bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 1882: Use of Speckle Tracking to Quantify Global LV Function: A Comparison with 2D and 3D Echo and Magnetic Resonance Imaging
Authors: Brown Joseph K , Marwick Thomas H
Published: July 2021

Background:
Ejection fraction (EF) plays a prominent role in clinical decision making but this calculation is time-consuming and dependent on load and geometry. A simple and quick technique for assessing global LV function would be useful. We sought to evaluate the robustness of global longitudinal strain (GLS) for assessment of LV function in comparison to Simpsons biplane ejection-fraction (2D-EF), 3D ejection fraction (3D-EF) and MRI ejection fraction (MRI-EF). We further investigated the automated measures of EF (auto-EF) from wall tracking.

Methods:
2D and 3D echo and MRI measurement of EF were performed in 53 pts with previous infarction. GLS was measured by offline speckle-tracking in the apical 4C and 2C views. Abnormal curves were excluded on the basis of visual assessment. Auto-EF was calculated using the method of discs, using the traced endocardial border to establish end-diastolic and end-systolic volumes.

Results:
Average global TQ (tracking quality) was 1.14±0.22, permitting reliable derivation of strain from all segments. GLS showed a significant linear correlation with MRI-EF, similar to that between 3D-EF and MRI and better than that between 2D-EF and MRI and automated EF and MRI (Table

). Of 26 pts with a normal MRI-EF (≥50%), 85% had GLS within normal limits and 81% had normal 3D-EF, but significantly fewer were recognized as normal by 2D-EF (Table

). In pts with ≤5 abnormal segments, 3D-EF was the most accurate modality for assessing global LV function, while GLS was better than 2D-EF and auto-EF. In pts with >5 abnormal segments, GLS was the most accurate modality of quantifying global LV function against MRI-EF (r = −0.83, p <0.0001), comparatively better than 3D-EF against MRI-EF (r = 0.75, p <0.0001).

Conclusion:
GLS is an effective method of quantifying global LV function. In pts with >5 abnormal segments, GLS offered the best correlation with MRI-EF, reflecting the benefit of a geometry independent and site-specific parameter.
Abstract 1891: Mortality After CRT: a Synergetic Effect Between Ventricular Remodeling and Reduced Frequency of Ventricular Arrhythmias. The InSync ICD Italian Registry
Authors: Di Biase Luigi , Gasparini Maurizio , Lunati Maurizio , Santini Massimo , Neri S. Filippo , Landolina Maurizio , Matteo S. , Boriani Giuseppe , Orsola S. , Curnis Antonio , Civili Spedali , Bocchiardo Mario , Vincenti Antonio , dei Tintori S. Gerardo , Denaro Alessandra , Valsecchi Sergio , Italia Medtronic , Natale Andrea , Padeletti Luigi
Published: July 2021

Introduction:
It is currently debated whether cardiac resynchronization therapy (CRT) has an effect on the burden of ventricular arrhythmias (VA). We investigated whether the reverse remodeling after CRT may reduce the occurrence of VA.

Methods
: The study included 398 patients enrolled in the InSync ICD Italian Registry, treated with CRT-D and with a follow-up of at least 12 months. Spontaneous VA detected by the device were reviewed and validated.

Results:
After 6 months of follow-up no VA episodes occurred in 319 patients (group 1), while VA episodes persisted in the remaining 79 (group 2). At baseline, clinical and echocardiographic characteristics of the two groups were comparable: NYHA class (2.9±0.6 vs. 3.0±0.7), QRS width (166±31ms vs. 163±34ms), ejection fraction (26±7% vs. 26±6%), LVEDV (251±98ml vs. 226±45ml), LVESV (182±84ml vs. 158±38ml) (All p=NS). At 6 month visit, ventricular remodeling was apparent only in group 2 pts: LVEDV (200±83ml, p=0.042 vs. Baseline), LVESV (133±65ml, p=0.002 vs. Baseline). No changes were evident in group 2 pts: LVEDV (216±69ml, p=0.769 vs. Baseline), LVESV (160±59ml, p=0.521 vs. Baseline). The long-term survival from all-cause death resulted higher in group 1 pts (Log-rank test: p=0.032). (Figure

)

Conclusions:
In patients treated with CRT, a reduction of ventricular arrhythmic events occurs during the initial 12 months following implant and is correlated with the degree of ventricular remodeling induced by the therapy. Patients demonstrating the remission of arrhythmic episodes will have better survival and more pronounced long term improvements.
Abstract 1900: Coronary MDCT based Detection of Coronary Stenosis and Plaque in the Assessment of Patients with Acute Chest Pain: Update from ROMICAT I
Authors: Hoffmann Udo , Bamberg Fabian , Seneviratne Sujith , Rogers Ian S , Truong Quynh A , Nichols John H , Shapiro Michael D , Abbara Suhny , Cury Ricardo C , Brady Thomas J , Achenbach Stephan , Nagurney John T
Published: July 2021

Objective
: To determine CT angiographic patterns of coronary plaque and stenosis and diagnostic test characteristics of these findings to predict ACS in patients presenting with acute chest pain to the emergency department (ED).

Methods
: We conducted a blinded, prospective, observational cohort study in patients presenting with acute chest pain to the ED between May 2005 and July 2006, who were admitted to the hospital to rule out acute coronary syndrome (ACS) with no ischemic ECG changes and negative initial biomarkers. Contrast-enhanced 64-slice cardiac CT was performed immediately before admission and caregivers were blinded to the cardiac CT results. An expert panel determined the presence or absence of ACS (unstable angina pectoris [UAP], Non-ST-Elevation Myocardial Infarction [MI] according to AHA/ACC criteria). Two independent observers evaluated cardiac CT data sets for the presence of (1) coronary atherosclerotic plaque, and (2) significant coronary artery stenosis (>50%).

