bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2645: Low Wall Motion Velocity of Left Atrial Appendage Predicts Thrombus Formation Caused by Atrial Appendage Dysfunction in Acute Stroke Patients with Atrial Fibrillation
Authors: Tamura Harutoshi , Hirono Osamu , Okuyama Hidenobu , Nishiyama Satoshi , Shishido Tetsuro , Miyashita Takehiko , Miyamoto Takuya , Nitobe Joji , Watanabe Tetsu , Kubota Isao
Published: July 2021

It is well established that transesophageal echocardiography (TEE) is the most useful examination to detect thromboembolic sources in acute stroke patients, in spite of semi-invasive procedure. Transthoracic echocardiography (TTE) is less invasive, whereas it is sometimes difficult to detect thrombus in left atrial appendage (LAA). The aim of this study was to elucidate whether LAA wall motion measured by TTE was useful for detecting LAA thrombus. We performed TTE and TEE in 169 consecutive acute ischemic stroke patients with AF within 7 days after the onset (male, n=117, 71 ± 11 years old; female, n=52, 75 ± 10 years old). LAA wall motion velocity (LAWV) was measured by tissue Doppler imaging at LAA tip from parasternal short axis view of TTE. Patients were prospectively followed-up until primary endpoints such as stroke recurrence or death (mean follow-up period of 362 days). LAWV was significantly lower in patients with LAA thrombus than in those without thrombus (8.1 ± 1.9 vs. 11.6 ± 4.1 cm/s, P<0.01). LAWV was significantly correlated with LAA peak emptying flow velocity (R=0.74, P<0.01). The multivariate logistic regression analysis showed that low LAWV (<9.3 cm/s) was an independent predictor of LAA thrombus formation (odds ratio, 16.45; 95% confidence interval, 4.57–59.25; P<0.01). Stroke recurrence occurred in 24 patients (14%) during follow-up. The Cox multivariate proportional hazard analysis revealed that low LAWV (<9.3 cm/s) was an independent predictor for stroke recurrence (hazard ratio, 5.0; 95% confidence interval, 1.14 –21.74; P<0.05). Kaplan-Meier survival analysis showed that stroke recurrence rates were markedly higher in patients with low LAWV than in those with high LAWV (26% vs. 6%, P<0.01). In conclusion, LAWV successfully detected LAA dysfunction which caused LAA thrombus. Low LAWV may be a non-invasive predictor for stroke recurrence in ischemic stroke patients.
Abstract 2648: Design of Carotid Intima-Media Thickness Trials
Authors: Evans Gregory W , Palmer Mike K , O’Leary Daniel H , Crouse John R , Bots Michiel L , Grobbee Diederick E , Raichlen Joel S
Published: July 2021

Carotid artery intima-media thickness (CIMT) assessed by B-mode ultrasound is an accepted marker for subclinical atherosclerosis commonly used in clinical trials. Their sample size and power calculations apply 2-sample independent t-tests and within group variance in progression rates from the literature. However, this approach obscures the impact of differences in study designs including length of follow-up and differences in the number of and interval between ultrasound scans. These effects can be assessed using common sample size formula for longitudinal models, but this approach requires decomposition of the total variance into between and within subject components that have not generally been reported in the literature. Here, we derive these variance components for the Measuring Effects on intima-media Thickness: an Evaluation of Rosuvastatin (METEOR) study, a randomized, double-blind trial that demonstrated treatment with 40 mg rosuvastatin significantly slowed CIMT progression in middle-aged patients with a low Framingham risk of coronary heart disease and subclinical atherosclerosis (baseline maximum CIMT ≥1.2-<3.5mm). We examined the impact of differing follow-up periods, use of intermediate scans, and use of duplicate scans using both sample size calculations and actual analyses based on subsets of the METEOR data. Reductions in study length or number of scans result in increased variances and larger sample sizes to detect a given treatment effect. Table

shows the impact of duplicate scans at baseline and end of the 2-year study, with and without intermediate scans performed every 6 months, on the sample size required to detect a treatment effect of 0.012 mm/year. These results underscore the importance of considering the number and spacing of ultrasound exams explicitly during study design, and suggest that reductions in scanning frequency may seriously erode study power and/or increase costs by requiring recruitment of additional subjects.
Abstract 2651: Ischemic Cascade: Sequence of ECG, Acoustic Cardiographic Changes, and Angina during Coronary Occlusion
Authors: Lee Eunyoung , Michaels Andrew D , Selvester Ronald H , Drew Barbara J
Published: July 2021

Background:
Previous studies suggest that ventricular function may be impaired without or prior to ECG changes during ischemia. Using diastolic third and fourth heart sounds (S3 and S4), a non-invasive measurement of ventricular function, our study investigated whether diastolic heart sounds occur earlier than electrical changes or angina during ischemia.

Methods:
To determine the sequence of ECG, diastolic heart sounds, and anginal ischemic symptoms, a prospective observational study was performed in 21 subjects undergoing cardiac catheterization and percutaneous coronary intervention (PCI). Subjects had both ST-segment amplitude changes >2 standard deviations above the baseline during PCI-related coronary occlusion, as well as new or increased intensity S3 or S4 measured by computerized acoustic cardiography. The sequence of resolution of these noninvasive signs of ischemia was also examined following balloon deflation.

Results:
Electrocardiographic ST amplitude changes were the earliest sign of ischemia (mean onset, 21 seconds), and they were also the first to resolve after balloon deflation. New or increased intensity diastolic heart sounds followed ECG changes (mean onset S4, 24.7 seconds; S3, 38.1 seconds: Tables 1

& 2

). Anginal symptoms occurred in only 2 of the 21 subjects during ischemia with a mean onset time of 67.5 seconds.

Conclusion:
ECG signs of ischemia precede functional changes as measured by new or intensified S3 and/or S4. Angina rarely occurs during PCI-induced ischemia, but if present, is the last event in the ischemic cascade.

