bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2405: Effect of Early Emergency Room Notification on Door-to-Balloon Time in Patients Presenting with ST Elevation Myocardial Infarction
Authors: Kardouh Youssef , Rao Anjani , Green Kimberly , Ymana Joselyn , David Shukri
Published: July 2021

Background:
The goal of mechanical reperfusion therapy in the setting of ST Segment Elevation Myocardial Infarction (STEMI) is to re-establish blood flow to the affected vascular bed as quickly as possible. Primary angioplasty has been shown to be superior to fibrinolysis when door-to-balloon (DTB) time is less than 60 minutes. The median DTB time in the United States is 185 minutes and only 3% of patients are currently being mechanically reperfused within the 90 minutes as recommended by American College of Cardiology guidelines. The purpose of this study is to see if an aggressive approach involving emergency medical services (EMS), emergency room (ER) personnel, and the early activation of cardiac interventional team could improve reperfusion times. We evaluated the feasibility of pre-hospital Electrocardiogram (phECG) to triage patients with STEMI directly to the cardiac catheterization laboratory (CCL) compared to the standard therapy at two primary PCI centers

Methods:
The EMS personnel obtained a 12-lead ECG during initial assessment in the field from patients with symptoms of myocardial infarction. The ECG was immediately transmitted to the ER physician by cellular link to a computer receiving station located in the ER. The ER physician reviewed the 12-lead ECG digital tracing. The cardiac catheterization laboratory (CCL) team was activated from the patients’ homes. Patients were transported from the field directly to the CCL by EMS bypassing ER admission.

Results:
From Oct 2003 to May 2007, 142 consecutive patients with STEMI who presented to Providence Hospital and Medical Centers were included in the study. The conventional treatment group (125 patients) had a mean DTB time of 123 minutes. We identified 359 phECGs transmitted to the ER, 43 of which had inadequate transmission signal. Adequate phECG transmission was detected in 88% cases. We diagnosed 17 patients with STEMI by phECG who were included for the analysis. The mean DTB time was significantly lower in patients diagnosed using phECG (46 minutes vs. 123 minutes, p<0.001).

Conclusion:
Utilizing the phECG as a tool to bypass ER triage significantly decreases DTB times in patients with STEMI. This technology has the potential to substantially expedite reperfusion therapy in patients with STEMI.
Abstract 2411: A Randomized, Controlled Trial Comparing the Arctic Sun to Standard Cooling for Hypothermia After Cardiac Arrest
Authors: Heard Kennon , Peberdy Mary Anne , Sayre Michael R , Sanders Arthur , Geocadian Romergryko G , O’Neil Brian J
Published: July 2021

Hypothermia therapy improves neurological outcome following out-of-hospital cardiac arrest (OOHCA). Standard surface cooling (SC) with ice packs and cold water blankets is readily available, but is labor intensive and often overcools the patient. The Arctic Sun® (AS) surface cooling system uses enhanced energy transfer pads and close computer control of patient temperature (temp). The objective of this study was to compare the AS to SC for treatment of patients with OOHCA. We hypothesized that a greater proportion of patients treated using the AS would reach 34°C within 4 hours of starting cooling (primary outcome) and AS treated patients would be less likely to be out of target range (32–34°C) during 24 hours of cooling than patients treated with SC. This multicenter trial enrolled unresponsive, hemodynamically stable patients resuscitated from witnessed OOHCA of presumed cardiac cause, with any initial rhythm. After randomization, sedation and paralysis, cooling devices were set to a target temp of 33.5°C and core temperature was monitored continuously. Assuming that 60% of SC treated patients will reach 34°C within 4 hours, a sample size of 64 has 80%power (α = 0.05) to identify a 30% absolute increase in the primary outcome. Thirty-four AS and 30 SC subjects were enrolled; three (2 AS, 1 SC) were withdrawn prior to initiating cooling. Overall, 75% of AS patients vs. 55% of SC patients reached 34°C within 4 hours (95% CI of the increase -4% to 43%). The mean (SD) time to 34°C was 200 (78) min for the AS group and 275 (195) min for the SC group. While 28/29 SC patients had a recorded temp outside of range, only 9/32 AC patients were out of range (Relative Risk=3.4; 95% CI 2.0 to 6.0). The rates of serious adverse events during cooling were similar (13% AS, 22% SC; p=0.3). The rate of Cerebral Performance Category of 1 or 2 recorded at final follow-up was similar (47% AS, 34% SC, p=0.4). In conclusion, the AS and SC are both safe and effective for inducing hypothermia. The AS may cool more quickly, but a lower than expected primary outcome rate in both groups limited our power to evaluate the primary outcome difference. After reaching 34°, AS patients were less likely to be out of range. Long-term neurological outcome was good among these comatose survivors of cardiac arrest.
Abstract 2419: The Presence of Q Waves, QRS Fragmentation or QRS Duration Does Not Correlate with Scar Volume in Patients with Ischemic Cardiomyopathy.
Authors: Carey Mary G , Luisi Andrew J , Baldwa Sunil , Thomas Joshua M , Canty John M , Fallavollita James A
Published: July 2021

Background.
Recent studies have suggested that scar volume is one of the predictors of ICD utilization. We hypothesized that noninvasive ECG predictors of myocardial scar (number of leads with Q waves and/or fragmented QRS complexes, fQRS) would correlate with infarct size and could predict patients with a depressed ejection fraction that would be the most likely to benefit from imaging scar volume.

Methods.
Patients with ischemic cardiomyopathy eligible for an ICD for the primary prevention of sudden death underwent PET imaging (n=78). Scar volume (% LV) was quantified from
18
FDG uptake during insulin stimulation and
13
N-ammonia flow using a validated algorithm (MyoPC, Ottawa Heart Institute). Pathologic Q waves and fQRS (RSR morphology or notching in R or S waves) on the 12-lead ECG were assessed by consensus of three blinded readers.

