bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2963: Association of Race and Socioeconomic Position with Graft Failure in Heart Transplant Recipients
Authors: Singh Tajinder P , Givertz Michael , Semigran Marc , Costantino Fred , DeNofrio David , Gauvreau Kimberlee
Published: July 2021

Race has been associated with patient survival in heart transplant (HT) recipients. We hypothesized that this association is mediated by socioeconomic (SE) factors. Block groups (average population 1000) are the smallest units of population in US census database with available SE data. We assessed whether SE position, determined for the block group of patient residence at time of HT, is associated with graft failure in HT recipients. We used the US census 2000 database to extract 6 SE variables of wealth, income, education and occupation and calculated a previously validated summary SE score for 520 patients who underwent first HT at one of 4 Boston centers during 1996–2005. Cox proportional hazards modeling was used to compare the risk of graft failure (time to death or re-transplant) in the lowest quartile SE group (low SE group, n = 129) with that of remaining patients (controls, n = 391). Low SE patients were younger (median age 48 yrs versus 52 yrs for controls, P < 0.015) and more likely to be nonwhite (32% versus 9% of controls, P = 0.001). The two SE groups were similar with respect to gender, listing status, cardiac diagnosis, hemodynamic support, year of HT and prevalence of diabetes, smoking and hypertension. Graft failure occurred in 142 HT patients (135 deaths, 7 re-transplants). Early Graft failure (within 6 months) was associated with earlier era (before 2001), pre-HT extracorporeal membrane oxygenation or ventricular assist device but not with age, cardiac diagnosis, race or low SE position. In patients who survived at least 6 months (conditional survival), nonwhite race (HR 2.0, 95% CI 1.3–3.3, P = 0.004), low SE position (HR 1.6, CI 1.1–2.5, P = 0.03) and pre-HT smoking (HR 1.6, CI 1.0 –2.4, P = 0.03) were all associated with subsequent graft failure. In multivariable analysis, nonwhite race (HR 1.9, CI 1.2–3.3) remained a significant predictor of late graft failure after controlling for low SE position (HR 1.3, CI 0.8 –2.1, P = 0.24) and pre-HT smoking (HR 1.6, CI 1.1–2.5, P = 0.03). There is no association of early post-HT survival with race or low SE position. Nonwhite race is associated with increased risk of death or re-transplant after 6 months of HT. Low SE position explains only a small fraction of this association.
Abstract 2964: Outcomes in Patients with Adriamycin Cardiotoxicity Undergoing Orthotopic Heart Transplantation: An Analysis of the United Network for Organ Sharing Database
Authors: Silverstein Cheri A , Hung Rebecca R , Ooi Henry , Wigger Mark A , Sawyer Douglas B
Published: July 2021

Background
: Anthracyclines are the mainstay of breast cancer, leukemia, lymphoma and sarcoma treatment. Since approval of doxorubicin (adriamycin), the first and most widely used anthracycline, in 1974, cardiac toxicity has been the major complication of use of these drugs. Although orthotopic heart transplant (OHT) is considered an option for cancer survivors in complete remission, to our knowledge, the outcomes of OHT in these patients have not been reported.

Methods
: We reviewed the United Network for Organ Sharing (UNOS) database to identify transplants performed from 1988 through 2007. Individuals were stratified between a primary diagnosis of Dilated Myopathy: Adriamycin (DMA) and all other diagnoses. Survival rates at 1, 12, 36, 60 and 120 months post-transplant and proportions of deaths due to malignancy and rejection were reviewed.

Results
: From 1988 to 2007, 68,863 persons were listed with UNOS. Of those, 487 (0.71%) had a primary diagnosis of DMA. In the same period, 43,113 persons received OHT. Of those, 328 (0.76%) had a primary diagnosis of DMA. The DMA group had a younger mean age (37.6 vs. 45.9) and a higher fraction of females (199/328 (60.67% [55.38 – 65.96]) vs. 10447/42785 (24.42% [24.01–24.83]); (z = 15.2, p < 0.001)) than all others. Survival at all time points was equivalent in DMA and all others (1mo: 94.12% [91.17–97.07] vs. 92.98% [92.74 –93.23]; 12mo: 86.53% [82.40 –90.66] vs. 84.79% [84.45–85.14]; 36mo: 78.31% [73.21– 83.42] vs. 77.37% [76.95–77.78]; 60mo: 69.73% [63.78 –75.69] vs. 70.53% [70.06 –71.00]; 120mo: 55.32% [48.03– 62.62] vs. 51.06% [50.44 –51.67]). Malignancy was reported as the primary cause of death in a similar portion of patients in both groups (10/115 (8.7% [3.55–13.85]) vs. 1901/17819 (10.67% [10.22–11.12]); (z = −0.682, p = 0.496)). Rejection was reported as a primary cause of death in a higher fraction of DMA patients (19/115 (16.52% [9.73–23.31]) vs. 1860/17819 (10.44% [9.99 –10.89]); (z = 2.12, p < 0.05)).

Conclusions
: Individuals with cardiomyopathy due to anthracycline cardiotoxicity are not higher risk candidates for OHT. The cause of the higher fraction of reported deaths due to rejection in DMA patients is likely multifactorial, including the younger mean age and higher fraction of females in this group.

This research has received full or partial funding support from the American Heart Association, AHA National Center.
Abstract 2965: QT Interval Prolongation during Severe Acute Rejection is Predictive of Sudden Cardiac Death in Heart Transplant Recipients
Authors: Vrtovec Bojan , Haddad Francois , Tsai Vivian , Al-Ahmad Amin , Deuse Tobias , Pham Michael , Fisher Patrick , Fearon William , Valantine Hannah , Hunt Sharon
Published: July 2021

Background.
QT interval prolongation is considered a risk factor for sudden cardiac death (SCD) in various non-transplant populations. Since acute allograft rejection is associated with a prolonged QT interval, we sought to investigate the effects of rejection-induced QT interval changes on SCD in heart transplant recipients.