Table 1.

Sequence of noninvasive signs of ischemia during coronary occlusion (n=21)

Table 2.

Resolution of noninvasive signs of ischemia after balloon deflation (n=18)
Abstract 2654: Differential Local versus Systemic Gene Expression Profiling in Acute Coronary Syndromes
Authors: Akhmedov Alexander , Yonekawa Keiko , Wyss Christophe , Corti Roberto , Kucher Nils , Landmesser Ulf , Alibegovic Jasmina , Maier Willibald , Luscher Thomas
Published: July 2021

Introduction: Monocytes and leucocytes (WBC) play a key role in acute coronary syndromes (ACS). We hypothesized that gene expression profiling of WBC from the site of coronary occlusion in direct comparison with peripheral WBC from patients with ACS might reveal genetic patterns involved in plaque rupture.

Methods: Thrombi (Thr) were aspirated during primary percutaneous coronary intervention (PCI), snap-frozen, and stored at −80°C. Peripheral blood leukocytes (PBL) from the same patients were extracted and treated accordingly. Total RNA was isolated from thrombi and PBL. The quality and quantity of the isolated RNA was determined using bioanalyzer and nanodrop devices. The cDNA was prepared using a primer mix and reverse transcriptase, followed by fragmentation and biotinilation. Biotin-labeled single-stranded cDNA samples were hybridized to Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays. An Affymetrix GeneChip Scanner was used to measure the fluorescent intensity emitted by the labelled target.

Results: Gene expression profiles of Thr and PBL from 4 patients during PCI were assessed by Affymetrix human genome U133 Plus 2.0 arrays (54′675 probe sets). 653 different genes were locally upregulated in Thr compared to PBL as defined by a more than 8-fold difference in expression and statistical significance (p≤0.01). Genes for proteins of inflammation, thrombosis, endothelial activation, extracellular matrix remodelling, and scavenger receptors were highly upregulated at the site of coronary occlusion (examples see table 1

).

Conclusion: The local gene expression profile in WBC from thrombi differs significantly from the pattern in PBL, reflecting the regulatory and effective role of these cells in plaque rupture and thrombosis. This study identifies the upregulation of genes encoding for a host of established and new pathways involved in inflammation, uptake of oxidized LDL, and coagulation, that might play a crucial role in ACS.

Table 1
Abstract 2667: Aspiration Coronary Thrombectomy for Acute Myocardial Infarction Improves Myocardial Salvage Index. Single Center Randomized Study
Authors: Ciszewski Michal , Pregowski Jerzy , Teresinska Anna , Karcz Maciej , Ruzyllo Witold
Published: July 2021

Primary percutaneus intervention (pPCI) is a recommended treatment strategy for acute myocardial infarction with ST segment elevation (STEMI). Adjunctive thrombectomy may add clinical benefits. The aim of our study was to compare the efficacy of aspiration thrombectomy versus standard pPCI for STEMI. The primary endpoint was salvage index assessed by sestamibi SPECT perfusion imaging. Single centre randomized study on aspiration thrombectomy in acute STEMI. 135 patients (88 males, mean age 64,3±12,4 yrs) with first acute STEMI were enrolled between Nov 2004 and Dec 2007. Inclusion criteria were: first anterior or inferior STEMI within 12 hours from pain onset with culprit lesion in left anterior descending (LAD) or right coronary artery (RCA) and TIMI flow ≤ 2. Patients were randomly assigned to thrombectomy with Rescue or Diver device followed by stent implantation (65) vs. standard pPCI with stenting (70 pts). 5 patients initially randomised to thrombectomy were finally treated with standard pPCI. Two SPECT examinations were performed: before and 5– 8 days after reperfusion therapy. Five patients died 3–7 days after the procedure, and in 3 pts second SPECT could not be performed because of patients’ severe condition. Thus two SPECT examinations were performed in 127 patients (63 treated with thrombectomy and 64 in control group). These 127 subject were the basis of the intention to treat analyses. There were 41 pts with anterior STEMI and 86 pts with inferior STEMI. Both treatment groups were similar regarding baseline demographic and clinical variables. Based on the SPECT perfusion imaging results, the final infarct size was assessed and myocardial salvage index (proportion of the myocardium at risk salvaged by reperfusion) was calculated. Baseline myocardium at risk area was 35,0%±2,8% in thrombectomy group vs 35,8%±10,9% in control patients. (p=NS). Myocardial salvage index was larger in patients treated with aspiration thrombectomy (0,33±0,27 vs. 0,20 ± 0,21 p = 0,004). Moreover, final infarct size was significantly smaller in patients treated with thrombectomy: 23,9% ± 13,1 % vs.28,3 % ±9,6% p = 0,005. Our results show that coronary thrombectomy is beneficial as an adjunctive therapy to pPCI in STEMI.
Abstract 2688: Automated Rhythm Analysis To Reduce Pauses During Cardiopulmonary Resuscitation
Authors: Sullivan Joseph L , Walker Robert G , Banville Isabelle L , Rea Thomas D , Chapman Fred W
Published: July 2021

Background
: Pauses in cardiopulmonary resuscitation (CPR) for Automatic External Defibrillator (AED) ECG analysis may adversely affect cardiac arrest resuscitation. Thus, approaches that analyze the ECG rhythm during CPR may improve outcomes. We developed and tested an Analysis During CPR (ADC) algorithm to determine if it would meet the American Heart Association recommended 90% sensitivity for coarse (>0.2 mV peak-peak) ventricular fibrillation (VF) and 95% specificity for non-shockable rhythms.

