bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4340: Left Ventricular Dyssynchrony Measured by Speckle-Tracking Radial Strain Analysis Predicts Survival After Resynchronization Therapy
Authors: Van Bommel Rutger J , Delgado Victoria , Ypenburg Claudia , Mollema Sjoerd A , Borleffs C. Jan Willem , van der Wall Ernst E , Schalij Martin J , Bax Jeroen J
Published: July 2021

Since the introduction of cardiac resynchronization therapy (CRT) in heart failure patients, many echocardiographic criteria, including left ventricular (LV) dyssynchrony, have been investigated in improving selection of suitable candidates. A novel method for the assessment of LV dyssynchrony is speckle-tracking radial strain analysis. Aim of this study was to investigate the impact of pre-implantation, speckle-tracking derived LV dyssynchrony on survival in patients treated with CRT A total of 537 consecutive patients undergoing CRT at our center were included. In all patients, speckle-tracking radial strain analysis was applied to standard LV short-axis images. Significant LV dyssynchrony was defined as a delay between the anteroseptal and posterior segments ≥130 ms. The primary endpoint was all-cause mortality Mean LV dyssynchrony in all 537 patients was 138±105 ms and 251 patients (47%) had predefined significant LV dyssynchrony ≥130 ms. For survival analysis, mean follow-up in the study population was 34±20 months. Within this period 145 patients (27%) died. Main cause of death remained heart failure (61% of all deaths). Multivariate Cox regression analysis with correction for age, gender, etiology, QRS duration, NYHA class, quality of life score, distance covered in the 6-minute walking test, LV volumes and LVEF, demonstrated a significant survival benefit for patients with significant LV dyssynchrony ≥130 ms (HR 0.63, 95% C.I. 0.43–0.92, p=0.017, Figure

). Presence of significant LV mechanical dyssynchrony, measured with speckle-tracking radial strain, is associated with improved survival probability after CRT
Abstract 4345: Identification of Responders to CRT by Stress Echo: No Contractile Reserve, No Party
Authors: Ciampi Quirino , Pratali Lorenza , Citro Rodolfo , Porta Massimo Della , Piacenti Marcello , Gregorio Giovanni , Villari Bruno , Picano Eugenio
Published: July 2021

Cardiac resynchronization therapy (CRT) is increasingly used, but the identification of “responders” remains challenging.

Aim: to assess the value of rest (for dyssynchrony, DYS) and stress (for contractile reserve, CR) echo to identify responders. In a prospective, multicentre study design, we enrolled 55 patients (age 69±8 years; 60% with ischemic etiology) referred to CRT, all with LV ejection fraction ≤35%, NYHA ≥IIb and QRS duration ≥130 milliseconds. All patients underwent a baseline study for DYS (Tissue Doppler criteria, 6-segment approach, Bax dyssynchrony index > 65 ms) and dobutamine stress echo (up to 40 mcg/Kg/min, with presence of CR defined as a wall motion score index, WMSI, increase > 0.20) with core lab reading. “Responders” were identified by clinical (survivors, with NYHA class improvement ≥1 grade) and/or echocardiographic (LV end-systolic volume, ESV, decrease ≥15% at 6-months follow-up) criteria. In the follow-up, 28 (51%) patients were responders to CRT. At individual patient analysis, CR was more often associated with a favourable outcome whereas DYS criteria were equally present in the 2 groups: see figure

. At multivariate analysis, CR (OR=6.2, 95% CI=1.4–27.6) and ischemic etiology (OR=0.20, 95% CI=0.05–0.73) were the best predictors of clinical and echo response to CRT, regardless of DYS. Patients with CR during stress echo show a favourable clinical and reverse LV remodelling response to CRT. This finding shifts the focus from electrical (DYS) to the myocardial substrate of functional response to CRT: no muscle, no party!
Abstract 4368: Differential Left versus Right Atrial Transcriptional Response to Angiotensin Stimulation
Authors: Hasin Tal , Kehat Izhak , Aronheim Ami
Published: July 2021

Introduction
: Angiotensin stimulation is associated with atrial arrhythmias. Atrial fibrillation is commonly initiated in the left atrium. Cardiac over-expression of members of the angiotensin receptor signaling pathway correlates with atrial dilatation. Similarly cardiac over-expression of the inhibitory basic leucine zipper (bZIP) transcription factors JDP2 and ATF3 result in atrial dilatation. We have recently found a signaling pathway in which Angiotensin and Isoproterenol induce ATF3 experssion in the atria.

Hypothesis
: ATF3 expression may differ in left versus right atria.

Methods and Results
: mice were IP injected with Angiotensin, Isoproterenol or Saline. ATF3 expression in the left and right atria and in ventricles was analyzed using western blots and by immuno- histochemisty staining of paraffin embedded sections. Whereas Isoproterenol induced ATF3 expression in both atria and in ventricular tissue. Angiotensin induced ATF3 expression in the left atrium and in the ventricls but not in the right atrium (fig

). Analysis for other bZIP transcription factors revealed a responce to angiotensin in both atria.

Conclusions and Implication
: Angiotensin but not isoproterenol induces ATF3 expression differentially in the left but not right atria. To the best of our knowledge this is the first description of left atrial specific angiotensin mediated expression. This finding may be important in understanding atrial pathophysiological response to hemodynamic challenge and pathologies such as dilatation and generation of arrhythmia.
Abstract 4396: Clinical Response to Recombinant Acid α-Glucosidase is Predicted by Cardiac Outcome Measures in Children with Pompe Disease
Authors: Spencer Carolyn T , Levine Jami , Corzo Deya , Colan Steven D , Graham Dionne , Kishnani Priya S , Nicolino Mark , Li Jennifer , Leslie Nancy , Wraith Ed , Mandel Hanna , Hwu Wuh-Liang , Byrne Barry J
Published: July 2021

Background
: Pompe disease is an autosomal-recessive glycogen storage disease due to deficiency of acid α-glucosidase (GAA). Clinical findings in infantile onset disease are due to glycogen accumulation leading to hypertrophic cardiomyopathy, skeletal myopathy, respiratory failure and death. Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA; Myozyme®) has been shown to prolong survival in infants. We assessed the hypothesis that myocardial response to rhGAA predicts clinical outcome in Pompe.