Methods.
Of all patients who underwent heart transplantation between 1998 and 2007, we enrolled those with severe acute cellular rejection episodes (ISHLT grade 3A or higher, accompanied with hemodynamic compromise). In this cohort, baseline ECGs were obtained within 7 days after transplantation; follow-up ECGs were recorded at the time of the rejection episode. On all ECGs, QT interval was defined as the mean duration QT interval measurements in all leads, and corrected for heart rate with Bazett formula. A significant increase of QTc during rejection (dQTc) was defined as a relative change in QTc ≥10%. Patients were followed for SCD for 1 year after the rejection episode.

Results.
Of 80 patients with a severe rejection episode, 9 (11%) were excluded because of the inadequate quality of ECG recordings. Within the 1-year follow-up, 21 of 71 (30%) patients died. Of these, 14 (67%) died of SCD, and 7 (23%) died of other causes. Patients who died of SCD and survivors did not differ with regards to age (44 ± 12 years in SCD group vs. 46 ± 16 years in survivors,
P
= 0.61), gender (male: 83% vs. 58%,
P
= 0.06), incidence of infections (0.21 ± 0.43 vs. 0.20 ± 0.40,
P
= 0.91), malignancy (0% vs. 8%,
P
= 0.84), or allograft vasculopathy (29% vs. 26%,
P
= 0.85). No difference in Qtc prolonging drug was noted. During acute rejection, QTc interval was significantly longer in SCD group than in survivors (475 ± 57 ms vs. 437 ± 36 ms,
P
= 0.01), and the same was true for the incidence of dQTc > 10% (50% vs. 16%,
P
= 0.008). SCD-free survival as evaluated by Kaplan-Meier analysis was significantly lower in patients with dQTc > 10% (P = 0.013). On multivariate analysis, dQTc > 10% was the only independent predictor of SCD (P = 0.02). The multivariate model included left ventricular dysfunction (LVEF < 30%) and dQTc.

Conclusion.
Heart transplant recipients who display a significant (> 10%) prolongation of QT interval during a severe acute rejection episode may be at increased risk for SCD.
Abstract 2998: Aortic Stiffness Is Correlated With Albuminuria and Glomerular Filtration Rate in Essential Hypertension: The Hippokration Hellenic Hypertension (3H) Study
Authors: Dimitriadis Kyriakos , Tsioufis Costas , Andrikou Eirini , Thomopoulos Costas , Giatrakos Ioannis , Tzamou Vanessa , Kallikazaros Ioannis
Published: July 2021

Introduction:
Arterial stiffness is an established marker of cardiovascular risk, whereas albuminuria and impaired renal function are associated with atherosclerosis progression.

Hypothesis:
Arterial stiffness may be associated with urinary albumin excretion, expressed as the albumin to creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) in a large cohort of hypertensives.

Methods:
A total of 893 consecutive essential hypertensives [482 men, mean age = 56 years, office blood pressure (BP) = 145/90 mmHg] that were included in the Hippokration Hellenic Hypertension (3H) Study, an ongoing Greek registry of hypertension-related target organ damage, were considered for analysis. In all participants, ACR values were determined as the mean of two non-consecutive morning spot urine and eGFR was calculated using the Modification of Diet in Renal Disease equation. Moreover, aortic stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (PWV), by means of a computerized method (Complior SP). The distribution of PWV was split by the median (8 m/sec) and accordingly subjects were stratified into those with high and low values.

Results:
Hypertensive patients with high PWV (n = 414) compared to those with low PWV values (n = 479) were older (61 ± 10 vs 51 ± years, p < 0.0001), had higher office systolic BP (150 ± 9 vs 142 ± 6mmHg, p < 0.0001) and left ventricular mass index (107.7 ± 16 vs 99 ± 13 g/m
2
, p < 0.0001). Moreover, hypertensives with high PWV compared to those with low PWV exhibited higher ACR (18.7 ± 9.5 vs 14.8 ± 7.5 mg/g, p < 0.05), whereas had lower eGFR (76 ± 17 vs 82 ± 17 ml/min/1.73m
2
, p = 0.006). In the total population, PWV was related to age (r = 0.525, p < 0.0001), office systolic BP (r = 0.242, p = 0.0001), ACR (r = 0.012, p < 0.001) and negatively associated with eGFR (r = −0.221, p < 0.0001). Analysis of covariance revealed that ACR and eGFR levels remained significantly different between groups after adjustment for confounders (p < 0.05).

Conclusions:
In essential hypertension, heightened PWV values are associated with pronounced albuminuria and impaired kidney function. These findings further support that aortic stiffening is a hallmark of diffuse renal and vascular atherosclerotic disease.
Abstract 3003: Central or Peripheral Systolic or Pulse Pressure: Which Best Predicts Target-Organ Damage and Mortality?
Authors: Wang Kang-Ling , Cheng Hao-Min , Chuang Shao-Yuan , Spurgeon Harold A , Ting Chih-Tai , Lakatta Edward G , Yin Frank C.P. , Chou Pesus , Chen Chen-Huan
Published: July 2021

Background

: Pulse pressure (PP) and systolic blood pressure (SBP), in central and peripheral arteries, may contribute differently to predictions of damage to different target organs and mortality.

Method

: We examined the relations of PP and SBP in central (calibrated tonometric carotid pulse) and peripheral (brachial, mercury sphygmomanometer) arteries to left ventricular mass index (LVMI), carotid intima-media thickness (IMT), glomerular filtration rate (GFR), and 10-year all-cause and cardiovascular (CV) mortality in 1272 participants (47% women, aged 30 –79 years) from a community of homogeneous Chinese.