Results:
Of 221 consecutive patients (44% female, mean age 55±12 years), 31 patients had ACS (10 NSTEMI, 21 UAP). The presence of any coronary atherosclerotic plaque could be excluded in 82 patients (37%). None of these subjects was determined to have ACS (Sensitivity and NPV: 100%, (95% CI: 0.91–1.00 and 0.96–1.00; respectively). The presence of a significant coronary artery stenosis could be excluded in 152 subjects (69%). Overall, three of these patients had ACS during the index hospitalization (NPV, 98 %; 95% CI: 0.94–1.00). In 69 patients (31%), a significant stenosis was either detected or could not be completely excluded. Among them were 28/31 patients with ACS (specificity: 78%, 95% CI: 0.72– 0.84; PPV: 41% 95% CI: 0.29 – 0.53).

Conclusions
: These data extend initial observations that nearly 40% and 70% of patients with acute chest pain demonstrate no detectable CAD or no significant coronary artery stenosis on cardiac MDCT, respectively. Randomized diagnostic trials are warranted to determine how this information will be used by ED physicians and whether it will decrease the number of unnecessary admissions.
Abstract 1931: Impact of Insulin Resistance on Elevation of Post-procedural Cardiac Biomarker and Long-term Clinical Outcomes in Patients Underwent Elective Coronary Intervention
Authors: Uetani Tadayuki , Amano Tetsuya , Kumagai Soichiro , Ando Hirohiko , Arai Kosuke , Yokoi Kiminobu , Kato Masataka , Marui Nobuyuki , Nanki Michio , Matsubara Tatsuaki , Ishii Hideki , Izawa Hideo , Murohara Toyoaki
Published: July 2021

Background:
Recently, some trials demonstrated that the presence of insulin resistance and metabolic syndrome was associated with short-term and long-term outcomes after percutaneous coronary intervention (PCI). The aim of this study is to evaluate potential association between homeostatic indices of insulin resistance (HOMA-IR) and post-procedural myocardial injury and clinical outcome after PCI.

Methods:
From January 2005 to December 2006, 230 consecutive patients who underwent elective stent implantations and evaluation of insulin resistance were enrolled in this study. Blood samples were collected from venous blood after overnight fasting. HOMA-IR was calculated according to the homeostasis model assessment as follows: HOMA-IR = fasting glucose (mg/dL) × fasting insulin (mU/L)/405. Patients were divided into two groups according 50 percentile (2.11) for HOMA-IR. Post-procedural myocardial injury was evaluated by analysis of troponin-T(TnT)and CK-MB 18 hours after PCI. Cardiac event was defined as the composite end-point of death of any cause, MI and revascularization of new lesion.

Results:
Post-procedural TnT and CK-MB were significantly higher in patients with higher HOMA-IR compared to those with lower HOMA-IR(0.05±0.09 vs 0.15±0.40, p<0.01 and 14.8±6.5 vs 19.9±20.7, p<0.05, respectively). Multivariate linear regression analysis demonstrated that HOMA-IR independently correlated with TnT. In Kaplan-Meier analyses, higher HOMA-IR was associated with worse clinical outcomes (Figure

).

Conclusions:
These results indicated an impact of insulin resistance on post-procedural cardiac biomarkers and worse clinical outcome after elective PCI.
Abstract 1933: Correlates of Bleeding After a 600 mg Loading Dose of Clopidogrel, With and Without Abciximab: A Pooled Analysis of 4 ISAR Randomized Trials.
Authors: Kalyanasundaram Arun , Berger Peter B , Ndrepepa Gjin , Mehilli Julinda , Schulz Stefanie , Schömig Albert , Kastrati Adnan
Published: July 2021

Background
. Bleeding complications during PCI have been shown to be related to mortality. Little is known about the frequency and correlates of bleeding in patients (pts) undergoing PCI after a 600 mg loading dose of clopidogrel.

Methods
. We performed a pooled analysis of the ISAR-REACT, ISAR-SWEET, ISAR-SMART 2, and ISAR-REACT 2 trials in which 5,384 pts undergoing PCI ≥2 hours after a 600 mg loading dose of clopidogrel were randomized to receive abciximab or placebo. Bleeding was assessed using the Thombolysis in Myocardial Infarction (TIMI) scale. Multiple logistic regression model was used to identify independent correlates of 30-day bleeding; 22 standard clinical and procedural variables were analyzed. Pts receiving abciximab received a single bolus of 70 units/kg of heparin; those who did not received a single bolus of 140 units/kg.

Results
. Following the PCI procedure, 215 pts (4.0%) bled; bleeding was major in 59 pts (1.1%) and minor in 156 (2.9%). Pts who bled were older, more likely to be female, have a lower body mass index (BMI), have an acute coronary syndrome and multivessel disease, a lower left ventricular ejection fraction and slightly shorter lesions than pts without bleeding. Multiple logistic regression model revealed that female sex (odds ratio 2.06 [95% CI 1.52–2.79], p<0.001), lower BMI (per decrease of 5 kg/m
2
) (1.54 [1.27–1.89], p<0.001), administration of abciximab (1.54 [1.15–2.04], p=0.003), age (per 10-year increase) (1.20 [1.03–1.41], p=0.02), and diameter stenosis (10% increase) (1.13 [1.03–1.24], p=0.008) were all independently associated with bleeding.

Conclusion
. Bleeding occurred in 4.0% of 5,384 pts who received a 600 mg loading dose of clopidogrel >2 hours, half of whom received abciximab, before a PCI in 4 ISAR trials. Abciximab was the only modifiable variable associated with bleeding. Abciximab should be utilized cautiously in women, older patients and those with lower BMI.
Abstract 1950: Role of Superoxide, Nitric Oxide and Peroxynitrite in Doxorubicin-induced Cell Death in vitro and in vivo
Authors: Mukhopadhyay Partha , Rajesh Mohanraj , Bátkai Sandor , Haskó György , Szabo Csaba , Liaudet Lucas , Pacher Pal
Published: July 2021

