bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4710: Diagnostic Accuracy of Myocardial Perfusion on Myocardial Contrast Echocardiography in Patients with Acute Coronary Syndrome: Results from the Assessment of Coronary Heart Disease with Myocardial Contrast Echocardiography 2 (ACTMCE2) Multicenter Trial
Authors: Sakata Konomi , Ito Hiroshi , Wada Hiroshi , Watanabe Hiroyuki , Sakuma Tadamichi , Yamada Satoshi , Doi Kaoru , Watanabe Tomoyuki , Yoshino Hideaki , Iwakura Katsuomi , Lin Young-jae , Ota Takahiro , Yoshikawa Junichi
Published: July 2021

Background: Intravenous myocardial contrast echocardiography (MCE) at rest and during vasodilator stress is a reliable bedside technique for assessment of myocardial perfusion in patients with coronary artery disease. The aim of this study is to evaluate diagnostic accuracy of myocardial perfusion abnormalities using MCE at rest in patients with acute coronary syndrome (ACS). This study is the first MCE multicenter trial for the evaluation of ACS in Japan.

Methods: We performed triggered MCE at rest in 102 patients (mean age: 65 ± 11 years) with suspected ACS. We obtained 1:1 and 1:6 end-systolic triggered MCE images at four- and two-chamber views. We detected myocardial ischemia by the appearance of myocardial perfusion abnormalities (defect or reduction) in 1:1 end-systolic triggered MCE image. We assessed the appearance of regional wall motion abnormality (RWMA) at the same time. Quantitative coronary angiography was performed in all patients within 1 week (2.6 ± 2.2 days) after MCE.

Results: Eighty-four of 102 (82%) patients were diagnosed ACS (unstable angina: 70 patients; non-ST-segment elevation myocardial infarction: 11 patients; ST-segment elevation myocardial infarction: 3 patients) and demonstrated significant coronary artery stenosis (stenosis = or >75%) that required coronary revascularization therapy. The sensitivity, specificity, and accuracy of myocardial perfusion abnormality by MCE at rest for diagnosing ACS were 79%, 86%, and 83%, respectively. On each coronary artery, the sensitivity, specificity, and accuracy of MCE for diagnosing ACS were 85%, 71%, and 79% in the left anterior descending artery; 70%, 92%, and 84% in the left circumflex artery; 77%, 89%, and 84% in the right coronary artery, respectively. The sensitivity, specificity, and accuracy of RWMA for diagnosing ACS were 49%, 90%, and 71%, respectively, and the sensitivity of MCE for diagnosing ACS was significantly higher than that of RWMA.

Conclusion: Intravenous myocardial contrast echocardiography at rest without stress examination is a feasible noninvasive method for accurate diagnosis of ACS. In this multicenter study, MCE at rest improved the diagnostic accuracy of echocardiography for diagnosing ACS.
Abstract 4718: Combined Adenosine Stress Perfusion and Coronary Angiography Using 320-Row Detector Dynamic Volume Computed Tomography in Patients with Suspected Coronary Artery Disease
Authors: George Richard T , Kitagawa Kakuya , Laws Katherine , Lardo Albert C , Lima Joao A
Published: July 2021

Dynamic volume 320-row detector computed tomography (CT), with full cardiac coverage, allows for the combination of non-invasive angiography (CTA) performed at rest with myocardial perfusion imaging (MPI) during adenosine stress. The purpose of this study was to test the accuracy of combined CTA and MPI using dynamic volume 320-row detector CT to identify atherosclerosis causing territorial ischemia. Eighteen patients with chest pain and intermediate to high pre-test likelihood of coronary artery disease (CAD) underwent rest CTA and stress CT-MPI following radionuclide MPI using the following prospective ECG-gated protocol: Rest CTA: 320 × 0.5mm, 120 kV, 400 mA, 70 – 80% R-R interval followed by Stress CT-MPI: adenosine (140μg/kg/min), 320 × 0.5mm, 120 kV, 400 mA, 70 – 80% R-R interval. CT-MPI images were reconstructed in the short axis with a 3 mm slice thickness. The transmural perfusion ratio (TPR) was calculated by dividing the endocardial attenuation density (AD) by the epicardial AD in each sector. Ischemia was defined as a TPR <0.99 on adenosine stress CT-MPI that normalized on the rest CTA images. CTA was analyzed for stenoses ≥50% and radionuclide MPI was analyzed for fixed and reversible perfusion abnormalities. Using a 17-segment model in a territory/vessel based analysis, the combination of CTA + CT-MPI was compared with CTA 3 radionuclide MPI (gold standard) for its ability to detect atherosclerosis causing territorial ischemia. Mean TPRs in ischemic and normal territories were 0.90±0.09 and 1.13±0.10, respectively (p<0.001). The sensitivity, specificity, positive (PPV) and negative predictive value (NPV) for CTA + CT-MPI were 86%, 85%, 67, and 94% compared with the gold standard; respectively. However, when adjusting for balanced multivessel disease the sensitivity, specificity, PPV, and NPV were 89%, 94%, 89%, and 94%; respectively. Mean effective radiation dose for the combined rest (4.9±0 mSv) and stress (8.5±0.5mSv) protocols was 13.4±0.5 mSv. The combination of CTA and CT -MPI, using 320-row detector dynamic volume CT, is capable of accurately identifying myocardial ischemia in the presence of obstructive atherosclerosis and compares well with CTA/radionuclide MPI.
Abstract 4725: Left Ventricular Myocardium Shows Base-to-Apex Deformation Gradient during Isovolumic Relaxation Period in Healthy Subjects
Authors: Buakhamsri Adisai , Popovic Zoran B , Lim Pascal , Greenberg Neil L , Thomas James D
Published: July 2021

Introduction: Deformation of LV myocardium during isovolumetric relaxation period (IVR) is not well described.