Methods
: Defibrillator ECG and impedance recordings from 162 patients were retrospectively gathered from 3 EMS systems. 1047 15-second CPR-artifacted segments (274 coarse VF + 773 non-shockable) were identified for analysis; their artifact and rhythm distributions reflect those found in the 162 patients. Each CPR artifacted segment was paired with an adjacent segment free of CPR artifact for reference. Independent reviewers manually annotated and verified Shock/No-Shock rhythm designations blinded to the ADC determination. The ADC algorithm automatically classified each segment into categories of Shock/No Shock/Pause CPR For Clean Analysis, where the last category is segments recognized by the ADC as too noisy for accurate Shock/No Shock determination. In those situations the device would revert to the current approach of a CPR pause for AED rhythm analysis.

Results
: Of the 1047 CPR-artifacted segments, the ADC recommended to “Pause CPR For Clean Analysis” in 10% (n=109), including 4.4% of VF segments (12/274) and 12% (97/773) of non-shockable segments. Of the 938 remaining segments, the ADC correctly identified VF in 97% (sensitivity: 255/262) and correctly identified nonshockable rhythms in 96% (specificity: 650/676). Corresponding positive and negative predictive values were 91% and 99% respectively.

Conclusions
: The ADC is the first algorithm for automated ECG rhythm analysis during ongoing CPR that has been demonstrated to meet the existing AHA sensitivity and specificity recommendations designed for traditional rhythm analysis during hands-off pauses. Incorporation of this algorithm into an AED may eliminate about 90% of analysis pauses without compromising analysis accuracy and in turn may improve the likelihood of resuscitation.
Abstract 2690: A Compression/Ventilation Metronome Prevents Hyperventilation by Professional Rescuers
Authors: Kern Karl B , Stickney Ronald E , Gallison Leanne , Smith Robert E , Chapman Fred W
Published: July 2021

Background
: The recent recommendation for hands-only (continuous chest compression) CPR has caused concern that professional rescuers may over-ventilate to compensate for a lack of ventilation before their arrival. Previous research shows that over-ventilation can be deleterious.

Methods
: We conducted a prospective, randomized, parallel design study of the effectiveness of a customized metronome to guide both compressions and ventilations during CPR with an unsecured airway or a secured airway. Firefighter EMTs performed 2-rescuer CPR on an instrumented manikin, 34 EMTs with and 34 EMTs without metronome guidance. Each session consisted of 2 min of 30:2 CPR with an unsecured airway, then 4 min of CPR with a secured airway (100/min continuous compressions and 8 –10 ventilations/min), repeated after the rescuers switched roles. The metronome gave “tock” prompts for compressions and a spoken “ventilate” prompt. Endpoints included compression and ventilation rates.

Results
: Metronome use significantly decreased the incidence of over-ventilation (11/34 CPR sessions vs 0/34; p<0.001). As previously documented, compression rate errors were significantly less with the metronome. For unsecured airways, mean compression rate error was 21/min for control vs. 0 for the metronome group, (p<0.001); for secured airways, mean compression rate error was 18/min for control vs. 1/min for the metronome group (p<0.001).

Conclusions
: A compression/ventilation metronome helps avoid over-ventilation and improves compression rate when used by professional rescuers on a manikin. The metronome may be highly effective in avoiding over-ventilation during CPR with a secured airway.
Abstract 2693: An Inflammatory Paradox in Acute Respiratory Distress Syndrome? Plasma C-reactive Protein Concentrations are Strongly Associated with Survival in ARDS
Authors: Januzzi James L , Bajwa Ednan , Khah Uzma , Gong Michelle , Thompson B. T , Christiani David
Published: July 2021

C-reactive protein (CRP) is a marker of systemic inflammation, and potently predicts adverse outcome in a number of diseases, but little is known about its characteristics in Acute Respiratory Distress Syndrome (ARDS). Experimental data suggest CRP may play a protective role in alveolitis; clinical correlates are lacking. We measured CRP in 177 patients within 48 hours of ARDS onset and tested the association of protein level with 60-day mortality, 28-day daily organ dysfunction scores, and number of ventilator-free days. CRP was significantly lower in non-survivors when compared with survivors (176.5 [IQR 173.0] vs.133.5 [IQR 161.0] mg/L;
P
= .02). Mortality rate decreased with increasing C-reactive protein decile (
P
= .02). After adjustment for age, APACHE score, and relevant covariates in a multivariable model, plasma CRP concentrations independently and potently predicted survival in ARDS (Hazard ratio=0.996;
P
= .009). When stratified into groups by higher or lower CRP level, patients with CRP had significantly higher probability of survival at 60 days (
P
= .005). Also, patients with higher CRP levels had lower organ dysfunction scores (
P
= .001) and more ventilator-free days (
P
= .02). Consistent with experimental data suggesting a possible protective role of CRP in experimental alveolitis, higher plasma levels of CRP within 48 hours of ARDS are associated with improved survival, lower organ failure scores, and fewer days of mechanical ventilation. These data appear to be contrary to the established view of CRP solely as a non-specific marker of systemic inflammation, and raise the potential for a therapeutic role for CRP in ARDS.
Abstract 2718: Cognitive Function is Poorer in Heart Failure
Authors: Pressler Susan J , Subramanian Usha , Kareken David , Perkins Susan M , Gradus-Pizlo Irmina , Sauve Mary Jane , Sloan Rebecca , Kim JinShil , Ding Yan , Jaynes Heather
Published: July 2021

Background:
Heart failure (HF) patients have been found to have cognitive deficits but studies have been limited by small samples and lack of comparison groups.

Objective:
To determine the types, frequency, and severity of cognitive deficits among patients (pts) with chronic HF compared to age- and education-matched healthy (HC) participants and participants with major medical conditions but not HF (MC).

Methods:
In this comparative study, face-to-face interviews were completed by 414 participants (249 HF pts, 63 HC, 102 MC) to assess function in cognitive domains of language, working memory, memory (verbal learning total and delayed recall), psychomotor speed, and executive function. Characteristics of HF pts were: mean age 62.9 yrs; 63% men; mean education 12.9 yrs; mean LVEF 28%; NYHA I-15%; II-34%; III-39%; IV-12%). HC and MC groups were matched on education and premorbid intellect, but HC were younger than HF and MC groups. Comparisons among the 3 groups were made using ANCOVA adjusting for intellect, age, and education. Family members of all participants were interviewed separately to validate cognitive deficits.