Methods:
Echos during one year of ERT were reviewed from patients enrolled in open label trials of rhGAA (n=38). A standardized echo protocol was used at specific time points (wks 0, 4, 8, 12, 26, 38, 52). A central reader made measurements off-line, blinded to study information. Variables including LV mass, volumes, and ejection fraction (EF) were determined. Clinical outcomes at study-end were analyzed in 2 groups: Group A, alive and free of assisted ventilation (AV) or Group B, died or requiring AV. Z-scores were calculated for all echo variables and median z-scores between outcome groups at wk 0 and wk 52 were compared using median scores tests. Non-linear random effects models were used to examine changes over time.

Results:
Mean age at first infusion = 10.9±9.8 months (range 1.2 – 43.1). At study onset, 7/38 received AV. At study end, mean time to last infusion = 115±44 weeks with 16/38 in Group A and 22/38 in Group B. For Group A vs. Group B, median z-scores at week 0 for LV mass = 6.11 vs. 7.41, mass to volume ratio (MVR) = 4.5 vs. 8.8, and EF = 0.8 for both groups; p≥ 0.12 for each measure. Median z-scores for the same outcome groups, respectively, at week 52 for LV mass = 0.57 vs. 3.41 (p=0.06), for MVR = 0.48 vs. 3.54 (p=0.001) and EF = −0.6 in both groups. In the subgroup not requiring AV at study onset (n=31), MVR is higher at all times in Group B (p≤ 0.03).

Conclusion:
rhGAA therapy can prolong life in young patients with Pompe, improving outcome compared to an untreated natural history cohort. Even with ERT, there is significant morbidity and mortality. Diminished myocardial response with persistence of significant LV hypertrophy predicts progression to poor clinical outcomes. These and other predictors are required to fully understand response to ERT in Pompe disease.
Abstract 4423: The AGELESS Study: The Effect of Aliskiren vs Ramipril Alone or in Combination with Hydrochlorothiazide and Amlodipine in Patients ≥ 65 Years of Age with Systolic Hypertension
Authors: Duprez Daniel A , Davis Pamela , Botha Jaco
Published: July 2021

Background:
Indirect renin-angiotensin blockade by ACE-inhibition has shown to be effective in lowering blood pressure (BP) in the elderly hypertensive patient. In contrast, the benefits of direct renin inhibition (DRI) on BP has not been extensively studied in an older hypertensive population.

Aim of the study:
The primary aim was to demonstrate non-inferiority between the DRI, aliskiren and ACE-I, ramipril on the change from baseline in systolic BP (SBP) after 12 weeks (w) of treatment with monotherapy among patients ≥ 65 years of age. If non-inferiority was demonstrated, then an analysis for superiority of aliskiren compared with ramipril would be conducted. The secondary aim was to compare aliskiren-based therapy to ramipril-based therapy after 36 w on SBP.

Methods:
In this double-blind parallel multi-center study, hypertensive patients with an age ≥ 65 years with a SBP ≥ 160 mmHg either untreated or after a wash-out period were randomized either to aliskiren 150 mg/day or ramipril 5 mg/day for 4 w. If SBP was not at goal at 4 w (< 140 mmHg), study medication doses were doubled to aliskerin 300 mg/day or ramipril 10 mg/day and SBP was evaluated at 12 w. If SBP was not at goal (<140 mmHg), HCTZ (12.5 → 25mg/day) followed by amlodipine (5→10mg/day) regimen were added and SBP was evaluated at 36 w. In the aliskiren group, 457 patients with a mean age of 72.0 years, (51 % females) and in the ramipril group 444 patients with a mean age of 72.2 years, (53 % females) were enrolled. Patients ≥ 75 years of age made up 32.5% of the total population.

Results
: Table 1

summarizes the results.

Conclusion:
In an elderly population with systolic hypertension, DRI monotherapy with aliskiren provided a greater reduction in SBP than ramipril after 12 w of treatment and was well tolerated. After 36 w an aliskiren-based regimen provided similar SBP lowering efficacy, compared with a ramipril-based regimen. The incidence of adverse and serious events was similar between the two groups.

Table 1:

Change from baseline in SBP at week 12 and 36 between the Aliskiren and Ramipril group
Abstract 4469: Reversal of No-Reflow/Slow-Flow during Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction–A Prospective Randomized Study Comparing Intracoronary Infusion of Diltiazem, Verapamil and Nitroglycerin
Authors: Huang Dong , Zhang Feng , Qian Juying , Wang Xiangfei , Ge Junbo
Published: July 2021