Methods: We performed echocardiography (Vivid 7, GE Medical) in 90 healthy subjects at rest (mean age 38 ±13 years, 34 males). Standard long and short LV axis views were acquired with high frame rate (65–100 fps) and used for strain rate (Sr) measurement by speckle tracking (EchoPac PC) in three directions: longitudinal (SrL), circumferential (SrC) and radial (SrR). Segmental Sr curves were the average Sr in each LV levels, i.e. base (B), mid (M) and apex (A) and normalized by R-R interval duration (Panel A and B). We then calculated Sr gradients during IVR as maximal instantaneous difference between apex-to-base or mid-to-base LV Sr (Sr(A-B) or Sr(M-B), Panel C). Pulsed wave Doppler flow profiles were used to determine cardiac intervals.

Results: SrL(A-B), SrC(A-B) and SrR(A-B) were 0.53 ±0.43, 0.67 ±0.46, −1.89± 1.52 s-1. SrL(M-B), SrC(M-B) and SrR(M-B) were 0.37±0.15, 0.5±0.34 and −2.14±1.4 s-1. Both types of gradient were identified for all strains (p<0.001 vs. zero), and were also different from each other (p<0.001, Sr(A-B) vs. Sr (M-B) for similar strain). The gradients were driven by faster relaxation in apical and mid LV segment and brief shortening in basal segment (see Figure

inset).

Conclusions: Differential deformation of LV exists during IVR. This deformation difference in the base to apex direction may facilitate changes in LV geometry that result in rapid intra-cavitary pressure reduction.
Abstract 4778: Postoperative ST2 Blood Concentrations Predict One Year Mortality in Coronary Artery Bypass Patients
Authors: Grant Michael C , Christenson Robert , Gray Jeffrey , Pollock Jeremy S , Christenson Eric , Joshi Ashish , Poston Robert S
Published: July 2021

Soluble ST2 (sST2) is released from myocytes in response to mechanical overload and predicts poor outcome in heart failure and myocardial infarction. We evaluated the capability of early sST2 release after coronary artery bypass surgery (CABG) to predict mortality during the first postoperative year. We prospectively evaluated sST2 baseline prior to CABG (BL), immediately after CABG (post), and 24h and 72h. The primary endpoint of the study was all-cause mortality at 1 year. Of the 210 patients enrolled, death occurred in 3 (1.5%) within 30 days and 20 (9.5%) by 1 year. sST2 levels did not change immediately post-CABG (BL: 0.32±0.42, post: 0.42±0.46) but became significantly elevated at 24h and 72h (3.39±3.08, 0.95±1.04 ng/ml; P<0.001). Compared to survivors, sST2 was significantly elevated in decedents at 24h (7.68±3.15 vs. 2.78±2.56, P<0.001) and 72h (1.56±1.62 vs. 0.88±0.44, P<0.03). On ROC analysis, sST2 at 24h strongly predicted death at 1 yr (AUC 0.868, 95% CI=0.77– 0.96). In multivariate analysis, sST2 level was a more powerful predictor of death (OR 17.0, P<0.0001) than traditional predictors (STS risk score, age, left ventricular ejection fraction) or other biomarkers (OR 1.59, P<0.0001) including troponin I, CPK-MB, and NT-pBNP. Although operative mortality was better than predicted by STS score, the 9.5% risk of death over 1yr highlights the need to better stratify mortality risk in order to guide appropriate follow-up after hospital discharge. As a strong predictor of 1yr mortality, independent of traditional laboratory or clinical variables, the sST2 level at 24 hrs may help advance this goal.
Abstract 4787: Half of Patients with Severe Symptomatic Aortic Stenosis Do Not Undergo Aortic Valve Replacement
Authors: Gualano Sarah K , Siao Derrick , Girard Steven E , Duvernoy Claire , McCallister Benjamin D , Bach David S
Published: July 2021

Although aortic stenosis (AS) is common, little data exist about the rate of aortic valve replacement (AVR) in patients with severe symptomatic AS. Many patients with severe symptomatic AS do not undergo AVR. Echocardiography databases for 3 large tertiary centers were searched for patients in 2005 with severe AS (mean gradient ≥ 40 mmHg, valve area of < 1.0 cm
2
, or overall clinical assessment of severe AS). Records were reviewed for symptoms, referral, surgical AVR, and outcome. Operative risk was calculated using the logistic EuroSCORE. Four hundred thirteen patients had an echocardiogram with severe AS; 44 were excluded based on additional testing or inadequate medical records. Of the remaining 368 patients, 188 (51%) underwent AVR, and 191 (49%) and were un-operated. Of 191 un-operated patients, 126 (66%, 34% of total) had symptoms consistent with AS, 182 (95%) were referred to cardiology, but 75 of 126 (60%) un-operated symptomatic patients were not referred for surgical assessment. Among un-operated symptomatic patients, operative risk was < 5% in 31 (25%) and < 10% in 59 (47%). The prevalence of un-operated patients was similar between institutions. Decisions not to operate most commonly were based on co-morbidities, patient preference, symptoms due to other conditions, and unrecognized AS. With an average follow-up of 13.9 ± 9.8 months, 52 of 191 (27%) un-operated patients died. Half of patients with severe symptomatic AS do not undergo AVR, with similar findings in multiple tertiary care environments. Some patients with severe symptomatic AS may be inappropriately denied access to potentially life-saving therapy.
Abstract 4838: Diffuse, Marked, Reversible Impairment in Coronary Microcirculation in Stress Cardiomyopathy: A Vasodilator Stress Echo Study
Authors: Rigo Fausto , Sicari Rosa , Citro Rodolfo , Ossena Giovanni , Buja Paolo , Picano Eugenio
Published: July 2021