Result

: LVMI was more strongly related to SBP (r = 0.420 and 0.379 for central and brachial arteries, respectively) than PP (r = 0.374 and 0.285, correspondingly). In contrast, IMT and GFR were more strongly related to central PP and SBP (r = 0.265 and 0.252 for IMT, and r = −0.256 and −0.218 for GFR, respectively) than brachial PP and SBP. A total of 130 participants died, 37 from CV causes. In univariate analysis, all four blood pressure variables significantly predicted all-cause and CV mortality. After adjustment for age, sex, current smoking, glucose, cholesterol/high-density-lipoprotein-cholesterol ratio, carotid-femoral pulse wave velocity, LVMI, IMT, and GFR, none of the blood pressure variables predicted all-cause mortality (Figure 1A

). Only central SBP independently predicted CV mortality (Hazards ratio = 1.21 per 10 mmHg) in multivariate analysis (Figure 1B

).

Conclusion

: PP and SBP contribute differently to damage to different target organs. Central SBP is more valuable than other blood pressure variables in predicting CV mortality.
Abstract 3031: Repeat Revascularisation following Multivessel Sirolimus-eluting Stent Implantation: Indications and Long-term Follow-up From the Arterial Revascularisation Therapies Study Part 2 (ARTS-II)
Authors: Kukreja Neville , Serruys Patrick , Ramcharitar Steve , Tanimoto Shuzou , Onuma Yoshinobu , de Bruyne Bernard , Colombo Antonio , Macaya Carlos , Richardt Gert , Fajadet Jean , Hamm Christian , Schuijer Monique , Pieters Magdaleen , Stoll Hans-Peter
Published: July 2021

Objectives: Although coronary-artery bypass grafting (CABG) has been considered the gold standard of treatment for multivessel coronary artery disease, percutaneous coronary intervention (PCI) with drug-eluting stents (DES) may be an alternative: the ARTS-II trial found that after 3 years, the major benefit of CABG was a decreased need for repeat revascularization. We reviewed the angiographic findings in all patients from ARTS-II who required repeat revascularization to investigate their prognosis and to establish the reasons for repeat revascularization in these high risk complex patients, including the relative contributions of procedural complications, neointimal hyperplasia, stent thrombosis, geographical miss and disease progression.

Methods: There was no routine angiographic follow-up in ARTS-II. All intercurrent angiograms within 3 years were reviewed. Patients requiring CABG due to index procedural complications or procedural failure were excluded (n = 8). The angiographic indications for repeat revascularization were categorized into target lesion revascularization (TLR), target vessel-non target lesion revascularization (TV-nonTLR) or non-target vessel revascularization (non-TVR). Patients undergoing TLR were further categorized into instent restenosis (ISR) according to the Mehran classification, stent edge restenosis (SER) or definite stent thrombosis (ST).

Findings: Within 3 years of the initial treatment, 81/607 patients required 103 repeat revascularizations to treat 150 lesions. These repeat revascularizations were classified as TLR in 74% of lesions, TV-nonTLR in 22% and non-TVR in 4%. The cases of TLR were due to ISR in 59%, SER in 25% and ST in 17%. The majority of ISR cases were Mehran Class IC (focal, body). ISR accounted for 42% of all repeat revascularizations, whilst ST accounted for 11%.

Conclusion: Repeat revascularization was due to ISR or ST in approximately half of the lesions; the remainder were due to either incomplete lesion coverage or disease progression. Hard clinical endpoint outcomes of patients stratified by the type of repeat revascularization will be presented at the meeting.
Abstract 3035: Sirolimus-eluting Stents Compared With Bare Metal Stents or Coronary Artery Bypass Grafting in Patients with Multivessel Disease including Involvement of the Proximal Left Anterior Descending Artery: Analysis of the Arterial Revascularization Therapies Study part 2 (ARTS-II)
Authors: Kukreja Neville , Serruys Patrick , de Bruyne Bernard , Colombo Antonio , Macaya Carlos , Richardt Gert , Fajadet Jean , Hamm Christian , Schuijer Monique , Pieters Magdaleen , Stoll Hans-Peter
Published: July 2021

Objectives: Although Coronary Artery Bypass Grafting (CABG) has been the historical gold standard treatment for patients with multivessel disease, the ARTS-II trial found no differences in survival or overall adverse events between sirolimus-eluting stents (SES) and the surgical arm of ARTS-I. Nevertheless, previous data have suggested that patients with disease of the proximal left anterior descending artery (pLAD) may derive particular benefit from CABG. We therefore investigated the 3-year clinical outcomes in all patients in ARTS-I and ARTS-II with pLAD (AHA segment 6) involvement.

Methods: Patients in ARTS-II with disease of the pLAD (289/607, 48%) were compared with 187/600 (31%) bare metal stent (BMS) patients (ARTS-I PCI) and 206/605 (34%) surgical patients (ARTS-I CABG) with pLAD involvement from ARTS-I. The primary endpoint was the incidence of major adverse cardiac and cerebrovascular events (MACCE). Secondary endpoints included all-cause mortality, the composite of death, stroke or myocardial infarction and the need for repeat revascularization.

Findings: Complete 3-year follow-up was available for 99.6% of patients in ARTS-I and ARTS-II. The ARTS-II pLAD subgroup had better survival than both ARTS-I subgroups (ARTS-II 98.6% vs. ARTS-I PCI 95.7%, p = 0.048 and vs. ARTS-I CABG 94.7%, p = 0.01) and lower rates of the hard clinical composite endpoint of death or nonfatal myocardial infarction (ARTS-II 3.1% vs. ARTS-I PCI 9.6%, p = 0.002 and vs. ARTS-I CABG 9.7%, p = 0.002). Although the ARTS-I CABG patients had a lower need for repeat revascularization than ARTS-II (5.5% vs. 13.3%, p = 0.005), the overall composite adverse event rates (death, myocardial infarction, stroke or any repeat revascularization) were not significantly different between the ARTS-I CABG and ARTS-II patients (15.1% vs. 18.1%, p = 0.4). After 1 year, the SES patients had a reduction in the composite endpoint of death/CVA/MI (vs. ARTS-I PCI RR 0.27, 95% CI 0.11– 0.63 and vs. ARTS-I CABG RR 0.31, 95% CI 0.13– 0.74), although this was not statistically significant after 3 years.