Results.
Subjects were 67 ± 12 years of age and 87% male. Average ejection fraction was 28 ± 10%. Myocardial scar encompassed 17.1 ± 7.3% of the left ventricle, with a very wide range among subjects (1.9 to 34.4%). In patients with a QRS duration <120 msec (n=47), there was very poor correlation between scar volume and the number of leads with Q waves, fQRS or both (R
2
=0.01– 0.06, Table

). Furthermore, patients with a wide QRS (>120 msec) did not have an increase in scar volume (Table

).

Conclusions.
These results indicate that 1.) The volume of scar varies widely in patients with ischemic cardiomyopathy that are eligible to receive an ICD for primary prevention and 2.) Infarct volume is independent of electrocardiographic indices of scar. Thus, imaging is necessary to stratify risk for SCD as a function of scar volume.
Abstract 2445: Comparison of Atrial Fibrillation Ablation Strategies for Paroxysmal patients presenting to the Electrophysiology Laboratory In atrial fibrillation
Authors: Di Biase Luigi , Elayi Claude S. , Ching Chi Keong , Hongo Richard , Hao Steven , Beheiry Salwa , Wu Chia-Tung , Patel Dimpi , Kanj Mohamed , Verma Atul , Wazni Oussama M. , Armaganijan Luciana , Sonnie Kai , Kanj Mohammed , Pelargonio Gemma , Russo Antonio Dello , Casella Michela , Santarelli Pietro , Potenza Domenico , Sofferenza Casa sollievo della , Massaro Raimondo , Sofferenza Casa Sollievo della , Cummings Jennifer E. , Saliba Walid I. , Khaykin Yaariv , Arruda Mauricio , Natale Andrea
Published: July 2021

BACKGROUND
: Whether different ablation strategies affect paroxysmal atrial fibrillation (AF) termination mode and long term cure is unclear. We compared the effect of different ablation strategies on the AF termination and long term success in patients with parox-AF presenting to the electrophysiology laboratory in AF.

METHODS
: One hundred and three (103) consecutive patients with parox-AF scheduled for AF ablation presenting in the lab in AF were selected for this study. The patients were randomized to PVAI only (35 pts) versus bi-atrial ablation of the complex fractionated atrial electrograms (CFAE defragmentation) including the coronary sinus (34 pts) versus CFAE followed by PVAI (34 pts) Modes of AF termination were: conversion to SR, organization into AT or persistence of AF requiring cardioversion following ablation.

RESULTS
are summarized below: There was no significant difference between the groups in term of sex, age, AF duration, LA size and EF. Follow up after a single procedure with AAD is summarized below

CONCLUSION
: Defragmentation alone had the smallest impact on both acute AF termination and one year follow-up cure rate. No difference in terms of acute and chronic success was seen between PVAI alone and PVAI asoociated with defragmentation. This suggests that PV isolation is critical to cure AF in paroxysmal AF and that adjunctive strategies have minimal impact on cure rate and should not be considered in all patients.
Abstract 2450: A Randomized Controlled Trial of Low Dose Hormone Therapy on Myocardial Ischemia in Postmenopausal Women with No Obstructive Coronary Artery Disease:Results from the NHLBI-sponsored WISE
Authors: Merz C. Bairey , Olson Marian , McClure Candace , Symons James , Sopko George , Kelsey Sheryl , Handberg-Thurmond Eileen , Johnson B. Delia , Cooper-DeHoff Rhonda , Sharaf Barry , Rogers Williams , Pepine Carl
Published: July 2021

Background:
Compared with men, women have more evidence of myocardial ischemia in the setting of no obstructive coronary artery disease (CAD). While low endogenous estrogen levels are associated with endothelial dysfunction, the role of low dose hormone therapy has not been fully evaluated in women suffering from myocardial ischemia and no obstructive CAD.

Objective:
This WISE ancillary trial evaluated the effect of low dose hormone therapy in postmenopausal women with myocardial ischemia and no obstructive CAD on:

endothelial dysfunction, assessed by brachial artery reactivity,

physical functional disability assessed by exercise testing, and

quality of life assessed by cardiac symptoms and psychological questionnaires.

Methods:
Using a multicenter, randomized, placebo-controlled design, seventy-four participants with normal/minimally diseased epicardial coronary arteries (<50% luminal diameter stenosis) who fulfilled the inclusion criteria were planned to be randomized to receive either 1 mg norethindrone/10 mcg ethinyl estradiol (1/10 NA/EE) or placebo for twelve weeks. Baseline and exit brachial artery reactivity (BART), exercise stress testing, WISE psychosocial questionnaires, SF-36, blood lipids and hormone levels were evaluated.

Results:
Recruitment was closed prematurely due to failure to recruit in the year following publication of the Women’s Health Initiative hormone trial results. Of the 37 women randomized, 35 completed the study. While there was no difference in the frequency of chest pain between groups at the baseline visit, at study exit there was less frequent chest pain in the 1/10 NA/EE group compared to the placebo group (p=0.02). Women taking 1/10 NA/EE also showed a trend to improved BART and exercise tolerance, and had significantly fewer hot flashes/night sweats (p=0.003), less avoidance of intimacy (p=0.05), and borderline differences in sexual desire and vaginal dryness (p=0.06).

Conclusion:
Among postmenopausal women with myocardial ischemia and no obstructive CAD, hormone therapy with 1/10 NA/EE is associated with reduced chest pain symptoms, menopausal symptoms and improved quality of life with trends for improved endothelial function and exercise performance.
Abstract 357: Novel Gain of Function SCN5A Mutation Causes Familial Atrial Fibrillation
Authors: Rutberg Julie , Huang Hai , Lemery Robert , Tang Anthony , Birnie David , Green Martin , Lam B. Khanh , Roberts Robert , Chahine Mohamed , Gollob Michael
Published: July 2021

Background
: Few genetic etiologies are known for familial or sporadic cases of atrial fibrillation, which is the most common arrhythmia in older adults. We report a mother and son, both with atrial fibrillation, who were found to have a novel mutation in the sodium channel gene, SCN5A.