No-reflow/slow-flow is a frequent observation during direct PCI for AMI and associated with a poor clinical outcome. The present pharmacological management involves the use of different vasodilators including nitrates, verapamil, adenosine and nicorandil. But no randomized trial has been conducted to assess any of these agents, or to determine the appropriate dosage. In a consecutive series of 236 direct PCI for AMI, no-reflow/slow-flow phenomenon [TIMI flow grade (TFG) <3] was observed in 30 patients (12.7%). All lesions in the infarction-related-coronary (IRC) were treated by stents. The 30 patients were randomised to one of three groups: intracoronary infusion of diltiazem (n=10), verapamil (n=10) and nitroglycerin (n=10). All the drugs were given via an infusion catheter distal to the angioplasty site. Pre-PCI, post-PCI and after drugs were given, IRC flow was assessed using TFG and TIMI frame count (TFC) by blinded angiographic readers. LVEF through echocardiography and NT-proBNP levels were measured at days 1 and 30 post-PCI. Patient, procedural characteristics and the baseline IRC flow post-PCI in the three groups were similar. The average intracoronary infusion drug dose was diltiazem 0.8mg, verapamil 0.4mg and nitroglycerin 0.4mg. All the three drugs could improve the IRC flow measured by TFG and TFC significantly (p<0.05). Compared with nitroglycerin, diltiazem and verapamil could improve the IRC flow more significantly (p<0.05). The improvements in TFG and TFC did not differ significantly between the diltiazem and verapamil groups (p>0.05). Five patients in the verapamil group developed transient heart block, not seen with diltiazem (p<0.01). During 30 days follow-up, the LVEF improved insignificantly in the three groups. The NT-proBNP levels in the diltiazem and verapamil groups were lower than nitroglycerin group (p<0.05). There is no significant difference in the NT-proBNP levels between the diltiazem and verapamil groups. The intracoronary infusion of diltiazem or verapamil can reverse no-reflow/slow flow phenomenon more effectively than infusion of nitroglycerin during direct PCI for AMI. The efficacy of diltiazem and verapamil is similar but diltiazem seems safer.
Abstract 4473: Coronary Flow Velocity Pattern Immediately after Percutaneous Coronary Intervention Predicts True Left Ventricular Aneurysm in Patients with Acute Anterior Myocardial Infarction
Authors: Yamamuro Atsushi , Akasaka Takashi , Kaji Shuichiro , Tamita Koichi , Katayama Minako , Kinoshita Makoto , Ehara Natsuhiko , Kobori Atsushi , Kitai Takeshi , Yamane Takafumi , An Yoshimori , Kim Kite , Funakoshi Syunsuke , Kimura Noriyuki , Tani Tomoko , Tanabe Kazuaki , Morioka Shigefumi , Furukawa Yutaka
Published: July 2021

Aggressive management of acute myocardial infarction (AMI), including prompt reperfusion, may diminish the incidence of true left ventricular (LV) aneurysm; however, it has been reported that even if successful reperfusion is achieved in epicardial coronary arteries, microvascular dysfunction causes insufficient reperfusion of the infracted myocardium, leading to LV dysfunction. Recent studies have shown that microvascular damage can be assessed quantitatively from coronary flow velocity (CFV) patterns immediately after successful reperfusion. The purpose of this study was to examine whether the CFV patterns may predict the risk of true LV aneurysm formation following successful percutaneous coronary intervention (PCI). Two hundred and one consecutive patients with first anterior AMI who underwent successful PCI were subjected to CFV measurement immediately after PCI with Doppler guidewires. The CFV spectrum provided systolic peak velocity (cm/s, SPV) and diastolic deceleration time (ms, DDT). Left ventriculogram obtained 6 months after the infarction was analyzed to measure the LV volume index. True LV aneurysm was defined as a deformity of the infarct segment that was apparent during diastole as well as during systole, and demonstrated diastolic contour abnormality. Patients were divided into the two groups: those subsequently complicated by true LV aneurysm (n=42; group 1) and those without true LV aneurysm (n=159; group 2) CFV analysis immediately after PCI showed significantly lower SPV (−29 ± 17 vs. 5 ± 22 cm/s; p<0.001) and shorter DDT (317 ± 156 vs. 665 ± 204 ms; p<0.001) in group 1 than in group 2. The optimal cutoff values to predict true LV aneurysm formation were −20 cm/s for SPV and 400 ms for DDT (sensitivity=0.83, specificity=0.82; and sensitivity=0.81, specificity=0.87, respectively). SPV and DDT correlated to the LV end-diastolic volume index obtained 6 months after AMI (r= −0.67; p<0.001 and r = −0.78; p<0.001, respectively). CFV pattern of infarct-related coronary artery immediately after PCI predicts true LV aneurysm formation, and enables accurate risk stratification in patients with anterior AMI.
Abstract 4487: Clopidogrel Resistance in Patients Undergoing Percutaneous Coronary Intervention: One Year Outcome
Authors: Chirumamilla Amala , Mehran Roxana , Weisz Giora , Brar Somjot S , Rabbani LeRoy , Morales Andy , Reddy Srilakshmi , Sugirtharaj Debora D , Franklin Dorothy , Fiscella Damiana , Sfakianakis Konstantinos , Collins Michael B , Leon Martin B , Stone Gregg W , Moses Jeffrey W , Dangas George
Published: July 2021

Background: Clopidogrel therapy is critical in patients undergoing percutaneous coronary intervention (PCI). Data are lacking on long term outcomes of clopidogrel resistance (CR) and its definition.

Methods: We identified 389 patients who underwent PCI during a 6 month period. Using the VerifyNow Point-of-care assay, P2Y12 platelet reaction units (PRU) and percent inhibition of platelet activation (IPA) were measured 16 –24 hours after the loading dose of clopidogrel (600mg for patients not on clopidogrel daily, and 300mg for patients on clopidogrel 75mg daily) but before the next day clopidogrel dose. CR was defined as PRU >200, %IPA<10% or IPA<20%. Major adverse cardiac events (MACE) included death, myocardial infarction, coronary artery bypass graft surgery and unplanned repeat coronary revascularization.

Results: Mean age of patients was 65±11 years, 24% females and 31% diabetics. PRU mean value is 173±93, IPA mean value=47.5±42, CR is found in PRU>200 =36%(140), IPA<10% =8%(31), IPA <20% = 16.4%(64) patients. Presence of myocardial infarction, hypertension, hyperlipidemia, renal disease, smoking history, stable or unstable angina at admission were similar between the PRU groups and between IPA groups. Diabetes and older age were more prevalent in clopidogrel resistance patients. 1-year MACE rates are shown below.