Although doxorubicin (DOX) is one of the most potent antitumor agents available, its clinical use is limited because of the risk of severe cardiotoxicity often leading to irreversible congestive heart failure. Apoptotic cell death is a key component in DOX-induced cardiotoxicity, but its trigger(s) and mechanisms are poorly understood. Here, we explore the role of peroxynitrite (a reactive oxidant produced from the diffusion-controlled reaction between nitric oxide and superoxide anion) in DOX-induced cell death. Using a well-established
in vivo
mouse model of DOX-induced acute heart failure, we demonstrate marked increases in myocardial apoptosis (caspase-3 and 9 gene expression, caspase 3 activity, cytochrome-c release, and TUNEL), iNOS but not eNOS and nNOS expression, 3-nitrotyrosine formation and a decrease in myocardial contractility following DOX treatment. Pre-treatment of mice with peroxynitrite scavengers markedly attenuated DOX-induced myocardial cell death and dysfunction without affecting iNOS expression. DOX induced increased superoxide generation and nitrotyrosine formation in the mitochondria, dissipation of mitochondrial membrane potential, apoptosis (cytochrome-C release, annexin V staining, caspase activation, nuclear fragmentation), and disruption of actin cytoskeleton structure in cardiac-derived H9c2 cells. Selective iNOS inhibitors attenuated DOX-induced apoptosis, without affecting increased mitochondrial superoxide generation, whereas NO donors increased DOX-induced cell death
in vitro
. The peroxynitrite scavengers FeTMPyP and MnTMPyP markedly reduced both DOX- or peroxynitrite-induced nitrotyrosine formation and cell death
in vitro
, without affecting DOX-induced increased mitochondrial superoxide formation. Thus, peroxynitrite is a major trigger of DOX-induced apoptosis, and its effective neutralization can be of significant therapeutic benefit.
Abstract 1969: Relationship of Right Ventricular Diastolic Function by Pulsed Tissue Doppler Imaging with Brain Natriuretic Peptide in Pulmonary Hypertension
Authors: Shiina Yumi , Funabashi Nobusada , Lee Kwangho , Daimon Masao , Sekine Tai , Kawakubo Miyuki , Sekine Yukiko , Takahashi Maiko , Yajima Rei , Wakatsuki Yu , Tanabe Nobuhiro , Kuriyama Takayuki , Komuro Issei
Published: July 2021

Purpose:
Right ventricular (RV) dysfunction is an important cause of mortality in patients with pulmonary hypertension (PH) and elevated serum level of brain natriuretic peptide (BNP) is also associated with poor prognosis in those patients. We evaluated relationship of RV diastolic function calculated by pulsed tissue doppler imaging (TDI) with BNP in patients with PH using multiple regression analysis.

Materials and methods:
In consecutive 91 patients with pulmonary hypertension (64 with chronic pulmonary thromboembolis (CPTE), 13 with primary PH and 13 with PH due to collagen disease), systolic wave (Sw) early diastolic wave(Ew) atrial wave (Aw) at tricuspid annulus and early (E) and atrial (A) RV inflow waves were obtained from 4-chamber view and E/Ew of RV was calculated as the parameter of RV diastolic function using TDI (Aplio 80 SSA-770A, Toshiba, Japan). BNP and other echo parameters including estimated pulmonary arterial systolic pressure (PASP) and cardiac output (CO) were also obtained.

Result:
In all subjects, elevated PASP (mean 64±33 mmHg) and BNP (mean 161±198 pq/dl) could be observed. BNP was positively correlated with E/Ew of RV, Aw and PASP(r=0.43, 0.24, and r=0.24, respectively all p<0.01). Next all predictor variables were used in a multiple regression model with serum BNP values as dependent variables, which was refined to include 2 predictors: E/Ew of RV, and PASP. And here, E/Ew of RV and PASP significantly influenced the serum BNP value (p<0.01) by the multiple regression formula Y =22.9X1** + 2.12X2 ** ** P values<0.01. Y=BNP level, X1=E/Ew of RV, X2=PASP (standard regression coefficients were 0.43 and 0.31, respectively)

Conclusion:
BNP were significantly correlated with RV diastolic dysfunction obtained by TDI in subjects with PH and increment of BNP may have relationship of decrement of RV diastolic function in those subjects.
Abstract 1976: Characteristics and Distribution of the Scar Tissue Detected by Magnetic Resonance Imaging may Predict Ventricular Tachycardia in Patients with Advanced Heart Failure
Authors: Yokokawa Miki , Tada Hiroshi , Koyama Keiko , Naito Shigeto , Hiramatsu Shigeki , Goto Koji , Oshima Shigeru , Taniguchi Koichi
Published: July 2021

Introduction:
Contrast-enhanced magnetic resonance imaging (CMR) reveals scar tissue as an enhanced area. Non-transmural scar regions may link to a scar-related reentrant ventricular tachycardia (VT).

Methods:
CMR was performed in 46 patients with advanced heart failure (dilated cardiomyopathy [DCM]-30, ischemic cardiomyopathy [ICM]-16; 36 males, 65±12 yrs; EF 28±12 %). Twenty-one patients (46 %) had documented sustained VTs. The scar volume (%; the percentage of the total scar volume) was obtained using MRI software. CMR images were also scored visually according to a 17-segment model (transmural score: 0= no damage, 4= transmural scar). The total number (No.) of segments with a transmural score of 4 (transmural scar) and transmural score of 1–3 (non-transmural scar), and the percentage of segments with non-transmural scar were obtained. The CMR parameters and clinical arrhythmic events were compared between the patients with DCM (DCM-Gr) and ICM (ICM-Gr).

Results (
Table

):
In the DCM-Gr, the scar was usually non-transmural, which presented mainly in the mid-wall layer and was characterized by a patchy distribution. The scar volume and total No. of segments with non-transmural scar were greater in DCM patients with VT than in those without. In contrast, patients in the ICM-Gr had transmural or subendocardial enhancement in the territory of coronary arteries, and the scar volume was smaller in ICM patients with VT than in those without. However, the total No. of segments with non-transmural scar and percentage of segments with non-transmural scar were greater in ICM patients with VT than in those without. In the VT patients in both Grs, non-transmural scar was always found at the VT exit site.

Conclusions:
CMR is useful for assessing the characteristics and distribution of myocardial scar. A wider and greater distribution of the non-transmural scar may provide the potential substrate for reentrant VTs in patients with advanced heart failure.

