bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2315: Markedly Enhanced Activity of Endothelin-1 in Transplant Coronary Arteriosclerosis
Authors: Larose Eric , Behrendt Dominik , Kinlay Scott , Selwyn Andrew , Ganz Peter , Fang James
Published: July 2021

Background: Coronary arteriosclerosis is the principal complication limiting long-term survival after heart transplantation. In humans, the mediators responsible for vascular proliferation and vasoconstriction typical of TCA are unknown. Endothelin-1 (ET-1) is a potent vasoconstrictor and mitogen derived primarily from endothelial and mononuclear cells. We tested the hypothesis that ET-1’s biological activity is increased in TCA and that it may contribute to the pathogenesis and manifestations of TCA. We inhibited the ET
A
receptor by administering a specific antagonist BQ-123 into the coronary arteries in heart transplant recipients undergoing routine annual cardiac catheterization. We compared the coronary vasomotor responses to BQ-123 in subjects with angiographic evidence of TCA and subjects free of angiographic evidence of TCA.

Methods: BQ-123 was infused into one proximal coronary artery (40nmol/min for 60min) of 18 subjects, age 18 –75, 6 +/− 4 years after transplantation. In each patient 3 coronary segments were studied in both the infused and in a non-infused control coronary artery (Total 108 segments). Changes from baseline in diameters of the infused arterial segments were compared to those of non-infused arterial segments at 15 minute intervals. Contribution of ET-1 to coronary constrictor tone was assessed by comparing vasodilation from BQ-123 infusion to dilation from intracoronary nitroglycerin (200μg bolus).

Results: BQ-123 induced dilation in coronary arteries of transplanted patients (8.4% at 60 minutes, vs. −0.4% in noninfused arteries, p<0.001). Dilation was greater for arteries with TCA defined as angiographic diameter stenosis ≥15% (dilation 15.2% with TCA, n=10, vs. 0.6% without TCA, n=8, p=0.004). As compared to dilation from nitroglycerin indicative of overall vascular tone, ET-1 was responsible for 53.2% of vascular tone in TCA arteries but only 12.9% in arteries without TCA.

Conclusions: The endogenous biological activity of ET-1 is markedly increased in humans with TCA compared to those without evidence of TCA. This supports a role for ET-1 in the pathogenesis of TCA and suggests that therapeutic targeting of ET-1 may slow the development and manifestations of TCA in cardiac transplant recipients.
Abstract 2318: The Type 2 Diabetes Gene
CDKAL1
Discovered by Genome-wide Association is Expressed in Beta Cells and Modulated by Glucose Concentration
Authors: Steinthorsdottir Valgerdur , Reynisdottir Inga , Thorleifsson Gudmar , Ghosh Shyamali , Benediktsson Rafn , Sigurdsson Gunnar , Kong Augustine , Gurney Mark , Gulcher Jeffrey R , Thorsteinsdottir Unnur , Stefansson Kari
Published: July 2021

In our genome wide association study on type 2 diabetes (T2D), a variant we had previously identified in
TCF7L2
stood out as the most significant finding. In addition, a variant of the
CDKAL1
gene was found to be associated with increased risk of T2D in a nearly recessive manner, with genotype odds ratio for the homozygous carrier 1.45 and 1.55 for individuals of European and Asian ancestry respectively. The function of the
CDKAL1
gene product is unknown but it is similar to another protein, CDK5RAP1, an inhibitor of the CDK5/p35 complex in neuronal tissue. This complex is also expressed in pancreatic beta cells and, in the presence of its active form, insulin expression is decreased under glucotoxic conditions. This led to the suggestion that CDKAL1 may be an inhibitor of the CDK5/p35 complex in beta cells, similar to the role of CDK5RAP1 in neuronal tissue. Furthermore, we have shown that the risk variant of
CDKAL1
is associated with reduced insulin secretion and this effect is mostly seen for the homozygote where a 24% reduction in insulin response is observed compared to the heterozygous carriers or non-carriers. This is in line with the nearly recessive mode of inheritance observed for this variant with respect to disease risk. The aim of this study was to gain further insight into the functional role of
CDKAL1
using the rat pancreatic beta cell line INS-1. The rat pancreatic beta cell line INS-1 was cultured in the presence of variable glucose concentration, ranging from 2.5–30 mM, to evaluate whether
CDKAL1
expression is regulated by glucose concentration. We demonstrated that the expression of
CDKAL1
in rat INS-1 cells varied according to glucose concentration in the culture medium with reduced expression detected under glucotoxic conditions compared to normal glucose concentration. This indicates that
CDKAL1
expression in pancreatic beta cells is sensitive to glucose concentration. It is possible that this response to glucose may be affected in individuals carrying the variant of
CDKAL1
that is associated to T2D. This could explain the reduced insulin secretion observed for these individuals in response to an oral glucose tolerance test.
Abstract 2330: Relationship Between Coronary Calcification, Myocardial Ischemia, and Outcomes in Patients With Intermediate Likelihood of Coronary Artery Disease
Authors: Schenker Matthew P , Dorbala Sharmila , Hong Eric C , Rybicki Frank J , Hachamovitch Rory , Kwong Raymond Y , Di Carli Marcelo F
Published: July 2021

Background
- Although the value of coronary artery calcium (CAC) for atherosclerosis screening is gaining acceptance, its efficacy in predicting flow-limiting CAD remains controversial and its incremental prognostic value over myocardial perfusion is not well established.

Methods and Results
- We evaluated 621 consecutive patients undergoing combined rest-stress Rubidium-82 PET perfusion imaging and CAC scanning on a hybrid PET-CT scanner. The frequency of abnormal scans among patients with CAC ≥400 was higher than that in patients with CAC 1–399 (53.3% vs 30.0%, p<0.001). Multivariate logistic regression analysis supported the concept of a CAC ≥400 threshold value governing this relationship (OR 2.74, p<0.001). However, the frequency of ischemia among patients with no CAC was 24.4%, and its absence only afforded a negative predictive value of 75.6%. Risk adjusted survival analysis demonstrated a stepwise increase in event rates with increasing CAC scores in patients with and without ischemia on PET. Among patients with normal PET, the annualized event rate in patients with CAC score=zero was lower than in those with a CAC ≥1,000 (2.4% vs 13.6%, respectively). Likewise, in patients with ischemia on PET the annualized event rate in those with CAC score=zero was lower than among patients with a CAC ≥1,000 (6.9% vs 19.4%).