Conclusion: Clopidogrel resistance is an important predictor of long-term MACE in patients undergoing PCI, particularly when defined as Platelet Reaction Units >200.
Abstract 4512: One-Year Clinical Outcome after Percutaneous Aortic Valve Implantation
Authors: de Jaegere Peter P , Kovac Jan , Otten Amber M , Sybt Tom , van Dijk Lucas , Piazza Nick , Bence Johan , Kappetein Arie P , Chin Derek , Orellana Francisco J , Bogers Ad J , Logtens Elaine , Oei Frans , Kik Charles , van Domburg Ron , Serruys Patrick W
Published: July 2021

Percutaneous Aortic Valve Replacement (PAVR) is increasingly being used to treat patients with aortic stenosis who are considered poor surgical candidates. Thirty-day mortality has been reported to vary between 12 and 20%. One study reported a one-year mortality of 18%. We sought to determine the one-year clinical outcome in the patients treated in two institutions by means of a prospective observational cohort study. Between November 2005 and May 2008, 81 patients with aortic stenosis and high surgical risk were treated with the CoreValve Revalving System. Predefined demographic, clinical, laboratory, echo and procedural variables were prospectively entered into a dedicated database. Prospective follow-up data were collected during out-patient clinic visits. Vital status was obtained by contacting the civil registries. Follow-up was complete for all patients. Mean ± SD age was 83 ± 6 years and 46 % were male. The mean logistic EuroSCORE was 17 ± 10. The baseline LV ejection fraction was 45 ± 13. Peak velocity (Mean ± SD) was 4.3 ± 0.8 m/sec pre-PAVR and was 2.0 ± 0.5 immediately post-PAVR. At 30 days, 4 patients (5%) died (cardiac tamponade during PAVR: 2 patients, sepsis 4 weeks after PAVR: 1 patient, subdural haematoma after an ill-fated fall during cardiac rehabilitation: 1 patient). PAVR was complicated by a stroke in 4 patients (5%) and by a myocardial infarction in 2 other patients (2%). The one-year mortality rate was 15%. In the present series of elderly patients treated with PAVR because of severe aortic stenosis, the 30-day mortality was only 3,8%. It was 15% at one year. In all patients, mortality was due to associated cardio-vascular disease. Clinically, there was no evidence of valve dysfunction.
Abstract 4588: Regional Safety and Efficacy of Prasugrel Compared to Clopidogrel: A TRITON - TIMI 38 Analysis
Authors: Wiviott Stephen D , Ruff Christian T , Antman Elliott M , Murphy Sabina A , Lee Peter N Ver , White Harvey D , Braunwald Eugene
Published: July 2021

Background:
Among patients with acute coronary syndrome (ACS), demographics, procedural characteristics and adjunctive therapies differ throughout the world. We examined whether there were consistent effects of prasugrel compared to clopidogrel in the multinational TRITON - TIMI 38 study.

Methods:
We divided the enrollment into 5 pre-specified geographic regions: North America (NA), South America (SA), Western Europe (WE), Eastern Europe (EE), and Africa/Asia Pacific/Middle East (AAM). Patients were randomized to prasugrel or clopidogrel without regard to country of enrollment for 6 –15 months. Event rates are expressed as Kaplan-Meier failure estimates through 15 months. Heterogeneity was evaluated using Cox proportional hazards model with NA serving as the referent.

Results:
13,608 patients were enrolled; 32% in NA, 26% in WE, 24% in EE, 14% in AAM, 4% in SA. Clinical characteristics including age, comorbidities, ACS presentation, stent types, and adjunctive medications differed broadly among regions. Despite these differences, consistency of the efficacy improvement and bleeding excess of prasugrel were observed (TABLE

). Stent thrombosis was substantially reduced with prasugrel in each region: NA (HR 0.42, P<0.001), SA (HR 0.49, P=0.23), WE (HR 0.72, P=0.23), EE (HR 0.41, P=0.005), AAM (HR 0.34, P=0.005), P interaction = NS for each. Net Clinical Benefit (Death/MI/Stroke/non-CABG Major Bleed) also showed consistency (P interaction = NS for each).

Conclusions:
Despite differences in patient demographics, procedural techniques and adjunctive medications, consistent effects of reduction of ischemic events and increased bleeding were seen with prasugrel compared to clopidogrel throughout the world.

Regional Outcoms of Prasugrel vs Clopidogrel (%)
Abstract 4646: Visually-Guided Ablation of the Pulmonary Venous Antrum Using a Compliant Balloon Catheter
Authors: Reddy Vivek Y , Doshi Shephal K , d’Avila Andre , Neuzil Petr , Kim Young-Hoon
Published: July 2021

Introduction: During AF ablation, placing contiguous point ablations to electrically isolate the PVs can be technically challenging. While balloon ablation catheters (BACs) using various energy sources can facilitate this procedure, they are limited by the relatively distal nature of the level of isolation; the PV antra remain largely un-ablated. This report details the
in vivo
evaluation of a compliant BAC with 1) the capability for endoscopic real-time visualization of the target tissue, and 2) an adjustable short arc of light energy for ablation.

Methods: In 3 normal pigs, transseptal access was achieved followed by placement of a deflectable sheath and the BAC (Cardiofocus Inc). Once in position, a 30° arc of laser energy (980 nm) was manipulated to create an isolating antral lesion set. PV isolation was confirmed using a circular mapping catheter. The level of isolation was also visualized by high-density electroanatomical mapping (NavX, St Jude Medical Inc).

Results: The BAC was able to conform to the PV antra (Fig-A/B

); a 3D reconstruction of the BAC while in position is shown in Fig C

. Circumferential endoscopic contact was observed for all 4 PVs targeted for ablation (3-RSPVs, 1-LSPV). Electrical PV isolation was achieved for all 4 PVs. The level of RSPV (arrow) isolation is seen on the voltage maps at baseline (Fig D

), post-partial ablation (Fig E

) and post-isolation (Fig F

); shown are PA views. There was no PV stenosis, thrombus formation or atrial perforation. Pathological examination confirmed the lesions to be both transmural and antral in location.

Conclusions: The PV antra can be targeted for ablation using this visually-guided compliant balloon ablation system.
Abstract 4648: Mechanism of Tissue Cooling With Cryoenergy Delivery to Pulmonary Veins: Tissue Temperature Distribution and Chonic Esophageal Effects
Authors: Dalegrave Charles , Henz Benhur D , Okumura Yasuo , Kolasa Mark , Miller Dylan V , Johnson Susan B , Packer Douglas L
Published: July 2021

Background:
Although pulmonary vein (PV) isolation has been used to treat AF, complications create important limitations. New energy sources, including cryothermal, have been developed to minimize these complications. The purpose of this study was to evaluate the effect of PV cryoablation on esophageal (ESO) temperatures acutely and correlate them with chronic effects on the esophageal wall.

