bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14797: Impact of Normalized Pulmonary Vein Flow Pattern After Percutaneous Mitral Valve Repair
Authors: Mizutani Yukiko , Kubo Shunsuke , Guangyuan Song , Cox Justin , Hussaini Asma , Makar Moody , Nakamura Mamoo , Siegel Robert , Alfred Trent , Kar Saibal
Published: July 2021

Background:
Systolic reverse pulmonary venous flow (PVF) assessed with pulsed Doppler echocardiography is a valuable marker of severe mitral regurgitation (MR). However, the relationship between PVF pattern after MR reduction by percutaneous mitral valve repair with MitraClip system and clinical outcome is not well established. We hypothesized that normalized PVF after MitraClip procedure was associated with successful MR reduction and clinical outcome.

Method:
146 consecutive patients with symptomatic MR who implanted the MitraClip were studied. The patients were divided into 2 groups on the basis of post-procedural left upper PVF pattern; the normalized group (n = 77) and the non-normalized group (n = 69). The normalized PVF was defined as a ratio of peak systolic to diastolic flow velocity ≧1.

Results:
In baseline characteristics, the normalized PVF was independently associated with age <75 (liner regression coefficient [B] = 0.521, 95% confidence interval [CI] = 0.146 - 0.822, P = 0.016) and degenerative MR (B = 0.969, 95% CI 0.049 - 0.383, P <.0001). The normalized group demonstrated significantly higher residual MR ≦2 rate than non-normalized group (100% vs. 97.3%, P = 0.003). At a mean of 2.9 ± 1.9 years follow up, the rate of freedom from the composite endpoint (defined as surgery or 2nd MitraClip procedure for mitral valve dysfunction or all cause death) was significantly higher in the normalized group. Mutivariable Cox regression analysis demonstrated that normalized PVF was an independent post-procedural parameter of freedom from composite endpoint (hazard ratio =0.571, 95%CI 0.339 - 0.948, P = 0.03).

Conclusion:
The normalized PVF after the MitraClip procedure was associated with successful MR reduction and a long-term clinical outcome. Prospective data should be used to validate this.
Abstract 14835: The Prevalence of Sleep Disturbance and Its Strong Impact on Depression Symptom in Patients Hospitalized With Cardiovascular Diseases
Authors: Matsuda Risa , Kohno Takashi , Fukuoka Ryoma , Kondo Mariko , Maekawa Yuichiro , Sano Motoaki , Fukuda Keiichi
Published: July 2021

Introduction:
There is increasing evidence that sleep disturbance significantly contribute to the development of heart disease. However, sleep disturbance often remains unrecognized and untreated because of barrier to its assessment. The aims of this study were to assess the prevalence of sleep disturbance in cardiovascular patients, and examine its related factors including mental status.

Methods and Results:
A total of 1087 patients (mean age, 65±15 years; 29% female) hospitalized for a spectrum of cardiovascular diseases in Keio University Hospital were enrolled (coronary artery disease n=348, arrhythmia n=459, heart failure n=81, valvular heart disease n=119, and other n=80). We assessed sleep disturbance using the Pittsburgh Sleep Quality Index (PSQI; mean 5.6±3.3). The sleep disturbance was defined as PSQI>7 (n=256 [24%]). We screened sleep-disordered breathing (SDB) using nocturnal pulse oximetry, a non-invasive method for detecting nocturnal intermittent hypoxia. The prevalence of SDB (3% oxygenation desaturation index>15/hour) was higher in patients with sleep disturbance (33% vs 26%, p=0.02). Sleep disturbance was associated with older age, higher BNP and CRP level, and lower eGFR and albumin level (all p<0.05). Sex, BMI, and the prevalence of hypertension or diabetics mellitus did not differ between patients with sleep disturbances and those without. The patients with sleep disturbance had significantly higher depression (Hospital Anxiety and Depression Scale [HADS]-Depression score; 6.4±3.7 vs 3.7±3.2, p<0.001, PHQ-9; 6.8±4.5 vs 2.7±2.9, p<0.001) and anxiety (HADS-anxiety score; 6.2±3.8 vs 3.6±2.9, p<0.001) symptoms. After adjustment for age, sex, and psychological disturbance, sleep disturbance was associated with heart failure (OR=1.81; P=0.027; 95% CI, 1.06-3.06). Multiple regression analysis revealed that depressive symptom was the most powerful factor related to sleep disturbance (OR=1.2; P<0.0001; 95% CI, 1.12-1.33).

Conclusions:
Given the high prevalence of sleep disturbances and their strong impact on psychological disturbance, increased efforts should be undertaken for their identification and treatment in patients with cardiovascular diseases, especially in the field of heart failure.
Abstract 14872: Sensitivity of Cinefluoroscopy Compared With Visual Inspection of the Extracted Lead for Detection of Conductor Externalization of Riata/Riata St ICD Leads
Authors: Azeem Ali A , Khalid Nauman , Guertin D , Kluger Jeffrey , Zweibel Steven , Cronin Edmond
Published: July 2021

Background:
The Riata/Riata ST implantable cardioverter defibrillator (ICD) lead series (St Jude Medical, Sylmar, CA) is vulnerable to a characteristic insulation failure mechanism which results in conductor externalization (CE). This may be visible on cinefluoroscopy, however the sensitivity of this test is unknown when compared with direct visible inspection of extracted leads.

Methods:
We retrospectively reviewed the records of patients with Riata leads extracted at our center since 01/01/2011, and compared CE on fluoroscopic imaging before extraction with the visual appearance of the extracted lead ex vivo. Cinefluoroscopy of the Riata lead was performed in three planes: posteroanterior, left and right anterior oblique. CE was defined as a conductor that had breached the outer insulation material and was clearly visible outside the lead body on fluoroscopy. Ex vivo, CE was defined as externalization of the conductor cable(s) visible on inspection of the extracted lead with a corresponding linear insulation defect.