Conclusions
- Although increasing CAC scores are generally predictive of a higher likelihood of ischemia, its absence does not eliminate the possibility of flow-limiting CAD. Importantly, there is a stepwise increase in the risk of adverse events with increasing CAC scores in patients with and without ischemia on PET.
Abstract 345: Effects Of Endothelial-targeted Overexpression Of Nox4 On Vascular Tone And Blood Pressure In Mice
Authors: Ray Robin , Zhang Min , Brewer Alison C , Shah Ajay M
Published: July 2021

NADPH oxidases (Noxs) are major sources of reactive oxygen species (ROS) that are involved in the pathophysiology of several cardiovascular disorders. Of the 5 Nox isoforms identified to date, Nox2 and Nox4 are the main isoforms expressed in the endothelium. Whereas Nox2 has been implicated in the genesis of endothelial dysfunction, the role of Nox4 remains unclear. Interestingly, the activation mechanisms of Nox2 and Nox4 appear to be distinct. To specifically examine the function of endothelial Nox4
in vivo
, we generated transgenic mice with endothelial-targeted overexpression of Nox4 using a Tie2 promoter construct. Nox4 transgenic mice (TG) backcrossed onto a C57BL/6J background had increased Nox4 mRNA in endothelial-rich tissues and in isolated coronary microvascular endothelial cells (CMEC) compared to wild-type littermates (WT) (2-fold increase in CMEC; p<0.001). Aortic Nox4 protein levels were 3-fold higher in TG compared to WT. CMEC isolated from TG mice had increased NADPH-dependent superoxide production compared to WT (237.6 ± 2.7 vs. 186.5 ± 7.1 integrated RLU; n = 3, p<0.01) as well as increased H
2
O
2
production (7.60 ± 0.70 vs. 3.22 ± 0.42 μM H
2
O
2
/105 cells; n=3, p<0.01). No changes were detected in mRNA expression of SOD1, SOD2, SOD3, catalase or eNOS in aorta of TG compared to WT mice. Isolated aortic rings from TG mice exhibited enhanced endothelial-dependent vasorelaxation to cumulative addition of acetylcholine compared to WT (−log EC
50
7.76 ± 0.07 vs. 7.20 ± 0.05; n =12, p<0.001), a difference that was abolished by catalase (1500 units/ml). There was no difference in endothelial-independent responses to sodium nitroprusside (−log EC
50
8.57 ± 0.11 vs. 8.54 ± 0.09; n = 12, p = NS).
In vivo
blood pressure measured both by tail-cuff plethysmography and ambulatory telemetry was significantly lower in TG compared to WT (systolic 117.4 ± 1.9 vs. 125.5 ± 2.1 mmHg and diastolic 90.1 ± 2.0 vs. 98.1 ± 2.1 mmHg by telemetry; n =5, p<0.05). These results indicate that modest endothelium-targeted overexpression of Nox4
in vivo
enhances endothelium-dependent relaxation and reduces blood pressure, probably through increased generation of H
2
O
2
. These
in vivo
effects are quite distinct from those that have been found with Nox2 overexpression.
Abstract 2340: Should Real-time Three-dimensional Echocardiography Become The Preoperative Standard For The Evaluation Of The Mechanisms Of Atrioventricular Valve Regurgitation In The Patient With Congenital Heart Disease?
Authors: Takahashi Ken , Inage Akio , Robertson Murray , John Dyck , David Ross , Ivan Rebeyka , Smallhorn Jeffrey F
Published: July 2021

Objective:
The purpose of this study was to determine whether Real-time three-dimensional echocardiography (RT3D) is superior to two-dimensional echocardiography (2D) in determining mechanisms and site(s) of atrioventricular valve (AV valve) regurgitation in congenital heart disease.

Background:
Data is lacking on the utility of RT3D echo in congenital abnormalities of the AV valves.

Methods:
Between May 2006 and April 2007, 35 cases were prospectively studied prior to AV valve repair (20 left and 15 right) by 2D transthoracic (2DTTE), 2D transesophageal (2DTEE) and RT3D (Philips matrix array X 3–1 and X 7–2). Thirty one had significant and 4 mild regurgitation. Ages ranged from 24 days to 30 years (mean 13.8 years), weight 2.2 to 42kg (mean 26.1Kg). The 2DTTE and TEE were reviewed by a blinded observer. The 3D data were analyzed by a separate observer. In 28 patients surgical findings and regurgitation from saline testing were recorded by digital video and later analyzed by an experienced cardiac surgeon. The remaining 7 had a detailed description of the valve morphology documented immediately after surgery. Surgical findings were used as the gold standard for the assessment of structural abnormalities, with RT3D for the evaluation of regurgitation.

Results:
See table

for structural abnormalities. For both the left and right AV valve, saline testing provided a poorer correlation with RT3D color Doppler jet location, in particular for regurgitant jets from the commmissures (p < 0.01).

Conclusion:
Transthoracic RT3D provides new and superior information as to the mechanisms and site(s) of AV valve failure in congenital heart disease.

Concordance between 2D TTE, 2D TEE and 3D TTE compared to surgical findings
Abstract 2362: Myonecrosis is Predicted by Lack of Platelet Inhibition Measured in Response to Multiple Agonists in Patients Undergoing Elective Stenting:The Risk of A Global High Platelet Reactivity Phenotype
Authors: Bliden Kevin , DiChiara Joseph , Tantry Udaya , Gurbel Paul
Published: July 2021

Background: Small studies have demonstrated the relation of clopidogrel nonresponsiveness to adverse clinical events. We sought to determine:

the relation between inhibition of ADP-induced platelet aggregation and inhibition of aggregation induced by other agonists and

the relation of clopidogrel responsiveness to periprocedural myonecrosis in patients undergoing stenting treated with a 600mg clopidogrel loading dose and bivalirudin.