Methods:
A 23 mm cryoballoon was placed in the LA of 10 dogs through a 12 Fr deflectable sheath. PV and ESO temperatures (TEMP) were recorded using 7–9 thermocouples (TC) outside the PVs and on the external and internal ESO surfaces during 2 cryoablations of 4 min duration.

Results
: Cryoablation of 15 PV (10 RIPV and 5 LIPV) during 1.7±0.6 ablations yielded a total of 168 TC time-TEMP profiles (6.4±2.4/PV). Minimum tissue TEMP was inversely dependent on the distance of the TC from the balloon surface (Table 1

). All PVs were isolated acutely and 14/15 (93%) chronically. Minimum TEMP achieved at the PV surface and external ESO were similar (−32±8 and −37±9 at targets within 2.5 mm from the balloon respectively [P=NS]). A TEMP decrease at the internal ESO was seen during 15 of 25 (60%) ablations, but was significantly less pronounced than the external TEMP (17.9°C±13.3 and 6.1°C±24.8 [p<0.05]) resulting in a minimum recorded internal TEMP of −6.2°C. The ESO histological examination in 5 dogs showed very limited external lesions in these dogs (depth= 2.2±1.1, width3 18.6±7.4 and length= 12±5.7 mm), but no transmural or internal ulceration, fibrosis or scarring seen.

Conclusion:
Although PV cryoablation decreases external ESO temperature and produces minor lesions, significant chronic disruptive tissue damage was not seen. Esophageal injury is an unlikely, but potential complication of cryoablation, with internal temperature proving unhelpful in predict negative outcome.
Abstract 4691: Endomyocardial Dysfunction in Patients with Severe Aortic Regurgitation and Preserved Ejection Fraction: A Speckle Tracking Echocardiographic Study
Authors: Seo Yoshihiro , Ishizu Tomoko , Iida Noriko , Machino Tomoko , Kawamura Ryou , Watanabe Shigeyuki , Aonuma Kazutaka
Published: July 2021

Potential myocardial dysfunction may be present in patients with significant aortic regurgitation (AR) and preserved left ventricular ejection fraction (LVEF). Newly developed software for speckle tracking imaging (STI) allows separate analysis of endo- and epimyocardial strain. The aim of this study was to assess the relationship between endo- and epimyocardial radial strain (RS) distribution and AR severity in identifying the potential myocardial dysfunction in patients with significant AR and LVEF>50%, and its correlation with postoperative LV function. We studied 47 patients with AR and 26 control subjects. Degree of AR was classified according to standard echocardiographic criteria as moderate in 16 and severe in 23 patients. STI was analyzed with the new software (Toshiba Medical Systems, Tokyo, Japan). For STI analysis, an endocardial and epicardial border line were each manually traced at end-systole on a short-axis B-mode image at the mid-ventricular level; peak RS of total, endomyocardium, and epicardium were automatically calculated. Endomyocardial RS was reduced in patients with severe AR compared to control subjects and patients with moderate AR (Figure

). Postoperative changes in LVEF were well correlated with the ratio of baseline endomyocardial RS to epimyocardial RS (n=21, r=−0.69, p<0.001). Endomyocardial RS was reduced in patients with severe AR. Assessment of STI-derived RS distribution may be useful to identify potential myocardial dysfunction and postoperative LV functional deterioration in patients with severe AR and preserved EF.
Abstract 4773: Racial Disparity In Outcomes After CABG Is Not Neutralized By Off Pump Techniques
Authors: Cooper William A , Thourani Vinod , Lattouf Omar , Chen Edward , Morris Cullen , Vega David , Vassiliades Thomas , Kilgo Patrick , Puskas John
Published: July 2021

Introduction

: Race has been shown to be an independent risk factor for operative mortality following coronary artery bypass grafting (CABG). This study sought to determine the extent to which race is a risk factor for adverse events and long-term mortality following CABG and whether off-pump surgery (OPCAB) modifies that risk.

Methods:

The STS Adult Cardiac Database at a single academic institution was queried for all primary isolated CABG patient records from 1997–2007. A propensity score was formulated based on 51 pre-operative risk factors to balance the patient groups with respect to treatment assignment (OPCAB or CABG on CPB). Multivariable logistic regression was used to assess the impact of African-American (AA) race and OPCAB on in-hospital outcomes (death, stroke, MI, and their composite, MACE). A Cox proportional hazards regression model and Kaplan-Meier curves determined whether AA race impacted long-term all-cause mortality. Interaction terms were constructed to test whether OPCAB surgery produces different results in AA patients than in Caucasian (CAUC) patients.

Results:

There were 12,874 consecutive CABG patients, including 2033 (15.8%) AA and 10,841 (84.2%) CAUC patients. AA patients had higher baseline rates of hypertension, diabetes, and renal failure, and suffered higher risk-adjusted incidence of death, stroke and MACE than Caucasian patients.. Risk-adjusted survival at 3, 5, and10 years for AA (87.5%, 81.4%, 63.8%) was significantly lower than for CAUC (90.7%, 85.2%, 67.1%, p<0.001). Both AA patients (AOR 0.77, CI 0.44 –1.36) and CAUC patients (AOR 0.72, CI 0.53– 0.99) who had OPCAB had lower risk-adjusted odds of MACE than their racial counterparts who had CABG on CPB. No interactions existed which suggest that OPCAB has the same effect in AA as it does in CAUC.

Conclusions:

OPCAB is similarly beneficial to both race groups in reducing perioperative morbidity. Short and long-term outcomes are significantly worse in AA than Caucasian patients.
Abstract 4784: The Ross Operation: Lessons From Long Term Follow-up
Authors: de Kerchove Laurent , Rubay Jean , Pasquet Agnès , Poncelet Alain , Boodhwani Munir , Ovaert Caroline , Noirhomme Philippe , Khoury Gebrine El
Published: July 2021

Background:
The Ross operation is considered the procedure of choice for aortic valve replacement in children and represents an attractive alternative in selected young adults. However, long term follow-up has demonstrated high rates of pulmonary autograft failure raising concern regarding its clinical utility. We analyze long term outcomes of our Ross series, focusing on predictors of autograft failure.