Results:
No differences were found among HF, HC and MC participants in language or working memory. In verbal learning total recall, HF pts had poorer scores than HC and MC participants (p<.0001). In delayed recall, HF pts had poorer scores than MC participants (p=.0152). In psychomotor speed, HF pts had poorer scores than HC and MC participants (p<.0001) on 1 test and poorer scores than MC (p=.0177) on the 2
nd
. In executive function (verbal fluency and mental flexibility), HF pts had poorer scores than MC participants (p = .0022; p = .0428). Family member reported more difficulty in memory among HF pts (p< .0001) than HC ((p< .0001) and more negative behavior changes than HC (p=.0025) and MC participants (p=.0291).

Conclusions:
This carefully characterized sample of HF pts had poorer cognitive function than HC and MC participants. Domains most affected were memory, psychomotor speed processing, and executive function. Studies are needed to 1) evaluate the trajectory of cognitive function across the trajectory of HF; and 2) test novel interventions to improve cognitive function in HF.
Abstract 2760: Termination or Persistence of Atrial Fibrillation during Left Atrial Substrate Modification Does Not Correlate with Long-Term Clinical Outcome in Longstanding, Persistent Atrial Fibrillation
Authors: Otomo Kiyoshi , Nagata Yasutoshi , Tachiguchi Hiroshi , Uno Kikuya , Fujiwara Hideomi , Iesaka Yoshito
Published: July 2021

It was recently reported that the abolition of atrial fibrillation (AF) during the left atrial (LA) ablation targeting AF maintenance substrates (LA-Ab) correlated with better clinical outcome in longstanding, persistent AF (LP-AF). This study was aimed to test if the AF termination or conversion to atrial tachycardia (AT) during LA-Ab was related to better subsequent clinical outcome in LP-AF. This study included 94 consecutive patients (pts) with drug-refractory, LP-AF (age: 62+/−9 years, AF duration: 80+/−76 months, LA diameter: 48+/−5 mm) who underwent the initial LA-Ab combined with extensive encircling PV isolation (EEPVI). After completion of EEPVI, the LA-Ab targeting the continuous, fractionated atrial electrograms was performed sequentially at the roof, inferoposterior region, septum, mitral annulus along the coronary sinus, mitral isthmus and base of LA appendage during sustained AF until AF terminated. The results of the initial session and follow-up data after the initial session were reviewed. Of the 94 pts, conversion of AF to AT (n=35) and/or AF/AT termination (n=34) were observed in 52 pts (55%: Group-1). In the remaining 42 pts (45%: Group-2), neither AF termination nor conversion to AT was observed during the LA-Ab. During the early phase (<1 month) of the follow-up, 40 pts (43%) had acute recurrences of AF (n=16) or AT (n=24) 8+/−9 days after the LA-Ab session, and its incidence was significantly lower in Group-1 than in Group-2 (15/52 (29%) vs 25/42 (61%); P=0.003). During the later phase (=/>1 month; average=257+/−130 days), 73 (78%) of the 94 pts were free from AF/AT episodes with antiarrhythmic medications in 40 pts (43%), while the remaining 21 pts (22%) had recurrence of AF (n=9) or AT (n=12). The AF/AT-free rate during the later phase of the follow-up was not significantly different between the groups (Group-1 vs Group-2: 41/52 pts (79%) vs 30/42 pts (76%); P=0.25). Although the termination of AF/AT or conversion of AF to AT during LA-Ab correlated with better clinical outcome in the early phase, it did not correlate with subsequent freedom from AF/AT in LP-AF. The termination of AF/AT or conversion of AF to AT might not be an optimal procedural endpoint during the LA-Ab.
Abstract 2769: Bradycardia-Dependent Augmentation of J-wave Elevation in Patients with Idiopathic Ventricular Fibrillation
Authors: Mizumaki Koichi , Fujiki Akira , Sakabe Masao , Sakamoto Tamotsu , Nakatani Yosuke , Tsuneda Takayuki , Inoue Hiroshi
Published: July 2021

Although J-wave elevation (JWE) in the inferior or lateral leads is characteristic of subtype of idiopathic ventricular fibrillation (IVF), difference between malignant and benign JWE remains to be elucidated. So, we assessed the hypothesis that the rate dependent changes in JWE could be different between patients with IVF and control subjects. Six male patients with IVF and 18 age matched male controls with JWE (>2 mm) in the lateral leads were studied. CM-5 lead digital Holter ECG was recorded and J wave amplitude was automatically measured. J/RR relationships were evaluated by means of J/RR linear regression lines for 24 hours, and according to four 6-hour periods. From J-RR linear regression lines, J-RR slope (mm/sec), J wave amplitude (mm) at RR intervals of both 0.6 sec and 1.2 sec (J
(0.6)
and J
(1.2)
) were determined. In all 6 patients with IVF, the time of spontaneous episodes of VF were investigated from the implantable cardioverter defibrillator (ICD) stored data. For 24 hours, J-RR slope was greater in IVF patients than in controls (3.5±0.7 vs 2.4±0.8, p<0.01). (J
(0.6)
) wasn’t different between 2 groups; however, J
(1.2)
was greater in IVF patients than in controls (2.8±0.9 vs 2.0±0.6, p<0.05). In IVF patients, ST/RR slope was highest during 18:00–24:00; however, these circadian changes were blunted in controls. J(1.2) was greater during 18:00 – 6:00 in IVF patients than in controls. Seven (59%) of total 9 episodes of spontaneous VF of IVF patients occurred during 18:00 – 6:00. In patients with subtype of IVF, JWE augmented during bradycardia especially at night. This could relate to nighttime occurrence of IVF.
Abstract 2803: Clinical Utility of Magnetic Resonance Imaging of Patients with Permanent Pacemakers and Implantable-Cardioverter Defibrillators at 1.5 Tesla
Authors: Nazarian Saman , Hansford Rozann , Roguin Ariel , Zviman Menekhem M , Lardo Albert C , Calkins Hugh , Berger Ronald D , Bluemke David A , Halperin Henry R
Published: July 2021