Case History:
The proband, a 50 year old male, first developed paroxysmal atrial fibrillation following orthopedic surgery. At age 57, he presented with increasing fatigue and shortness of breath and was found to have chronic atrial fibrillaion. Cardiac testing found no evidence of ischemia, normal left ventricular function and mild left atrial dilation. His mother had paroxysmal atrial fibrillation, diagnosed at age 63, and a history of well-controlled hypertension and palpitations. Her atrial fibrillation was initially controlled by sotalol, but worsening symptoms led to a change to amiodarone at age 83. Her echo showed mild biatrial enlargement. ECGs for the proband and his mother have never demonstrated conduction system disease, long QT, or a Brugada pattern.

Methods and Results:
Genomic DNA isolated from blood lymphocytes was screened using direct sequencing techniques. Genes previously reported to be associated with atrial fibrillation, KCNA5, GJA5 and KCNQ1, were screened and no mutations were found. In the sodium channel gene, SCN5A, a novel missense mutation was identified (c. 1493K>R) in both the proband and his mother, but not in an unaffected sibling or in the proband’s 2 asymptomatic offspring. The mutation is in a highly conserved lysine residue in the voltage-gated sodium channel gene family. Functional studies recorded macroscopic sodium currents from tsA201 cells expressing both the wild-type (Nav1.5/WT) and mutant channel (Nav1.5/K1493R). The mutant channel exhibited fast activation and inactivation kinetics and an increase in current density. No effect on steady-state activation and inactivation were observed, however, current deactivation was faster in mutant Nav1.5/K1493R as compared to the WT channels.

Conclusions:
This is the first report of an inherited SCN5A mutation in familial atrial fibrillation. Functional studies suggest a ’gain-of-function’ effect of the identified Nav1.5/K1493R mutation.
Abstract 359: Highly Malignant Perinatal Variant of Long-QT Syndrome Caused by a Profoundly Dysfunctional
SCN5A
Mutation Successfully Treated with Mexiletine and Propranolol
Authors: Wang Dao W , Crotti Lia , Ferrandi Chiara , Rhodes Thomas H , Cantu Francesco , Filippo Paolo D , Schwartz Peter J , George Alfred L
Published: July 2021

Perinatal presentation of long-QT syndrome (LQTS) is uncommon but typically more severe and often fatal. We studied the functional and pharmacological properties of a novel
SCN5A
mutation associated with a highly malignant perinatal variant of LQTS successfully treated with mexiletine and propranolol. The proband was delivered by emergency C-section at 32-weeks because of fetal arrhythmia. Immediately after birth, the infant had polymorphic ventricular tachycardia and a slow sinus rate that were unresponsive to Mg and isoproterenol. Lidocaine controlled ventricular arrhythmia and allowed recognition of a prolonged QTc (520 ms). Treatment with propranolol (1 mg/kg/d) and mexiletine (11 mg/kg/d) normalized the QTc (410 ms) and suppressed ventricular ectopy. One month after discharge, the infant survived ventricular fibrillation and later developed paroxysmal atrial flutter. Genetic testing revealed a novel,
de novo
missense
SCN5A
mutation (G1631D) located immediately before the 4
th
arginine residue in D4/S4.
In vitro
electrophysiological studies using whole-cell patch clamp recording of channels expressed in tsA201 cells revealed a profound defect in channel function characterized by ∼10-fold slowing of inactivation, increased persistent current, marked slowing of recovery from inactivation, depolarized voltage-dependence of activation and steady-state channel availability. Single channel recordings demonstrated increased frequency of late openings, increased open times and bursting. These biophysical properties were distinct from typical LQT3 mutations and represent the most severely dysfunctional
SCN5A
mutation ever reported. The mutant also exhibited 2-fold enhancement of tonic and use-dependent block by mexiletine as compared with wild-type channels. Unexpectedly, the mutant channel also exhibited enhanced tonic block (2.4-fold) and use-dependent block (∼5-fold) by propranolol. Our study demonstrated the molecular basis for a highly malignant perinatal variant of LQTS, illustrated novel functional and pharmacological properties of
SCN5A
-G1631D which caused the disorder, and illustrated an unexpected clinical benefit of propranolol in blocking mutant Na channels in this setting.
Abstract 2454: Long-Term Administration of Thiazolidinedione Provides Multiple Antiatherosclerotic Effects Independent of Diabetic Improvement for Type-2 Diabetics With Coronary Artery Disease Receiving Statin
Authors: Murakami Tatsuaki , Kokado Hiromasa
Published: July 2021

Background:
Insulin resistance and type-2 diabetes mellitus are thought to be highly involved in complex atherothrombogenic processes, but the long-term effects of insulin sensitizing agents remain partially clarified. We assessed hypothesis that long-term use of thiazolidinedi-one, an insulin sensitizer, pleiotropically inhibits atherosclerotic progression in patients treated with statin one of the standard antiatherosclerotic therapies.

Methods:
Thirty type-2 diabetic patients with stable coronary artery disease were randomized to group-T where they received troglitazone (400mg/day) or pioglitazone (30mg/day), or to group-C where they continued therapy without thiazolidinedione for more than 2 years. We noninvasively quantified flow-mediated dilation of brachial artery after 5 minutes forearm occlusion (FMD), dilation of brachial artery after sublingual administration of nitroglycerin (TNG), and intima-media thickness of common carotid artery (IMT) using high-resolution ultrasonography. Changes in FMD, TNG, and IMT were compared between the 2 groups.