Methods: Platelet inhibition by low and high dose ADP, collagen and TRAP by conventional aggregometry (LTA) was determined at 2 hr and 24 hr post-stenting in 50 patients treated with aspirin, bivalirudin and 600 mg clopidogrel. Patients were stratified into low clopidogrel responders (LR)[≤10% relative platelet inhibition (RPI)], moderate responders (>10 – <30% RPI) and high responders (>30% RPI)].

Results: Inhibition measured by 5uM ADP correlated with inhibition by 20uM ADP, collagen and TRAP (r =0.98, 0.91, and 0,83, respectively, p < 0.001 for all). Myocardial marker release occurred in the LR and MR groups only. (Table

)

Conclusions: 600 mg clopidogrel markedly inhibits platelet reactivity to multiple agonists in selected patients who are in turn protected from periprocedural MI during elective stenting. These data suggest that low and high risk patients can be identified by platelet function testing that may enhance decision making for adjunctive antithrombotic therapy in elective stenting.
Abstract 2368: Baseline Dietary Glycemic Load as a Predictor of Weight Loss on the Atkins, Zone, Weight Watchers and Ornish Diets.
Authors: Buchsbaum Aaron F , Schaefer Ernst J , Dansinger Michael L
Published: July 2021

Background:
Methods for matching patients with optimal diets are lacking. We previously reported that 4 popular diets (Atkins, Zone, Weight Watchers and Ornish), which range from low to high in dietary carbohydrate and glycemic load, produced similar 1-year weight loss in a randomized trial. We tested the hypothesis that dietary glycemic load at baseline (prior to dietary intervention) would affect the magnitude of weight loss from each diet.

Methods:
We randomized 160 overweight and obese adults (mean BMI=35) to follow the Atkins, Zone, Weight Watchers, or Ornish dietary advice. Participants attempted maximum dietary adherence and attended 4 small-group classes during the first 2 months, then self-selected dietary adherence levels for the following 10 months. One-year weight loss for each diet was determined according to tertiles of baseline dietary glycemic load, assessed by 3-day food records, nutrition analysis software, and published glycemic index tables. Missing data were replaced with baseline values in an intent-to-treat analysis (n=40 per diet).

Results:
The association between 1-year weight loss and dietary glycemic load at baseline differed significantly according to diet type (p<.01 for interaction). Participants in the highest tertile of dietary glycemic load at baseline had greater weight loss on lower carbohydrate diets (−4.6 kg, −4.6 kg, −2.1 kg, −1.5 kg for Atkins, Zone, Weight Watchers, and Ornish, respectively; p=0.05 for linear trend), and participants in the lowest tertile of dietary glycemic load at baseline had greater weight loss on higher carbohydrate diets (+0.3 kg, −1.0 kg, −3.2 kg, −5.3 kg for Atkins, Zone, Weight Watchers, and Ornish, respectively; p=0.01 for linear trend). For the middle tertile of baseline dietary glycemic load, weight loss did not differ between diets (−1.7 kg, −4.1 kg, −3.8 kg, −1.5 kg for Atkins, Zone, Weight Watchers, and Ornish, respectively, p=0.6 for linear trend, p=0.3 for two highest vs. two lowest).

Conclusions:
Dietary glycemic load intake prior to dietary intervention may impact the effectiveness of popular diets for weight loss, and may be an important consideration in optimal diet selection for individual patients. These results should be verified in other study populations.
Abstract 2386: Growth-Differentiation Factor-15 is a Strong Predictor of Adverse Outcomes in Heart Failure: Results from Val-HeFT.
Authors: Anand Inder S , Kempf Tibor , Tapken Heike , Allhoff Tim , Kuskowski Michael , Carlson Marjorie , Cohn Jay N , Drexler Helmut , Wollert Kai C
Published: July 2021

Background: Growth-Differentiation Factor-15 (GDF-15) is a member of the TGF-β family that is induced in the heart after myocardial injury. In patients with non-ST segment elevation ACS, GDF-15 is increased and provides prognostic information. Its role in heart failure is unknown.

Methods & Results: GDF-15 was measured in 1125 Val-HeFT patients at baseline. Baseline median GDF-15 was 2027 ng/L (IQ range 1447 to 2942) and was abnormal (>1200 ng/L) in 86% of patients. Patients with GDF-15 above the median had higher NYHA class, greater volume load, lower LVEF and eGFR, higher hsCRP, norepinephrine, BNP and aldosterone, lower use of beta-blockers and higher use of diuretics (all p<0.01). In a multivariate COX model including all baseline variables, GDF-15 was a significant independent predictor of death (HR, 1.5, 95% CI, 1.06–2.14), first morbid event (HR 1.56, 95% CI, 1.19–2.04), and hospitalizations for HF (HR, 1.93, 95% CI, 1.33–2.80), as was BNP for all the three endpoints (HR, 1.7, 95% CI, 1.27–2.3), (HR 1.84, 95% CI, 1.45–2.35), and (HR, 1.98, 95% CI, 1.43–2.7). Spearman correlation of BNP with GDF-15 was 0.33 p<0.001. To test whether GDF-15 adds prognostic information over that provided by BNP, patients were sub-grouped using the median BNP (96 pg/mL) and GDF-15 (2027 ng/L). Figure

shows survival curves for the four subgroups. In a multivariate COX analysis when both GDF-15 and BNP were above the median, the risk of death was nearly three times as great (HR 2.75, 95% CI 1.75–4.30, p<0.001) compared to those with both below the median.