Conclusion: In this historical, non-randomized evaluation, SES had favorable outcomes compared to CABG or BMS in patients with multivessel coronary disease including involvement of the pLAD.
Abstract 3036: Effect of High-Dose Quinapril on In-Stent Restenosis Rate and Association with Apoptosis Indices
Authors: Deftereos Spyridon , Kaoukis Andreas , Giannopoulos Georgios , Raisakis Konstantinos , Kossyvakis Charalampos , Driva Metaxia , Panagopoulou Vasiliki , Ntzouvara Olga , Kouvousis Nikolaos , Matsakas Evangelos
Published: July 2021

The regulation of apoptotic processes has been implicated in the evolution of restenosis after percutaneous coronary interventions (PCI) and angiotensin II has been shown to increase proliferation of vascular smooth muscle cells, while its blockade could result in increased apoptosis of the cellular components of restenotic plaques. We studied 60 symptomatic patients with significant obstructive (> 70%) lesions of the left anterior descending artery (LAD), submitted to elective PCI. The patients were randomly assigned to receive 40 mg of quinapril qd, starting one week before PCI and continued for 6 months, or placebo, in addition to standard treatment. Anti-hypertensive treatment (with the exception of angiotensin converting enzyme [ACE] and angiotensin receptor inhibitors) was administered as required to maintain desired blood pressure levels in both groups. Coronary angiography (CAG) was performed 6 months after the PCI to assess restenosis (at least 50% of lumen diameter). Plasma levels of apoptotic mediators soluble Fas and Fas ligand were measured (ELISA) in blood samples drawn during catheterization from the LAD artery (at the time of PCI and 6 months later). Restenosis rates in the quinapril-treated and in the control group were 21.2% and 29.7% respectively (p < 0.05, odds ratio 1.84, 95% CI 1.38 –2.5) and the late loss in minimum lumen diameter was 0.88 ± 0.4 mm and 1,05 ± 0.6 mm, respectively (p = 0.001). Plasma concentrations of Fas and Fas ligand in the LAD blood were significantly increased in the quinapril group at the 6-month CAG compared to baseline (4.8 ± 0.3 ng/ml vs 2.9± ng/ml for Fas and 54.4±3.3 pg/ml vs 32.5±1.9 pg/ml for Fas ligand, respectively), while no significant difference was observed in the control group. We report a potential effect of a relatively high dose of the ACE inhibitor quinapril on apoptotic markers in blood drawn form the LAD, which may be linked to the observed difference of in-stent restenosis, following PCI in the LAD. Increased apoptotic activity may be associated with inhibition of the neo-intimal hyperplasia and the overall atherogenic process, resulting in reduction of in-stent restenosis.
Abstract 3048: Incidence and Management of Procedural Complications Associated with Transcatheter Aortic Valve Implantation
Authors: Masson Jean-Bernard , Altwegg Lukas A , Ali Abdullah Al , Bugami Saad Al , Boone Robert H , Carere Ronald G , Lichtenstein Sam V , Cheung Anson , Moss Robert , Munt Brad , Thompson Christopher R , Ye Jian , Webb John G
Published: July 2021

Background.
Transcatheter aortic valve implantation (TAVI) is increasingly recognized as an alternative to surgery for patients with severe, symptomatic aortic stenosis and high or prohibitive operative risk. Despite prospective evidence that TAVI can be performed with acceptable 30-day mortality, the potential for vascular, neurologic or cardiac complications exists.

Method.
One hundred and sixty-three balloon-expandable TAVIs were performed between November 2005 and February 2008 at St. Paul’s Hospital, Vancouver, Canada. Valves were implanted using a transarterial (n=110) or transpical approach (n=53). Clinical and echocardiographic data was prospectively collected.

Results.
Overall 30-day mortality rate was 11.0% in this selected high risk population but mortality decreased by 50% in the second half of this cohort. Current systems require a large sheath (22 to 24 Fr) potentially injurious to femoral and iliac arteries. Unplanned percutaneous (n=2) or surgical (n=11) interventions were performed in 14 patients to treat peripheral vascular complications. Temporary endovascular balloon occlusion can provide hemostasis while definitive treatment is implemented. Acute complications associated with apical access include bleeding and tamponade. Intra-procedural deaths occurred in 1.2% of patients due to arterial perforation (n=1) and apical hemorrhage (n=1). Stroke rate was 4.3%. Positioning errors can result in significant paravalvular regurgitation, mitral valve injury (n=1) and valve embolization (n = 7). Paravalvular leak can be reduced by redilation of an under-expanded prosthesis or implantation of a second valve to extend the sealing cuff. Cases of embolization were all satisfactorily managed with re-expansion of the prosthesis distally in the aorta. Coronary ostial obstruction by a bulky leaflet was confirmed in 1 patient. Permanent pacemakers were implanted in 9 patients (5.5%) due to new heart block.

Conclusion.
This early TAVI experience demonstrated the potential for a variety of potential complications. However as experience and knowledge increased over time the rate of adverse events appeared to fall. Careful screening, technological advances and greater experience will allow for safer procedures.
Abstract 3086: Transcatheter Pulmonic Valve Replacement in Sheep using a Grafted Self-Expanding Stent with Tissue Valve
Authors: Bonhoeffer Philipp , Huynh Rany , House Morgan , Douk Nareak , Kopcak Mike , Hill Alex , Rafiee Nasser
Published: July 2021

Background

: The initial repair of tetralogy of Fallot (TOF) involves placement of a trans-annular patch (TAP) in the majority of patients. Over time, however, TAP often causes free pulmonary insufficiency (PI), necessitating follow-up treatment. Importantly, TAP also leads to an enlargement of the right ventricular (RV) outflow tract, which precludes a less-invasive approach to treat PI with currently available trans-catheter techniques. To address this unmet clinical need, a new trans-catheter device was created and tested in an animal model.