Results:
Of 424 patients with Riata leads 37(8.7%) patients underwent extraction with a mean implant duration of 6.24 years ±1.9 years. The indication for extraction was infection in 12 (32.4%); 7 (18.9%) for electrical or structural lead failure and other indications in 18 (48.6%). CE was evident on cinefluoroscopy in 8 (21.6%) patients before extraction including 2 (25%) leads extracted for electrical failure. Post extraction, CE was visible in an additional 3 (8.1%) leads including 1 (33%) extracted for electrical failure. Overall sensitivity was 72.7%.

Conclusions:
Cinefluoroscopy has suboptimal sensitivity for detection of CE in Riata ICD leads. The absence of CE on cinefluoroscopy does not imply that the outer insulation is structurally intact. Our results suggest that routine cinefluoroscopy of Riata/Riata ST leads is of limited utility.
Abstract 15018: Idiopathic, Isolated, Fibrotic Atrial Cardiomyopathy: An Overlooked Type of Cardiomyopathy
Authors: Chen Minglong , Ju Weizhu , Wang Daowu , Li Mingfang , Qi Rundi , Tang Lijun , Yang Bing , Chen Hongwu , Zhang Fengxiang , Wang Jiaxian , Liu Hailei , Cui Chang
Published: July 2021

Introduction
Myocardium fibrosis is a hallmark of cardiomyopathy and a proposed substrate for cardiac arrhythmias. Nevertheless, fibrosis of atrial myocardium and fibrotic atrial cardiomyopathy has not been systemically addressed.

Hypothesis
We hypothesized that idiopathic, isolated, fibrotic atrial cardiomyopathy (IIF-ACM) is a specific cardiomyopathy, which is characterized by atrial fibrosis and related arrhythmias.

Methods
In the past 8 years, 34 patients (male 13, mean age 46.5±13.3 yrs) were diagnosed with IIF-ACM based on: 1) clinical evaluation; 2) cardiac image examination; and 3) electro-anatomic mapping detected atrial scarring. Serum biomarkers of collagen metabolism and cardiomyopathy-related genetic screening were performed. Tissue pathology and virus detections were done for two patients.

Results
During clinical evaluation, electric silent areas were detected in all patients by intra-cardiac electro-anatomical mapping. Among 34 patients, 26 presented with atrial tachycardia (AT), 5 with sick sinus syndrome (SSS) and 3 with atrial standstill. 5 AT patients further developed SSS during the correction of AT by radiofrequency ablation. Late gadolinium-enhancement cardiovascular magnet resonance showed mild to severely dilated atria, without bilateral ventricular scarring or functional impairment. Serum biomarkers of collagen screening demonstrated significant increased collagen synthesis than collagen degradation in IIF-ACM patients. Cardiomyopathy-related genetic screening depicted no clinically relevant mutation. Histological studies showed global fibrosis of atria (Fig. 1).

Conclusions
We systemically reported 34 patients with IIF-ACM, which is characterized by atrial scarring and relevant arrhythmias. Ventricular functions of note were preserved in all patients. However, the underlying etiology of IIF-ACM remains to be investigated.
Abstract 15031: Defining a Coupling Ratio: Tissue Doppler Velocities in Systole and Diastole Predict Greater Diastolic Than Systolic Impairment in Hypertrophic Cardiomyopathy
Authors: Malhotra Rohit , Tachjian Ara , Aurigemma Gerard P
Published: July 2021

Introduction:
Mitral annular velocities, E’ and S’, (cm/s) measured by Tissue Doppler Imaging, are used in clinical cardiology and in research as important descriptors of systolic and diastolic function. We hypothesized that the relationship between these velocities in normal individuals would be linear, and would define a ventricular systolic/diastolic coupling ratio. We further hypothesized that departure from this normal coupling ratio might provide insight into certain disease states.

Methods:
We reviewed consecutive ECHOs performed at our institution to define the coupling ratio in normal individuals (n=57) and in 2 disease states dilated cardiomyopathy (DCM) (n=20), and hypertrophic cardiomyopathy (HCM) (n=19). The average of peak septal and lateral velocities, obtained in systole and diastole were compared (ANOVA).

Results:
Baseline characters as depicted in the table.

In normals, there is a linear relationship between S’ and E’. While the S’ and E’ velocities are lower in absolute terms in DCM, the coupling ratio is similar to that seen in Normals. HCM, by contrast shows a relatively lower coupling ratio than Normals or DCM (Figure attached).

Conclusion:
We have defined a simple coupling ratio of systolic and diastolic velocities in normal and cardiomyopathy. The greater relative impairment on diastolic velocities in HCM appears to reflect a greater relative impairment in diastolic filling than in systolic shortening. In other words, for a given degree of systolic fiber shortening, fiber lengthening/stretch and perhaps utilization of the Frank Starling mechanism would be disproportionately impaired.
Abstract 15038: Transplantation of Genomic Integration-free Human iPS Cell-derived Cardiac Tissue Sheets Into Porcine Infarct Hearts Produced No Lethal Arrhythmia: A Preclinical Study for a Safer Human iPS Cell Therapy
Authors: Aoki Takayuki , Masumoto Hidetoshi , Ohara Hiroshi , Nakamura Yuji , Izumi-Nakaseko Hiroko , Ando Kentaro , Ikuno Takeshi , Kawatou Masahide , Ishigami Masanosuke , Minakata Kenji , Ikeda Tadashi , Sugiyama Atsushi , Yamashita Jun K , Sakata Ryuzo
Published: July 2021