Results:
All the patients in group-T (n=15) manifested good compliance to the treatment and improvements in diabetic variables represented by HbA1c while group-C showed no improvement. FMD (%) increased after medication in group-T (p<0.01) but remained unchanged in group-C (p=0.84). TNG (%) remained unchanged in group-T (p=0.13) and in group-C (p=0.76). IMT (mm) decreased in group-T (p=0.04) but remained unchanged in group-C (p=0.21). Changes of FMD or IMT did not correlate to those of HbA1c (FMD: r=0.20, p=0.74, IMT: r=0.25, p=0.49).

Conclusion:
These results indicate long-term therapy with thiazolidinedione in diabetic patients receiving statin additionally improves endothelial function and reduces arterial wall thickness independent of reversal for clinical glucose metabolic status, which may have novel potential benefit for management of atherosclerosis in type-2 diabetics.
Abstract 2457: Left Ventricular Assist Device Therapy with the HeartMate II Continuous Flow Rotary Pump as a Bridge to Heart Transplantation
Authors: Pagani Francis D , Miller Leslie W , Russell Stuart D , John Ranjit , Aaronson Keith D , Conte John V , Naka Yoshifumi , Delgado Reynolds M , MacGillivray Thomas E , Farrar David J , Frazier O. H
Published: July 2021

Background: The HeartMate (HM) II continuous flow rotary pump represents a new generation of implantable left ventricular assist device (LVAD) that has recently completed clinical evaluation in an FDA-approved study for bridge to transplantation (BTT). Through a continued access protocol (CAP), an additional cohort of patients has undergone implantation of the HMI II device. We report on a comparative analysis of outcomes from both the primary and CAP cohorts.

Methods: In a prospective, multi-center study, 297 patients with refractory heart failure and on intravenous inotrope therapy underwent implantation of the HM II to evaluate safety and efficacy as a BTT (n=133 patients-primary study cohort; n=164 patients-CAP; 61 patients in the CAP cohort completed 6 mo followup).

Results: Baseline demographics, hemodynamics, renal and hepatic function were not significant between groups (Table 1

). Number of patients with positive outcomes at 6 mo (transplant, cardiac recovery, alive on LVAD) were similar between cohorts (79% vs 80%). HM II therapy improved 6 minute walk distance at 3 month followup (by 250±232 m vs 226±180 m), and quality of life (Minnesota Living with Heart Failure; by 37% vs. 41%) to similar degrees for each cohort. The incidence of significant adverse events (pump replacements, 5 vs. 1; postoperative bleeding requiring surgery, 31% vs 23%; ischemic and hemorrhagic stroke, 8.0% vs 9.8%; need for RVAD, 4% vs 8%) were not significant between groups.

Conclusions: Outcomes from patients implanted with the HMII device during CAP were similar to outcomes of patients implanted in the primary cohort. These analyses validate the original findings regarding efficacy and risk profile of the HM II continuous flow LVAD in this patient population as a BTT.

table 1
Abstract 2459: A Potentially Novel Role Of The Follistatin-activin Pathway In Heart Failure And Myocardial Recovery Following Lvad Combination Therapy
Authors: Lara-Pezzi Enrique , Felkin Leanne E , Sarathchandra Padmini , George Robert , Hall Jennifer L , Yacoub Magdi H , Rosenthal Nadia , Birks Emma J , Barton Paul J
Published: July 2021

Background
- Recent evidence suggests that the activin pathway may play an important role in the pathogenesis of heart failure. Follistatins are potent inhibitors of activin signalling but their role in the heart is unknown. The purpose of this study was to investigate myocardial expression of follistatin (FST) and follistatin-like (FSTL1 and FSTL3) in heart failure and following recovery in patients who received combined mechanical unloading using left ventricular assist device (LVAD) and pharmacologic therapy.

Methods and results
- Real time quantitative PCR was used to examine gene expression in myocardial samples from donors (n=9), end-stage heart failure patients (n=27) and patients who recovered from heart failure sampled at the time of LVAD implant, at the time of LVAD removal following recovery, and one year post explant. Both FSTL1 and FSTL3 were elevated in heart failure (1.51 and 2.50 fold respectively p<0.005) with expression returning to normal following recovery. Whereas FSTL3 correlated with molecular markers of disease severity, FSTL1 showed negative correlation with skeletal α-actin and positive correlation with the endothelial cell marker CD31, suggesting a potential link with extent of vascularization. FSTL1 expression levels at LVAD implant also correlated with significantly higher ejection fraction following recovery suggesting initial levels may have an influence on long term outcome. Immunohistochemical analysis showed that FST was localised in fibroblasts and endothelium, FSTL1 in myocytes, endothelium and smooth muscle cells, and FSLT3 in myocytes and endothelium. Microarray analysis showed that FST and FSTL1 expression correlate with extracellular matrix-related and calcium binding proteins, whereas FSTL3 is associated with cell signalling and transcription.

Conclusion
- These data show for the first time that elevated myocardial expression of follistatin-like genes is a feature of heart failure and that this may be linked both to disease severity and to mechanisms underlying recovery thereby revealing new insight into the pathogenesis of heart failure and offering novel therapeutic targets.
Abstract 2467: Stentless Aortic Valve Replacement Increased the Requirement for Permanent Pacemaker
Authors: Lehr Eric , Allen Elizabeth , Mullen John , MacArthur Roderick , Ross David , Koshal Arvind , Gelfand Elliot , Modry Dennis , Wang Shao Hua
Published: July 2021

BACKGROUND: Stentless aortic valve prosthesis are thought to provide a superior hemodynamic profile compared to mechanical or other tissue valve replacements. Unlike other aortic valve prostheses, stentless valves are most commonly implanted in the subcoronary position, potentially resulting in the placement of sutures in the atrio-ventricular node of the heart’s conduction system. We assessed the incidence of permanent pacemaker insertion following aortic valve replacement.

METHODS: We performed a retrospective cohort analysis of all patients who underwent aortic valve replacement at the University of Alberta Hospital between January 1996 and December 2004. The primary outcome was heart block requiring permanent pacemaker insertion. Binary logistic regression analysis was performed to assess the influence of a number of factors on the requirement for permanent pacemaker insertion.