Table:

CMR-parameters in Patients with DCM and ICM
Abstract 1988: Non-culprit Coronary Plaque Morphology in Patients WIth Acute Myocardial Infarction : An Optical Coherence Tomography Study in Vivo
Authors: Fujii Kenichi , Masutani Motomaru , Okumura Takahiro , Kawasaki Daizo , Akagami Takafumi , Sakoda Tsuyoshi , Masuyama Tohru , Ohyanagi Mitsumasa
Published: July 2021

Background:
In vivo imaging studies in patients with acute myocardial infarction (AMI) have demonstrated important lesions at sites other than the culprit. However, it is not well assessed whether non-culprit plaques in the
non-infarct-related
artery have similar markers of plaque instability compared to non-culprit plaques in the
infarct-related
artery. The aim of this study is to investigate the morphologic features of the non-culprit plaque in infarct-related artery in comparison with that in non-infarct-related artery for AMI patients using optical coherence tomography (OCT) in vivo.

Methods:
OCT examinations were attempted prospectively using motorized pullback in all 3 major coronary arteries (at least 2/3 segment of each artery) for 34 AMI patients. In 34 patients, 118 focal plaques were identified (3.5 plaques per patient). Qualitative OCT analyses for each focal atherosclerotic plaque were performed using the previously validated criteria. TCFA was defined as a plaque with lipid content in a quadrant and the thinnest part of a fibrous cap measuring <65 μm. A plaque rupture contained a cavity that communicated with the lumen with an overlying residual fibrous cap fragment. A thrombus was defined as an irregular mass protruding into the lumen. Non-culprit plaques were divided into two groups according to their location:

plaques in infarct-related artery (n=35) and

plaques in non-infarct-related artery (n=83).

Results:
Non-culprit TCFA, plaque rupture, and thrombus were observed in 50 lesions of 26 patients (76%), 14 lesions of 11 patients (34%), and 27 lesions of 15 patients (44%), respectively. OCT analyses are shown in the Table

.

Conclusions:
The morphology of non-culprit plaques in AMI patients is similar whether these plaques occur in the infarct-related artery or the non-infarct-related artery. This suggests that plaque destabilization is a systemic phenomenon rather than a local, artery-specific process.

OCT Analyses
Abstract 307: Systemic Deficiency Of The Map Kinase Activated Protein Kinase 2 Reduces Atherosclerosis In Hypercholesterolemic Mice
Authors: Jagavelu Kumaravelu , Tietge Uwe F , Gaestel Matthias , Drexler Helmut , Schieffer Bernhard , Bavendiek Udo
Published: July 2021

Background:
Atherosclerosis is a chronic inflammatory disease and represents the major cause of cardiovascular morbidity and mortality. The mitogen activated protein kinase (MAPK) activated protein kinase 2 (MAPKAP-2, MK2), a direct substrate of the stress activated MAPK p38α/β, critically regulates inflammatory processes such as production of inflammatory mediators (e. g. TNFα, IL-6) as recently demonstrated in vitro and in vivo. Therefore, we investigated the functional role of MK2 in atherogenesis in hypercholesterolemic mice in vivo as well as potentially underlying mechanisms in vitro.

Methods & Results:
Activation of MK2 (phospho-MK2) was predominantly detected in the endothelium and macrophage-rich plaque areas within aortas of hypercholesterolemic LDL-receptor-deficient mice (
ldlr
−/−
). Systemic MK2-deficiency of
ldlr
−/−
-mice (
ldlr
−/−
/mk2
−/−
) significantly decreased accumulation of macrophages (MOMA-2 staining: −50%, n = 8–10, p < 0.001) and lipids (oil-red-O staining: −55%, n = 8–10, p< 0.001) in the aortic arch (cryo-sections) as well as lipid-depositions in the aorta descendens (
en face
, oil-red-O: −70%, n = 8–10, p < 0.001) after feeding an atherogenic diet for 8 or 16 weeks. MK2-deficiency significantly decreased oxLDL-induced foam cell formation
in vitro
(oil-red-O positive cells, dil-oxLDL-uptake: −50%, n = 3–5, p < 0.01), diet-induced foam cell formation
in vivo
(16 weeks atherogenic diet, oil-red-O positive cells: −60%, n = 3, p < 0.05) and expression of scavenger receptor A in peritoneal macrophages (qRT-PCR, westernblot: −70%, n = 3–5, p < 0.05). In addition, silencing of MK2-expression in endothelial cells by siRNA markedly and significantly reduced the IL-1β-induced expression of the adhesion molecule VCAM-1 (westernblot, n = 3) and the chemokine MCP-1 (ELISA: −40%, n = 5, p < 0.01). In line, MK2-deficiency significantly reduced VCAM-1 expression in the endothelium of
ldlr
−/−
-
mice in vivo (aortic arch, immunhistochemistry, −60%, n = 8, p < 0.01).

Conclusions:
MK2 critically promotes atherogenesis by fostering foam cell formation and recruitment of monocytes/macrophages into the vessel wall. Therefore, MK2 might represent an attractive novel target for the treatment of atherosclerotic cardiovascular disease.
Abstract 1996: Non-culprit Lesions Detected During Primary PCI: Treat Invasively Or Follow The Guidelines?
Authors: Dambrink Jan H , Debrauwere Jan P , van ’t Hof Arnoud W , Ottervanger Jan Paul , Gosselink A T , Hoorntje Jan C , de Boer Menko J , Suryapranata Harry
Published: July 2021

Background.
Evidence regarding the optimal treatment of non-culprit lesions detected during primary PCI is lacking. A conservative approach is advocated by the current guidelines. However, a more aggressive approach may prevent recurrent cardiac events and improve left ventricular function.

Methods
. Of 120 patients with at least 1 non-culprit lesion, 80 were randomized to early follow-up coronary angiography including Fractional Flow Reserve (FFR)-guided PCI (invasive group), and 40 to medical treatment followed by ischemia detection at a later stage (conservative group). Primary endpoint was left ventricular ejection fraction at 6 months.