Conclusion: GDF-15 is an important prognostic marker in HF, independent of other markers and adds prognostic information to that provided by BNP alone.
Abstract 2387: Co-Localisation of C-Reactive Protein and the Terminal Complement Complex in Dilated Cardiomyopathy - Implications for Non-Ischaemic Heart Failure
Authors: Zimmermann Oliver , Manolov Dimitar E , Kaya Ziya , Zwaka Thomas P , Bienek-Ziolkowski Magdalena , Wolf Bettina , Hombach Vinzenz , Torzewski Jan
Published: July 2021

Background: C-reactive protein (CRP) has been suggested as a risk factor in cardiovascular disease. Recently, it has been shown that CRP binds to ligands exposed in ischaemic damaged tissue and activates the complement system. Furthermore, CRP was demonstrated to be strongly and independently associated with the occurrence of heart failure in men. In this study we have investigated the presence of CRP and the Terminal Complement Complex (C5b-9) in the myocardium of patients suffering from non-ischaemic heart failure.

Methods and Results: Endomyocardial biopsies were taken from 151 patients suffering from dilated cardiomyopathy. Biopsies were immunohistochemically analysed for the presence and distribution pattern of CRP and C5b-9. In 39 patients plasma levels of hsCRP and NT-proBNP were measured and correlated with myocardial biopsy findings. In 47 patients a positive staining for CRP and in 141 patients a positive staining for C5b-9 was detected. CRP and C5b-9 significantly co-localised within the myocardium. A negative correlation was observed for plasma hsCRP levels and myocardial CRP.

Conclusions: This study shows for the first time that CRP is frequently present in the myocardium of patients suffering from non-ischaemic dilated cardiomyopathy and co-localises with the Terminal Complement Complex. CRP may contribute to myocardial damage in dilated cardiomyopathy via activating the complement system.
Abstract 2403: Effect Of Prehospital Cath Lab Activation On Door To Balloon Time Of STEMI Patients Presenting During Normal Workday Hours
vs.
After Hours
Authors: Bachour Fouad , Smith Stephen , Hildebrandt David , Simegn Mengistu , Asinger Richard
Published: July 2021

BACKGROUND
: We significantly reduced door-to-balloon-time (DBT) after instituting prehospital cath lab activation for STEMI, without EKG transmittal or MD involvement.

OBJECTIVE:
To study the effect of the protocol on DBT in normal workday hours (cath lab team is in-house)
vs.
after-hours (cath lab team is not in-house).

METHODS
: For all STEMI patients (pts), data are collected prospectively. Since 2001 all pts transported by our institution’s EMS, with symptoms suggesting MI, have had prehospital EKG. In April 2005, we started the following additional protocol (with no other changes in our acute MI program): if the chief complaint is Chest Pain and the Zoll® M Series Interpretive EKG (Marquette 12SL algorithm) reads ``**Acute MI**,” Paramedics call the ED unit coordinator from the scene to activate the cath lab without MD involvement. For all EMS transported pts from Jan 2004 to Jan 2007, we analyzed demographics, symptoms, Zoll interpretation, door-to-EKG-time, and DBT. We compared the time saved before and after protocol change for normal workday hours vs. after hours. Statistics were by Kruskal Wallis and the two-tailed Fisher Exact test.

RESULTS:
There were 104 patients with STEMI transported in the time period. 36 were excluded: 26 with no chest pain (14 cardiac arrest), 8 with a non-diagnostic Zoll EKG and 2 others. Of 68 eligible patients (65% of all STEMI), 36 had prehospital activation (20 workday, 16 after hours) and 32 did not get prehospital activation (12 Workday and 20 after hours). See table

for results. Overall mean DBT was reduced from 86.0 ± 9.6 (CI) min. in the before group to 56.1 ± 7.7 min. in the prehospital activation group.

CONCLUSION
: Prehospital activation significantly reduces DBT in STEMI patients presenting during both normal workday hours and after hours. Significant time savings and exceptionally short DBTs (< 60 min) were achieved by prehospital activation for STEMI patients presenting during normal workday hours.
Abstract 2429: ICD Efficacy In Patients Who Developed New Onset Atrial Fibrillation After Enrollment In The MADIT-II Trial
Authors: Vyas Anant K , Goldenberg Ilan , Zareba Wojciech , McNitt Scott , Moss Arthur J
Published: July 2021

Introduction:
In the Multicenter Automatic Defibrillator Implantation Trial-II (MADIT-II), the presence of atrial fibrillation (AF) at baseline was associated with an increased risk of death, and these patients received a substantial benefit from ICD therapy. In the current study, we evaluated the risk of death and the efficacy of ICD therapy in patients who developed new-onset AF after enrollment in the MADIT-II study.

Methods/Results:
Hazard ratios (HR) were determined using multivariate Cox proportional hazards method. Age ≥ 65 (HR 3.02, p < 0.01), QRS duration > 120 ms (HR 2.30, p < 0.01), and NYHA functional class ≥ 2 (HR 1.78, p = 0.03) were independent predictors of new-onset AF. In both treatment arms, there was a significant increase in the risk of death after developing new-onset AF (Post-AF) (n = 25 in conventional arm, n = 51 in ICD arm) than among patients before or without AF (Pre-AF) (n = 416 in conventional arm, n = 624 in ICD arm) as shown in the Mantel-Byar graphs. After adjusting for relevant covariates (including age, BUN, EF, and beta-blocker use), ICD therapy was associated with a greater reduction in the risk of death in patients who developed new-onset AF (HR 0.31, p = 0.013) compared to patients with no interim AF (HR 0.73, p = 0.055) [p = 0.085 for interaction between interim AF and ICD therapy].