RESULTS: In total, 1,451 patients underwent aortic valve replacement (69% male, age 17–92). Permanent pacemaker insertion was required in 32 (5.0%) of 644 patients receiving mechanical valves and in 24 (4.4%) of 543 patients who had a stented tissue aortic valve replacement. In contrast, 27 (10.2%) of 264 patients who had a stentless bioprosthetic valves implanted developed heart block necessitating permanent pacemaker insertion (P = 0.02). Logistic regression demonstrated that implantation of a stentless tissue valve and postoperative inotropic support were the only two significant predictors of the development of heart block following aortic valve replacement.

CONCLUSIONS: Aortic valve replacement with a stentless valve prosthesis increases the risk of heart block and the requirement for permanent cardiac pacing.

Multivariate predictors of requirement for permanent pacemaker
Abstract 2475: Time Course Of Response To Cardiac Resynchronization Therapy In Patients With Ischemic And Non-ischemic Cardiomyopathy
Authors: Marsan Nina Ajmone , Van de Veire Nico R , Ypenburg Claudia , Bleeker Gabe B , Holman Eduard R , van der Wall Ernst E , Schalij Martin J , Bax Jeroen J
Published: July 2021

Background.
Cardiac resynchronization therapy (CRT) results in improved left ventricular (LV) systolic function expressed by reduction in LV end-systolic volume (ESV). However, it is still not well known whether this reduction in LVESV occurs immediately after CRT (acute response) or whether some pts need more time to improve in LVESV. Aim of the study was to evaluate the time course of response (improvement in LVESV) to CRT. Particularly, the time course of response was compared between pts with ischemic and non-ischemic cardiomyopathy.

Methods.
95 consecutive heart failure pts (84 men; 65±10yrs, 60 pts with ischemic cardiomyopathy and 35 pts with non-ischemic cardiomyopathy) scheduled for CRT, were included. 2D echocardiography was performed before, immediately after CRT and at 6 months follow-up (6MFU) to evaluate LVESV and LV ejection fraction (EF).

Results.
Immediately after CRT, a significant reduction in LVESV was observed combined with a significant increase in LVEF. At 6MFU a further improvement in LVESV and LVEF was noted (Table

).When a reduction in LVESV>15% was used to define response to CRT, 38% exhibited an acute response, with an additional 18% at 6MFU resulting in a total of 56% responders to CRT. In pts with ischemic cardiomyopathy (63%), 28% exhibited an acute response, with an additional 17% at 6MFU resulting in 45% responders. In non-ischemic pts, 54% (P<0.05 vs ischemic pts) exhibited acute response, with an additional 20% at 6MFU resulting in 74% responders.

Conclusions.
The beneficial effect of CRT on LV systolic function occurs immediately after CRT implantation, with an additional improvement at 6MFU. Pts with ischemic cardiomyopathy need more time to respond to CRT.
Abstract 2491: Neurohumoral Effects Of A New Oral Direct Renin Inhibitor In Stable Heart Failure: The Aliskiren Observation Of Heart Failure Treatment Study (ALOFT).
Authors: Pitt Bertram , McMurray John J , Latini Roberto , Maggioni Aldo , Solomon Scott D , Smith Beverly A , Bush Christopher A , Prescott Margaret F
Published: July 2021

Background:
Treatments that inhibit the renin-angiotensin-aldosterone system (RAAS) are of established benefit in heart failure (HF). These include ACE-inhibitor, angiotensin receptor blockers (ARB) and aldosterone antagonists (AA). In addition, beta blockers (BB) are also effective inhibitors of renin secretion. In this first placebo-controlled study, we have investigated whether the new orally-active direct renin inhibitor, aliskiren, has additional neurohumoral actions when added to these proven therapies.

Methods:
Inclusion criteria for the
AL
iskiren
O
bservation of Heart
F
ailure
T
reatment study (ALOFT) were: age 18 years or older, stable heart failure with NYHA functional class II–IV, prior or current hypertension, plasma B-type natriuretic peptide (BNP) concentration >100 pg/mL and treatment with an ACE-I or ARB and BB, unless contraindicated or not tolerated. Patients were randomized to 3 months double-blind treatment with placebo or aliskiren (150 mg qd), added to standard therapy.

Results:
Overall, 302 patients (78% male, mean age 68 years, mean LVEF 31%) were randomized. Baseline treatment: 84% ACE-I, 15% ARB, 94% BB and 33% AA. Change in neurohormones versus baseline are shown in the table

(expressed as % change using geometric means in an analysis of covariance model). Aliskiren significantly suppressed plasma renin activity (PRA), BNP and urinary aldosterone excretion overall and to a similar extent in patients treated and not treated with an AA.

Conclusions:
Aliskiren suppresses PRA in patients treated with a beta blocker and has additional and potentially beneficial neurohumoral effects in patients already comprehensively treated with neuroendocrine antagonists.
Abstract 2495: Pharmacodynamic Profile of a Novel Chimeric Natriuretic Peptide, CD-NP, as Compared to C-Type Natriuretic Peptide
Authors: Lee Candace Y , Boerrigter Guido , Harty Gail J , Lisy Ondrej , Burnett John C
Published: July 2021

Background:
C-type natriuretic peptide (CNP), a 22-amino-acid peptide and a ligand of the natriuretic peptide receptor-B (NPR-B), exhibits venodilating, anti-fibrotic, and vascular-regenerating properties but limited renal actions. A Mayo-designed chimeric peptide, CD-NP, which consists of CNP and the C-terminus of
Dendroaspis
NP, was synthesized to test the hypothesis that CD-NP would possess CNP-like properties with an improved pharmacodynamic profile.