Methods

: Six sheep underwent echocardiography and were chosen to have the device implant on the basis of their pulmonary artery (PA) size (>28 mm). A dumb-bell shaped, self-expanding covered stent with a central valve-baring portion of 22 mm diameter was developed. This device was mounted on a 22F delivery system, introduced via a jugular approach and delivered in native pulmonary position. Hemodynamic data, echocardiograms and magnetic resonance images (MRI) were acquired at baseline, immediately post-implant and at term (4wks: n=2; 5wks: n=1; 8wks: n=2; 19wks: n=1). Gross pathologic and ultra-structural (Faxitron®) evaluations were performed at term.

Results:

The device was successfully implanted in 6/6 (100%) sheep with procedure times of less than 20 minutes and fluoroscopy times less than 5 minutes. Immediately post-implant, all animals had good valve function on echocardiography (‘none’: n=5, ‘trivial’: n=1). Mean RV-to-PA gradients were slightly increased from baseline to post-implant and term (3.3, 4.7 and 7.5 mmHg, respectively). One animal showed moderate tricuspid regurgitation (TR), which was caused during device delivery. Chronically, TR and PI remained unchanged at term. While stent fractures were observed at term (n=3), no device migration or related complications were observed. On ultra-structural evaluation, valve leaflets were pliable and displayed no-to-minimal fibrin deposition and mineralization at term.

Conclusion:

Trans-catheter delivery and implantation of a self-expanding grafted stent with tissue valve was successful in a chronic sheep model. Stent design and material properties merit further investigation for the application in humans.
Abstract 3995: Comparison of the Effects of Prasugrel and High Dose Clopidogrel on
In Vivo
and
In Vitro
Platelet Activation: Results from PRINCIPLE-TIMI 44
Authors: Frelinger Andrew L , Michelson Alan D , Braunwald Eugene , Trenk Dietmar , Neumann Franz-Josef , Miller Debra L , Jakubowski Joseph A , Cairns Richard , Murphy Sabina A , McCabe Carolyn H , Antman Elliott M , Wiviott Stephen D
Published: July 2021

In PRINCIPLE-TIMI 44, a randomized study in 201 patients undergoing cardiac catheterization for planned PCI, we reported that prasugrel resulted in greater inhibition of
in vitro
ADP-stimulated platelet aggregation than clopidogrel 600 mg loading dose (LD) and 150 mg maintenance dose (MD). Here we compare the effects of prasugrel and clopidogrel on
in vivo
and
in vitro
platelet activation. As prespecified end points of PRINCIPLE-TIMI 44, we measured circulating platelet-monocyte aggregates (PMA), circulating platelet-neutrophil aggregates (PNA), circulating P-selectin-positive platelets (PSPP), plasma soluble CD40 ligand (sCD40L) and (because activated platelets induce its release from leukocytes) myeloperoxidase (MPO). We also evaluated
in vitro
ADP-stimulated PMA, PNA and PSPP. At 6 h post LD, clopidogrel and prasugrel resulted in similar reductions in circulating PMA (Fig. A

), PNA and PSPP.
In vitro
ADP-stimulated PMA (Fig. B

), PNA and PSPP were inhibited to a greater degree by prasugrel than clopidogrel during the LD and MD phases. At 6 h post LD, clopidogrel- but not prasugrel-treated patients had elevated plasma MPO compared to pre-treatment (Fig. C

). Plasma sCD40L was unaffected by time or treatment. In this randomized study:

Prasugrel, like clopidogrel, inhibited
in vivo
platelet activation.

Prasugrel, to a greater degree than clopidogrel, inhibited ADP-stimulated PMA, PNA and PSPP – which may be mechanistically important, given the high local concentrations of ADP at sites of thrombus formation.

Prasugrel, unlike clopidogrel, prevented the post-PCI-induced increase in the inflammatory marker MPO.
Abstract 4005: Morning Preference In The Onset of Tako-Tsubo Cardiomyopathy
Authors: Citro Rodolfo , Luca Ospedale San , Previtali Mario , Bovelli Daniella , Astarita Costantino , Ciampi Quirino , Vriz Olga , Civile Ospedale , Provenza Gennaro , Luca Ospedale San , Camporotondo Rita , Gallerani Massimo , Bossone Eduardo , Manfredini Roberto
Published: July 2021

Background
: Aim of this study is to assess the circadian variation in the occurrence of Tako-tsubo cardiomyopathy(TTC).

Methods:
We evaluated 78 consecutive pts (76 F, median age 61 yy) with TTC occurring between 2002 and 2008 at the Tako-Tsubo Cardiomyopathy Italian Network (TIN) Centers. All pts fulfilled the following diagnostic criteria for TTC:

transient akinesia/diskinesia beyond a single major coronary artery vascular distribution;

no angiographic evidence of significant coronary artery disease;

new electrocardiographic changes;

absence of intracranial bleeding, pheochromocitoma, myocarditis or hypertrophic cardiomyopathy.

The time of symptom onset during day was categorized into four 6-hour intervals (night: 00:00 – 06:00; morning: 06:00 –12:00; afternoon: 12:00 –18:00; evening: 18:00 –24:00) for circadian analysis. Information on timing of the event that allowed categorization in to 1 of the 4 groups was available in 70 of 78 cases (90%). The distribution was tested for uniformity by the χ
2
test goodness of fit.

Results:
A circadian pattern, characterized by a significant peak in the morning (χ
2
=13,38, p=0.004), was found in patents with TTC (figure

). This pattern persisted even after adjustment according to a worst-case scenario in which untimed cases were arbitrarily assigned equally to each period according to the null amplitude hypothesis.