Stress cardiomyopathy, also referred to as Takotsubo cardiomyopathy (TC) has been linked to excessive sympathetic stimulation, which can be toxic for myocytes and coronary microcirculation. Aim: To assess coronary flow reserve (CFR) in TC. Methods: 30 consecutive patients (5 males; 68±12 years) meeting diagnostic criteria for TC were evaluated with transthoracic dipyridamole (0.84 mg/kg over 6′) stress echo and Pulsed Doppler CFR assessment on mid-distal left anterior descending (LAD) and posterior descending of right coronary artery (PD). Wall Motion Score Index (WMSI) was evaluated at baseline and during stress. All patients were followed-up clinically and - on day 1, day 7 (±2 days) and at 6 months - by repeat stress echo. Twenty-one age and gender matched controls were also studied. Results: CFR was obtained in all patients on LAD and in 25 on PD. All pts showed a transient apical ballooning in the acute phase (day 1 of admission), with progression recovery of function at follow-up (WMSI, day 1=1.7±.2; day 7=1.4±.14; 6-months=1.0±0.1; p<0.001 vs day 1 and vs. day 7). When compared to controls, CFR was reduced on day 1 (upon admission) and it showed early recovery in the subacute (pre-discharge) assessment on day 7. CFR values remained stable at 6-months follow-up (see figure

). Conclusion: TC is characterized by a profound, diffuse, coronary microcirculatory disturbance in the acute phase, with early reversal to near-normal values within a few days, paralleling the functional recovery in regional wall motion. The reversible coronary microcirculatory abnormality can be observed also in the territory of right coronary artery.
Abstract 4839: Colocalization of Regional MEF2 Activity With Myocardial Scarring in Hypertrophic Cardiomyopathy
Authors: Konno Tetsuo , Chen Dan , Wang Libin , Wakimoto Hiroko , Teekakirikul Polakit , Seidman Christine , Seidman Jonathan
Published: July 2021

Background- The molecular triggers activated by a sarcomere gene mutation that remodel the heart and produce histopathologic manifestations of hypertrophic cardiomyopathy (HCM) are incompletely known. Myocyte enhancer factor 2 (MEF2) has emerged as a critical regulator of gene expression in the heart.

Objective- To examine whether MEF2 is essential for HCM pathogenesis, we assessed in vivo MEF2 expression versus myocyte hypertrophy, disarray and interstitial fibrosis, the prototypic histopathology of HCM.

Methods and Results- Wild-type or heterozygous mice harboring an Arg403Gln missense mutation in the alpha-myosin heavy chain gene (MHC403/+ mice) were crossed with transgenic mice harboring a MEF2-dependent reporter gene. Mouse hearts at 30 weeks of the age were evaluated by beta-galactosidase staining to detect transcriptional activity of MEF2 in vivo. Activity of MEF2 was heterogeneously increased in the left ventricle of MHC403/+ mouse hearts compared with wild-type mouse hearts. Gomori’s trichrome staining for collagen revealed that regional activation of MEF2 uniquely colocalized with myocardial scarring in MHC403/+ mouse hearts whereas only baseline activity of MEF2 was detected in the area without myocardial scarring. von Kossa staining revealed myocardial necrosis near to MEF2 staining. To further explore whether MEF2 activity is involved in the pathogenesis of myocardial necrosis, mice carrying a homozygous Arg403Gln mutation (MHC403/403) and the MEF2-dependent reporter gene were analyzed. MEF2 was regionally activated in 3-days old MHC403/403 mouse hearts, in advance of the myocardial necrosis that occurs in homozygous mutant hearts. At 6-days, greater MEF2 activity was observed compared with 3-days old MHC403/403 hearts, and massive necrosis was present where MEF2 was activated.

Conclusions- These findings provide the first evidence for regional activation of the MEF2-pathway is involved in evolution of myocardial fibrosis and necrosis in HCM. Because myocyte loss and myocardial scarring is implicated in the progression of ventricular dysfunction, these data indicate that strategies to prevent MEF2 activation may attenuate remodeling and heart failure development.
Abstract 4845: Hypertrophic Cardiomyopathy due to Sarcomere Gene Mutations is Associated with More Severe Derangement of Microvascular Function Compared to Myofilament Negative Disease
Authors: Olivotto Iacopo , Girolami Francesca , Ackerman Michael J , Sciagra Roberto , Nistri Stefano , Bos J. M , Sotgia Barbara , Torricelli Francesca , Camici Paolo G , Cecchi Franco
Published: July 2021

Coronary microvascular dysfunction (CMD) is an important primary feature of hypertrophic cardiomyopathy (HCM), contributing to myocardial ischemia and ventricular remodelling, and is predictive of adverse outcome. Whether there is any association between presence/severity of CMD and HCM’s pathogenic substrate remains to be determined. To address this issue, we used positron emission tomography (PET) to assess CMD in an HCM cohort that received comprehensive genetic testing for sarcomeric/myofilament-HCM. We measured maximum (intravenous dipyridamole, 0.56 mg/kg) myocardial blood flow (Dip-MBF), using
13
N-labeled ammonia and PET in 46 HCM patients (age 38±14 years, 32 male). Genetic testing was performed by denaturing high performance liquid chromatography and automatic DNA sequencing of nine myofilament-encoding genes including both thick filament proteins (myosin binding protein C, beta-myosin heavy chain, regulatory and essential light chains); and thin filament proteins (troponin-T, troponin-I, troponin-C, alpha-tropomyosin and alpha-actin).

Results
. Thirty-four mutations were identified in 30/46 patients (myofilament-HCM; 65%), including 29 with thick filament and 6 with thin filament mutations, as well as 4 with complex genotype. Despite similar age and clinical features, patients with myofilament-HCM showed lower Dip-MBF values than the patients with a negative genetic test (1.6±0.7 versus 2.2±0.9 ml/min/g, respectively; p=0.03). Specifically, 13/30 (43%) patients with myofilament-HCM had a Dip-MBF below the lower tertile for the study group (≤1.38 ml/min/g), compared to 2/16 (12%) patients with a negative genetic test (p=0.034). No difference in Dip-MBF was evident with respect to the particular sarcomeric gene involved (ANOVA p=0.63). HCM due to sarcomere gene mutations is characterized by more severe impairment in microvascular function compared to myofilament negative disease, irrespective of the involved contractile protein. These findings suggest that sarcomeric mutations might be implicated in adverse remodelling of the microcirculation in patients with HCM, and account for the greater prevalence of ventricular dysfunction and failure in this subset.
Abstract 4852: Changes In Left Ventricular Structure And Function Over 12 Months In Patients With Mild Or Asymptomatic Heart Failure With Previous Symptoms In The Resynchronization Reverses Remodelling In Systolic Left Ventricular Dysfunction (reverse) Study
Authors: Sutton Martin St. John , Ghio Stefano , Plappert Ted , Tavazzi Luigi , Daubert Jean Claude , Abraham William T , Gold Michael R , Gold Michael R , Linde Cecilia
Published: July 2021

Background:
Cardiac Resynchronization Therapy (CRT) induces LV reverse remodeling that translates into symptom relief and improved survival in New York Heart Association (NYHA) symptom class III/IV heart failure (HF). We hypothesized that CRT would also result in LV reverse remodeling in NYHA class I/II (asymptomatic or minimally symptomatic) HF and slow disease progression.