Results.
The number of non-culprit lesions per patient was identical in both groups (1.25 ± 0.44 vs 1.25 ± 0.44, p=1.00). In the invasive group, follow-up angiography was performed 13 ± 13 days after primary PCI. Only 60 % of the non-culprit lesions that were considered significant during primary PCI had a FFR < 0.75 at follow up indicating hemodynamic significance. Subsequent PCI of at least 1 non-culprit lesion guided by FFR was performed in 50% of patients, PCI without preceding FFR was performed in 15% and CABG was done in 5%. After 236 ± 152 days of follow up, PCI of non-culprit lesions was more frequently needed in the conservative group (18% vs 4%, p=0.015) but the incidence of recurrent myocardial infarction was higher in the invasive group (10% vs 0%, p=0.051), half of which were non-culprit lesion related (5% vs 0%, p=0.150). Death and total major adverse cardiac events were not different between groups.

Conclusion:
The hemodynamic significance of non-culprit lesions detected during primary PCI is frequently overestimated (40%). Early PCI of non-culprit lesions guided by FFR prevents later PCI procedures but does not result in a reduction of total major cardiac events compared to a more conservative strategy. Data on the primary endpoint at 6 months (EF) will be presented.
Abstract 2015: Survival from Out-of-Hospital Cardiac Arrest is Better for Children than Adults: The ROC Epistry-Cardiac Arrest
Authors: Atkins Dianne L , Everson-Stewart Siobhan , Berg Robert A , Davis Daniel P , Daya Mohamud R , Osmond Martin H , Sears Gena K , Warden Craig R
Published: July 2021

Objectives
Population-based data for pediatric cardiac arrest are scant and concentrated from large urban areas. The Resuscitation Outcomes Consortium (ROC) Epistry-Cardiac Arrest is a prospective population-based EMS registry of out-of-hospital non-traumatic cardiac arrest (OHCA). The purpose of this study is to examine the characteristics of OHCA in patients <20 yrs.

Methods

Design

: Prospective population based cohort study with uniform data definitions.

Setting

: 11 US and Canadian urban and rural sites participating in the ROC.

Population

: Persons <20 years who

receive CPR by EMTs and/or receive a bystander AED shock or

are pulseless but receive no EMS resuscitation between 12/2005 thru 11/2006.

Hypothesis

: Survival from pediatric OHCA is less than adult survival. Survival is discharge from hospital. Patients were divided in 3 groups: <1 yr, 1–11 yrs, 12–<20 yrs. Adult data derived from same registry, n = 16829.

Results
Data from 389 OHCAs in children were submitted: 315 (81%) patients received EMS treatment. Table 1

shows data from all children with OHCA. Table 2

shows EMS-treated OHCAs. Survival of pediatric patients was statistically better than adults for all OHCAs (7.5% vs. 3.9%, p < 0.009) and for EMS-treated OHCAs (9.2% vs 6.9% p = 0.001). EMS scene time was <10 minutes for 22% of children vs 3.6% of adults, p < 0.001.

Conclusions
Survival from OHCA is better among children than adults, and this current survival rate is better than most previous studies. Bystander CPR is provided for <40% of all patients. Ventricular fibrillation occurs in all age groups. Short scene times are more common in infants and children, suggesting a scoop and run approach for younger patients.

Table 1

Baseline Characteristics for all OHCA Patients

Table 2

EMS-Treated OHCA Patients
Abstract 2018: Cardiac Arrest in the Emergency Department: A Report from the National Registry of Cardiopulmonary Resuscitation
Authors: Kayser Robert G , Ornato Joseph P , Peberdy Mary Ann
Published: July 2021

Background: Little is known about cardiac arrests (CA) in the Emergency Department (ED). The objective of this study was to determine the characteristics of ED CA’s.

Methods: Included were 60,852 adult, in-patient CA index events in the National Registry of Cardiopulmonary Resuscitation. Multiple regression analysis compared ED CA with those occurring in the ICU, telemetry, or general floors. Subgroup analysis examined traumatic vs. non-traumatic ED CA and ED CA occurring after a successful pre-hospital resuscitation (recurrent) vs. primary ED CA.

Results: In multivariate analysis, ED location significantly predicted improved survival to discharge (OR 0.74, 95% CI[0.67–0.82], p<0.0001). Patients with CA occurring in the ED had better Cerebral Performance Category scores (ED 1.59, ICU 1.73, Tele 1.96, Floor 1.69, p<0.0001), shorter mean post-event length of stays (ED 8.6, ICU 17.5, Tele 16.5, Floor 14.2 days, p<0.0001) and were less likely to be declared DNR (ED 23.0%, ICU 31.7%, Tele 28.8%, Floor 31.8%, p<0.0001) than CA in other locations. Secondary analysis showed that ED patients with recurrent CA were less likely to survive to discharge (10.1% vs. 24.6%, p<0.0001) and were more likely to be declared DNR (27.9% vs. 22.2%, p<0.0006.) than primary ED CA. Mean length of stay for survivors in both groups was similar (8.85 vs. 8.54 days, p=ns). Major traumatic injury preceded 6.3% of all ED CA. Patients whose ED CA was related to traumatic injury were younger (46.2 vs. 65.0 years, p<0.001), more likely to be male (78.2% vs. 58.1, p<0.0001), less likely to have the CA caused by an arrythmia (23.6% vs. 32.5%, p<0.0008), and more likely to have the CA preceded by hypotension or shock (41.6% vs. 29.0%, p<0.0001) than ED patients whose CA was not due to traumatic injury. ED trauma CA patients had a significantly lower survival to discharge rate than ED patients whose CA was not due to trauma (7.5% vs. 23.8%, p<0.0001).

Conclusions: ED CA patients are a unique population and have better survival and neurologic outcomes compared to patients in other hospital locations. Primary ED CA patients have a better chance of survival to discharge than those who re-arrest following a successful pre-hospital resuscitation. Traumatic ED CA patients have worse outcomes than non-traumatic CA.
Abstract 2021: Adrenergic Receptor Polymorphisms and Prevention of Ventricular Arrhythmias with Bucindolol in Patients with Heart Failure
Authors: Sauer William , Lowery Christopher M , Budhathoki Chakra , Lowes Brian D , Bristow Michael R
Published: July 2021

Background:
β-blockers have been shown to prevent ventricular arrhythmias (VT/VF) in patients with low left ventricular ejection fraction (LVEF) and chronic heart failure (CHF). We hypothesized that there may be genotype specific responses to β-blocker therapy for prevention of VT/VF.