Background:
Any preclinical study of a human iPS cell(hiPSC)-based cardiac regenerative therapy must confirm that the therapy in question does not produce lethal arrhythmias. In a recent study, we succeeded in long-term (<9 months) tumor-free transplantation of genomic integration-free hiPSC-derived cardiac tissue sheets (CTS) into a rat myocardial infarction (MI) model. In the present study, we attempted to prove that the integration-free CTS do not produce life-threatening arrhythmias after transplantation into a porcine MI model. We chose porcine hearts because they have a heart rate similar to that of the human heart. METHODS & RESULTS: We induced a mixture of cardiomyocytes (CMs) and vascular cells (endothelial cells [ECs] and vascular mural cells [MCs]) from integration-free hiPSCs and generated CTSs using temperature-responsive culture dishes (UpCell, CellSeed, Tokyo, Japan). Self-pulsating CTSs were approximately 3.5cm diameter with approximately 7x106 of cells containing cTnT+ CMs (41±11.9%), VE-cadherin+ ECs (7.0±2.6%) and PDGFRβ+ MCs (32.7±25.0%). In the transplantation group (Tx group: n=4), we induced MI in microminipigs (13-21 months old) by two-stage ligation of the left anterior descending coronary artery, and transplanted CTSs at 2 weeks after MI induction (4 sheets per recipient heart) under immunosuppression. Neither arrhythmia-related sudden death nor tumor formation was observed in any transplanted animals during the observation period (8 weeks). In the Tx group, echocardiogram showed a significant improvement in systolic function of the left ventricle (fractional shortening: 36.7%±2.3 vs 25.2%±2.2, p<0.05, sham-operated animals [Sham]: n=3 ). Holter electrocardiogram showed no episode of ventricular tachycardia in the Tx group during the observation period, whereas 67% (2/3) of Sham exhibited ventricular tachycardia. In the Tx group, beat to beat variability of ventricular repolarization, a surrogate marker of ventricular tachycardia, was lower than that in the Sham (1.95±0.6 ms vs 3.65±0.47 ms). CONCLUSIONS: This preclinical study using genomic integration-free CTS indicated a promising feature of hiPSC-based cardiac regenerative therapy for clinical use.
Abstract 15068: Expression of PW1 Identifies a New Candidate Cardiac Progenitor Population in the Adult Heart
Authors: Yaniz-Galende Elisa , Mougenot Nathalie , Chen Jiqiu , Nadaud Sophie , Marazzi Giovanna , Fuster Valentin , Hajjar Roger , Sassoon David , Hulot Jean Sebastien
Published: July 2021

Rationale:
Adult myocardium contains a rare population of cardiac progenitor cells (CPCs), recruited in response to tissue injury, which are of central importance for the cardiac microenvironment after cardiac injury. However, their phenotype characterization and function in physiological and pathological has not yet been reported.

Objective:
Based on the identification of a cell population with very high expression of PW1 in different tissues, our goal was to determine the role that PW1+ cells play in the heart in a murine myocardial infarction model.

Methods and Results:
In this study we show that high expression of PW1 in cardiac cells (PW1+ cells), identified a rare population, located in the epicardium and interstitium in resting heart, increased in the injured and border area in response to myocardial infarction (MI). Using PW1-reporter mice, we defined three populations of CPCs that include fraction I (PW1-ckit+), II (PW1+ c-kit+) and III (PW1+ckit-) based on differential expression of PW1 and c-kit. We found that MI led to an increase of all the fractions especially fraction II. Furthermore, isolated PW1+ cells showed clonogenic capacity, measured as fibroblastic colony-forming units frequency, and differentiation capacity to give rise in vitro to several cardiac lineages. The phenotypic characterization of fractions I, II and III has also been studied by utilizing comparative gene expression profile as a screening tool. Taken together, these data identify a novel PW1+ cardiac progenitor population with the potential to undergo differentiation into multiple cardiac lineages, suggesting their involvement in cardiac repair in normal and pathological conditions.

Conclusion:
Based on the comparative phenotype analysis, we could demonstrate that the expression of PW1 identified a pure population of CPCs, augmented following MI, with clonogenic and multipotent capacity, which is likely to provide a novel target for therapeutic approaches aimed at improving cardiac repair.
Abstract 15159: Differential Recovery Between Regional Cerebral Oxygen Saturation and Physiological Parameters in Cardiopulmonary Arrest Patients After Return of Spontaneous Circulation
Authors: Tajima Goro , Shiozaki Tadahiko , Ogawa Yoshihito , Hirose Tomoya , Mori Nobuto , Ueki Tomohiro , Izumino Hiroo , Yamano Shuhei , Hirao Tomohito , Inokuma Takamitsu , Yamashita Kazunori , Tasaki Osamu
Published: July 2021

Objective:
We aimed to clarify the change in rSO2, blood pressure (BP) and arterial oxygen saturation (SpO2) in CPA patients who got return of spontaneous circulation (ROSC).

Method:
We measured rSO2 in CPA patients who were transferred to two tertiary emergency medical centers. On arrival, rSO2 sensor was attached to the forehead of patients, and monitored continuously during cardiopulmonary resuscitation. In the patients who got ROSC, we compared change in rSO2 and BP, SpO2, and evaluated the correlation between rSO2 and physiological parameters.

Result:
There were 79 CPA patients transferred to the tertiary emergency medical centers, and 38 patients got ROSC(Mean Age 74.8,M:F=25:13). rSO2 increased after ROSC, and showed the significance after 10 minutes after ROSC. Median rSO2 just after ROSC (ROSC 0) was 54.4% (47.2-59.5), and 66.0% (61.8-70.0) in 10 minutes after ROSC (ROSC 10) (Figure, p<0.01 ROSC 0 vs ROSC 10). However, in BP and SpO2, there were no significant difference between in ROSC 0 and ROSC 10. BP rather showed lower tendency in ROSC 10 compared to ROSC 0. BP; 97mmHg (82.0-127) vs 82.0mmHg (67.0-120), SpO2; 86.0% (70.8-95.0) vs 93.0% (76.0-98.3)

Conclusion:
We clarified that there is a delay in rSO2 recovery compared to BP, SpO2 recovery after ROSC in CPA patients. It might be a therapeutic point to correct the delay in rSO2 recovery.
Abstract 15224: Importance of Beta Blocker Subtype for the Risk of Perioperative Adverse Events in Patients Without Heart Failure and Myocardial Infarction
Authors: Jørgensen Mads E , Gislason Gunnar H , Torp-Pedersen Christian , Hlatky Mark , Andersson C harlotte
Published: July 2021

Objective:
Beta blocker therapy in patients undergoing surgery is being revisited. Previous studies have demonstrated increased risks of perioperative adverse outcomes associated with beta blocker therapy, but whether some beta blocker subtypes may be superior to others remains unknown.