Method:
All patients in the
RE
synchronization re
VE
rses
R
emodeling in
S
ystolic left
v
Entricular dysfunction (REVERSE) study had an EF<40% and a QRS>120ms and had optimal HF therapy for at least 1 month. Echograms were obtained at baseline, pre-hospital discharge (PHD), 6 and 12 months. At the PHD visit two limited echos were performed (one with CRT OFF and one with CRT ON), to assess the acute mechanical effect of pacing. LV volume indices, EF, LV mass and severity of mitral regurgitation (MR) were quantified at all time points by a Core Echo lab.

Results:
Of 610 patients, 82% had NYHA class II and 18% had class I HF. Patients were randomized 2:1 to CRT ON (n=419) or CRT OFF (n=191). LV volume indices at end-systole and end-diastole decreased and EF increased significantly from baseline to 12 months in CRT ON, but did not change in CRT OFF. LV mass and severity of MR did not change in either group at 12 months (Table

). When CRT ON was switched to CRT OFF at PHD, there were no significant acute changes in LV size or function.

Conclusion:
CRT results in major structural and functional LV reverse remodeling in patients with NYHA class I/II HF that may delay the natural disease progression. The progressive reverse LV remodeling is demonstrated on top of the attenuation seen with optimal medical therapy in NYHA class I/II (CRT OFF group). The echo findings in REVERSE may have important clinical implications for use of CRT in the optimal therapy of patients with NYHA class I/II heart failure.

Table.

Mean ± S.D. (n) Echocardiographic Parameters: CRT ON vs. CRT OFF
Abstract 4870: Cardiovascular Effects Of Apelin In Healthy Volunteers And Patients With Heart Failure
Authors: Japp Alan G , Cruden Nicholas L , Denvir Martin A , Flapan Andrew D , Newby David E
Published: July 2021

BACKGROUND Apelin is the most potent inotrope yet described. In preclinical models, it increases cardiac output in normal and failing hearts and lowers blood pressure through peripheral vasodilatation. We have recently demonstrated that apelin causes nitric oxide-dependent vasodilatation in man. Here, we aimed to establish the effects of apelin on cardiac and systemic hemodynamics variables.

METHODS All studies were performed in a randomized, double-blinded manner. Forearm blood flow responses to intrabrachial infusions of (Pyr1)apelin-13 (0.3–3 nmol/min), acetylcholine (5–20 μg/min) and sodium nitroprusside (SNP; 1– 4 μg/min) were measured by venous occlusion forearm plethysmography in 12 patients with stable chronic heart failure (CHF; NYHA class II–III) and 12 matched controls. Cardiac index (CI; assessed non-invasively by thoracic electrical bioimpedance) blood pressure and heart rate (HR) were measured during intravenous infusions of (Pyr1)apelin-13 (30 –300 nmol/min) and saline placebo in 6 patients with stable CHF and 7 matched controls. The maximum rate of pressure rise within the left ventricle (dP/dt max) was measured in 4 patients following intracoronary boluses of apelin-36 (20 and 200 nmol) and saline placebo.

RESULTS Apelin infusions were well tolerated with no reported symptoms or ECG abnormalties. Apelin, acetylcholine and SNP caused vasodilatation in forearm resistance vessels of both CHF patients and controls (all p<0.0001). Responses to acetylcholine (P=0.01) but not apelin (p=0.3) or SNP (p=0.9) were diminished in patients with CHF compared with controls. In CHF patients, apelin increased cardiac index by 16% (p<0.05) and lowered mean arterial pressure (MAP) by 7% (p<0.05) but had no effect on HR (p=0.17). In controls, apelin increased CI by 8% (p<0.05) and HR by 13% (p<0.01) and lowered MAP by 8% (P<0.01). Intracoronary injection of apelin appeared to increase cardiac contractility (dP/dt max rise of 8%, p=0.056).

CONCLUSIONS Apelin increases cardiac output and lowers blood pressure in man, through both peripheral arteriolar vasodilatation and increased cardiac contractility. These effects of apelin are preserved in patients with CHF suggesting a potential therapeutic role for apelin agonism in heart failure.
Abstract 4874: Large-Scale Candidate Gene Association with Human Heart Failure
Authors: Cappola Thomas , Li Mingyao , He Jing , Ky Bonnie , Gilmore Joan , Keating Brendan , Reilly Muredach , Syed Faisel , Matkovich Scot , Dorn Gerald
Published: July 2021