Methods:
The β-blocker Evaluation of Survival Trial (BEST) is a randomized trial of bucindolol in patients with NYHA Class III – IV CHF and LVEF ≤0.35. From a substudy of 1040 genotyped subjects, we identified those with the high functioning Arg389 β1 adrenergic receptor polymorphism and the loss of function 322–325 α2c adrenergic receptor deletion polymorphism. The incidence of VT/VF was prospectively recorded as an adverse event during the trial.

Results:
Of the 1040 subjects in the genotyped cohort, there were a total of 493 Arg389 β1 homozygotes vs. 547 Gly389 carriers and 207 α2c deletion carriers vs. 833 wild-types. The diplotypes included 418 subjects with both Arg/Arg389 β1 receptors and wild type α2c, 484 with one of these, and 134 carrying both the α2c deletion and β1 Gly389. For the genetic substudy, bucindolol was associated with less VT/VF that placebo (5.5% vs. 12.1%; p<0.01) There was a significant drug-gene interaction for prevention of VT/VF with both polymorphisms (β1 overall p<0.01; α2c overall p<0.01). Arg389 homozygotes randomized to bucindolol had a lower incidence of VT/VF during the trial than those randomized to placebo (4.3% vs. 14.4%; P<0.01) as for wild type α2c homozygotes (5.4% vs. 12.7%; p<0.01). This reduction in VT/VF was not significant in other genotypes (β1 Gly389 carriers: 6.6% vs. 10.4%; P=0.13 and α2c deletion carriers: 4.9% vs. 10.6%; P=0.19). Subjects with the Arg/Arg389 β1/wild type α2c receptor diplotype randomized to bucindolol had a lower rate of VT/VF occurrence than those with only one or neither of these genotypes (both: 4.7% vs. 14.6%; p<0.01; one: 4.9% vs. 11.2%; p=0.01; neither: 8.5% vs. 9.3%; p=1.0).

Conclusion:
Subjects with CHF and Arg/Arg389 β1 or wildtype α2c adrenergic receptors treated with bucindolol had a lower rate of VT/VF than those randomized to placebo. This treatment effect was not observed in the population of β1 Gly389 or the α2c deletion carriers, indicating a pharmacogenetic interaction.
Abstract 315: Krüppel-like Factor 5 Promotes Vascular Remodeling in a Biphasic Manner by Inhibiting Vascular Smooth Muscle Cell Apoptosis and Stimulating Cell Growth
Authors: Sawaki Daigo , Suzuki Toru , Aizawa Kenichi , Matsumura Takayoshi , Kada Nanae , Mizuno Yoshiko , Munemasa Yoshiko , Nagai Ryozo
Published: July 2021

Introduction:
Vascular remodeling is characterized by cell proliferation and/or apoptosis with further phenotypic change of vascular cells. Vascular smooth muscle cell (VSMC)s, in particular, play a major role in the proliferative process such as neointimal formation and restenosis after angioplasty. In deciphering the transcriptional regulatory mechanisms in cardiovascular remodeling, Krüppel-like factor 5 (KLF5) was originally isolated as a regulatory factor of phenotypically modulated VSMCs. Past studies collectively have shown that KLF5 can induce cell growth pathologically in non-cardiovascular cells. However, how KLF5 contributes to vascular remodeling, notably its effects on apoptosis in the vascular lesion, had yet to be addressed. In the present study, we have aimed to address the effects of KLF5 not only on VSMC growth but also on apoptosis in vascular remodeling.

Methods&Results:
We performed adenoviral overexpression of KLF5 and other related factors after rat carotid balloon injury. In the early phase (48 hours after injury), KLF5 administered animals showed significantly decreased TUNEL positive cells in the medial layer. In the chronic phase (14 days after injury), apoptotic cells were recognized neither in the KLF5 animals nor in the others. While, neointimal formation and PCNA labeling index significantly increased in the KLF5 animals. Rat VSMCs transfected with KLF5 showed marked increase in cell proliferation and BrdU uptake. Additionally, cleavage of caspase-3 recognized in the quiescent VSMCs was attenuated after transfection of KLF5. Even under apoptotic stimulation using anisomysin, KLF5 overexpression resulted in significant inhibition of apoptosis induction. Further, KLF5 up-regulated gene expression of cell cycle factors such as cyclin D1, and conversely, knockdown of KLF5 by RNA interference showed down-regulation of cyclin D1 and impairment of VSMC proliferation.

Conclusion:
These findings taken together suggest that KLF5 plays a central role in VSMC proliferative pathologies such as vascular remodeling through biphasic contribution; inhibition of apoptosis and growth stimulation. Therapeutic intervention targeted against KLF5 may be potentially exploitable for VSMC proliferative pathology.
Abstract 2034: Clinical Significance of Sleep-disordered Breathing (SDB) in a Large Population of Japanese Patients: Efficacy of CPAP Therapy in SDB-associated Arrhythmias
Authors: Abe Hidetoshi , Kyoritsu Matsumoto , Takahashi Masafumi , Yokota Daisuke , Tsukioka Katsuaki , Suzuki Jun , Yaegashi Hironobu , Clinic Hiro , Eda Seiichiro , Tsunemoto Hideo , Kamikozawa Mamoru , Yamazaki Kyohei , Ikeda Uichi
Published: July 2021

OBJECTIVES:
The purpose of this study was to determine the relationship between Sleep-disordered breathing (SDB) and cardiovascular disorders in a large Japanese population, and to assess the efficacy of continuous positive airway pressure (CPAP) in the treatment of SDB-associated arrhythmias.

BACKGROUND:
SDB is associated with cardiovascular disorders, such as hypertension, ischemic heart disease, and arrhythmias, and CPAP is one of the effective treatments for SDB; however, this relationship and the efficacy of CPAP treatment in a large population of Japanese patients remain undefined.