Methods:
Using nationwide Danish registries we included all non-cardiac surgeries in patients without heart failure or myocardial infarction in 2005-2011. Patients were grouped according to beta blocker use prior to surgery. Risks of 30-day MACE (major adverse cardiovascular events; non-fatal myocardial infarction, non-fatal stroke or cardiovascular death) were estimated using logistic regression models adjusted for gender, age, body mass index, pharmacotherapy, comorbidities, type of surgery and surgery risk.

Results:
We included 607,338 patients in the study. Patients on beta blockers (n=50,480) were older with similar gender distribution (mean age 66 years [sd=12.9], 45%male) compared with patients not on beta blockers (n=556,858) (mean age 52 years [sd=17.6], 44%male). Patients on beta blockers had more comorbidities and received more pharmacotherapy (all p<0.001). Unadjusted absolute risks of MACE were increased with all beta blocker subtypes (range 1.7% for propranolol to 4.2% for sotalol) compared with untreated patients (0.8%). Odds ratios for the risk of 30-day MACE are shown in the Figure

Conclusion:
Patients without chronic heart failure and prior myocardial infarction were at increased risk of 30-day perioperative MACE when treated with beta blockers, with the exception of bisoprolol. Patients treated with carvedilol seemed to be at especially high risk.
Abstract 15249: Loss of Early Vasodilator Response at the Brachial Artery Predicts the Presence of Critical Coronary Stenoses
Authors: De Rosa Salvatore , Irace Concetta , Ambrosio Giuseppe , Carallo Claudio , Covello Caterina , Tripolino Cesare , Gareri Clarice , Abramo Ennio , Indolfi Ciro , Gnasso Agostino
Published: July 2021

Cardiovascular diseases (CVD) are the leading cause of mortality and morbidity in Western Countries. Coronary artery disease is the etiology underlying the most prevalent clinical manifestations of CVD. Atherosclerosis is often diagnosed only at late stages, when it manifests in clinically overt forms. Coronary angiography often does not show critical stenoses. We recently showed that the latency of flow mediated dilation (FMD) correlates with the presence of carotid atherosclerosis and the individual cardiovascular risk. Hence, we aimed at evaluating whether the latency of the vasodilator response at the brachial artery could predict the presence of critical coronary stenoses. We evaluated FMD in 74 consecutive patients, before performing coronary angiography for clinical indication at our hospital. Patients were classified in early (ED), late (LD) and no dilators (ND), based on the latency of the vasodilator response. Briefly, ED showed maximal dilation at 60s after ischemic stimulus, and LD over 60s. Very interestingly, lost of early vasodilator response showed a much better diagnostic performance than maximal FMD for the prediction of critical (>70%) coronary stenoses. In fact, classification match of loss of early vasodilator response with coronary angiography was twice as good as with FMD max (72% vs 39%, p=0.002). Using this approach, the number of false negative results was quite low at 4/74 (0.5%), yielding a 89% specificity. Furthermore, ischemia extension - measured by means of the Gensini score - was progressively larger with longer latency (4.5±13.5 in ED, 17.5±27.1 in LD, 39.7±55.0 in ND; p<0.02). In conclusion, using the lost of early vasodilator response as a diagnostic cutpoint allowed to confidently rule out the presence of critical coronary stenoses be means of a simple non-invasive examination. In our cohort, this could have avoided a useless exposition of patients to the potential complications of an invasive coronary angiography in 42% of cases. Once confirmed in larger studies, measurement of latency in vasodilator response could largely improve the selection of patients to refer for coronary angiography, reducing useless patients’ exposition to a potentially harmful diagnostic procedure and healthcare costs.
Abstract 15287: Muscle Sympathetic Nerve Activity and Arterial Stiffness in Resistant Hypertensive Patients With Metabolic Syndrome
Authors: Tsioufis C. , Dimitriadis K. , Koutra E. , Kasiakogias A. , Kordalis A. , Kintis K. , Georgiopoulos G. , Tousoulis D.
Published: July 2021

Introduction:
Resistant hypertension is related to sympathetic overdrive and arterial stiffening, while there are scarce data whether metabolic syndrome further potentiates sympathetic activity and vascular abnormalities in this setting.

Hypothesis:
The aim of this study was to assess the effect of the metabolic syndrome on muscle sympathetic nerve activity (MSNA) and arterial stiffness in resistant hypertensive patients.

Method:
We studied 24 patients with resistant hypertension [age: 58±10 years, 15 males, office blood pressure (BP): 178/94±15/12 mmHg, 24-hour BP: 149/84±15/11 mmHg, under 4.2±0.5 drugs] that underwent transthoracic echocardiographic study and blood sampling for assessment of the metabolic profile. Metabolic syndrome was defined according to the Adult Treatment Panel III criteria and arterial stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (PWV). In all participants sympathetic drive was assessed by MSNA estimations based on established methodology (microneurography).

Results:
Resistant hypertensive patients with metabolic syndrome (n=11) compared to those without (n=13) exhibited higher waist circumference (108.1±5.4 vs 94.6±9.2 cm, p=0.001), fasting glucose (131.8±2.9 vs 94.6±2.1 mg/dl, p<0.05), office systolic BP (186±17 vs 171±15 mmHg, p<0.001) and left ventricular mass index (134.2±18.1 vs 124.6±17.2 g/m2, p=0.001). Moreover, metabolic syndrome patients compared to those without were characterized by greater levels of carotid to femoral PWV (11.7±0.8 vs 9.3±1.1 m/sec, p<0.001) and sympathetic nerve traffic as reflected by MSNA levels (84.2±2.8 vs 75.1±2.2 bursts per 100 heart beats, p<0.001). In all participants MSNA was related to waist circumference (r=0.38, p=0.002) and office systolic BP levels (r=0.35, p<0.05) but there was no association with PWV values (p=NS).

Conclusions:
In resistant hypertensive patients, metabolic syndrome is associated with high MSNA and PWV levels. These findings support that metabolic syndrome further deteriorates sympathetic activity and arterial stiffening characterizing resistant hypertension.
Abstract 15337: The Prevalence of Clinically Significant Ischemia in Patients Undergoing Percutaneous Coronary Intervention, a Report From the Multicenter Registry
Authors: Fujita Jun , Kohsaka Shun , Ueda Ikuko , Inohara Taku , Maekawa Yuichiro , Kawamura Akio , Kanazawa Hideaki , Hayashida Kentaro , Tabei Ryota , Tohyama Shugo , Seki Tomohisa , Suzuki Masahiro , Sano Motoaki , Fukuda Keiichi
Published: July 2021

Background:
Myocardial perfusion scintigraphy (MPS) plays an important role in the evaluation and quantification of myocardial ischemia, and those with significant ischemia (SI) benefit most from revascularization procedures. This study aimed to identify the clinical factors and anatomical features associated with SI in patients with stable ischemic heart disease (SIHD).