Methods:
Normal anesthetized dogs were given CD-NP 50 ng/kg/min (n = 10) or an equimolar dose of CNP 29.3 ng/kg/min (n = 9) i.v. for 75 min. Hemodynamic, renal, and hormonal data were obtained pre-infusion (pre-I), at 30 and 60 min I, and post-I, and were compared both within group
vs
pre-I (mean ± SE,
P<
0.05*, < 0.01
†
) and between groups (
P
< 0.05
‡
, < 0.01
§
, < 0.001
¶
). Plasma BNP was measured by radioimmunoassay.

Results:
CD-NP resulted in greater increases in plasma cGMP (7±.4 to 25±3
†¶
to 36±3
†¶
to 23±3
†¶
pmol/ml), urinary cGMP excretion (978±145, 3170±205
†¶
, 5919±616
†¶
, 3077±298
†¶
pmol/min)
vs
CNP (8±.8, 10±.6
†
, 11±.7
†
, 8±.5 pmol/ml; 976±110, 1104±115, 1317±103, 998±101 pmol/min, respectively). CD-NP also increased urine Na
+
excretion (19±4, 168±24
†§
, 237±26
†¶
, 96±12
†
μEq/min), urine flow (0.2±.1, 1.3±.2
†
, 1.8±.3
†
, 0.8±.2
†
ml/min), and GFR (37±2
‡
, 48±3
†
, 51±3
†
, 53±4
†
ml/min)
vs
CNP (36±12, 68±10, 85±26, 81±25 μEq/min; 0.4±.1, 0.9±.2, 1.2±.3*, 0.9±.3 ml/min; 52±5, 53±7, 50±4, 49±6 ml/min, respectively). CD-NP reduced PCWP (5.7±.7, 4.1±1*, 3.2±.7
†
, 4.3±.8 mmHg), RAP (1.8±.4, 1.1±.4
†
, 0.9±.5
†§
, 1.3±.5
§
mmHg), PAP (12±.6, 10±.4*, 10±.6, 11±.7 mmHg)
vs
CNP (6±.6, 5±.8, 6±.8, 7±.9
†
mmHg; 2.6±.3, 2.5±.3 to 2.9±.3 to 3.5±.5
†
mmHg; 13±1, 12±1, 12±1, 13±1 mmHg, respectively). Mean blood pressure was unchanged in either group. CD-NP increased circulating BNP during infusion
vs
CNP (40±4
vs
18±2 pg/ml, P<0.001).

Conclusion:
This study demonstrates the successful transformation of CNP to a CNP-like peptide with enhanced natriuretic, diuretic, GFR-enhancing, and cardiac-unloading actions. CD-NP may also promote increases in plasma BNP which via the NPR-A receptor may contribute to its biological actions. The therapeutic potential of CD-NP in heart failure warrants further studies.
Abstract 2503: The Influende of Renal Function on Clinical Outcome and Response to Beta-Blockade in Systolic Heart Failure: Insights from MERIT-HF
Authors: Ghali Jalal , Wikstrand John , Veldhuisen Dirk V , Fagerberg Bjorn , Goldstein Sidney , Hjalmarson Ake , Johansson Peter , Kjekshus John , Klibaner Michael , Ohlsson Lis , Samuelsson Ola , Waagstein Finn , Wedel Hans
Published: July 2021

Objective:
We analyzed the data from MERIT-HF in order to determine the impact of renal function on absolute risk for and type of clinical events, and to study any interaction between renal function and the risk reducing effect and tolerability of metoprolol CR/XL in systolic HF

Methods:
Glomerular filtration rate was estimated using the simplified MDRD formula (eGFR
MDRD
). Patients were divided in four subgroups according to defined cut off points for renal dysfunction: Normal renal function: eGFR
MDRD
≥ 90 (n = 411); mild renal failure ≥ 60 < 90 (n = 2085); moderate renal failure ≥30 < 60 (n = 1387); and severe renal failure < 30 ml/min/1.73m
2
BSA (n = 82).

Results
: Table

shows one year risk per patient year of follow-up (placebo). Risk reduction with metoprolol CR/XL was consistent regardless of renal function Metoprolol CR/XL was well tolerated in renal failure.

Conclusion:

The risk for death and hospitalizations from worsening HF increased steeply with a decrease in renal function.

The beneficial effect of metoprolol CR/XL on outcomes was maintained regardless of renal function.

Metoprolol CR/XL was well tolerated in renal failure.
Abstract 2514: Automatic Biventricular Capture Verification Based On Morphological Analysis of the Intracadiac Electrogram Signal
Authors: Lian Jie , Garner Garth , Muessig Dirk
Published: July 2021

Objective: We test a new biventricular capture verification algorithm, which can be used to adjust the pacing output in right ventricle (RV) and left ventricle (LV), to ensure the safety and efficacy of the cardiac resynchronization therapy (CRT).

Methods: The algorithm calculates a novel index called ASCI, which measures the morphological similarity between the intracardiac electrogram (IEGM) signal and a template waveform representing captured paces. Ventricular capture (CAP) is verified if ASCI is greater than a predefined threshold, whereas non-capture (NC) is declared otherwise. CRT pacemakers were implanted in 6 dogs. During a mean follow-up of 23 days, 175 biventricular threshold tests were conducted by running a customized program, with various combinations of pace/sense polarities. Wideband RV and LV IEGM were recorded and downloaded for off-line analysis by the algorithm. Template signals for each pace/sense configuration in each chamber were created from the average of 4 captured beats. Each pace was annotated for CAP or NC by visual examination of the IEGM and based on stored data log of the pacing parameters.

Results: A total of 9991 CAP paces (5104 RV, 4887 LV) and 4474 NC paces (2136 RV, 2338 LV) were eligible for morphology analysis. In both RV and LV, the calculated ASCIs were well separated for CAP and NC paces (Figure

): 0.83 ± 0.12 (RV CAP), 0.85 ± 0.11 (LV CAP), -0.06 ± 0.13 (RV NC), -0.07 ± 0.14 (LV NC). The classification accuracy of the algorithm remained >= 99% for any ASCI threshold value choosing between 0.18 and 0.52.