METHODS AND RESULTS:
The study population comprised 1413 Japanese subjects (mean age: 56.6 years old, 1123 men and 290 women) who were divided into 2 groups: SDB group (
n
= 1064, apnea-hypopnea index (AHI)≥20)and control group (
n
= 349, AHI < 20) by polysomnography (PSG) analysis. In baseline characteristics, age (58.3±14.7vs.50.0±18.4,
p
<0.0001), gender (male: 88.4%vs.72.9%,
p
<0.0001), BMI (25.9±4.4vs.23.2±3.7,
p
<0.0001), hypertension (38.0%vs.19.3%,
p
<0.0001), diabetes (10.4%vs.5.2%,
p
=0.015), or hyperlipidemia (15.6%vs.9.3%,
p
=0.018) were significantly associated with SDB. PSG revealed predominant occurrence of paroxysmal atrial fibrillation (PAF: 108/1064 vs. 3/349, p=0.005), premature ventricular complex (PVC: 359/1064vs.17/349, p=0.0012) and pause (sinus arrest ≥2 sec: 172/859vs.6/349, p=0.002) in SDB group. In the SDB group, 291 patients underwent CPAP titration and were then re-evaluated. CPAP therapy significantly reduced the occurrences of PAF (59/291vs.2/291, p=0.005), sinus bradycardia (18/291vs.0/291, p=0.002), and sinus pause (26/291 vs. 4/291, p=0.016).

CONCLUSIONS:
The results of this study provide a significant relationship between SDB and several cardiac disorders, and efficacy of CPAP in preventing SDB-associated arrhythmias in a large population of Japanese patients.

Effect of CPAP on the arryhthmic events in patients with SAS during PSG recording
Abstract 2036: Severe Autonomic Failure in Diabetic Postinfarction-Patients
Authors: Schmidt Georg , Barthel Petra , Schneider Raphael , Bauer Axel , Arnoldi Elisabeth , Joeinig Anke , Ulm Kurt
Published: July 2021

Background: Diabetic post-infarction patients are at high risk of subsequent death. Deceleration Capacity (DC) and Heart Rate Turbulence (HRT) are a risk predictors that quantify different aspects of autonomic performance (tone and reflex function). Sever Autonomic Failure (SAF) was assumed if DC and HRT were compromised. This study investigates the predictive value SAF in diabetic post-infarction patients. Patients: 416 consecutive diabetic post-infarction patients, age < <26> 75 years, in sinus rhythm were enrolled. Primary endpoint was total mortality at 5 years. Mean follow-up period was 4.4 years.

Methods: DC and HRT were determined according to the published methodology. Severe autonomic failure (SAF) was defined as DC < <26> 4.5 ms and HRT category 2. Cox-proportional hazards analyses were performed with respect to age, history of previous myocardial infarction, mean heart rate, HRV index and arrhythmia count during 24-h Holter monitoring, QRS duration and LVEF, all with prospectively defined dichotomies.

Results: During follow-up, 61 patients died. There were 36 cardiac deaths, out of which 23 occurred suddenly. 24 patients presented with SAF, 13 patients with LVEF < <26> 30%. Five-year all-cause mortality rates of patients with and without SAF were 63% and 11%, respectively (Figure

, left panel). For LVEF 30%, these figures were 51% and 15% (Figure

, right panel). Similar figures were observed for cardiac mortality. In multivariable analysis, presence of SAF indicated a hazard ratio of 5.1 (LVEF 4.2; age 3.5, mean heart rate 1.9).

Conclusion: Diabetic post-infarction patients with SAF have a poor outcome, whereas mortality rates of patients without SAF were low.
Abstract 2047: Effect of Amlodipine on the Clinical Outcome in Diabetic Patients with Coronary Artery Disease after Angioplasty : Results from the Cardiovascular Events Follow-up Trial in Kokura (CAVEFT-Kokura)
Authors: Yokoi Hiroyoshi , Iwabuchi Masashi , Yasumoto Hitoshi , Nosaka Hideyuki , Nobuyoshi Masakiyo
Published: July 2021

Background: CAMELOT Study showed that the administration of amlodipine to diabetic patients with coronary artery disease (CAD) resulted in reduced adverse cardiovascular events, especially repeat coronary revascularization.

Objective: To compare the effects of amlodipine versus placebo on restenosis and clinical outcome after percutaneous coronary intervention (PCI) for diabetic patients.

Methods: In a prospective, double-blind design, 540 patients with 659 denovo lesions were randomized to receive 5–10mg of amlodipine or placebo. Diabetic patients were enrolled in171 patients (32%). The primary angiographic endpoint was minimal lume diameter (MLD) at 6 month assessed by follow-up (FU) quantitative coronary angiography (QCA). Clinical end points were death, myocardial infarction, coronary bypass surgery and repeat any PCI at 12 months.

Results: Angioplasty was performed in all patients without complications ;461 patients (85%) had received coronary stent implantation.FU QCA was obtained in all patients. The MLD at FU was significantly larger in the amlodipine group (1.50±0.52mm in the amlodipine group versus 1.42±0.52mm in the placebo group: p=0.035). The loss index was tendency to be lower in the amlodipine group (0.54±0.66 in the amlodipine group versus 0.61±0.56 in the placebo group: p=0.076). The binary restenosis (defined as >50% diameter stenosis at FU) rate was 22.6% in the amlodipine group versus 28.5% in the placebo group (p=0.078). The composite incidence of clinical events were occurred in 89 patients (32%) in the amlodipine group versus 102 patients (39%) in the placebo group (p=0.103). The composite incidence of clinical events in diabetic patients were occurred in 30 patients (37%) in the amlodipine group versus 51 patients (57%) in the placebo group (p=0.007).

Conclusion: Administration of amlodipine in diabetic patients resulted in reduced adverse cardiovascular events after PCI.
Abstract 2050: Differential Effects of Natriuretic Peptides on Arterial and Venous Coronary Artery Bypass Conduits
Authors: Nguyen Hao , Korach Amit , Collura Chey , Eskenazi Ben , Shapira Oz M
Published: July 2021

Background: Long-term patency of arterial grafts used for coronary bypass grafting (CABG) is superior to that of venous grafts. Natriuretic peptides (NP’s) have a major role in vascular homeostasis. We characterized the effects of NP’s and their receptors (NPR) in commonly used CABG conduits.