Conclusions:
The development of new-onset AF is associated with a significant increase in mortality and this group may be a target for closer follow-up and more aggressive treatment. ICD therapy was highly effective in reducing mortality in MADIT-II patients who developed new-onset AF after enrollment in the trial.
Abstract 2446: Determination of Key Sites of CFAE-targeted AF Ablation and Correlation with Cardiac Ganglionic Plexi
Authors: Lockwood Evan E , Nademanee Koonlawee
Published: July 2021

Substrate-targeted AF ablation relies on accurate locating of sites with Complex Fractionated Atrial Electrograms (CFAE). Our objectives were to determine if key sites of CFAE are predictably located and to determine the overlap of these sites with the locations of ganglionic plexi (GP). Utilizing a cardiac CT via image integration, we mapped all sites of CFAE on 54 pts (age 66 ±10 yrs; 78% male; 26% paroxysmal (pAF), 74% persistent or permanent AF (ppAF)) undergoing AF ablation. All patients were in SR at the end of the procedure. Ibutilide was used in 21% pAF vs. 85% ppAF (p<0.001) & DDCV was used in none of the pAF vs. 20% ppAF (p=ns). Mean number of lesions & mean RF duration were 46 ± 27 & 29.5 ±12 min for pAF; 62 ± 23 & 30 ±12 min for ppAF (p=0.04 & p=ns, respectively). A detailed grid of 44 regions in the LA, RA, & CS was created and applied to each CARTOMERGE (mean alignment 2.39 ± 0.43 mm). The prox CS & septal wall anterior to the RSPV were most common sites of CFAE regardless of AF type. The RSPV, LSPV, & anterior wall medial to the LAA were with next most common in pAF and the anterior wall medial to the LAA, the ridge between the LAA & LSPV, and the septal wall anterior to the RIPV were the next in ppAF. A CTI line was done in 21% pAF and 8% ppAF (p=ns) and targeted ablation within any PV antrum in 86% pAF and 83% ppAF (p=ns). Ablation near a GP occurred in >98% of pts (Figure

shows pts with ablation on each GP as %pAF / %ppAF).

Conclusion: the distribution of substrate that perpetuates AF (as indicated by CFAE) is not homogeneous, and predominant sites are the CS and areas near the PV’s and LAA. A PVI technique utilizing a wide antrum lesion set would affect similar areas in patients with pAF, but not necessarily ppAF.
Abstract 356: Loss of Function Mutations of Sodium Channel Beta-1 and Beta-2 Subunits Associated with Atrial Fibrillation and ST-segment Elevation
Authors: Watanabe Hiroshi , Darbar Dawood , Ingram Christiana R , Jiramongkolchai Kim , Chopra Sameer S , Kucera Gayle , Stubblefield Tanya , Wang Janey , Roden Dan M
Published: July 2021

Background:
We have recently reported mutations in the cardiac sodium channel gene
SCN5A
in 5.9% of patients with atrial fibrillation (AF). In this study, we tested the hypothesis that mutations in sodium channel β subunit genes
SCN1B-4B
contribute to AF susceptibility.

Methods and results:
All 4 βsubunit genes were resequenced in 376 patients with AF (118 patients with lone AF and 258 patients with AF and cardiovascular disease) and 188 ethnically-defined controls. We identified 2 non-synonymous variants in
SCN1B
(resulting in R85H, D153N) and 2 in
SCN2B
(R28Q, R28W) in patients with AF; these occur at residues highly conserved across mammals and were absent in controls. In 3 of 4 mutation carriers, there was saddle back type ST-segment elevation in the right precordial leads of electrocardiogram. Transcripts encoding both
SCN1B
and
SCN2B
were detected in human atrium and ventricle. To assess function
in vitro
, CHO cells were transfected with
SCN5A
without β subunit,
SCN5A
with wild-type (WT) β subunit, or
SCN5A
with mutant β subunit: all 4 mutants altered
SCN5A
current to a variable extent compared to WT β subunits. WT β1 increased
SCN5A
currents by 75%, and induced a negative shift in steady-state activation (−10.2 mV) and inactivation (−6.7 mV), compared to
SCN5A
alone. D153N β1 caused partial loss of function, with increased
SCN5A
current but to a smaller extent (24%) than WT β1, and a negative shift in steady-state activation (−12.1 mV) and inactivation (−8.1 mV) similar to WT. R85H β1 produced a pure loss of function, with currents no different from
SCN5A
alone. WT β2 did not change
SCN5A
current amplitude, while R28Q β2 and R28W β2 decreased current by 36% and 30%, respectively; and positively shifted steady-state activation by +7.4 mV and +5.1 mV, respectively, compared to WT.

Conclusion:
Loss of function mutations in sodium channel β subunits were identified in patients with AF, and were associated with a distinctive ECG phenotype. These findings further support the hypothesis that decreased sodium current enhances AF susceptibility.
Abstract 2468: Is the LV Reverse Remodeling Imparted by Aortic Valve Replacement for Severe Aortic Stenosis Durable? A Cardiovascular MRI Study
sponsored by the American Heart Association
Authors: Biederman Robert W , Magovern James A , Grant Saundra , Williams Ronald , Yamrozik June , Vido Diane A , Rathi Vikas K , Doyle Mark
Published: July 2021

Background

In patients with severe aortic stenosis (AS), long-term data tracking surgically induced beneficial effects of afterload reduction on reverse LV remodeling are not available. Echocardiographic data is available short term, but in limited fashion beyond one year. Cardiac MRI (CMR) offers the ability to track changes in LV metrics with small numbers due to its inherent high spatial resolution and low variability.

Hypothesis

We hypothesize that progressive changes following aortic valve replacement (AVR) are detectable by CMR and changes in LV structure and function, triggered by AVR, continue for an extended period following AVR.

Methods

Ten patients (67±12 yrs, 6 female) with severe, but compensated AS, underwent CMR pre-AVR and post AVR at 6±2mo, 1yr±2mo, 4yrs±5mo. LV mass index (LVMI), LV geometry, volumetrics and EF were measured (GE, EXCITE 1.5T, Milwaukee, WI). A Kruskall-Wallis one-way ANOVA was performed.

Results

All 10 pts survived AVR and underwent CMR at the 4-year time point (40 total time points). LVMI markedly decreased at 6 months (157±42 to 134±32g/m
2
, p<0.005) and continued to trend down at 4 yrs (127±32g/m
2
). Similarly, EF increased pre to post AVR (55±22 to 65±11%, (p<0.05)) and continued trending upward, remaining stable at years 1–4 (66±11 vs. 65±9%). LVEDV index, initially high pre AVR, normalized post AVR (83±30 to 68±11ml/m
2
, p<0.05) trending even lower by yr 4 (66±10 ml/m
2
). LV stroke volume increased rapidly from pre to post AVR (40±11 to 44±7ml) continuing to increase at 4 yrs (49±14ml, p=0.3). Most importantly, LVMI/volume, a 3D measure of LV geometry, remained unchanged initially but over 4 yrs markedly improved (1.07±0.2 to 0.94±0.24, p<0.05) all paralleling improvements in NYHA (3.2±1.0 to 1.5±1.1, p<0.05).