Methods and Results:
Data were analyzed from 4197 SIHD patients undergoing PCI in The Japan Cardiovascular Database (N = 11,258) between September 2008 and April 2013. MPS was used to evaluate 1070 (25.5%) patients. Significant ischemia (SI) was defined as more than 10% ischemic region. Logistic regression analysis was performed to identify any clinical factors associated with SI. Patients with a history of heart failure, stroke, or anginal symptoms with Canadian Cardiovascular Society class 2 or more were more likely to have SI (odds ratio [OR] 1.63, p = 0.025, OR: 1.85, p = 0.009, and OR: 1.49, p = 0.003, respectively). When angiographic variables were considered, a proximal left anterior descending artery (pLAD) lesion was the sole factor associated with SI (OR: 1.46, p = 0.012) (Table). Importantly, those with SI had more complications (p = 0.006), most notably post-PCI infarcts (p = 0.008) (Figure).

Conclusions:
Patients’ background data, such as stronger anginal symptoms or a pLAD lesion, were associated with SI. Since patients with SI are necessary to be treated with PCI to improve long-term prognosis, however procedure-related complications happen more frequently than non-SI patients. Physicians must give their full attention to the PCI procedure in SI patients to minimize their complication rate.
Abstract 15370: Genetic Study Identifies Common Variation in PHACTR1 to Associate With Fibromuscular Dysplasia
(Best of Basic Science Abstract)
Authors: Kiando Soto Romuald , Tucker Nathan , Katz Alexander , Tréard Cyrielle , D’Escamard Valentina , Castro-Vega Luis J , Ye Zi , Smith Carin Y , Austin Erin , Barlasina Cristina , Cusi Daniele , Galan Pilar , Empana Jean-Philippe , Jouven Xavier , Brunval Patrick , Olin Jeffrey W , Gornik Heather , Plouin Pierre-François , Kullo Iftikhar J , Milan David J , Ganesh Santhi K , Boutouyrie Pierre , Kovacic Jason , Jeunemaitre Xavier , Bouatia-Naji Nabila
Published: July 2021

Fibromuscular dysplasia (FMD) is a nonatherosclerotic vascular disease leading to arterial stenosis, aneurysm and dissection, mainly in renal and carotid arteries. FMD has higher prevalence in females (80-90%) and is associated with hypertension and stroke. The pathophysiology of FMD is unclear and a genetic origin is suspected.

We performed a genetic association study in European ancestry individuals. The discovery included 249 cases and 689 controls, in which we analyzed ∼26K common variants (MAF>0.05) using an exome-chip array. We followed up 13 loci (P<10-4) in 393 cases and 2537 controls and replicated a signal on Chr6. Three additional studies (combined Ncases=512, Ncontrols=669) confirmed this association, with an overall OR of 1.39, (P=7.4х10e-10 , All Ncases=1154, All Ncontrols=3895).

The FMD risk variant is intronic to the phosphatase and actin regulator 1 gene (PHACTR1), involved in angiogenesis and cell migration. PHACTR1 is a risk locus for coronary artery disease, migraine, and cervical artery dissection, which may occur in FMD. We found a significant association between the risk allele and higher central pulse pressure (P=0.0009), increased intima media thickness (P=0.001) and wall cross-sectional area (P=0.003) of carotids assessed by echotracking in 3800 population-based individuals. The correlation of genotypes with the expression of PHACTR1 in primary cultured human fibroblasts showed higher expression in FMD risk allele carriers, compared to non carriers (N=57, P=0.02). Finally, Phactr1 knockdown of zebrafish showed significantly dilated vessels (P=0.003) indicating impaired vascular development.

In conclusion, we report the first risk locus for FMD with the largest genetic association study conducted so far. Our data reveal a common genetic variant at PHACTR1 providing indices of shared pathophysiology between FMD and other cardiovascular and neurovascular diseases.
Abstract 15408: Long-term Antithrombotic Management Patterns After Acute Coronary Syndromes: 2-[[Unsupported Character - Codename ­]]years Follow-up in the EPICOR Asia Study
Authors: Huo Yong , Lee Stephen W , Sawhney Jitendra P , Kim Hyo-Soo , Krittayaphong Rungroj , Pocock Stuart J , Nhan Vo T , Chin Chee Tang , Han Xiaoning , Vega Ana , Itoh Yohji , Ong Tiong K
Published: July 2021

Introduction:
Guidelines recommend dual-antiplatelet therapy (DAPT) for 12 months in patients with acute coronary syndromes (ACS). Information on patterns and duration of DAPT use after hospital discharge in ACS patients in Asia is sparse.

Objective:
We describe changes in real-life antithrombotic management patterns (AMPs) up to 2-y post discharge based on data from the EPICOR Asia study (NCT01361386).

Methods:
This observational study enrolled 12 922 hospital survivors post ACS from 218 hospitals in 8 countries/regions in Asia. Data were collected from symptom onset for the index event (ST-segment elevation myocardial infarction [STEMI] 51.2%, non-STEMI (NSTEMI) 19.9%, or unstable angina [UA] 28.9%), during hospitalization, at discharge and over 2 y follow-up.

Results:
Overall, 90.6% of patients were on DAPT at hospital discharge which declined to 79.6%, 71.8%, 53.7%, and 45.6% at 6, 12, 18, and 23 months post discharge (Fig). At discharge, most patients (87.6%) received aspirin + clopidogrel, with 79.5%, 71.8%, 53.6%, and 45.4% on this combination at 6, 12, 18, and 23 months. At discharge only 3.0% of patients received aspirin + prasugrel and 1.7% of patients received aspirin + cilostazol. Only 8.3% of patients were on single antiplatelet therapy (SAPT) at discharge with 12.2%, 15.6%, 28.1%, and 30.3% on SAPT at 6, 12, 18, and 23 months post discharge; aspirin being the most commonly used single agent. No notable differences were seen among index event groups. Of the patients on DAPT at discharge, STEMI 93.4%; NSTEMI 90.2%; UA 85.9%, comparable proportions across groups remained on DAPT at 23 months follow up; STEMI 51.0%; NSTEMI 51.9%; UA 47.6%.