Methods: The relaxation and tissue levels of cGMP in response to 3 NP’s (ANP, BNP and CNP) were assessed in pre-contracted segments of internal mammary artery (IMA), radial artery (RA) and saphenous vein (SV) obtained from the same patients (n=12) in the absence/presence of the LY83583 (Guanylyl Cyclase inhibitor) or L-NAME (Nitric Oxide synthase inhibitor). NPR expression was assessed using immunohistochemistry and Western blotting.

Results: Results are summarized in the Tables

. Maximal relaxation of the IMA and RA to ANP, BNP and CNP were similar and greater than SV, correlating with increased tissue levels of cAMP in both arterial conduits. Relaxation response to all 3 NP’s were nearly abolished in the presence of LY83583. Exposure of the conduits to L-NAME resulted in only a modest blunting of the relaxation response to the NP’s. NPR-A, NPR-B and NPR-C were strongly expressed in both the endolethium and vascular smooth muscle layer of the IMA and RA and significantly less in SV.

Conclusion: NP’s are potent vasodilators of the IMA and RA but not the SV. The relaxation response is mediated via NPRs/cGMP and the Nitric Oxide systems. These observations provide additional insight into the potential physiological mechanisms underlying the superior patency of arterial conduits and may form a basis for potential therapeutic interventions aimed to improve vein grafts performance.

Vessel Relaxation Response to NP’s

Tissue cGMP levels in response to NP’s and NPR Protein Expression
Abstract 2065: Uncorrected Moderate Tricuspid Regurgitation Impacts Late Survival In Patients Undergoing Mitral Valve Replacement
Authors: Chan Vincent , Price Joel , Burwash Ian , Lam B-Khanh , Mesana Thierry G , Ruel Marc
Published: July 2021

Introduction:
Little is known regarding the evolution and clinical impact of moderate tricuspid regurgitation (TR) in patients undergoing mitral valve replacement (MVR). This natural history study was conducted to determine:

the predictors of TR progression and

the impact of TR progression on late survival.

Methods:
Between 1989 and 2005, 352 patients (mean age 63.5 ± 12.4y) who underwent mitral valve replacement with contemporary prostheses (mechanical/bioprostheses = 70%/30%) were followed for the evaluation of their concomitant tricuspid regurgitation (mean grade 2.0+ at mitral surgery). These patients did not undergo concomitant tricuspid valve repair or replacement. Concomitant coronary artery bypass grafting (CABG) was performed in 34% of patients, with a mean of 2.1 grafts. Clinical and echocardiographic follow-up was 100% complete and averaged 5.7 ± 3.9 years. Parametric and semi-parametric techniques were used to determine predictors of outcomes.

Results:
Thirty-day mortality was 2.2%. Postoperative progression of TR was noted in 36% of patients. Multivariate predictors of TR progression included female gender (odds ratio (OR) 10.3; p=0.03) and right ventricular systolic pressures ≥ 50 mmHg preoperatively (OR 8.1; p=0.05). Atrial fibrillation, concomitant CABG, the degree of preoperative mitral regurgitation, and mitral prosthesis size were not predictive of TR progression. TR progression in patients whose TR was 2+ or more at the time of initial surgery was associated with significantly decreased late survival (hazard ratio 3.7; p=0.05).

Conclusions:
Based on these data, it appears that if TR is not surgically corrected at time of MVR, it may progressively worsen over time in a sizable proportion of patients. In patients with TR 2+ or more at the time of MVR, TR progression is associated with decreased late survival. It therefore appears indicated to repair TR of grade 2+ or more at the time of mitral surgery, particularly in female patients and in patients with right ventricular systolic pressures of 50 mmHg or more, which are both predictive of postoperative TR progression.
Abstract 2066: Does Mitral Regurgitation Regress After Aortic Valve Replacement For Aortic Stenosis ? A Prospective Multicenter Study
Authors: Unger Philippe , Plein Danièle , Cosyns Bernard , Van Camp Guy , Xhaët Olivier , Henrard Valérie , Lancellotti Patrizio
Published: July 2021

Background:
Mitral regurgitation (MR) is common in patients undergoing aortic valve replacement (AVR) for aortic stenosis (AS). Whether its severity may decrease after AVR remains controversial. Previous studies were mainly retrospective and the degree of MR was assessed at best semi-quantitatively. This study sought to prospectively and quantitatively assess how AVR may affect MR severity.

Methods:
Patients with AS scheduled for isolated AVR and presenting holosystolic MR which was not considered for replacement or repair were included. Previous mitral valve surgery; severe aortic regurgitation and poor acoustic windows were excluded. Thirty-five patients (mean age 77±7 years) were studied before (median 1, range 1– 41 days) and after AVR (median 7, range 4 –19 days). All patients underwent a comprehensive echocardiographic examination; MR was assessed by Doppler echocardiography using color flow mapping of the regurgitant jet and the PISA method. No patient had prolapsed or flail mitral leaflet as mechanism of MR.

Results:
Preoperative maximal and mean transaortic pressure gradients and aortic valve area were 74±26 mmHg, 44±16 mmHg, and 0.57±0.18 cm
2
, respectively. Left ventricular (LV) ejection fraction increased from 49±16 % to 55±15 % after AVR (p<0.001). LV end-diastolic volume decreased from 91±32 ml to 77±30 ml (p<0.001).The ratio of MR jet to left atrial area decreased from 30±16% to 20±14% (p<0.001). MR effective regurgitant orifice (ERO) and regurgitant volume decreased from 10±5 mm
2
to 8±6 mm
2
(p=0.015) and from 19±10 ml to 11±9 ml (p<0.0001). The decrease in ERO and in regurgitant volume was similar in patients with preserved or depressed LV ejection fraction (≤45 %) (2±3 vs 3±6 mm
2
and 7±9 vs 8±7 ml; p=NS, respectively).

Conclusions:
AVR is associated with an early postoperative reduction of the quantified degree of MR. This mainly results from a decrease in regurgitant volume and only modestly from a reduction in ERO, emphasizing the contributing role of the decrease in driving pressure accross the mitral regurgitant orifice.