Genetic factors that contribute to non-familial heart failure (HF) are largely unknown. Attempts to identify such by whole genome association have implicated genomic loci, but not specific polymorphisms. In contrast, single candidate gene studies have suggested specific variants and mechanisms, but have not all been replicated. Here, we combined the strengths of whole-genome and single candidate gene association studies in the first large-scale candidate gene study of HF in two independent populations. A custom Illumina SNP array containing 45,000 SNPs in ~2,100 genes prioritized by mechanistic relevance in cardiovascular disorders was used to genotype matched Caucasian HF cohorts (ACC/AHA stage C/D; LVEF 31±16%) from two centers, U. of Pennsylvania (708 CHF, 350 controls) and U. of Cincinnati (900 CHF, 300 controls). After careful assessment of genetic ancestry, we compared genotype frequencies in cases vs. controls using logistic regression (PLINK) adjusting for age and gender. To minimize false positives, genes were ranked according to P-value in both study populations and in a combined analysis of all cases vs. all controls. 13 SNPs were associated with all-cause heart failure with P-values ranging from 10
−2
to 10
−5
. These SNPs were located within genes HSPB7, PCSK6, IL1F10, FRMD4B, F2RL1, SLIT2, NOS1AP, MMP12, and IL1RN. Stratified analyses identified 18 SNPs specific for ischemic heart failure (F10, F7, IRS1, NFATC2, IL1R1, SLIT2, CASP8, CORIN, CDKAL1, TRIAD3, CSMD1) and 12 SNPs for non-ischemic heart failure (ACTC1, RYR2, PRKAG2, SCL5A7, ADRA1,TIE1), replicating several previous observations and identifying intriguing new associations. Most of the SNPs were in non-coding regions, and several of these were in genes that show significant changes in expression in failing vs. non-failing human myocardium (NOS1AP, IL1R1, NFATC2). These findings suggest that common variants in cardiovascular genes contribute to the pathogenesis of human heart failure, in part by affecting level of gene expression, and identify specific targets for further mechanistic analyses.
Abstract 4925: Noninvasive Angiographic Follow-Up 18 Months after Bioabsorbable Everolimus-Eluting Stent Implantation Using 64-Slice Computed Tomography (ABSORB)
Authors: Nieman Koen , Weustink Annick , Onuma Yoshinobu , Bruining Nico , Klimeczek Piotr , Bottcher Morten , Ormiston John A , Dudek Dariusz , Thuesen Leif , De Feyter Pim J , Serruys Patrick W
Published: July 2021

While assessment of metal stents by CT angiography is complicated by blooming artifacts, noninvasive follow-up should be possible after implantation of non-metal, radiolucent, bioabsorbable stents. In a multicenter, prospective, open-label study (ABSORB) 30 patients underwent implantation of a 3.0 ×12-mm (N=28) or 3.0 × 18-mm(N=2) bioabsorbable everolimus-eluting stent made of polylactic acid (Abbott Vascular, Santa Clara, CA). At 19.2 ±1.1 months 64-slice CT angiography (Siemens Somatom Definition, Germany; Philips Brilliance 64, The Netherlands; GE LightSpeed VCT, WI) was performed in 25 patients (65 ±11 years, 15 male). Five patients were lost due to target-lesion re-intervention (N=1), contrast allergy (N=1), withdrawn consent (N=3). Cross-sectional, in-stent lumen areas were measured at submillimeter intervals using quantitative CT software (Circulation®, Siemens). Minimal in-stent lumen area was compared to the reference lumen area, based on adjacent proximal and distal lumen areas. Motion artifacts excluded one CT study. Radiopaque indicators (figure

) at the egdes of the absorbed stent were the only visible remains: distance 11.4 ±0.5 mm (12-mm stents). All stents were patent. Mean lumen area 5.2 ±1.3 mm
2
(range 3.2 – 7.4 mm
2
). Minimal lumen area 3.6 ±0.9 mm
2
(range 2.2 – 5.7 mm
2
), compared to a reference lumen area of 5.5 ±1.0 mm
2
(range 3.3 – 7.6 mm
2
), resulting in a lumen area stenosis of 31 ±15% (range -2 - 51%). One case showed local lumen enlargement (12.0 mm
2
). CT angiography was feasible and demonstrated moderate in-stent lumen loss without significant obstruction after bioabsorbable stent implantation.
Abstract 5597: Does Warfarin-Based Anticoagulation Improve Outcomes After Acute Myocardial Infarction? A Meta-Analysis of Randomized Clinical Trials
Authors: Haq Salman A , Heitner John F , Sacchi Terrence J , Brener Sorin J
Published: July 2021

Antiplatelet therapy is the principal component of the antithrombotic regimen after acute myocardial infarction (AMI). It remains unclear whether additional routine antithrombin therapy with chronic oral anticoagulation (OAC) improves outcomes. Using the Ovid SP and PubMed databases, we performed a comprehensive search for randomized clinical trials comparing warfarin-containing regimens with or without aspirin (OAC) with non-warfarin-containing regimens with or without aspirin (No OAC) for patients with recent AMI, regardless of reperfusion and adjunctive medical therapies provided during hospital stay. The studies had to provide follow-up for at least one month and have mortality as endpoint. Meta-analysis techniques were employed to calculate the relative risk (RR, fixed effect) for all-cause death at the longest interval of follow-up available. Between 1965 and 2006, 32 studies were identified and 11 were included in the meta-analysis. Among 23,803 patients, 13,070 were assigned to OAC and 10,733 to No OAC. The patients were followed for 3–79 months. Death occurred in 1,199 and 1,162 patients, respectively, RR 1.00 (0.995–1.010) (Figure

). After excluding studies without background aspirin therapy, death occurred in 1,057 and 993 patients, respectively (8 studies, RR 1.00 [0.992–1.008]). OAC with or without aspirin background therapy does not reduce mortality after AMI.
Abstract 5608: Prognostic Impact of the Baseline White Blood Cell Count in Patients with Acute Myocardial Infarction Undergoing Primary PCI: Results from the HORIZONS-AMI trial
Authors: Mehran Roxana , Dangas George D , Parise Helen , Guagliumi Giulio , Witzenbichler Bernard , Grinfeld Liliana , Peruga Jan Z , Kornowski Ran , Dudek Darius , Hoard Rita , Kastrati Adnan , Herzzentrum Deutsches , Brar Somjot , Wu Roland , Fiscella Damiana , Brodie Bruce , Lansky Alexandra J , Stone Gregg W
Published: July 2021

Background:
Inflammation plays a crucial role in atherosclerosis. Previous studies have suggested an association between elevated white blood cell (WBC) and adverse outcomes in patients with ST-elevation acute myocardial infarction (STEMI). We sought to determine the relationship between admission WBC count and mortality in patients with STEMI in the HORIZONS-AMI trial.