Conclusion

After the initial beneficial effects imparted by AVR in severe AS patients, there are, as expected, marked improvements in LV reverse remodeling. We have shown, via CMR, that surgically induced benefits to LV structure and function, including favorable alterations in LV geometry, are durable
and,
unexpectedly, show continued improvement past 4 years concordant with sustained improved clinical status. This supports down regulation of both mRNA and MMP activity acutely and robust suppression long term.
Abstract 2490: Non-uniformity of Three-dimensional Left Ventricular Relaxation Abnormalities in Hypertensive Left Ventricular Hypertrophy by Speckle Tracking Global Strain Rate Imaging
Authors: Takamura Takeshi , Dohi Kaoru , Onishi Katsuya , Fujimoto Naoki , Kurita Tairo , Kato Shinya , Yamada Norikazu , Nakamura Mashio , Isaka Naoki , Ito Masaaki
Published: July 2021

Background:
We tested the hypothesis that global strain rate imaging can quantify and stratify the severity of left ventricular (LV) relaxation abnormality in patients with left ventricular hypertrophy (LVH) ranged from normal to reduced LV systolic function independently from longitudinal (L), circumferential (C), and radial axes (R).

Methods:
Fifty-seven patients with hypertensive LVH and thirty age matched controls (Control, EF 65 ± 5 %) had echo-study with speckle tracking strain and strain rate imaging from (L), (C), and (R). LVH were divided into two groups; normal EF (LVH-NEF) defined as EF ≥ 55% (n = 35, EF 64 = 5 %), and systolic dysfunction (LVH-SD) defined as EF < 55% (n = 22, EF 48 ± 8 %). Global peak systolic strain (PSS) and peak relaxation rate (PRR) were used as indices of global LV contraction and relaxation, respectively (Vivid 7 and EchoPAC, GE Electronic).

Results:
PSS was maintained in LVH-NEF but reduced in LVH-SD from all three perpendicular axes. PRR (L) was impaired in LVH-NEF and was further decreased in LVH-SD (0.95 ± 0.33* and 0.58 ± 0.24*
†
1/s, *p <0.05 vs. Control and
†
p <0.05 vs. LVH-NEF, respectively)compared to Control (1.14 ± 0.30 1/s). PRR (C) was maintained in LVH-NEF but reduced in LVH-SD (1.24 ± 0.50 and 0.73 ± 0.36 1/s*, p <0.05 vs. Control) compared to Control (1.30 ± 0.48 1/s). PRR (R) was impaired in both LVH-NEF and LVH-SD in the same degrees (-1.53 ± 0.60* and -1.27 ± 0.64* 1/s, p <0.05 vs. Control: -2.08 ± 0.84 1/s).

Conclusion:
Speckle tracking strain rate imaging quantified and stratified the severity of LV relaxation abnormality in patients with LVH ranged from normal to reduced LV systolic function independently from all three perpendicular ventricular axes.
Abstract 2500: Left Ventricular Recovery in Peripartum Cardiomyopathy: Impact of Beta Blockade
Authors: Palmer Brittany A , Janosko Karen M , McTiernan Charles , Sherman Fred , McNamara Dennis M
Published: July 2021

Introduction
: Peripartum cardiomyopathy (PPCM) remains a major cause of maternal morbidity and mortality. PPCM is associated with acute myocardial dysfunction with a high rate of spontaneous recovery. For subjects with chronic non-ischemic cardiomyopathy, beta blockade (BB) increases left ventricular ejection fraction (LVEF), reverses remodeling and improves survival. The impact of beta blockade (BB) on recovery in acute inflammatory cardiomyopathy is less certain. We investigated the impact of BB on left ventricular recovery in a single center series of women with PPCM.

Method:
Thirty-six subjects with PPCM referred within the first six months post partum from 1994 to 2006 to the University of Pittsburgh Heart Failure Program were retrospectively reviewed. LVEF and LV diastolic diameter (LVEDD) were assessed by echocardiography at the time of referral (entry) and at approximately 6 and 12 months post partum. Medical therapy was assessed and LV recovery compared by treatment subset.

Results:
The mean age was 29.7 ± 6.9 years, gravida 2.9 ± 1.9, and para 2.3 ± 0.9. LVEF at presentation was 0.23 ± 0.09. Therapy at entry included ACE inhibitors in 95% of subjects Overall 19 (53%) subjects were not on BB at entry (Group A) while 17 were treated with BB (Group B). BB use differed based on year of presentation with 12% prior to January of 2000 and 80% post on BB therapy. Significant recovery was evident by 12 months by LVEF(0.23 ± 0.09 to 0.41 ± 0.16, p = 0.03)and LVEDD( 5.8 ± 0.9 to 5.3 ± 0.9, p = 0.01). Of note, recovery did not differ significantly by year of presentation or BB therapy(table

).

Conclusion
: Similar recovery was evident in subjects with PPCM treated with BB and recent historical controls not on therapy. While BB clearly plays an important role in treatment of women with chronic PPCM, they do not appear to enhance the probablity of spontaneous resolution.

Impact of Beta Bockade on LV remodeling in PPCM
Abstract 2546: Resting Regional Left Ventricular Function as Assessed using Cardiac 64-slice Computed Tomography to Predict Acute Coronary Syndrome in Patients with Acute Chest Pain
Authors: Rogers Ian S , Seneviratne Sujith K , Shapiro Michael D , Bamberg Fabian , Lehman Sam J , Hoffmann Udo
Published: July 2021

Background
: Cardiac computed tomography based noninvasive assessment of coronary atherosclerotic plaque and stenosis may be useful to improve risk stratification of patients with acute chest pain. Our goal was to determine the diagnostic accuracy of regional LV dysfunction assessed by MDCT for ACS in patients with acute chest pain but normal initial biomarkers and non-ischemic ECG.