Conclusion: This study demonstrated the feasibility to perform automatic biventricular capture verification based on morphology analysis of the IEGM.
Abstract 2529: Chromosome 2 and Vascular Inflammatory Responses
Authors: Viel Emilie C , Schiffrin Ernesto L
Published: July 2021

Microvascular inflammation contributes to the pathogenesis of cardiovascular disease and hypertension. The purpose of this study is to identify the contribution of chromosome 2 (chr2) to vascular inflammatory responses. We hypothesize that transfer of chr2 from normotensive rats (Brown Norway - BN) to hypertensive rats (Dahl salt-sensitive - SS), a model known as a consomic strain (SSBN2), allows recovery of the normal inflammatory response that might be altered in SS compared to BN. Results showed that SS rats exhibited a higher blood pressure than BN and SSBN2 (181±5 vs 122±12 and 154±11 mmHg respectively). Using ELISA-luminex assay, plasma cytokine levels (IL-1α, IL-1β, IL-2, IL-6, IL-10 and TNFα) were increased in SS (
P
<0.001) compared to BN. SSBN2 exhibited reduced plasma IL-1α, IL-1β, IL-2 and IL-6 level compared to SS. To identify vascular smooth muscle cell (VSMC) contribution to cytokine production, the time-course of expression of cytokine mRNA and cytokine secretion in cultured VSMCs in response to angiotensin II (Ang II) was evaluated. IL-1α, IL-1β, IL-10, and TNFαproduction were not measurable in VSMCs from any strain. IL-6 production increased with AngII in a time-dependent manner in BN and SSBN2 but not in SS. Interestingly, IL-2 levels were higher (
P
<0.001) in SS than in BN and SSBN2. IL-2 protein levels were not affected by AngII. These observations demonstrate that chr2 plays a role in blood pressure regulation and systemic inflammation in salt-sensitive hypertensive rats. Furthermore, secretion of IL-2 by the microvasculature in salt-sensitive hypertensive rats is modulated by chr2. In conclusion, chr2 is involved in the vascular response of IL-2, and may play an important role in vascular inflammation in salt-sensitive hypertension.
Abstract 2545: Clinical Value of Multidetector Computed Tomography for Early Evaluation of Myocardial Viability, Left Ventricular Remodeling and Prognosis After Acute Myocardial Infarction
Authors: Sato Akira , Nozato Toshihiro , Hikita Hiroyuki , Ohigashi Hirokazu , Tamura Mieko , Takahashi Atsushi , Hiroe Michiaki
Published: July 2021

Background:
The clinical value of multidetector computed tomography (MDCT) in assessing myocardial reperfusion after acute myocardial infarction (AMI) is currently unclear. We aim to validate the ability of MDCT for assessing myocardial viability and predicting left ventricular (LV) remodeling after AMI.

Methods:
In 52 consecutive patients with first AMI, 64-slice MDCT without iodine reinjection was performed immediately after selective coronary angiography. ECG-gated thallium-201 SPECT was performed using QGS programs within 5 days and 6 months after onset. Transmurality and extent of myocardial delayed enhancement (DE) were assessed, and results combined with angiographic, SPECT, clinical follow-up data at 6 months to evaluate functional and prognostic significance of DE findings.

Results:
Among the 52 patients, 18 patients (Group A) showed transmural contrast DE, 20 patients (Group B) showed subendocardial contrast DE, and 14 patients (Group C) had no contrast DE. In the acute phase, peak CK-MB (483 ± 286, 223 ± 155, 129 ± 117 IU/ml, respectively,
p
= 0.0017) was significantly higher in Group A, while the incidence of myocardial blush grade 3 (22, 67, 75%, respectively,
p
= 0.0071) and LV ejection fraction (41 ± 8, 53 ± 13, 62 ± 11%, respectively,
p
< 0.001) were significantly lower in Group A. During the 6-month period, LVEDV increased significantly (110 ± 25 to 125 ± 21 mm
3
, p = 0.042) in Group A, and LV remodeling (
p
= 0.0064) and the number of re-hospitalization for heart failure (
p
= 0.0121) was more significantly observed in Group A.

Conclusions:
Myocardial contrast DE patterns provide promising information regarding myocardial viability, LV remodeling and prognosis in AMI.
Abstract 2552: Hypertrophic Cardiomyopathy in Children: Do Adult Risk Factors for Cardiac Death Apply
Authors: Decker Jamie A , Rossano Joseph W , Smith E. O’Brian , Cannon Bryan C , Clunie Sarah K , Jefferies John L , Kim Jeffrey K , Price Jack F , Dreyer William J , Towbin Jeffrey A , Denfield Susan W
Published: July 2021

Introduction
: Annual mortality in children with hypertrophic cardiomyopathy (HCM) has been reported to be 1– 6%. Risk factors for death in adult HCM patients have been characterized; their application to pediatric HCM is unknown. The purpose of this study was to correlate adult risk factors with outcomes in our pediatric population using a standard management strategy.

Methods
: A retrospective cohort study of children with HCM was performed. Death and cardiac transplant were the primary outcomes. Diagnosis was based on asymmetric septal or concentric hypertrophy as determined by echocardiography. Exclusion criteria included: genetic syndrome, mitochondrial or metabolic disorder, infants of diabetic mothers, congenital heart disease, systemic hypertension, diagnosis >18 years of age, or follow-up <1 year.