Conclusions:
Most ACS patients remain on DAPT at 12 months and around half remain at 23 months post-discharge. Further study should assess between-country differences, the benefit/risk balance from prolonged DAPT, why DAPT is discontinued before 12 months, and impact on clinical outcomes.
Abstract 15427: Oxidative Stress From Altered Cardiac β3-adrenergic Receptor-activated Inducible Nitric Oxide Synthase/NO Pathways Promotes Cardiac Aging
Authors: Cheng Che Ping , Cheng Heng-Jie , Zhou Peng , Li Tiankai , Zhang Xiaowei , Kitzman Dalane , Callahan Michael
Published: July 2021

Background:
There is substantial evidence supporting oxidative stress as an important mechanism to age-related cardiac dysfunction and altered β
3
-adrenergic receptor (AR)-activated nitric oxide synthase (NOS) pathway contributing to this process. However, the NOS isoforms involved are controversial. The mechanism of how β
3
-AR stimulation impacts ROS, SERCA2a, and cardiac function in cardiac aging (CA) is unclear. We tested the hypothesis that oxidative stress from up-regulation of cardiac β
3
-AR-activated iNOS uncoupling promotes CA.

Methods:
We compared myocyte subtypes of β-ARs, three NOS, peroxynitrite (NT), NADPH, GTPCH and SERCA2a expressions and myocyte contractile and [Ca
2+
]
i
transient ([Ca
2+
]
iT
) responses to β-AR stimulation with isoproterenol (ISO, 10
-8
M). LV myocytes were isolated from 2 young (Y) (~4 to 6 m) and 2 aged (A) (~28 to 31 m) groups (5/group) of wild-type (WT) and β
3
-AR knockout (β
3
KO) mice.

Results:
Compared to YWT, AWT myocytes had significantly increased protein levels of β
3
-AR (0.31 vs 0.16) and iNOS (0.48 vs 0.21) accompanied with increased oxidative stress indicated by significant increases in NT formation (increased 102%) and NADPH (P67
-phox
, 35% and p22
-phox
, 28%), but decreased GTPCH expression (41%, 0.48 vs 0.82) and activity. AWT myocytes had significantly decreased β
1
-AR protein (0.38 vs 0.59), SERCA2a (0.26 vs 0.72) and the ratios of SERCA2a/PLB. These changes were associated with reduced basal cell contraction (dL/dt
max,
76.4 vs 122.8 μm/s), relaxation (dR/dt
max
, 58.9 vs 94.3 μm/s), and [Ca
2+
]
iT
(0.16 vs 0.24) accompanied by diminished β-AR-stimulated positive inotropic response. Importantly, in contrast to age-caused changes in AWT, versus Yβ
3
KO, in Aβ
3
KO myocytes, there were no significant alterations in iNOS (0.19 vs 0.16), NT (increased 9%), β
1
-AR (0.60 vs 0.62), and SERCA2a (1.2 vs 1.4). Aβ
3
KO myocytes had normal cell contraction and relaxation with preserved ISO-stimulated positive inotropic response.

Conclusions:
Myocardial aging is associated with up-regulation of cardiac β
3
-AR-activated iNOS pathway, which leads to imbalance in NO/superoxide production, favoring subsequent iNOS uncoupling and directly contributes to age-associated deficits in LV myocyte function and [Ca
2+
]
i
regulation.
Abstract 15453: CD34+ Cell Therapy May Affect Extracellular Matrix Turnover in Patients With Non-ischemic Dilated Cardiomyopathy
Authors: Ksela Jus , Poglajen Gregor , Boznar Alic Elizabeta , Skitek Milan , Sever Matjaz , Knezevic Ivan , Haddad Francois , Wu Joseph C , Vrtovec Bojan
Published: July 2021

Introduction:
The underlying mechanisms of CD34+ cell therapy in patients with non-ischemic dilated cardiomyopathy (DCM) remain poorly defined

Hypothesis:
We sought to evaluate the effects of CD34+ cell therapy on extracellular matrix.

Methods:
We performed a cohort analysis of 23 consecutive patients with DCM who underwent transendocardial CD34+ cell transplantation between January and December 2013. All patients received 5-day stimulation with G-CSF; CD34+ cells were selected with apheresis and injected transendocardially guided by electroantomical mapping. Patients were followed for 6 months and good clinical response was defined as an increase of left ventricular ejection fraction (LVEF) ≥5%. Extracellular matrix turnover was evaluated by measuring changes in galectin-3 serum levels.

Results:
Within 6 months after cell therapy galectin-3 levels decreased in 9 (39%) patients (Group A) and increased in 14 (61%, Group B). The two groups did not differ with regards to gender (male: 100% in Group A vs. 78% in Group B; P=0.15), age (51±10 years vs. 52±11 years; P=0.79), serum creatinine (86±22 μmol/L vs. 82±17 μmol/L, P=0.62), bilirubine (20±11 μmol/L vs. 17±9 μmol/L, P=0.51), or NT-proBNP levels (1465±1448 pg/mL vs. 1380±1626 pg/mL, P=0.72). Baseline LVEF (28±9% vs. 33±7%, P=0.10) and left ventricular end-diastolic diameter (7.1±0.8 cm vs. 6.5±0.7 cm, P=0.22) were also comparable in the two groups. Both groups received comparable doses of CD34+ cells (84±51 million cells in Group A vs. 132±96 million cells in Group B, P=0.21). At 6 months LVEF increased significantly more in Group A than in Group B (9.2±5.1% vs. 3.4±5.2%, P=0.01) and the same was true for 6-minute walk test distance (83±47 m vs. 37±27 m, P=0.03). NT-proBNP decreased in Group A (-356±684 pg/mL), but not in Group B (+449±1040 pg/mL, P=0.07) and overall clinical response was significantly better in Group A than in Group B (responders: 88% vs. 33%, P=0.008).