Methods:
HORIZONS-AMI enrolled 3602 patients with STEMI undergoing primary PCI. We compared rates of 30-day major adverse cardiac events (MACE: death, reinfarction, target vessel revascularization for ischemia, or stroke), non-CABG major bleeding, and net adverse clinical events (NACE: MACE or major bleeding) in patients with baseline WBC count >12,000 cells/mm
3
vs ≤12,000 cells/mm
3
.

Results:
Of the 3497 patients with baseline WBC data, 2206 (63.1%) had a WBC count of ≤12,000 and 1291 (38.9%) had a WBC of >12,000 (median 10,800 mm
3
, mean 11,700 mm
3
). Patients with WBC ≤12,000 were older, had more hypertension, hyperlipidemia, diabetes, prior MI, and prior CABG. Compared to patients with WBC ≤12,000, those with WBC >12,000 had significantly higher rates of 30-day adverse outcomes (Table

). By multivariate analyses, WBC >12,000 was an independent predictor of 30-day mortality (HR [95% CI] = 2.51 [1.61–3.91], p30.001), MACE (1.82 [1.36, 2.44], p<0.0001), and major bleeding (1.52 [1.16 –1.99], p=0.003).

Conclusions:
In patients presenting with STEMI undergoing primary PCI, an elevated WBC count identifies a high risk cohort with significantly higher mortality, MACE and major bleeding at 30-days. These results further support the pivotal role of inflammation in ACS/AMI.
Abstract 5612: Embolic Protection Devices in Acute Myocardial Infarction. Do They Confer the Same Clinical Benefit?
Authors: Masotti Mònica , Salazar Héctor , Kiamco Ricardo , Freixa Xavier , Betriu Amadeo
Published: July 2021

Background
Thromboembolic debris liberated during primary percutaneous coronary intervention (PCI) may result in impaired clinical outcomes. Conflicting data from randomized control trials (RCT’s) have precluded the widespread application of embolic protection devices (EPD’s) to complement primary PCI. Furthermore, current guidelines do not recommend routine use of EPD’s in this setting and longer follow-up data are lacking.

Objective
The aim of this study was to combine data from all RCT’s using EPD’s in patients presenting with ST-elevation myocardial infarction (STEMI). The primary end-point of our meta-analysis was to assess the impact of EPD’s on survival at 6 months.

Methods
Data from 8 RCT’s, including 2527 patients (pts), were analyzed. EPD’s used aspiration in 3 studies (De Luca, DEAR-MI, TAPAS; N=1295 pts), thrombectomy in 1 (X AMINE ST; N=201 pts), and filters in 4 (DIPLOMAT, ASPARAGUS, EMERALD, PREMIAR; N=1031 pts). In total, 1268 pts underwent active treatment and 1259 were controls.

Results
As shown in Table 1

, at 6 months the use of aspiration significantly reduced (by 51%) the risk of death. On the contrary, no benefit was derived from the use of either thrombectomy or filters. There was homogeneity among the trials, and when comparing the different types of EPD’s.

Conclusion
Aspiration devices, but not thrombectomy or filters, improve mid term mortality of STEMI patients undergoing primary PCI. This translates into 34 lives saved per 1000 patients treated.

Table 1.

Mortality at 6 months
Abstract 5672: Novel SCN5A Mutations and SNP in Patients with Brugada Syndrome
Authors: Nakamura Kazufumi , Miura Daiji , Kobayashi Kaoru , Ouchida Mamoru , Shimizu Kenji , Ohmori Iori , Nishii Nobuhiro , Nagase Satoshi , Morita Hiroshi , Hata Yoshiki , Oka Takefumi , Kusano Kengo , Ohe Tohru
Published: July 2021

Background: Sodium channel alpha 5 subunit (SCN5A) mutations are important genetic abnormalities of Brugada syndrome (BS). Here we report novel SCN5A mutations in patients with BS.

Methods and Results: Genomic mutations in the SCN5A gene were analyzed by PCR and direct sequencing in 121 patients with BS (119 men and 2 women). Thirteen (11%) of the patients had SCN5A mutation and five (4%) of the patients had single nucleotide polymorphisms (SNP) associated with BS. Eleven patients had single point mutations, one patient had a deletion (1380 del N) and one patient had a mutation within the splicing junction (IVS21+1 g>a). The whole-cell patch clamp technique revealed that four novel mutations (F532C, R814Q, G833R, R878C) showed loss of function, and peak INa of a novel SNP (L1988R) transiently expressed in HEK 293 cells was significantly reduced (P<0.05). RT-PCR analysis revealed that the intronic mutation (IVS21+1 g>a) resulted in exon 21 deletion of SCN5A in cardiac biopsy specimens from the patient (Figure

).

Conclusions: We detected five novel SCN5A mutations (1380 del N, F532C, R814Q, G833R, R878C) and a novel disease-associated SNP (L1988R) in patients with BS. We showed a novel analysis of splicing mutation (IVS21+1 g>a) that resulted in exon skipping in the heart.
Abstract 5675: Brugada-Type ST Segment Elevation after Sodium Channel Blockade is Caused by Right Ventricular Excitation Failure in Discontinuous Myocardium
Authors: Hoogendijk Mark G , Potse Mark , Linnenbank Andre C , Verkerk Arie O , den Ruijter Hester M , Klaver Eva C , van Amersfoorth Shirley C , Beekman Leander , Bezzina Connie R , Wilde Arthur A , Coronel Ruben
Published: July 2021

Introduction:
Brugada-type ST segment elevation has been associated with reduced sodium channel function and structural heart disease and is a risk marker for sudden cardiac death. Depolarizing and repolarizing abnormalities in the right ventricular wall have been described in patients. The mechanism of ST segment elevation however, is still debated. We determined depolarization and repolarization characteristics in an isolated heart of a young patient carrying a sodium channel mutation previously described in a family with Brugada syndrome.