Background: Magnetic resonance imaging (MRI) offers excellent soft tissue resolution and is the preferred imaging modality for diagnosis of musculoskeletal, neurological and many thoracic and abdominal conditions. While MRI is currently unavailable for millions of patients because of the presence of implantable cardiac devices, we and others have previously reported the safety of noncardiac and cardiac MRI at 1.5T using a protocol that incorporates device selection and programming and limits the estimated specific absorption rate of MRI sequences. In this study we report the clinical utility of MRI in implantable cardiac device recipients.

Methods: One hundred and eighty six patients with devices shown to be MRI safe by in vitro phantom and in vivo animal testing underwent 228 MRI studies. Pacing mode was changed to “asynchronous” for pacemaker-dependent patients and to “demand” for others. Magnet response and tachyarrhythmia functions were disabled. Blood pressure, ECG, oximetry, and symptoms were monitored. Efforts were made to limit the system-estimated whole-body average specific absorption rate to 2.0 W/kg (successful in >99% of sequences) while maintaining the diagnostic capability of MRI.

Results: No episodes of inappropriate inhibition or activation of pacing were observed. There were no significant differences between baseline and immediate or long-term sensing amplitudes, lead impedances, or pacing thresholds. The diagnostic yield of alternative testing was 19% in 47 patients who underwent ultrasound, nuclear imaging or computed tomography prior to MRI. In contrast, diagnostic questions were answered in 95% of MRI studies.

Conclusions: The diagnostic benefits of MRI significantly outweigh the theoretical risks in patients with implanted cardiac devices when appropriate safety measures are implemented.
Abstract 2819: Identification and Characterization of Super-Responders to Cardiac Resynchronization Therapy: An Echocardiographic Study
Authors: Zaroui Amira , Reant Patricia , Donal Erwan , Mignot Aude , Bordachar Pierre , Deplagne Antoine , Solnon Aude , Leclercq Christophe , Roudaut Raymond , Lafitte Stephane
Published: July 2021

In some patients, cardiac resynchronization therapy (CRT) has been recently shown to induce a spectacular effect on left ventricular (LV) function and inverted remodeling with nearby normalization of LV contraction.

Objectives: To analyze and characterize super-responders (CRTSR) by echocardiography before CRT. 186 patients have been investigated before and 6 months after implantation of a CRT device with conventional indication according to ESC guidelines. Echocardiographies including measurements of LV dimensions, and contraction by 2-dimensional strain, and pressure assessment, mitral valve analysis were performed at baseline and at 6 months in an independent core-center lab. CRTSR were defined as a reduction of end-systolic volume of at least 15% and an ejection fraction (EF)>50% and were compared to normal responder patients (CRTNo, patients with a reduction of end-systolic volume of at least 15% but an EF <50%). 17/186 patients (9.1%) were identified as CRTSR, only 2 with ischemic cardiomyopathy (p<0.01). No difference was observed regarding NYHA status, EKG duration or EF between CRTSR and CRTNo at baseline. CRTSR presented with significant lower end-diastolic and end-systolic diameters (64±9mm vs 73±9mm (p<0.01) and 53±7.4mm vs 63±8.4mm (p<0.01), respectively), and end-diastolic and end-systolic volumes 161±44ml vs 210±76ml (p<0.02) and 123±43ml vs 163±69ml (p<0.01)) as well as a higher LV dP/dt
max
(714±251mmHg.s
−1
vs 527±188 mmHg.s
−1
(p<0.05)). Regarding strain analysis, CRTSR had significantly higher longitudinal values than CRTNo (−12.8±3% vs −9±2.6%, p<0.001) whereas no difference was observed for other components (p ns). Global longitudinal strain obtained by ROC curves was identified as the best parameter for predicting CRTSR with a cut-off value of −11% (Se=80%, Spe=87%, AUC=0.89, p<0.002) and was confirmed as an independent predictor by the logistic regression (RR: 21.3, p<0.0001). In a large multicenter study, CRT super-responders (EF>50%) were observed in 9% of the population and were associated with less-depressed LV function as determined by strain analysis. Global longitudinal strain appears to be the best predictor of CRTSR.
Abstract 2830: Additional Value of Myocardial Perfusion Imaging during Dobutamine Stress Magnetic Resonance for the Assessment of Coronary Artery Disease
Authors: Gebker Rolf , Jahnke Cosima , Manka Robert , Hamdan Ashraf , Schnackenburg Bernhard , Fleck Eckart , Paetsch Ingo
Published: July 2021

Background:
Dobutamine stress magnetic resonance (DSMR) imaging has emerged as a valuable tool for the detection of inducible wall motion abnormalities (WMA). The role of perfusion imaging during DSMR is not well defined. We examined whether the addition of myocardial perfusion imaging during DSMR provides incremental benefit for the evaluation of coronary artery disease (CAD).