Conclusions:
In non-ischemic DCM, clinical response to CD34+ cell therapy appears to correlate with changes in galectin-3 serum levels. This suggests that the effects of CD34+ cell therapy may be partially mediated through remodelling of the extracellular matrix.
Abstract 15578: Adiposity, Systolic Blood Pressure, Smoking and Atrial Fibrillation: Analyses of 2.3 Million US Adults Attending Cardiovascular Screening
Authors: Bulbulia Richard , Sherliker Paul , Clack Rachel , Halliday Alison , Peto Richard , Lewington Sarah
Published: July 2021

Aims:
Unlike other vascular conditions, and for reasons that are incompletely understood, the prevalence of atrial fibrillation (AF) is rising sharply. Analysis of a large healthy cohort which was screened for AF allows reliable assessment of its association with several classical vascular risk factors.

Methods:
Between 2009 and 2013, around 3 million US adults attended cardiovascular screening clinics and had an ECG to identify AF. Personal and family medical history, medication use, smoking and alcohol consumption were recorded via questionnaires, and height, weight and blood pressure were measured. Age and gender-specific incidence of AF and associations between body mass index (BMI), systolic blood pressure (SBP) and smoking were measured in 2,320,190 participants with no reported prior history of AF, stroke or CHD.

Results:
The median age was 65, and two-thirds were female. The overall incidence of AF was 0.36%, but it was over twice as common in males (0.59%) than in females (0.23%) and rose sharply with age, doubling in each decade in both men and women. A positive association was seen between adiposity and AF in men and women across all ages studied: approximately 50% increase per 5 unit rise in BMI. By contrast, AF was only weakly associated with SBP - 10% increase per 10mmHg rise in SBP among participants aged under 70 years, and flat or even inversely associated among those over 70 years. Smoking was not associated with AF in men or women at any age (Odds Ratio for current vs never smokers = 0.97 [95% CI 0.79-1.19]).

Conclusion:
A 10 unit increase in BMI (ie, going from an “ideal” weight to “obese”) doubled the risk of AF. However, blood pressure was less strongly associated with AF, and only in those under 70 years, suggesting some other mechanism behind the BMI - AF association. Current smoking was not associated with AF. Rising rates of obesity may be driving the observed increase in AF in the developed world.
Abstract 15595: Improved Clinical Performance and Teamwork of Pediatric Interprofessional Resuscitation Teams With a Simulation-Based Educational Intervention
Authors: Gilfoyle Elaine , Koot Deanna , Annear John , Bhanji Farhan , Cheng Adam , Duff Jonathan , Grant Vincent , St George-Hyslop Cecilia , Delaloye Nicole , Kotsakis Afrothite , McCoy Carolyn , Ramsay Christa , Weiss Matthew , Gottesman Ronald ,   Teams4Kids Investigators,   Canadian Critical Care Trials Group
Published: July 2021

Introduction:
Human errors occur during resuscitation despite individual knowledge of resuscitation guidelines. Poor teamwork has been implicated as a major source of such error; therefore interprofessional resuscitation teamwork training is essential.

Hypothesis:
A one-day team training course for pediatric interprofessional resuscitation team members improves adherence to PALS guidelines, team efficiency and teamwork in a simulated clinical environment.

Methods:
A prospective interventional study was conducted at 4 children’s hospitals in Canada with pediatric resuscitation team members (n=300, 51 teams). Educational intervention was a one-day simulation-based team training course involving interactive lecture, group discussions and 4 simulated resuscitation scenarios followed by debriefing. First scenario of the day was conducted prior to any training. Final scenario of the day was the same scenario, with modified patient history. Scenarios included standardized distractors designed to elicit and challenge specific teamwork behaviors. Primary outcome measure was change (before and after training) in adherence to PALS guidelines, as measured by the Clinical Performance Tool (CPT). Secondary outcome measures: change in times to initiation of chest compressions and defibrillation; and teamwork performance, as measured by the Clinical Teamwork Scale (CTS). Correlation between CPT and CTS scores was analyzed.

Results:
Teams significantly improved CPT scores (67.3% to 79.6%, P< 0.0001), time to initiation of chest compressions (60.8 sec to 27.1 sec, P<0.0001), time to defibrillation (164.8 sec to 122.0 sec, P<0.0001) and CTS scores (56.0% to 71.8%, P<0.0001). Significantly more teams defibrillated under AHA target of 2 minutes (10 vs. 27, P<0.01). A strong correlation was found between CPT and CTS (r=0.530, P<0.0001).

Conclusions:
Participation in a simulation-based team training educational intervention significantly improved surrogate measures of clinical performance, time to initiation of key clinical tasks, and teamwork during simulated pediatric resuscitation. A strong correlation between clinical and teamwork performance suggests that effective teamwork optimizes clinical performance of resuscitation teams.
Abstract 15627: Identification of Cardiovascular Risk Factors Associated With Bone Marrow Cell Subsets in Patients With STEMI: A Biorepository Evaluation From the CCTRN TIME and LateTIME Clinical Trials
Authors: Contreras Ariadna , Orozco Aaron F , Schutt Robert C , Resende Micheline M , Sampaio Luiz , Cooke John P , Bhatnagar Aruni , Bolli Roberto , Cohen Michelle , Willerson James T , Moyé Lem , Taylor Doris A
Published: July 2021

Objective:
Results from several randomized, controlled cell therapy trials suggest that the use of autologous bone marrow mononuclear cells (BMMNCs) results in only modest benefits in patients with ST-segment elevation myocardial infarction (STEMI). However, the patients in these trials had varying combinations of underlying cardiovascular risk factors (CVRFs) and comorbidities. The autologous BMMNC product administered to each patient was unique. Based on our previous findings, the purpose of this study was to identify potential associations between specific CVRFs and BMMNC subsets in patients with STEMI.