Methods:
Between 1991 and 2006, 260 consecutive patients underwent Ross operation. Mean age was 35±15 years (range: 1 day to 64 years) and 75% were male. The technique for autograft implantation was a full root replacement in 70% (n=183), inclusion cylinder in 28% (n=73) and subcoronary in 2% (n=4). Right ventricular outflow tract (RVOT) was reconstructed with a pulmonary homograft in 94% (n=245) and with a xenograft in 6% (n=15). Mean clinical follow-up (97% complete) was 97±46 months (13 to 196 months). Echocardiographic follow-up was available in 234 survivors (94%).

Results:
Hospital mortality was 1.9% (n=5) and 7 patients died during follow-up (3 non cardiac). Twelve year overall survival was 93±4% and freedom from autograft reoperation and from autograft valve replacement was 83±7% and 94±5% respectively. Twenty-five patients (9.6%) underwent autograft reoperation either for insufficiency (n=8), autograft or ascending aorta dilatation (n=6), or both (n=11) with no mortality. In 76% (n=19) of these patients, the autograft valve was preserved. Predictors for autograft dilatation (≥45 mm) were preoperative aortic insufficiency and full root technique. RVOT reintervention was required in 10 (4%) patients (reoperations n=7, balloon dilatation n=3). Twelve year freedom from RVOT reintervention was 95±4. Twelve year freedom from thrombo-embolic and bleeding events was 99±1% (1 stroke, 1 TIA, 1 bleeding event).

Conclusions:
This long terms study confirms the excellent survival after Ross operation with an extremely low rate of thrombo-embolic and bleeding events. Autograft reoperation rate remains acceptable. Full root technique is associated with increased risk of autograft dilatation, and should be avoided especially in adults with preoperative aortic insufficiency. Autograft valve preservation is feasible in autograft reoperation.
Abstract 4846: Long-Term Follow-Up in Patients with Tako-Tsubo Cardiomyopathy
Authors: Parodi Guido , Del Pace Stefano , Zampini Linda , Bellandi Benedetta , Salvadori Claudia , Carrabba Nazario , Gensini Gian Franco , Antoniucci David
Published: July 2021

This study sought to assess the long-term outcome of patients with Tako-tsubo Cardiomyopathy (TTC). TTC is a recently described acute cardiac syndrome of uncertain etiology and outcome. One-hundred and one consecutive patients (94 female; mean age 73±10 years; range: from 33 to 90 years) with a confirmed diagnosis of TTC by angiography were prospectively identified and included in the study. Primary end-points were: death, syndrome recurrence and hospitalization from any cause. Over a mean follow-up of 2.0±1.3 years, only 55 patients resulted free from symptoms or major events. Chest pain (n=7) and dyspnea (n=5) were also the more frequent reasons for the high rehospitalization rate (22%). Only one patient had a recurrence of TTC. During long-term follow-up, 11 patients died (7 from cardiovascular cause). The only independent predictor of death at Cox analysis was age (HR 1.159, 95% CI 1.047–1.283; p=0.005). The use of beta-blockers was associated with a trend towards lower mortality rate (8% vs 16%; p=0.098). However, chest pain recurrence (26% vs 6%; p=0.021) and hospitalization rate (34% versus 16%; p=0.06) were more frequent in patients with beta-blockers therapy than in those without. The recurrence of TTC is rare. While, recurrence of chest pain or dyspnea is common in TTC patients and frequently results in hospital admission. Mortality was mainly related to patient’s old age. The role of beta-blockers therapy in the long-term management of patients with TTC is still to be clearly defined.
Abstract 4853: Association of Physician Certification with Rates of CRT-D Implantation in Eligible Patients: Insights from the ICD Registry
Authors: Curtis Jeptha P , Leubbert Jeffrey , Wang Yongfei , Lampert Rachel , Rathore Saif S , Hammill Stephen , Heidenreich Paul , Krumholz Harlan M
Published: July 2021

Current guidelines recommend cardiac resynchronization therapy (CRT-D) in appropriate patients undergoing ICD implantation. However, not all physicians who implant ICDs are trained to perform CRT-D. We examined the ICD Registry to assess whether use of CRT-D implantation varied by physician certification. We determined the certification of 2128 physicians who had submitted >=10 cases between April 2006 and June 2007. We excluded patients with a prior ICD, an epicardial lead, or aged ≤18 years, leaving 111,293 patients. Physicians were grouped into mutually exclusive categories reflecting highest current certification- Electrophysiology (EP), Cardiovascular Disease (CVD), Thoracic Surgery (TS), Internal Medicine (IM), Heart Rhythm Society alternative pathway (HRS), and Other. Patients were considered eligible for CRT-D if they met the following criteria: QRS duration >=120ms, LVEF ≪26>35%, and NYHA Class III-IV. We examined crude rates of CRT-D across physician categories and developed a logistic regression model to assess the association of physician certification and CRT-D implantation. Candidate variables included demographics, cardiac status, comorbidities, and physician volume. Odds ratios were converted to relative risks. 35,851 patients met all three eligibility criteria for CRT-D, and 28,932 (80.7%) had a CRT-D implanted. EP physicians implanted the majority of CRT-D (73.6%), with fewer CRT-D placed by CVD (20.6%), TS (0.9%), IM (0.8%), HRS (1.1%), or Other (3.1%). The crude rate of CRT-D implantation was highest among EP physicians and lower in all other categories: EP- 83.1%, CVD-75.8%, TS- 57.9%, IM- 76.5%, HRS- 77.1%, Other- 73.5% (p<0.001). In multivariable analysis, CVD and TS physicians were less likely to implant CRT-D in eligible patients compared with EP physicians (EP: Ref; CVD: RR 0.92 (0.90 – 0.94); TS: RR 0.76 (0.71– 0.85)). CRT-D rates were comparable for other physician groups (IM RR 0.95 (0.87–1.01); HRS: RR 0.97 (0.90 –1.02); Other RR 0.97 (0.93–1.00)). Among eligible patients, use of CRT-D varies by physician certification. Given the benefits of CRT-D, clinicians should consider referring eligible patients to physicians with familiarity and expertise in CRT-D implantation.
Abstract 4868: Subendmyocardial Perfusion Reserve Correlated with Left Ventricular Diastolic Function in Patients with Various Types of Left Ventricular Hypertrophy
Authors: Kurita Tairo , Onishi Katsuya , Sakuma Hajime , Takamura Takeshi , Nagata Motonori , Nakajima Hiroshi , Ishida Masaki , Fujimoto Naoki , Dohi Kaoru , Takeda Kan , Ito Masaaki
Published: July 2021