Conclusions
: Our data indicate a morning prevalence in the onset of TTC similar to other cardiovascular conditions and might be related to the circadian catecholamine activity.
Abstract 4010: Soluble TRAIL in Peripheral Blood is a Novel Marker for Acute Coronary Syndromes
Authors: Sato Kayoko , Gomita Keiko , Kitamura Kazutaka , Hagiwara Nobuhisa
Published: July 2021

Background:
Apoptosis of vascular smooth muscle cells and endothelial cells in the fibrous cap is prone to plaque vulnerability. Recently, we found that CD4 T cells trigger the TRAIL/TRAIL receptor 2 (DR5) pathway and cause VSMC apoptosis in acute coronary syndrome (ACS). We also showed that activated plasmacytoid dendritic cells (pDC) produce INFα through TRL9 and amplify cytotoxic CD4 T cell functions by enhancing TRAIL expression. In this study, we examined whether soluble TRAIL (sTRAIL) in peripheral blood shows changes in ACS that may serve as predictive marker of vulnerable patients.

Methods and Results:
The sTRAIL levels were measured by ELISA in 110 patients undergoing coronary angiography, including 90 ACS patients and 20 chest pain syndrome patients without apparent coronary atherosclerosis. Fresh CD4 T cells were isolated from the peripheral blood of patients. The sTRAIL levels were lower in ACS than in controls (P<0.001). CD4 T cells capable of inducing HUVEC apoptosis expressed high levels of TRAIL in ACS patients (P<0.03), and negatively correlated with the sTRAIL levels (R=0.372, P<0.02). To examine whether sTRAIL levels could be used as marker of vulnerable patients with ACS, we measured sTRAIL levels in the time course and compared them with CPK and TnT after onset of ACS. While CPK and TnT of acute myocardial infarction elevated in the acute phase and recovered after 3days, sTRAIL showed negative parallel changes. Meanwhile, sTRAIL showed the same changes in unstable angina without CPK and TnT elevation. The levels of sTRAIL more decreased in patients with multiple coronary artery stenosis than in that without coronary artery stenosis while the levels of hsCRP did not. Furthermore, given a cutoff value of 48.6pg/ml, sTRAIL was able to discriminate ACS from control groups with sensitivity of 62.4%, specificity of 85.0%, and area under the receiver-operating characteristic curve (AUC) of 0.736. In contrast, an hsCRP cutoff value of 1.25mg/l showed lower sensitivity (47.3%), specificity (77.8%), and AUC (0.597) for the diagnosis of ACS.

Conclusions:
Monitoring of TRAIL levels in ACS patients with both acute myocardial infarction and unstable angina was found useful in predicting vulnerability in patients with vulnerable plaques.
Abstract 4012: Mild Troponin Elevation In subjects Presenting With Atrial Fibrillation With Rapid Ventricular Rate Is Associated With Adverse Cardiovascular Outcomes
Authors: Biria Mazda , Abu-Salah Tareq , Pescetto Micah , Annapureddy Chandra , Pillarisetti Jayasree , Vanga Subbareddy , Patel Akshar , Watkins Lisa , Ryschon Kay , Lakkireddy Dhanunjaya , Gupta Kamal
Published: July 2021

Introduction:
Cardiac markers are frequently checked in patients presenting with atrial fibrillation (AF) and rapid ventricular rate (RVR). Clinical significance of mild troponin elevation in this setting and clinical value of this practice is not well known. It has been suggested that mild troponin elevation in this setting represents rate related demand ischemia and not ACS.

Hypothesis:
We hypothesized that measuring Troponin in AF/ RVR without signs/ symptoms of myocardial infarction has low yield and limited clinical value in predicting cardiovascular events.

Method:
Multi-center, retrospective cohort study of 452 subjects (age 67±14, M:F=4:1) presenting with AF/ RVR between 2000 and 2006. Occurrence of MI at one year after discharge was primary outcome.

Results:
Of all cases presenting with A fib/ RVR, Troponin was checked in 351 cases (77.7%). Of these 197 (age 70±11, M:F=7.1) had elevated Troponin(group-I) and 154 (age 61±16, M:F=1.1) had a normal Troponin (group-II) (1.4±5.3 vs 0.02±0.01 ng/ml, P=0.003). Group-I was older with more renal failure compared to group-II (P=0.0001, 0.0001, 0.0002 respectively). However, there was no difference in the rate of diabetes, anemia and symptom of chest pain at the time of presentation (P=0.9, 0.07 and 0.058 respectively). There was no significant difference in ventricular rate (123+31vs 123+33, P=0.3), duration of symptoms (61±186.6 vs 30.3±46.1
h
, P=0.2), and ST-T changes (38(21%) vs 38 (28%) P=0.8) between two groups. During hospitalization, 76(38.6%) stress tests were performed on subjects in group-I vs. 48(31%) in group-II (p=0.17). These stress tests led to 37(48.7%) vs 12(25%) coronary angiographies (P=0.013). In group-I at one year follow up, 15 (7%) of subjects developed MI, but none in group-II. Based on these data, Troponin has sensitivity, specificity, positive and negative predictive values of 84.6%, 27.8%, 29.7% and 83.3% respectively for detecting coronary disease in A Fib weith RVR and 100%, 45.8%, 7.6% and 100% respectively for occurrence of MI in one year.

Conclusion:
Even mild troponin elevation in the setting of AFib with RVR predicts a significant increase in risk of MI at 1 yr. A normal Troponin in this setting is predictive of a favorable cardiovascular outcome at one year.
Abstract 4030: Resuscitation with Intraosseous Infusion of Artificial Oxygen Carrier of Liposome-Encapsulated Hemoglobin (LHb) from Lethal Hemorrhagic Shock and Its Effect on Cytokines
Authors: Takase Bonpei , Shono Satoshi , Kinoshita Manabu , Nogami Yashiro , Ogata Yoshitaka , Hattori Hidemi , Ishihara Masayuki
Published: July 2021

Liposome-encapsulated hemoglobin (LHb), which is structurally similar to red blood cells (RBC) except smaller size (250 nm), can serve as blood substitute comparable to RBC. We have reported that intraosseous blood infusion (IOI) is effective treatment in shock mice model. IOI is alternative to peripheral i.v. infusion and is expected as an important field treatment in civilian emergency because of no collapse of intramedullary blood vessels in the bone marrow in shock. However, we did not evaluate the side effects of LHb in IOI. Total 70% hemorrhagic shock was induced by femoral vein bleeding. Immediately after bleeding, 17 mice were resuscitated with tibial bone IOI of 5% albumin (5% albumin), 18 mice resuscitated with mouse-washed RBC (Wash RBC) and 14 mice resuscitated with LHb (LHb-group). Survival rates were compared and the temporal changes in cytokins (TNF, INFγ) as well as liver and renal function (s-ALT, s-creatinine) were measured. All mice survived 48 h after IOI of LHb whereas only 47% and 45% mice survived in 5% albumin and Wash RBC, respectively (Fig. 1

). The changes in TNF and INFγlevels after IOI were not statistically different among 3 groups (Fig. 2

) and no side effects were found on liver and renal function..

