were significantly smaller in AMI group than in SAP group (51.6% vs 71.3% p<0.0001, 10.1% vs 15.5% p<0.0001). Dense-calcium area and Necrotic core area were significantly larger in AMI group than in SAP group (15.2% vs 2.6% p<0.0001, 22.9% vs 9.9% p<0.0001). Coronary atherosclerosis assessed by Virtual Histology-IVUS was more advanced and severe, and coronary distensibility was impaired even in non-culprit lesions of AMI compared to those of SAP.
Abstract 5601: Statin-Use and Increase of Adiponectin Enhance the Stabilization and Regression of Coronary Arterial Plaques Characterized by Low- and High-Density Lipoprotein Cholesterols
Authors: Kojima Shinobu , Kojima Sunao , Nagayoshi Yasuhiro , Kaikita Koichi , Sumida Hitoshi , Sugiyama Seigo , Ogawa Hisao
Published: July 2021

Low levels of low-density lipoprotein cholesterol (LDL-C) or promotion of the biologic activity of high-density lipoprotein cholesterol (HDL-C) have a dramatic impact on atheroma burden. We assessed the hypothesis that lipoprotein cholesterol levels played major roles in the development of coronary plaque characterization. Preintervention intravascular ultrasound-Virtual Histology (IVUS-VH), using a continuous pullback (0.5 mm/s) was performed prospectively in 92 coronary vessels in consecutive 92 patients with coronary artery disease. The morphological distribution of plaque was evaluated up to a total length of 60 mm per coronary vessel. The levels of LDL-C were positively correlated with % necrotic core (NC) tissue (r=0.31, P=0.003). Whereas, HDL-C levels were negatively correlated with plaque volume (r=−0.30, P=0.003). These relations were closely observed in patients with acute coronary syndrome (ACS) compared with those with stable angina pectoris. Based on a receiver operating characteristic curve, the best cutoff LDL-C levels on % NC tissue and HDL-C levels on plaque volume were plotted regarding ACS patients (Figure

). In multiple regression analyses, % NC tissue and plaque volume were associated with statin-use and adiponectin levels, respectively (Table

). IVUS-VH may help to explain missing link between lipids and coronary plaque characterization. Statin-use and increase of adiponectin have a huge potential for stabilization and regression of coronary arterial plaques. The levels of LDL-C ≤ 70 mg/dL and HDL-C ≥60 mg/dL are recommended and may contribute to the development of preventive strategies of ACS.