Methods:
This study evaluated a cohort of patients with STEMI who were enrolled in either the CCTRN TIME or LateTIME trials and underwent BMMNC or placebo treatment (N=139). Flow cytometric analysis targeting phenotypic markers (eg, CD45, CD14, CD11b, CD3, CD19, CD31, and CD34) was used to assess the frequency of BMMNC subsets at baseline. The GRACE ACS Risk Score 2.0 - 3 year death (GRS) was used to stratify patients according to cardiovascular risk (low: GRS <12%, moderate: GRS 12-30%, high: GRS >30%). Multivariable models were then applied to assess relationships between BMMNC subsets and CVRFs, including age, smoking, hypertension, hyperlipidemia, and sex.

Results:
Patients were grouped as low GRS (n=69, 49.6%), moderate GRS (n=49, 35.3%), and high GRS (n=21, 15.1%). Patients with a high GRS had significantly lower frequencies of CD45+CD31+ cells than those with a low GRS (35.6% vs 40.3%, respectively, P=0.041). In multivariable analyses, age was inversely associated with the frequencies of CD34+ (P=0.011) and CD45+CD31+ (P=0.001) cells, and smoking was associated with a decrease in CD45+CD31+ cells (P=0.022). In addition, higher frequencies of CD11b+ cells were associated with hypertension (P=0.010) and hyperlipidemia (P=0.029). In contrast, the CD11b+ cell frequency was less in females (P=0.005).

Conclusions:
This study identified associations between specific CVRFs and BMMNC subsets. These associations may contribute to the heterogeneity of the cell product received. Thus, differences in patients’ comorbidities should be considered when designing future autologous cell therapy trials.
Abstract 15696: Cytochrome B5 Reductase 3 Sensitizes Soluble Guanylate Cyclase to Nitric Oxide
Authors: Nguyen Anh T , Rahaman Mizanur M , Mutchler Stephanie M , Miller Megan , Prchal Josef T , Gordeuk Victor , Martin Emil , Straub Adam C
Published: July 2021

Impaired soluble guanylyl cyclase (sGC)-dependent nitric oxide (NO) signaling has been linked to numerous cardiovascular diseases (CVD) such as hypertension, myocardial infarction and atherosclerosis. Despite emerging evidence indicating the importance of sGC function within the cardiovascular system, the basic mechanisms that regulate sGC activity remain incompletely understood. Herein, we provide in vitro and in vivo evidence that cytochrome b5 reductase 3 (Cyb5R3) is an sGC heme iron reductase and regulates downstream cGMP signaling. Of major significance, we also demonstrate that a Cyb5R3 T116S polymorphism with allele frequency of 0.23 in African Americans associates with increase blood pressure and is incapable of reducing sGC. Proximity ligation assay (PLA) experiments show that endogenous Cyb5R3 and oxidized sGC associate. Knockdown of Cyb5R3 results in reduced cGMP production and downstream signaling in rat aortic smooth muscle cells (SMC). Overexpression of Cyb5R3 not only rescues cGMP production but also increases baseline cGMP, whereas T116S mutant does not. Finally, inhibition of Cyb5R3 in mice significantly increases systemic blood pressure. Our studies are the first to identify an sGC heme iron reductase, provide evidence for Cyb5R3 as a key biological regulator of sGC activity and vascular tone in SMC, and link a human polymorphism of Cyb5R3 to increased blood pressure; all of which may lead to the development of novel therapeutics targeting Cyb5R3 for the treatment of CVD. Importantly, the co-expression of Cyb5R3 and sGC in multiple cells types suggests that this regulation of sGC activity may have broad applications for multiple physiological and pathophysiological processes.

Results: Conclusions:
Abstract 15755: Adverse Cardiac Remodeling in Obese Children
Authors: Kulkarni Aparna , Lorenzo Jose Miguel Mateo D , Gulesserian Talin , Kaskel Frederick , Mahgerefteh Joseph
Published: July 2021

Background:
Obesity (OB) and hypertension (HTN) are risk factors for early cardiovascular disease (CVD). The aim of this study was to determine the effect of OB and HTN on myocardial mechanics in children using speckle-tracking echocardiography (STE).

Methods:
Echocardiograms (echo) and ambulatory blood pressure monitors were performed in children referred for HTN from 2009 to 2014. Traditional echo Doppler indices, mass and volume parameters, 24-hr systolic blood pressures (24SBP) and 24-hr diastolic BP indices were obtained. Post-processing was performed on the 2D gray scale images of LV in apical 4-chamber and parasternal short axis mid-papillary views to obtain strain indices (Image Arena, Tomtec). Associations of obesity and BP to the myocardial indices were explored independently using Spearman correlation coefficient.

Results:
Among 107 patients, 6 - 21 yrs age, 79.4% were males; 42% OB and 53% were hypertensive. Mean Z scores for BMI were 1.5 ± 1.1 and SBP were 1.5 ± 1.2. Mean LV mass (LVM, 2D area-length) was 131
+
42.8 gms, LVMI
2.7
was 40.7
+
9.6 gms, LVM/volume ratio was 0.94
+
0.17. Mean mitral septal E/e’ was 8.3
+
2.1, lateral E/e’ was 5.9
+
1.5 and mitral E/A ratio was 1.8
+
0.4. The mean global longitudinal strain (GLS) was – 17.7
+
3.6, global circumferential strain (GCS) was -20.4
+
3.8, average radial strain (ARS) was 22
+
11.9, average longitudinal strain rate (ALSR) was -1.0
+
0.35 and average circumferential strain rate (ACSR) was -1.5
+
0.5 for all patients. BMI Z scores positively correlated with LVM (r=0.38, p<0.01), LVM/vol (r=0.32, p<0.01), mitral E/e’ (r=0.28, p<0.01), LVMI
2.7
(r=0.5, <0.01). Increased BMI negatively correlated to GLS, GCS and ACSR (r=0.3, p<0.01). Higher SBP, diastolic and mean BP were associated with higher mitral medial E/e’ (r=0.3, p<0.01), however did not have statistically significant correlations to strain indices.

Conclusions:
Obesity causes adverse cardiac remodeling in obese children. This may provide insights into mechanisms of long-term CV effects of obesity. Myocardial effects of HTN were not apparent, possibly due to heterogeneity of the study group and low power.