Methods
: We included consecutive subjects without a known history of MI or left ventricular dysfunction who presented to the emergency department (ED) with acute chest pain but had negative initial troponin and no ischemic ECG changes. All subjects underwent standard contrast-enhanced 64-slice cardiac MDCT (0.6mm slice thickness, 120 kVp, 850 mAs) within = hours of presentation. Images were reconstructed at 10% intervals throughout the cardiac cycle and analyzed using short and long axis cine images of the LV cavity created with four-dimensional viewing software. All MDCT scans were assessed qualitatively for regional LV function using the AHA/ACC 17-segment model independently by two experienced readers, who were blinded to the clinical course and coronary plaque and stenosis findings.

Results
: One-hundred and seventy-three consecutive patients (mean age 56.2 ± 14 years, 56% male) were included. Twenty-two of these patients were ultimately diagnosed with ACS (MI 5, UAP 17) during their index hospitalization. Overall, 23 patients had impaired regional LV function, 17 of them had ACS (MI 5, UAP 12). The specificity (96%) and negative predictive value (96.6 –100%) for detection of ACS was excellent, even when patients with MI or UAP were excluded from subanalysis. Findings are summarized in table 1

.

Conclusion:
The absence of regional LV dysfunction at rest by MDCT has a excellent specificity for ACS in patients without a known history of CAD who present with acute chest pain of uncertain origin. This information may be complimentary to the detection of coronary plaque and stenosis.

Summary of Left Ventricular Function Analysis
Abstract 2547: Quantification of Myocardial Perfusion in Patients Using 256-Row Multidetector Computed Tomography: Evaluation of Endocardial vs. Epicardial Blood Flow
Authors: George Richard T , Yousuf Omair , Kitagawa Kakuya , Chang Hyuk-Jae , Bluemke David A , Lardo Albert C , Lima Joao A
Published: July 2021

Introduction:
The advent of 256x0.5 mm high resolution multidetector computed tomography (MDCT) created the potential to quantify subendocardial myocardial blood flow (MBF) reduction, the hallmark of ischemia. The purpose of this study was to test the hypothesis that adenosine stress / rest 256x0.5mm MDCT can detect ischemia by measuring differences in subendo-cardial versus subepicardial MBF.

Methods:
Nineteen patients with abnormal SPECT perfusion studies underwent adenosine (140μg/kg/min) stress 256x0.5mm MDCT perfusion imaging (CTP): 120kV, 100mAs, 3 gantry rotations at 0.5 secs, followed by rest 256x0.5mm MDCT angiography (CTA): 120kV, 175mAs, 3 gantry rotations at 0.5 secs. CT perfusion images were reconstructed in the short axis with a 3 mm slice thickness. Endocardial and epicardial borders were defined, myocardium was sectored according to the standard 17 segment model, and divided circumferentially into endocardial and epicardial layers. The transmural perfusion ratio (TPR) was calculated by dividing the endocardial attenuation density (AD) by the epicardial AD in each sector. Ischemia was defined as TPR <0.8 in more than one sector. The TPR results were compared to the presence or absence of stenoses ≥50% on CTA and perfusion deficits on SPECT.

Results:
Mean TPR in abnormal and normal sectors was 0.71±0.05 and 1.01±0.06, respectively (p<0.01). Mean number of abnormal sectors for patients with no stenoses, 1-vessel, and multi-vessel disease were 1.6, 2.5, and 6.3; respectively (p<0.05). The sensitivity and specificity of TPR for detecting a stenosis ≥50% severity was 62% and 86% compared with 62% and 71% for SPECT (NS). When defining territorial ischemia as a SPECT perfusion abnormality plus a stenosis ≥50%, the sensitivity, specificity, positive and negative predictive values were 75%, 95%, 75%, and 95% for combined CTA/CTP imaging, respectively.

Conclusions:
The transmural perfusion ratio measured from 256x0.5mm MDCT perfusion images can detect the presence of obstructive atherosclerosis with similar accuracy compared with SPECT imaging. The combination of 256x0.5mm MDCT angiography and perfusion imaging may avoid the high false positive rate seen with SPECT imaging alone as well as improve its prediction of territorial ischemia.
Abstract 2553: Effect of Pre-Transplant Extracorporeal Membrane Oxygenation on Pediatric Heart Transplantation Outcomes: An Analysis of the United Network for Organ Sharing Database
Authors: Patel Nishant D , Weiss Eric S , Nwakanma Lois U , Scheel Janet , Cameron Duke E , Vricella Luca A
Published: July 2021

Introduction
: Extracorporeal membrane oxygenation (ECMO) has been used as salvage therapy in children with intractable heart failure as a bridge to transplantation, but outcomes have not been examined in a large pediatric transplant database.

Methods
: All pediatric (<18 years of age) primary heart transplant recipients reported to the United Network for Organ Sharing database from 1999 –2007 were reviewed and segregated according to need for pre-transplant ECMO. Survival was estimated by Kaplan-Meier method before and after propensity match analysis. Propensity-adjusted Cox regression modeling was used to identify predictors of mortality.

Results
: During the study period, 2141 children underwent first time heart transplantation: 154 (7%) were on ECMO. On univariate analysis, children bridged to heart transplant with ECMO had lower weight at operation (15 vs 27 kg;
p
<0.0001), shorter time on the organ waitlist (31 vs 92 days;
p
=0.0002), longer post-transplant length of stay (40 vs 24 days;
p
<0.0001), and higher incidence of stroke (5% vs 2%,
p
=0.02), reoperation (16% vs 8%;
p
=0.002), and infection (50% vs 25%;
p
<0.0001). Kaplan-Meier 5-year survival was inferior for the pre-transplant ECMO group (55% vs 73%) (Figure

), both before and after propensity matching (
p
<0.0001). After propensity score adjustment, pre-transplant ECMO was a significant predictor of mortality (HR 2.7; 95% CI 1.8 – 4.1;
p
<0.001).

Conclusion
: Patients on ECMO before heart transplant have inferior outcomes, even after adjustment for propensity scores, but still have acceptable 5-year survival. Improvement in survival will likely require refinement in mechanical support technology and practice.