Methods and Results:
A 15-year old female patient with a loss-of-function mutation (G752R) in the gene encoding the cardiac sodium channel underwent cardiac transplantation for end-stage heart failure in dilated cardiomyopathy. The explanted, perfused heart was submerged in perfusion fluid. We simultaneously recorded an “Einthoven” configuration pseudo-ECG and 194 unipolar electrograms from the endo- and epicardium of both ventricles. At baseline, a single shortly coupled premature stimulus resulted in more fractionated electrograms in the right than left ventricle (38 vs 6%, p < 0.001, Z-test). After sodium channel blockade by ajmaline, ST segment elevation of 0.3 mV was observed in pseudo-aVR which coincided with the virtual disappearance of the QRS complex in unipolar electrograms at the basal epicardium of the right ventricle followed by monophasic ST segment elevation. The local origin of this phenomenon was demonstrated by Laplacian electrograms. Neither early repolarization nor late activation correlated with the ST-change. Marked epicardial fatty infiltration was present at sites of local ST segment elevation, but not elsewhere. Simulations in a bidomain whole-heart computer model showed that either sodium current reduction or random replacement of 50% of the right ventricular epicardium by fat alone does not cause ST segment elevation. In combination however, part of the epicardial myocardium was not excited throughout the cardiac cycle by current-to-load mismatch resulting in Brugada-type ST segment elevation.

Conclusions:
Brugada-type ST segment elevation after sodium channel blockade is caused by excitation failure in discontinuous myocardium at the right ventricular epicardium.
Abstract 5700: Worsening Renal Function and Arrhythmic Event in Implantable Cardioverter Defibrillator Patients with Nonischemic Heart Failure
Authors: Takahashi Atsushi , Shiga Tsuyoshi , Yagishita Daigo , Futagawa Keisuke , Serizawa Naoki , Yamada Norihiro , Suzuki Tsuyoshi , Ejima Koichiro , Satoh Takahiro , Manaka Tetsuyuki , Shoda Morio , Hagiwara Nobuhisa
Published: July 2021

Purpose: Implantable Cardioverter Defibrillator (ICD) prevents sudden cardiac death in high risk patients with heart failure (HF). Worsening renal function (WRF) is associated with mortality in patients with myocardial infarction or HF, but its effect on lethal arrhythmia is unknown. We evaluated the influence of WRF on the occurrence of arrhythmic events in patients with nonischemic HF and ICD.

Methods: A total of 286 nonischemic HF patients who underwent ICD implantation between 1990 and 2007 were studied. Estimated Glomerular Filtration Rate (eGFR) was calculated using the Modification of Diet in Renal Disease. Renal dysfunction was defined as eGFR <60mL/min/1.73m
2
and WRF was defined as 15mL/min/1.73m
2
per year. Differences in arrhythmia recurrences according to the eGFR and WRF were compared by Kaplan-Meier survival curves.

Results: During a mean follow-up time of 2.2+/−1.0 years, 94 (33%) of 286 patients (mean age; 57+/−15 years, 72% male) experienced appropriate ICD shock therapy. There was a significantly higher cumulative rate of appropriate ICD shock therapy (p<0.05) and electrical storm (p<0.05) in patients with renal dysfunction than others. The patients with renal dysfunction at baseline experience WRF more frequently than other patients (53% vs. 23%, respectively, p<0.01). After correcting for age, sex, left ventricular ejection fraction (LVEF), indication for ICD implantation, and use of beta-blockers in a Cox regression model, WRF was still an independent predictor of the time to first appropriate shock (HR 2.21, 95% CI 1.32–3.69, p<0.05) and electrical storm (HR 2.22, 95% CI 1.19 – 4.13, p<0.05). The result of subgroup analysis of 147 patients with low LVEF (LVEF<35%) indicated that the patients with WRF experienced electrical storms more frequently (p<0.05).

Conclusion: WRF is associated with increased rate of arrhythmic event in nonischemic HF patients. Especially, those patients with low LVEF and WRF experience more frequent ICD shocks.
Abstract 5702: Oxidative Stress in Patients with Lone Atrial Fibrillation
Authors: Kusano Kengo , Nakamura Kazufumi , Ohe Tohru
Published: July 2021

Background: Lone atrial fibrillation (LAF) is a common arrhythmia, but its mechanism and the aggravated factor of arrhythmia are poorly understood. Oxidative stress has been implicated in the pathogenesis of heart failure. We have previously demonstrated that the amount of 4-hydroxy-2-nonenal (HNE) modified protein, which is a major lipid peroxidation product and a cytotoxic aldehyde, causes intracellular Ca2+ overload via reactive oxygen species (ROS) formation in cardiomyocytes and leads to develop arrhythmia. Accordingly we examined the levels of HNE and major histocompatibility complex (MHC) with the disease severity in LAF patients.

Method: Atrial and ventricular myocardial samples were obtained from twelve patients (11 men and 1 woman, mean 48±14 years old) by endomyocardial biopsy in 10, autopsy sample in 1 and surgical resection sample in 1. Histological assessments and immunohistochemical analysis for HNE modified protein, MHC class-I and -II antigens (grade 0 to 3) were performed and compared with LAF severity.

Results: Histological assessment showed that increased number of interstitial cells (mainly activated T cells) was observed only in the atrium but not in the ventricle. Moderate to severe expression of MHC antigens (grade 2 or 3) was more observed in the atrium than the ventricle (MHC-I: seven in atrium and three in ventricle; MHC-II: ten in atrium and four in ventricle). Atrial myocarditis was detected in 6 out of 11 samples. HNE modified protein was also more observed in the atrium than that in the ventricle. In addition, more severe expression of HNE staining was observed in the samples from persistent/chronic LAF than that in paroxysmal LAF.