Conclusions:
LHb has a better anti-shock effect than RBC by using IOI probably due to smaller size and IOI of LHb could be useful in disaster medicine. In addition, IOI of LHb shows no significant effects on cytokins, liver and renal function.

Figure 1

Figure 2
Abstract 4108: Myocardial Injury Can Be Identified by Magnetic Resonance Imaging in the Course of Ablation Procedures for Atrial Fibrillation
Authors: Sinha Anil-Martin , Ritscher Guido , Mahnkopf Christian , Oakes Robert S , Badger Troy J , Schmidt Martin , Marschang Harald , Dibella Edward V , Marrouche Nassir F , Brachmann Johannes
Published: July 2021

Background:
Pulmonary vein antrum isolation (PVAI) is regarded as an effective therapy in patients with atrial fibrillation (AF). Extension and location of ablation lesions often remain unclear during the procedure. We report a new approach on visualization of myocardial injury using magnet resonance imaging (MRI) during PVAI procedure.

Methods:
Patients who underwent PVAI, received MRI before and at the terminal phase of PVAI. Delayed enhancement (DE-) MRI sequences were applied, and maximum intensity projections (MIP) obtained. Myocardial injury size was then measured on manually segmented 3D images by a computer algorithm using dynamic thresholding.

Results:
30 patients received PVAI from January 2008 to May 2008. In a subset of 15 patients, MRI was performed before and during the procedure. Using DE-MRI, the average lesion to healthy myocardium ratio was 7.56±1.27% during PVAI. The figure

shows an example of MIP of a DE-MRI scan in 2D (A,B) and 3D segmentation (C,D) in a anterior view pre (A,C), and during PVAI (B,D). Myocardial injury is identifiable as white tissue around PV single ostia (full arrows) and common trunk (dashed arrows).

Conclusions:
Using MRI is feasible in the course of ablation procedures. In PVAI patients, DE-MRI allowed identification of location and extension of myocardial injury. Therefore, this new MRI approach might improve ablation techniques, and thus long-term success of PVAI.
Abstract 4109: First experiences for Pulmonary Vein Isolation with the High Density Mesh Ablator
Authors: Meissner Axel , Plehn Gunnar , van Bracht Marc , Christ Martin , Butz Thomas , Maagh Petra , Borchard Rolf , Trappe Hans-Joachim
Published: July 2021

Interventional therapy of atrial fibrillation (AF) still is a complex procedure often associated with long examination- and fluoroscopy times. The use of mapping catheters in addition to the ablation catheter requires multiple transseptal sheats for left atrial access. The purpose of this prospective study was to evaluate feasibility and safety of pulmonary vein (PV) isolation using the high density mesh ablator (HDMA), a novel single, expandable electrode catheter for both mapping and radiofrequency (RF) delivery at the left atrium/PV junctions. 26 patients (PTS) with highly symptomatic paroxysmal AF (14, 53.8%) and persistent AF (12, 46.2%) were studied. Segmental PV isolation via the HDMA was performed using a customized pulsed RF energy delivery program (target temperature 55– 60 degrees, power 70 –100 Watt, 600 –900 seconds RFapplication time/PV). All 104 PV in 26 PTS could successfully be ablated by the HDMA. Segmental PV isolation was achieved with a mean of 3.25±1.4 RF applications for a mean of 603±185 sec. Entrance conduction block was obtained in >94% of all PV. Mean total procedure and fluoroscopy time was 159.0±32 min and 33.5±8.6 min respectively. None of the PTS experienced severe complications. In this first study of PV isolation using the HDMA, our findings suggest that this method is safe and yields good primary success rates. Anatomical orientation and signal quality were good, allowing for excellent electrophysiological control. The HDMA simplifies the complex procedure of AF ablation, favorably impacting procedure and fluoroscopy times. Further studies are required to assess the long-term outcome.
Abstract 4124: Polymorphisms can Predict Appropriate Therapies in Patients with Heart Failure and Implantable Cardioverter Defibrillators
Authors: Chemello Diego , Rohde Luis E , Zimerman Leandro , Pimentel Mauricio , Abreu Lais P , Gonzalez Vinicius , Rosa Priscila R , Dalsasso Eliza , Clausell Nadine
Published: July 2021

Introduction:
The use of implantable cardioverter defibrillators (ICD) reduces mortality in patients with heart failure (HF). However, given its elevated cost, an adequate selection of individuals with higher risk is warranted. Yet, known predictors of risk of sudden cardiac death have shown limited value to select use of ICD. More recently, genetic polymorphisms have been considered as potentially interesting tools to guide therapeutic strategies.

Objective:
To study the role of three genetic polymorphisms (β1 Arg389Gly, GNB3 C825T and GP IIb/IIIa Pl
A1
/Pl
A2
) as predictors of appropriate ICD therapies in patients with heart failure (HF) who received an ICD implant for primary or secondary prevention.