Kaplan -Meler Estimates of Morality 1999–2007 Stratified by ECMO
Abstract 2570: Effects Of Exercise On Left Ventricular Diastolic Function Depend On Homogenous Increase In Diastolic Strain Rates
Authors: Goh Teck Hwa , Popovic Zoran B , Buakhamsri Adisai , Greenberg Neil , Thomas James D
Published: July 2021

Objectives:

It has been speculated that early diastolic left ventricular (LV) suction depends on LV apex relaxing more promptly than LV base, and that these relationships are accentuated during exercise. In this study, we sought to determine impact of exercise on the relationship between parameters of LV diastolic mechanics (peak early longitudinal (E SrL), circumferential (E SrC) and radial (E SrR) strain rate, and peak LV untwisting velocity) and intraventricular pressure gradient (IVPG) as marker of diastolic suction.

Methods:

We studied 23 healthy volunteers (age 38 ± 10 years, 13 females) by Vivid 7 ultrasound machine (GE) during supine bicycle stress. Segmental diastolic strain rates and untwisting velocity were obtained by speckle tracking software (EchoPac, GE Medical) while IVPG was measured by applying the Euler equation to the transmitral color Doppler M mode of the LV inflow. Segmental diastolic strain rates were averaged over basal, mid, and apical levels.

Results:

Absolute values of E SrL, E SrC and E SrR homogenously increased during exercise (P<0.001 for all) by the same degree at all LV three levels (p=NS for the difference between levels). (see table

) Untwisting velocity during exercise increased from -1.54 ± 0.69 to -3.40 ± 1.54 rad/s while IVPG increased from 1.41 ± 0.67 to 3.90 ± 1.69 mmHg (p<0.001 for both). Out of strain parameters, average E SrL increase during exercise showed strongest correlation with IVPG (r=0.64, p<0.001) and untwisting velocity (r=0.62, p<0.001). Higher untwisting velocity was associated with the greater IVPG (r=0.70, p<0.001).

Conclusions:

Increase of suction during exercise is related to homogeneous augmentation of relaxation throughout left ventricle. Longitudinal strain rate was the best predictor of the increase of untwisting velocity and IVPG. These data could serve as a reference for diastolic stress testing.
Abstract 2573: Usefulness of 2D Speckle Tracking Echocardiography for Assessment of Tako-Tsubo Syndrome
Authors: Mansencal Nicolas , Pillière Rémy , Mahmoud Rami El , Farcot Jean-Christian , Joseph Thierry , Dubourg Olivier
Published: July 2021

Background:
The pathogenesis of Tako-Tsubo (TT) syndrome (stress-induced cardiomyopathy) is not yet understood. Velocity vector imaging (VVI) is a new echocardiographic technology that measures myocardial velocity and deformation using 2D speckle tracking. The aim of this study was to compare the pattern of VVI in pts with TT sy, coronary artery disease (CAD) and in healthy pts.

Methods:
We prospectively studied 36 consecutive pts divided in 3 groups: 12 pts with confirmed TT sy (group 1), 12 pts with CAD defined as a documented LAD occlusion (group 2) and 12 healthy pts (group 3) and all groups were age- and sex-matched. We systematically performed echocardiography in all pts, with the use of VVI technology, allowing to measure peak velocity (V), strain (S) and strain rate (SR) in basal, mid and apical septum and free wall (FW) in apical 4-chamber view.

Results:
Mean age was 76 ± 8 yo in each group (36 women). Mean values of V, S and SR in mid and apical septum and FW were significantly lower in TT sy (p<0.04), as compared to group3, but not with group2. In group 1 as well as in control group, no significant differences for the values of V, S and SR were observed between basal septum and bas.FW, between mid septum and midFW and between apical septum and ap.FW (p=NS, Fig

), whereas in patients with CAD (group 2), basal septal V was significantly higher versus basal FW V (p=0.04) and apical septal V was significantly lower versus apical FW V (p=0.02).

Conclusion:
Our study suggests that VVI allows to distinguish patients with TT sy from those with CAD. In TT sy, left ventricular dysfunction is circular, whereas pts with LAD occlusion presented segmental wall motion abnormalities detected by VVI.
Abstract 2583: Successful Use Of Immune Monitoring (Cylex) In Heart Trasnplantation For Rejection And Infection Risk
Authors: Kobashigawa Jon , Kiyosaki Krista , Kubak Bernard , Patel Jignesh , Kittleson Michelle , Ardehali Abbas
Published: July 2021

Background: An unmet need in heart transplantation (HTx) has been the lack of a reliable immune monitoring test to indicate recipient immunoresponsiveness (IR). Trough immunosuppression blood levels do not reflect a recipient’s IR state. Recently, immune monitoring with Cylex (measure of ATP levels from activated lymphocytes) has been reported to predict risk of rejection or infection in kidney transplant patients. We now review our experience with immune monitoring and clinical course after HTx.

Methods: Between 2005 and 2007, 41 HTx patients had 82 immune monitoring assays obtained from 12 to 3034 days after HTx. ATP activity was graded as low IR (<225 ng/ml), moderate IR (225–525 ng/ml), or high IR (>525 ng/ml). Immune monitoring scores were correlated to infection and rejection episodes. All patients were treated with triple drug immunosuppression (tacrolimus, mycophenolate, and corticosteroids).

Results: For infectious episodes (n=34), immune monitoring scores <225 were found in 18/25 (72%) samples, compared to 16/57 (28%) samples >225, p < 0.001. The average immune monitoring score during infection compared to those samples without infection was 259 vs. 378, p <0.001. For rejection episodes (n=6), immune monitoring scores <225 were found in 0/24 (0%) samples compared to 6/58 (10%) samples >225, p = 0.101. The average immune monitoring score during rejection compared to those scores without rejection was 454 vs. 318, p = 0.041. There were 34 infections (1 parasitic, 8 viral, 13 bacterial, and 12 fungal infections).

Conclusion: Immune monitoring with Cylex for HTx patients appears to reflect the degree of recipient IR state and risk for rejection and infection.