Methods and Results:
DSMR was combined with perfusion imaging (DSMRP) in 455 consecutive patients who were scheduled for clinically indicated invasive coronary angiography. Perfusion images were acquired in three standard short axis views at rest and during maximum dobutamine-atropine stress. Wall motion and perfusion images were interpreted sequentially, blinded to other data. Significant (≥70%) stenoses were present in 285 patients in invasive coronary angiography. For the overall population the addition of perfusion imaging improved sensitivity for the detection of CAD (91% versus 85%, P=0.001) with a significant reduction in specificity (70% vs. 82%, P=0.001) and no difference in diagnostic accuracy (84% vs. 84%, P n.s.). DSMRP enabled the correct diagnosis of CAD in an additional 13% of patients. DSMRP enhanced diagnostic accuracy in patients with left ventricular hypertrophy (LVH) (87% vs. 80%, P<0.001), resting WMAs (84% vs. 80%, P<0.001), prior CAD (85% vs. 82%, P<0.001) and it improved sensitivity in patients with single vessel disease (91% vs. 84%, P<0.001).

Conclusion:
The addition of perfusion imaging during DSMR is a useful technique for the diagnosis of CAD and adds additional diagnostic value in patients with LVH, resting WMAs, prior CAD and single-vessel disease.
Abstract 2834: A Short-Term High Fat Diet Impairs Cardiac High Energy Phosphate Metabolism, Exercise Capacity and Cognitive Function
Authors: Holloway Cameron J , Edwards Lindsay M , Emmanuel Yaso , Cochlin Lowri , Tyler Damian J , Robson Matthew D , Szmigielski Cezary , Knight Nicholas , Murray Andrew J , Saxby Brian K , Francis Jane M , Neubauer Stefan , Clarke Kieran
Published: July 2021

Background:
Heart failure patients have low cardiac phosphocreatine/ATP (PCr/ATP) ratios, abnormal exercise tolerance and impaired cognitive function, which may be related to elevated circulating free fatty acids (FFAs). We tested whether briefly raising plasma FFAs, using diet, causes abnormalities in heart, brain and skeletal muscle in healthy subjects

Methods and Results:
Healthy males (n = 16, age 22 ± 1 years), recruited from the University of Oxford, were randomised to five days of a high fat diet containing 75 ± 1% of calorie intake through fat consumption, or an isocaloric control diet, providing 23 ± 1% of calorie intake as fat. In a cross-over design, subjects undertook the alternate diet after a two week wash out period. Cardiac
31
P magnetic resonance (MR) spectroscopy and MR imaging, echocardiography, exhaustive cycling for 1 h, and CDR computerised cognitive tests were used to assess cardiac PCr/ATP, cardiac function, exercise capacity and cognitive function, respectively, before and after the diets. Subjects on the HFD had a two-fold elevation in plasma FFAs, 12% lower cardiac PCr/ATP with no change in cardiac function, and a 12% lower maximal exercise performance (see Figure

). They also had impaired attention and speed (2.2 vs. 1.9 s, p < 0.001, and 1.10 vs. 1.05 s, respectively, p < 0.01)

Discussion:
We have shown a short term, high fat diet raised plasma FFA concentrations, impaired myocardial energetics, exercise capacity and cognition. Therefore high plasma FFAs may be detrimental for heart, skeletal muscle and brain in normal subjects and suggests a potential mechanism of impairment in heart failure patients.
Abstract 2844: Preload Augmentation by Leg Elevation is Helpful in Triaging the Patients with Grade 1 Diastolic Dysfunction
Authors: Choi Eui-Young , Kim Sung-Ai , Rhee Sang Jae , Her Ae Young , Shim Chi Young , Ha Jong-Won , Chung Namsik
Published: July 2021

Grade 1 diastolic dysfunction (DD) is a spectrum of a variety of conditions.

Objectives: We sought to investigate whether the responses of mitral inflow and annular velocity to leg elevation can provide additional information regarding triaging patients with grade 1 DD. One hundred fifty-four consecutive patients with hypertension with abnormal left ventricular (LV) relaxation on Doppler mitral inflow (early (E)/late (A) mitral inflow velocity <0.75 or deceleration time > 240 ms) were enrolled. Patients with LV ejection fractions less than 50%, a previous history of ischemic heart disease, inducible regional wall motion abnormality, valvular or myocardial disease, or any other volume overloading diseases were excluded. After resting evaluation, echo-Doppler measurements were performed during passive leg elevation and symptom-limited graded bicycle exercise. Patients were divided into two groups according to resting E/E’: Group I (E/E’<15) and II (E/E’≥15, n=23). Group I subjects were further subdivided into IA (persistent E/E’ <15, n=112) and IB (change to E/E’≥15, n=19) according to response to leg elevation. Group II had lower systolic (S’), early (E’), and late (A’) diastolic annular velocity, and diastolic reserve index to exercise (E’xΔE’50W) and higher LV elastance index (E/E’/stroke volume) than that of group IA; there was no significant difference compared to group IB. Group IB had more female predominance, older age, lower E’, higher diastolic elastance index, and higher E/E’ at 25W and 50W exercise accompanied by lower exercise capacity compared to group IA. Preload augmentation by leg elevation might provide additional information in triaging patients with grade 1 DD.
Abstract 2847: High Prevalence of ’Unclassifiable’ Diastolic Dysfunction Using Current Criteria
Authors: Narayanan Arumugam , Aurigemma Gerard P , Hill Jeffrey C , Kane Jennifer , McNamee Allison , Tighe Dennis A
Published: July 2021

Background:
Cross sectional studies have shown that diastolic dysfunction is prevalent and impacts mortality. Classification of diastolic function (DF) requires several Doppler variables. However, in clinical practice, pts may not necessarily have concordant data, leading to confusion about classification. The issue is compounded in hospitalized patients, who are tachycardic and may have limited Doppler data.

Objective:
The aims of this study were (1) to determine the percentage of pts with measurable DF data, and (2) to determine the percentage of pts with concordant data.

Methods:
Data from 100 consecutive in- and outpts in sinus rhythm, compiled by a single experienced sonographer were reviewed; transmitral (E/A), deceleration time (DT), pulmonary vein flow - S/D ratio and A reversal duration (PV A dur), and tissue Doppler E’ were attempted in all. DF was classified as normal, or mild, moderate or restrictive dysfunction, based on the validated and widely used scheme of Redfield et al (JAMA 2003). E/A was used as the primary classification variable.