Patients and Methods:
Retrospective cohort study of patients with ICD use during at least 6 months for primary and secondary prevention, followed at our HF outpatient clinic. Clinical data were registered and ICD analyses were made by telemetry. ICD therapies were defined as appropriate or inappropriate by a cardiac electrophysiologist. Twenty mL of blood were collected for polymorphism analysis by the PCR-RFLP technique. For univariate analysis, Student’s t-test and the χ

2

(chi-square) test were used; logistic regression was used for multivariate analysis.

Results:
The sample included 73 patients (75% male, 89% white and 56% ischemic etiology). The mean ejection fraction was 34.9 ± 9.8%. Individually, the Arg389 allele of the β1 Arg389Gly polymorphism, the T825 allele of the GNB3 C825T polymorphism, and the Pl
A2
allele of the GP IIb/IIIa Pl
A1
/Pl
A2
polymorphism were not associated with appropriate ICD therapy. Nevertheless, the combined presence of these alleles identified patients with higher risk for appropriate shocks (p=0.03). Survival rate free of appropriate shocks was significantly lower in patients with 2 or 3 risk genotypes when compared with others (p=0.03).

Conclusions:
When analyzed in combination, the presence of the β1 Arg389Gly, GNB3 C825T, and GP IIb/IIIa Pl
A1
/Pl
A2
polymorphisms possibly act as predictors of appropriate therapies in ICD recipients with HF. Further studies are needed to determine the clinical applicability of these genetic markers.
Abstract 4185: Does Combined Stress, Delayed Enhancement, and Functional Cardiac Magnetic Resonance Imaging Yield Incremental Prognostic Value and Risk Stratification?
Authors: Bingham Scott , Hachamovitch Rory
Published: July 2021

Background.
Evaluation of the intermediate risk patient (Pt) using combined cardiac magnetic resonance imaging (CMR) assessment of adenosine stress perfusion (STRESS), myocardial delayed enhancement viability (MDE), and ventricular wall motion imaging (WM) is a promising clinical approach. Whether this technique yields risk stratification and incremental prognostic value over pre-CMR data is uncertain.

Methods.
We identified 1,002 consecutive patients [Age 64±14, 58% male, 50% prior coronary artery disease (CAD)] undergoing combined CMR for suspicion of CAD or ischemia. STRESS first-pass gadolinium gradient echo pulse sequence, MDE, and steady state free precession WM were interpreted using 17-segment, 5 point scoring. Summed scores (SS) were calculated for each. The primary endpoint was all-cause death (ACD), the secondary endpoint cardiac death (CD). Incremental prognostic value was defined as an increased Cox proportional hazards model (CPH) global chi-square with the addition of CMR data after adjustment for clinical and historical data.

Results:
Follow-up (FU) at 2.6±1.2 years after CMR (2.4% lost to FU) identified 78 ACD (8.0%) and 38 CD (3.9%). Compared to pts with normal stress CMR (STRESS, MDE, and WM all normal), pts with abnormal results had greater ACD rates over FU (5.9% vs 11%, p=0.006). After adjusting for the most predictive pre-CMR data (dyspnea, rest heart rate, age, and known renal disease; global chi-square 55, p<0.001), the addition of SS from STRESS, MDE, or WM added incremental value for prediction of ACD (chi-squares: 66, 64, 67; all p<0.001, respectively). After adjusting for pre-CMR data and WM SS, only MDE SS added further (chi-square 71, p<0.001); STRESS SS did not add to WM SS (p=0.17). CPH predicting CD identified both STRESS and SWMS as incremental predictors (chi-square 55, p<0.001)

Conclusion
: STRESS, MDE and WM all add incremental value for prediction of ACD and CD over pre-CMR data and can be combined to further enhance prognostication.
Abstract 4187: Identification of Late Gadolinium Enhancement by Contrast-Enhanced Magnetic Resonance Imaging as a Major Risk Factor for Sudden Death in Hypertrophic Cardiomyopathy
Authors: Rubinshtein Ronen , Glockner James F , Ommen Steve R , Araoz Philip A , Ackerman Michael J , Tajik A J , Gersh Bernard J
Published: July 2021

Background:
Myocardial late gadolinium enhancement (LGE) on Contrast-Enhanced Magnetic Resonance Imaging (CE-MRI) of patients (pts) with hypertrophic cardiomyopathy (HCM) may indicate intra-myocardial fibrosis. We explored whether the presence and extent of LGE on CE-MRI among pts with HCM predicted ventricular arrhythmogenicity, and decreased survival.

Methods:
424 HCM pts [age = 55 ± 16 years (range 2 – 90), 41% females], without prior history of septal ablation/myectomy, underwent CE-MRI (GE 1.5T) during a 6-year period. We compared the presence and amount of LGE with degree of ventricular ectopy on Holter ECG (available in 220 pts) recorded during the same time period of the CE-MRI. All cause death and appropriate, VF-terminating ICD therapies were then recorded during a mean follow-up of 34 ± 14 months (range 7 – 85).

Results:
239 pts (56%) had LGE ranging from 0.4 – 65% of the myocardium. LGE -positive pts were more likely to have non-sustained ventricular tachycardia on Holter ECG [34/126 (27%) vs 8/94 (8.5%), p < 0.001], and had more total ventricular extrasystoles/24 hours (700 ± 2080 vs 103 ± 460, p < 0.001). During follow-up, 7 pts died and 4 received appropriate ICD discharges (9.7% of 41 pts with ICD). All 11 pts were LGE-positive. Event free survival was excellent (100%) in pts without LGE, and lower (95.4%) in pts with LGE (log rank, p < 0.002). Multivariate analysis (adjusting for age, gender, morphologic and functional data, and comorbidities) identified LGE involving ≥ 5% of LV mass (p=0.03, present in 7/11 pts with events), septal thickness≥30mm (p=0.03), and atrial fibrillation (p=0.02) as independent predictors of death or appropriate ICD discharges.

Conclusions
: In pts with HCM, LGE by CE-MRI was strongly associated with surrogates of arrhythmia and was independently associated with subsequent death and/or ICD discharge. If replicated, LGE may be considered a major risk for sudden death in HCM.