Results
: From 1/1/85 to 10/1/06, 96 patients met inclusion criteria. Mean age at diagnosis was 10.6 ± 5.4 years. Mean follow-up was 6.5 ± 5.2 years. 11 patients had an adverse outcome (7 deaths, 4 transplants). Kaplan-Meier analysis predicts an 82% survival over 20 years. Evidence of left ventricular outflow tract obstruction (LVOTO) occurred in =6% of patients, syncope in 23% and a family history for malignant HCM in 17%. Aborted sudden death occurred in 6%. 10% had non-sustained ventricular tachycardia. 58% of patients underwent at least one exercise treadmill test. All patients were restricted from strenuous activity. 95% of patients were on a β-blocker or calcium channel blocker, with 10% on both. Additional intervention depended on symptoms, family history, and degree of LVOTO. 17% had an implantable defibrillator (ICD). 10% were given a pacemaker due to LVOTO, and 5% underwent left ventricular myectomy. Only extreme LVH (>6 z-scores for BSA) and a blunted blood pressure response to exercise were statistically significant for worse outcomes (both p<0.02).

Conclusions
: A low mortality/transplantation rate occurred in children with isolated HCM whose management consisted of exercise restriction and medication, with or without an ICD. Management that included myectomy was uncommon. Patients with extreme LVH and a blunted blood pressure response to exercise are high-risk individuals.
Abstract 2554: Natural History of Apical Hypertrophic Cardiomyopathy: Outcome Not as Benign as Previously Suspected
Authors: Jost Christine H Attenhofer , Binder Josepha , Klarich Kyle W , Ommen Steve R , Connolly Heidi M , Bailey Kent R , Freeman William K , Schaff Hartzell V , Nishimura Rick A , Tajik A. J
Published: July 2021

Background.
Apical hypertrophic cardiomyopathy (AHCM) has been considered a ``benign” form of HCM in Asian and non-Asian patients (pt). However, data on long-term outcome of pt with AHCM are limited. The purpose of this study was to determine the natural history of pt with AHCM followed at a tertiary referral center in North America.

Methods.
Between July 1976 and September 2006, 193 pt with the diagnosis of AHCM were seen at the Hypertrophic Cardiomyopathy Clinic. The last echocardiographic exam was reviewed in all pt. Follow-up data were obtained where possible (clinic visit).

Results.
Mean age at diagnosis 56±17 years, mean age at first presentation at our center was 58±17 years. Symptoms included chest pain in 69 pt (36 %), and exertional dyspnea ≥NYHA II in 97 pt (50 %). A family history of either HCM and/or sudden cardiac death was reported by 36 pt (19 %). Coronary artery disease was proven in 40 pt (21 %). Median follow up was 50 months (1–318) and obtained in 124 pt (64 %). The following events were reported at the last clinic visit: heart failure in =5 pt, syncope in =0 pt, ventricular tachycardia in =7 pt, ICD implantation in 22 pt, and stroke in 22 pt. Death from all causes occurred in 51 of 193 pt (26 %) at a mean age of 72 years (14–78). Kaplan-Meier survival analysis was used to examine survival from all causes of death since first presentation. Observed survival in patients with AHCM was significantly less than expected in an age- and gender matched Minnesota white population (p=0.009). The observed survival at 5, 10 and 15 years was 87 %, 82 %, and 57 % respectively, while the expected survival for these time points was 91 %, 81 %, and 72 %.

Conclusions.
AHCM in this predominantly North American patient population is associated with an increased mortality. Patients with AHCM have a high incidence of significant cardiovascular symptoms and ventricular arrhythmias. As the disease is less benign than previously suspected, careful longitudinal care by a cardiologist is warranted.
Abstract 2556: A Comparative Analysis of Outcomes for Pediatric Patients with Biopsy-Proven Myocarditis, Clinically-Diagnosed Myocarditis and Idiopathic Dilated Cardiomyopathy.
Authors: Foerster Susan , Canter Charles , Carey Amy , Sleeper Lynn A , Jefferies John L , Kantor Paul , Lamour Jacqueline , Margossian Renee , Messere Jane , Pahl Elfriede , Rusconi Paolo , Shaddy Robert , Webber Steven , Towbin Jeffrey , Lipshultz Steven
Published: July 2021

Background:
Data on outcomes in children with myocarditis is sparse and challenging to interpret given no ``gold standard” for diagnosis. The NHLBI Pediatric Cardiomyopathy Registry provides a large, multi-center cohort with clinical and echocardiographic follow-up of up to 16 years.

Methods/Results
: We compared cases of biopsy-confirmed myocarditis (BCM, N=119) and clinically-diagnosed myocarditis (CDM, N=253), with idiopathic dilated cardiomyopathy (IDCM, N=1123). BCM and CDM patients were older at diagnosis than those with IDCM (median age 1.6, 1.9, 1.2 yr, respectively). For BCM, heart failure symptoms (86%) and admission (97%) at diagnosis were more common (p<0.05 compared to either CDM/IDCM). LV end-diastolic dimension (EDD) Z-score was abnormal (>2) in 71% with myocarditis and 86% with IDCM. Systolic function was impaired in all groups, with a median fractional shortening (FS) Z score of -9 for myocarditis and -10 for IDCM; 23% of myocarditis patients had impaired function without dilation. Two-year death/transplant rates were 24% (BCM), 24% (CDM), and 47% (IDCM). Of myocarditis survivors, 46% had normalization of both EDD and FS Z-scores at 2 years vs. 25% for IDCM (p<.0001). Baseline echo status was strongly associated with later echo status for IDCM pts. Recovery from myocarditis at 2 years was not strongly associated with baseline echocardiographic characteristics, but transplant-free survival was lower in myocarditis patients when both baseline FS and EDD were abnormal (logrank p=.03). When therapeutic data were available, the BCM group received IVIG/steroids most often (44% vs. 23% CDM, 6% IDCM); this was not significantly associated with 2-year echo recovery or transplant-free survival, but power was limited.

Conclusions
: In this dataset, children with BCM and CDM have similar profiles and a better outcome than those with IDCM, with 76% surviving without transplant at 2 years. Nearly
1
/
2
have normalization of LV size and function, but the presence of both dilation and poor function at presentation is associated with increased risk for death or transplant. Echocardiographic normalization occurs in 25% of IDCM survivors by 2 years. This study is limited by being an analysis of available information in a database collected for other purposes.