Conclusion: These data indicates that oxidative stress plays an important role as an aggravating factor in LAF patients.
Abstract 5733: Coronary Flow Reserve obtained by Transthoracic Echocardiography in Patients with Normal Coronary Arteries and Systolic Dysfunction, Normal Function and Coronary Artery Disease and Normal Function and Normal Coronary Arteries
Authors: Lima Marta F , Tsutsui Jeane , Kowatsch Ingrid , Osorio Altamiro , Mathias Wilson
Published: July 2021

Coronary Flow Reserve (CFR) has already been shown a reliable marker of physiological significance of coronary artery disease (CAD) and has recently been demonstrated to be an independent predictor of events in patients with dilated cardiomyopathy (DCM). Objective: To determine CFR in patients (pts) with DCM without obstructive CAD and in pts with normal systolic function and with obstructive CAD.

Methods:
We prospectively studied 67 pts with normal systolic function (mean age 46+/− 12 years, 48% male, left ventricular ejection fraction (EF) >65%) and 47 pts with DCM (mean age 59 +/− 11 years, 52% male, EF<35%) who underwent coronary angiography within 6 months from stress echocardiography. Diastolic velocity flow in the mid left anterior descending coronary artery was obtained by transthoracic echocardiography with use of intravenous commercially available contrast agent (Definity, Bristol-Myers Squibb) at baseline and during adenosine infusion (140 mcg/Kg/min, for 6 minutes). CFR was determined as the ratio of peak diastolic velocity in hyperemic/baseline conditions. All pts underwent quantitative coronary angiography (QCA).

Results:
Feasibility for assessing CFR was 83% in pts with normal function and 91% in DCM. Among the 56 pts in the final study with normal function, 25 had significant CAD and 31 had normal coronary arteries. Peak diastolic velocities in each group are described in Table

. CFR was 2.86+/−0.58 ín pts with normal function and no CAD, 1.57+/−0.32 in pts with normal function and CAD, and 2.14+/−0.49 in pts with DCM and no CAD (p<0.01 between groups). Sensitivity, specificity and accuracy for detecting CAD in pts with normal function was 96%, 94% and 95%, respectively. However, when considering the group with DCM, sensitivity was 74%, specificity 66% and accuracy 69%.

Conclusions:
CFR can accurately detect pts with CAD when systolic function is normal. Pts with DCM have diminished CFR that lowers the predictive value of this parameter to detect CAD.
Abstract 5736: Diagnosis of Chronic Myocardial Ischemia by Speckle Tacking Echocardiography -A Comparative Animal Study-
Authors: Kimura Koichi , Takenaka Katsu , Uno Kansei , Ebihara Aya , Fujiu Katsuhito , Iwata Hiroshi , Sata Masataka , Nagai Ryozo
Published: July 2021

A number of systolic and diastolic indexes for ischemic damage can be measured by 2D speckle tracking echocardiography (STE) including radial strain and strain rate as well as circumferential strain and strain rate on LV short-axis view. In addition, they could be derived from the subendocardium, subepicardium, mid-layer or total layer of the LV wall with new tracking software. The aim of our study is to compare the diagnostic abilities of these indexes in animal experiments. An Ameroid constrictor was placed around the left circumflex coronary artery in 19 pigs. Before and 4 weeks after the surgery, LV short-axis images were obtained at rest by transthoracic 2D echocardiography. Three pigs that had died after the surgery and 2 that had focal infarction in pathological studies were excluded from the study. Thus, in 14 pigs with 99% stenosis on coronary angiograms, we measured peak strain, peak S′, peak E′, time from QRS to peak strain, time from QRS to E′, and incidence of post-systolic shortening (PSS) in the endocardium, midcardium, and epicardium of the LV posterior wall using a new prototype speckle tracking software. None of the time indexes and PSS showed statistically significant results. ROC curve analysis (Table

) revealed that endocardial circumferential strain is the most diagnostic index of ischemia, which showed 79% sensitivity and 93% specificity. Endocardial circumferential strain measured by STE on LV short-axis view was the most useful index for detecting chronic severe myocardial ischemia.

Table.

Results of measurement in chronic ischemia(mean±SD)
Abstract 5753: The Warranty Period of a Zero Calcium Score: 5-Year Serial Follow-Up of 422 Individuals by Non-Contrast Computed Tomography
Authors: Min James K , Weinsaft Jonathan W , Gidseg David , Callister Tracy Q
Published: July 2021

Presence and severity of coronary artery calcium (CAC) by Agatston scoring is a well established index for stratification of cardiovascular prognosis. Absence of CAC is associated with excellent clinical prognosis. To date, for patients with baseline absence of CAC, rates of conversion to positive CAC (i.e., CAC>0) and severity of CAC at the time of conversion is unknown. 9,838 asymptomatic individuals underwent CAC screening with multidetector row or electron-beam computed tomography. Within this cohort, 422 asymptomatic subjects (mean age 48.8±8.9 yrs; 52.1% male, 9% diabetes; 46.0% hypertension, 66% dyslipidemia, 32% smoker) with an initial baseline CAC Agatston score of zero agreed to undergo annual CAC screening for five consecutive years or until conversion to a positive CAC. 106 patients (25.1%) converted from no CAC to a positive CAC within the 5-year follow-up period (mean conversion time 4.08±1.10 yrs). No subject exhibited CAC conversion within the first year. Rates of CAC conversion were low in year 2 (2/422, 0.5%) and year 3 (5/420, 1.1%). No differences were noted for time to CAC conversion in patients with or without diabetes, hypertension, dyslipidemia, or tobacco use (p=NS for all). Similarly, time to CAC conversion was similar among male and female subjects (p=NS). However, subjects with diabetes (p=0.001), hypertension (p=0.02) and tobacco use (p<0.0001) were more likely to transition from absence to presence of CAC during the entire study period, compared to non-diabetic, normotensive and non-smoking subjects. Furthermore, for subjects who exhibited conversion from absence to presence of CAC, Agatston CAC scores at the time of conversion were higher for diabetic (33.0 vs. 16.0, p=0.005) and hypertensive (24.3 vs. 12.4, p=0.001) subjects, compared to their non-diabetic and normotensive counterparts. In subjects with baseline absence of CAC, rates of conversion to positive CAC scores is low during five-year follow-up with rare conversion in the first three years. Conversion rates and severity of CAC at time of conversion is highest amongst individuals with diabetes, hypertension and tobacco use.