Results:
E/A, DT and E/E’ were measurable in 3/4 of pts while PV S/D and A dur were measurable in 1/2 and 1/4 of pts, respectively. The most common reason for inability to record E/A was tachycardia (E/A fusion). Of pts with measurable data, only 55% had ≥3 concordant variables and most of those had
normal
DF.

Summary/Conclusions:
Applying the validated DF classification scheme to a wider variety of pts demonstrates: (1) 30% pts could not be classified and (2) only 55% pts have ≥3 concordant measurements. These data suggest the need for a weighted classification scheme which, perhaps, incorporates LA and LV structure, and PA pressure.
Abstract 2866: The Ross-Yacoub Operation For Aneurismal Autograft Roots: A Strategy To Preserve Autologous Pulmonary Valves And Normal Quality Of Life
Authors: Luciani Giovanni Battista , Viscardi Francesca , Pilati Mara , Prioli Maria Antonia , Faggian Giuseppe , Mazzucco Alessandro
Published: July 2021

Background: Prevalence of autograft dilatation late after the Ross procedure is increasing. To define feasibility and outcome of autograft valve-sparing root reoperation, a 14-year clinical experience was reviewed.

Methods: One-hundred-twenty-five late survivors after the Ross procedure (7.0±1.9, 0.5–14 years) had cross-sectional clinical and echocardiographic examination. End-points were freedom from autograft dilatation (Ø>4 cm), from root reoperation, from root replacement and functional outcome after valve-sparing reoperation.

Results: Autograft dilatation was found in 33 (26%) patients (freedom of 46±12% at 14 years):12 (10%) patients had aortic aneurysm (>5.0 cm). Age at Ross was 22.6±8.8 years, diagnosis was AI in 9, AS in 1, mixed in 2; 10 had bicuspid aortic valve and 3 prior cardiac operations. All, but one (cylinder inclusion), had undergone root technique. Risk factors for root reoperation were younger age (p=0.04), prior operation (p=0.01), root technique (p=0.001). Nine of 12 had reoperation for aneurysm at 7.8±1.8 years after the Ross procedure, 3 are scheduled. During this study, 2 additional patients underwent root reoperation 12.6 years after Ross procedure done abroad. Two patients had root replacement and 9 (82%) remodelling with autograft-valve preservation (7 Yacoub, 2 sinotubular junction/ascending aorta): all survived. Severe AI, but not root diameter, was associated with failure to preserve the valve (p=0.015). Fourteen-year freedom from root reoperation was 80±8% and from full root replacement 96±3%. Up to 6 years (mean 3.1±1.5) after reoperation, all pts are in NYHA class I and medication-free: 8/9 patients have mild AI or less, while 1 required valve replacement 51 months after remodeling. One patient carried out an uncomplicated pregnancy 3 years after Ross-Yacoub operation.

Conclusions: Root reoperation with pulmonary valve preservation is feasible in most patients with autograft aneurysm, allowing for maintenance of normal quality of life. Referral of patients with dilated root for surgery prior to onset of severe valve insufficiency increases likelihood of pulmonary valve-sparing. Mid-term functional behaviour of remodelled autograft roots is rewarding, however continued observation is warranted.
Abstract 2878: Emergency Intracoronary Stem Cell Transplantation in Patients with Acute Myocardial Infarction (TCT-STAMI-2): Long-Term Outcome
Authors: Huang Rongchong , Yao Kang , Qian Juying , Ge Lei , Li Yanlin , Niu Yuhong , Zhang Yiqi , Sun Aijun , Zhang Feng , Zou Yunzeng , Ge Junbo
Published: July 2021

In this prospective, randomized, controlled study, we evaluate the safety and change of left ventricular systolic function and infarct area with varied imaging techniques after BMCs transplantation in AMI patients within 3 h after emergency percutaneous coronary intervention (PCI). A total of 271 patients with a first ST-segment-elevation myocardial infarction who had undergone stenting of the infarct-related artery were randomly assigned to receive either unselected BMCs (n=137) transplant or saline (n=134) within 3 hours after successful PCI to the distal vessel of the infarct-related artery through micro-catheter. All patients were followed up within 12 months. Intracoronary BMCs application did not incur cardiovascular events, including ventricular arrhythmias or syncope, occurred during 12-month follow-up. By quantitative LV angiography at six months, LV ejection fraction (LVEF) significantly increased (
p
<0.001) and the change of LVEF significantly higher than that in the control group (
p
<0.001). Contrast-enhanced magnetic resonance imaging after one year revealed an increased EF (7.7%±6.9%), reduced infarct size (−7.0%±7.5%). In patients with AMI, intracoronary infusion of BMCs within 3 hours after primary PCI is effective and safe in long-term follow-up.
Abstract 2893: Enhanced Myocardial Ischemic Tolerance in Hypercholesterolemic APOE Knockout Mice is Associated with Increased Expression of Caveolin 1 and Metallothionein
Authors: Xi Lei , Dursun Ali D , Rao Yuan J , Loesser-Casey Kathryn , Kukreja Rakesh C
Published: July 2021

Hypercholesterolemia (HC) is an established risk factor for atherosclerosis and vascular endothelial dysfunction. Paradoxically, we and other investigators have found that animals with HCL are more resistant to myocardial ischemia-reperfusion (Isch-Rep) injury. However, the molecular mechanisms underlying this clinically relevant ischemia-resistant phenotype remain poorly understood. To this context, the present study was designed to identify novel molecular mediators for the HC-induced cardioprotection against Isch-Rep injury. Adult male C57BL/6J wild-type (C57BL-WT) mice and homozygous apolipoprotein E knockout (APOE-KO) mice were fed with regular rodent chow. The hearts were isolated and subjected to 20 min of zero-flow global Isch and 30 min of Rep in Langendorff mode. Infarct size and ventricular contractile function were assessed. Blood samples were collected from each mouse after the heart isolation procedure to measure serum total cholesterol (TCL). As summarized in Table 1