Reduced myocardial perfusion reserve (MPR) and left ventricular (LV) diastolic dysfunction were frequently observed in patients with LV hypertrophy (LVH). The purpose of this study was to determine the relationship between MPR assessed by stress-rest perfusion MRI and LV diastolic function in patients with various types of LVH. In patients with diastolic heart failure (DHF, n=34), hypertrophic cardiomyopathy (HCM, n=28), hypertensive LVH (n=42), cardiac amyloidosis (n=4), and control subjects (n=46), stress-rest perfusion MR images were acquired with saturation recovery balanced TFE sequence. Blood input and myocardial output curves were analyzed to determine absolute myocardial blood flow (MBF). MPR were quantified in subendocardial (subend) and subepicardial (subepi) sides of LV wall. LV diastolic function was evaluated using echocardiography, and peak early diastolic mitral annular velocity (Ea) and the ratio of peak early diastolic mitral inflow to Ea (E/Ea) were obtained. MBF at rest was 1.08 mg/ml/min and, subend and subepi MPR were 3.5 and 3.6 in control subjects. To compare with control subjects, subend MPR tended to be decreased in LVH, subend MPR was decreased in DHF, subend and subepi MPR were decreased despite preserved subend and subepi MBF in HCM, and both subend and subepi MBF as well as MPR were decreased in cardiac amyloidosis. According to the disease subgroup, Ea and subend MPR showed a significant correlation(r=0.95), and E/Ea and subend MPR showed an inversed correlation (r=−0.97). (Figure 1

) Subend MPR significantly correlated with LV diastolic function in patients with various types of LVH.
Abstract 4875: The Micro RNA but not the Messenger RNA Signature of Failing Human Hearts is Reversed by Mechanical Unloading
Authors: Matkovich Scot J , Margulies Kenneth B , Youker Keith A , Torre-Amione Guillermo , Van Booven Derek J , Dorn Gerald W
Published: July 2021

Clinical and experimental congestive heart failure (CHF) is characterized by a program of regulated messenger RNA (mRNA) gene transcripts. Much is known about transcriptional control of cardiac gene expression in CHF, but less is known about the alternate mechanism of mRNA stability and translation by micro RNAs (miR). Specifically lacking is information on possible dynamic regulation of miRs during CHF treatment, and the effect on target mRNAs.

Methods
: We performed comprehensive microarray analyses of both mRNA transcript and miR levels in myocardial specimens from CHF without (n=16) or after (n=10) mechanical unloading with left ventricular assist devices (LVAD), in comparison to 7 non-failing hearts. Individual myocardial RNA samples were hybridized to NCode v2 arrays (Invitrogen, 467 human miRs) and Affymetrix HuEx v1.0 arrays (>1 million exon clusters representing 290,000 full-length mRNAs). miR data were analyzed by a dye swap, loop design algorithm (NCode Profiler) after quality control; mRNA data were analyzed with Partek GS v6.3.

Results
: Of 467 miRs represented on arrays, 106 were reliably detected in nonfailing and failing hearts, representing cardiac-expressed miRs. Of these, 21 miRs (19.8%) were significantly (P<0.05) regulated >1.5-fold in CHF; 12 of these were increased >10-fold. Hierarchical clustering showed no specific pattern of regulated miRs. Strikingly, all 21 significantly regulated miRNAs reverted toward nonfailing levels in the post-LVAD hearts (P<0.05 vs CHF) with complete normalization observed for 5 miRs. In contrast, of 755 mRNAs that were altered by >1.3-fold in failing hearts, 38% remained uncorrected post-LVAD. Neither the miR nor mRNA signatures differed between ischemic and nonischemic hearts, suggesting that the RNA profiles reflected advanced CHF, rather than a specific disease etiology.

Conclusions
: There is a distinct miR signature of end-stage heart failure that is reversible with mechanical unloading. This contrasts with mRNA profiles from the same hearts in which only a fraction of dysregulated mRNAs were normalized by LVAD support. Our findings suggest that regulation of translation by miR may account for some of the discordance between transcriptional and other phenotypic responses to LVAD support.
Abstract 4877: Clinical Phenotypes and Outcome of 101 LMNA Gene Mutation Carriers
Authors: Pasotti Michele , Serio Alessandra , Pilotto Andrea , Serafini Elena , Grasso Maurizia , Marziliano Nicola , Tagliani Marilena , Cassini Pamela , Digiorgio Barbara , Agozzino Manuela , Campana Carlo , Gambarin Fabiana , Ghio Stefano , Viganò Mario , Tavazzi Luigi , Arbustini Eloisa
Published: July 2021

Purpose To analyze the cardiac phenotype and long-term follow-up of dilated cardiolaminopathies. Lamin A/C (LMNA) gene mutations cause a variety of phenotypes. In the cardiologic setting, patients diagnosed with idiopathic dilated cardiomyopathy (DCM) plus atrio-ventricular block (AVB) constitute the majority of reported cases.

Methods This was a longitudinal retrospective observational study conducted in 32 consecutive families in which LMNA gene defects were identified in the probands, sharing DCM phenotype.

Results Of the 171 family members, 101 were carriers of LMNA gene mutations. Sixty-five of 101 (64 %) were phenotypically affected while 36 (36 %) were only genotypically affected, including 5 with preclinical signs. The 65 patients had DCM with AVB (n=44), DCM with Ventricular Tachycardia/Fibrillation (VT/VF) (n=12), DCM with AVB and Emery-Dreifuss Muscle Dystrophy type 2 (EDMD2) (n=6), AVB plus EDMD2 (n=2), magnetic resonance imaging signs of arrhythmogenic right ventricular dysplasia associated with mild left ventricular dilation and VT (n=1). The disease was proven to be familial autosomal dominant (AD) in 23 of the 32 families; likely familial AD (based on pedigree and family history) in 8; and associated with a de novo mutation in 1. During a median follow-up of 57.4 months (interquartile range 26 –115 months) we observed 54 events in 47 DCM patients (7 had a later event excluded from the analysis) whereas no event was observed among the 36 non-affected carriers. The events were related to heart failure (HF) [15 heart transplants, 2 death from end-stage HF] and ventricular arrhythmias [17 sudden cardiac deaths (SCD) and 13 appropriate implantable cardioverter defibrillator (ICD) interventions]. By multivariable analysis, NYHA class III–IV and competitive sport ≥10 years were independent predictors of total events. By a bivariable Cox model, splice site mutations and competitive sport predicted SCD.

Conclusions DCMs caused by LMNA gene defects are highly penetrant, adult-onset, malignant diseases characterized by high rate of HF and life-threatening arrhythmias predicted by NYHA class, competitive sport activity and type of mutation.
Abstract 4881: Interaction of Genetic and Pharmacologic
β
-adrenergic Signaling Inhibitors Determines Long-term Mortality after Acute Coronary Ischemia
Authors: Cresci Sharon , Kelly Reagan , Kardia Sharon , Spertus John A , Dorn Gerald W
Published: July 2021

Introduction: While chronic β-blocker (BB) therapy after myocardial infarction (MI) reduces the long-term risk of death, recent studies suggest that BB within 24h after MI is associated with increased death from cardiogenic shock. We have described a naturally-occurring G-protein Receptor Kinase (
GRK
)5 L41 polymorphism that mimics BB effects in experimental models and human heart failure raising the possibility that pre-existing “genetic β-blockade” might also affect outcomes after MI.

Methods: 3,244 patients hospitalized with acute coronary ischemic syndromes (ACS; 2,943 MI; 301 unstable angina) were followed for an average of 2.7 years. Primary endpoint was time to death. A sub-cohort (n=973) was followed for time to rehospitalization. Independent variables were antecedent BB therapy (a-BB), discharge BB therapy (d-BB), and
GRK5
Q41L genotype. Differences were assessed with Kaplan Meier curves, log-rank tests, and Cox proportional hazards modeling (HR).

Results: Complete data were available for 2,732 subjects (24% African American [AA], 33% female, 32% a-BB, 87% d-BB). Overall mortality rate was 12%, and rehospitalization occurred in 41%. AA had increased mortality risk (HR=1.32, CI= 1.017–1.71, p=0.037). a-BB significantly increased mortality in both AA (HR=1.69, CI=1.006–2.84, p=0.047) and Caucasians (HR=1.98, CI=1.523–2.57, p=0.00000033).
GRK5
L41 is more common in AA.
GRK5
L41 carrier status did not significantly affect mortality in AA or Caucasian non-BB subjects, but protected against death in AA with a-BB (HR=0.456, CI= 0.256 – 0.812, p=0.0076; p value for gene-drug interaction=0.041). In the rehospitalization sub-study,
GRK5
L41 protected AA from rehospitalization, independent of BB use (HR=0.605, CI=0.388 – 0.943, p=0.026). d-BB status was not associated with mortality or rehospitalization after discharge.

Conclusions: Antecedent, but not discharge, treatment with BB is associated with adverse long-term outcomes in ACS patients requiring hospitalization. In contrast, AA patients carrying the
GRK5
L41 polymorphism are protected against death and rehospitalization. “Genetic β-blockade” may have advantages over, and can oppose some untoward consequences of, pharmacological β-receptor antagonism in ACS patients.
Abstract 4952: Differential Expression in the Determinants of Extracellular Matrix Remodeling in Pediatric and Adult Dilated Cardiomyopathy
Authors: Hsia Tain-Yen , Ringewald Jeremy M , Stroud Robert E , Graves Michael C , Bradley Scott M , Spinale Francis G
Published: July 2021

Ventricular phenotype of idiopathic dilated cardiomyopathy (DCM) can appear similar in pediatric and adult patients, but a more aggressive clinical course often occurs with pediatric DCM. A structural underpinning of DCM is extracellular matrix changes, which are determined by a balance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). This study tests the hypothesis that different MMP/TIMP profiles occur in pediatric and adult DCM patients. Left ventricular samples were taken from pediatric (age 12±4 yr; n=5) and adult (age 63±3 yr; n=11) patients during heart transplantation for DCM. Myocardial levels were quantified for all MMP classes: gelatinases (MMP-2, -9), collagenases (MMP-8, -13), lysins (MMP-7), membrane-type (MT1-MMP), and for all 4 known TIMPs. Patients with structural or ischemic etiologies of DCM were excluded. Compared to adults, MMP-8 levels increased by over 350% (Figure

), and MMP-7 and MT1-MMP levels (75±9% and 76±9%, respectively; p<0.05) were lower in pediatric patients. In contrast, pediatric TIMP-1 levels were reduced by over 50% (Figure). Pediatric DCM patients manifest a robust increase in MMP-8, which degrades all components of the extracellular matrix, and a decrease in TIMP-1, which inhibits MMP-8. This heightened MMP-8/TIMP-1 ratio would favor aggressive matrix remodeling in pediatric DCM. Since MMP-8 is primarily expressed by macrophage cell lineage, a unique proteolytic program may exist in pediatric DCM. These distinct differences in determinants of myocardial matrix structure and function likely contribute to the more progressive nature of DCM in children.