, the APOE-KO mice had developed HC, which was accompanied with significantly better post-Isch cardiac contractile function (DF and ±df/dt
max
) and smaller infarct size as compared with C57BL-WT control mice. In a parallel series of experiments, heart tissues were collected from C57BL-WT and APOE-KO mice and total tissue lysates were prepared for Western blot analysis. We found significant enhancement in cardiac expression of caveolin 1 (Cav-1) and metallothionein (MT) in APOE-KO mice, whereas caveolin 3 (Cav-3) and T-complex protein 1beta (TCP-1beta) were significantly downregulated under HC. Electron microscopy revealed a selective increase in caveolae density on the endothelial cell membranes of APOE-KO mice. This study has provided the first evidence demonstrating that the remarkable ischemia-resistant phenotype of HC is associated with enhanced expression of two cytoprotective proteins - Cav-1 and MT in the heart.

This research has received full or partial funding support from the American Heart Association, AHA National Center.

Table 1
Abstract 2894: Essential Role of ERK 1/2 in Sildenafil-Induced Early and Delayed Cardioprotection in Mice
Authors: das Anindita , Xi Lei , Salloum Fadi N , Rao Yuan J , Kukreja Rakesh C
Published: July 2021

Background:
Sildenafil (SIL), a potent inhibitor of phosphodiesterase-5 induces powerful protection against myocardial ischemia-reperfusion (I-R) injury through activation of protein kinase G (PKG). However, the downstream targets of PKG in SIL-induced cardioprotection remain unclear. We hypothesized that PKG-dependent activation of survival kinase, ERK may play a critical role in SIL-induced cardioprotection in mice.

Methods & Results:
Ventricular myocytes were isolated from adult male ICR mice and exposed to 40 min of simulated ischemia (SI) with/without 1 hr pre-incubation of SIL (1 μM). Myocyte necrosis and apoptosis were determined after 1 hr or 18 hrs of reoxygenation (RO) using trypan blue or TUNEL assay, respectively. Pretreatment with SIL protected cardiomyocytes after SI-RO (necrosis 18.5±0.5% and apoptosis 6.6±0.7%; n=4, p<0.001) as compared with controls (necrosis 42.1±1.8% and apoptosis 23.3±0.9%). Co-incubation of PD98059 (20 μM), a selective ERK1/2 inhibitor blocked both anti-necrotic and anti-apoptotic protection in cardiomyocytes. Furthermore, intra-coronary infusion of SIL (1 μM) in Langendorff isolated mouse hearts 10 min prior to zero-flow global I (20 min) and R (30 min) significantly reduced myocardial infarct size (from 29.4±2.4% to 16.0±3.0%; p<0.05, n=6). Co-treatment of PD98059 abrogated SIL-induced protection (33.0±5.9; n=4). To evaluate the role of ERK1/2 in delayed cardioprotection, mice were treated with saline or SIL (0.7 mg/kg i.p.) 24 hours before global I-R in Langendorff mode. PD98059 (1 mg/kg) was administered (i.p.) 30 min before the treatment of SIL. Infarct size was reduced from 27.6±3.3% in saline-treated controls to 6.9±1.2% in SIL-treated mice (P<0.05, n=6). The delayed protective effect of SIL was also abolished by PD98059 (22.5±2.3%). Western Blots revealed that SIL significantly increased phosphorylation of ERK1/2 which was blocked by PKG inhibitor, KT5823 in the heart and adult myocytes. Selective knockdown of PKG in cardiomyocytes with short hairpin RNA of PKG also blocked the phosphorylation of ERK1/2.

Conclusion:
SIL-induced cardioprotection involves the activation and phosphorylation of ERK which appear to be intimately linked with a PKG-dependent survival pathway.

This research has received full or partial funding support from the American Heart Association, AHA Mid-Atlantic Affiliate (Maryland, North Carolina, South Carolina, Virginia & Washington, DC).
Abstract 2942: High Mortality Rates are Associated with Withdrawal of Beta Blockers and Ace Inhibitors in Chemotherapy-Induced Heart Failure
Authors: Shukla Ashish , Yusuf S Wamique , Daher Iyad , Lenihan Daniel , Durand Jb
Published: July 2021

Beta blockers (BB) and ACE inhibitors (ACE) are recommended for management of left ventricular (LV)dysfunction including patients with chemotherapy-induced cardiomyopathy (CCM). There is a scarcity of data for the long term requirement of these medications in cancer patients, and the effect of their withdrawal after improvement of LV function is unknown. We report a cohort study involving patients with CCM on BB and ACE who underwent withdrawal of these medications and their outcome.

Methods:
In a cohort of patients with CCM stabilized on BB (commonly carvedilol) and ACE, sixteen patients were identified that had therapy withdrawn and then presented with acute heart failure. Patients resumed BB and ACE therapy and outcomes of LV function and survival were evaluated. The change in LVEF by ECHO was compared using paired t-test, with a matched control population with t-test and survivability compared and calculated using Kaplan-Meier estimates and log rank test.

Results:
A total of 48 patients, case (n=16) and matched control (n=32), on maximal tolerated doses of ACE+BB, mean EF of 49.62% Upon withdrawal mean EF decreased to 30.62% (p<0.0001). Nine patients died within six months of discontinuation of therapy, three of sudden cardiac death. Reinstitution of carvedilol+ACE improved LVEF to a mean of 45% (p<0.0001).

Discussion:
This study demonstrates acute deterioration in cardiac function and survival upon withdrawal of BB and ACE in patients with CCM, and a mortality of 56.25% for case patients and 28.12% for control patients. These data indicate that BB and ACE are pivotal in cancer patients with CCM and necessitates their indefinite use.