bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18061: Supplementation to Treat Antithrombin Deficiency Improves Sensitivity to Heparin, Anticoagulation and Decreased Thrombogenecity in Neonates and Infants Undergoing Cardiac Surgery With Cardiopulmonary Bypass
Authors: McCrindle Brian W , Manlhiot Cedric , Holtby Helen M , Chan Anthony K , Brandao Leonardo R , Rolland Martha , Stenyk Lia , Crawford-Lean Lynn , Foreman Celeste , Van Arsdell Glen S , Gruenwald Colleen E
Published: July 2021

Introduction:
Preoperative antithrombin (AT) deficiency is common in infants undergoing cardiac surgery with cardiopulmonary bypass (CPB), and is associated with heparin resistance, difficulties achieving optimal intraoperative anticoagulation and post-operative thrombosis.

Methods:
We performed a pilot randomized trial of pooled human AT supplementation for children <1 year with preoperative AT <0.85U/ml. Subjects received a split (patient and CPB prime) dose of AT before heparinization. AT was dosed to reach a predicted AT activity of 1.2U/ml during CPB calculated from preoperative AT level and patient weight.

Results:
We randomized 18 subjects; 17 completed the study (9 controls, 8 AT). Mean preoperative AT level was similar between groups (Control: 0.65±0.10 vs. AT: 0.68±0.15 U/mL, p=0.66). AT group subjects had higher AT than controls immediately after start of CPB (Control: 0.44±0.10 vs. AT: 1.15±0.20 U/mL, p<0.001) and at the end of CPB (Control: 0.67±0.14 vs. AT: 1.19±0.16 U/mL, p<0.001). AT supplementation was associated with increased activated clotting time (ACT) post-heparinization (Control: 500±72 vs. AT: 639±172 seconds, p=0.02), increased heparin sensitivity (Control: 89±23 vs. AT: 114±22 ACT seconds per 100U/kg heparin, p=0.02), and decreased heparin dose given during CPB (Control: 1126±344 vs. AT: 845±165 U/kg, p=0.03). After primary heparinization, 56% of control subjects did not achieve ACT target vs. 25% of AT subjects. At the end of CPB, AT group subjects had lower prothrombin levels (Control: 746±372 vs. AT: 460±102 ng/mL, p=0.02) and lower levels of inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-8 and TNFα). Supplementation with AT was not associated with increased chest tube volume loss or blood product requirements. One subject in each group had severe bleeding, and one in each group had post-operative infection. Thrombosis was noted for 3 controls and 1 AT subjects.

Conclusions:
AT supplementation to treat preoperative AT deficiency in young children is associated with decreased heparin resistance, improved anticoagulation and decreased thrombogenecity. Safety profile regarding bleeding and infections appears favorable. Equipoise exists for a larger definitive outcome trial.
Abstract 18134: Phenome-wide Study of Electronic Medical Record Data Reveals Novel Association of Natriuretic Peptide A Genetic Variant With Rheumatoid Arthritis
Authors: Pereira Naveen , Jenkins Gregory , Kullo Ifthikar , Bielinski Suzette , Burnett John , Pathak Jyotishman
Published: July 2021

Introduction:
Phenome-wide association studies (PheWAS) using electronic medical record (EMR)-linked biobanks have been used not only to identify and replicate known associations of genetic variants with disease phenotypes but have also resulted in the discovery of potentially novel genotype-phenotype relationships. The natriuretic peptide (NP) system plays an important role in a broad range of disease processes including cardiovascular and inflammatory diseases. We hypothesized that performing a PheWAS using previously known functional genetic variants of the NP system may result in novel disease associations that could provide mechanistic insights in an unbiased manner.

Methods:
We scanned for associations between 9 single-nucleotide polymorphisms (SNPs) in the NP system and 27 EMR-derived chronic disease phenotypes in 3,025 individuals participating in a case-control study of peripheral arterial disease. The EMR phenotypes were identified using two or more ICD-9-CM diagnosis codes based on the AHRQ Clinical Classifications Software (CCS). The relationship of SNPs and phenotypes were modeled using logistic regression adjusting for gender.

Results:
We identified rs5065, a SNP located in the stop codon of exon 3 of the NPPA gene, to be the strongest associated SNP with rheumatoid arthritis (RA) (OR=0.78, p=0.0008, q-value=0.11). The SNP leads to the extension of atrial natriuretic peptide (ANP) by 2 additional arginines at the C terminus. Cardiovascular disease is known to be the leading cause of death in patients with RA and ANP plays an important immunomodulatory role by inhibiting inducible nitric oxide synthase, reducing TNF-α production and attenuating prostaglandin E2 production in macrophages. Circulating NPs have been used to screen for occult cardiac disease and are associated with mortality in RA. This study demonstrates for the first time the importance of the relationship between genetic variation in the NP system and RA.

Conclusions:
PheWAS was successfully used as a tool to identify a novel association of functional genetic variation in the NPPA gene with RA. The observation is hypothesis generating and further replication studies are required to determine the role of rs5065 in cardiovascular outcomes of RA.
Abstract 18245: Palmitic Acid-induced Endothelial Dysfunction in Human Leptomeningeal and Adipose Arterioles
Authors: Truran Seth , Karamanova Nina , Serrano Geidy , Franco Daniel , Burciu Camelia , Beach Thomas , Roher Alex , Migrino Raymond Q
Published: July 2021

Introduction:
Epidemiologic data show strong link between cardiovascular risk factors and dementia-related illnesses (DRI) such as Alzheimer’s disease (AD) with evidence that the earliest changes in AD involve vascular dysfunction. The mechanisms behind vascular impairment in DRI remain poorly understood, and lack of a human model to study them impedes progress towards a cure.

Aim:
The aim of the study is to determine the effects of acute exposure to palmitic acid (PA), a saturated fatty acid implicated in atherosclerosis, on endothelium-dependent and smooth muscle dependent function in human leptomeningeal arterioles (LMA) and peripheral adipose tissue arterioles (AA).

Methods:
LMA from cadavers of brain donors (post-mortem interval 3.3±0.4 hours; 2 with mild cognitive impairment, 1 Parkinson's disease, 1 Lewy body dementia) and abdominal subcutaneous AA from living subjects with no vascular disease undergoing routine surgery were isolated, cannulated and pressurized. Following preconstriction with endothelin-1, baseline (control) dilation response to acetylcholine and papaverine was measured. Arterioles were then exposed to 1 hour of PA (150 μM) and a second dilation response was measured.

Results:
(see Figure) PA decreased dilator response to acetylcholine in both LMA and AA (PA-induced change in dilator response to acetylcholine 10-4M: -28.1±6.8 % for LMA and -33.8±7.4% for AA, both p<0.05 versus baseline control). There was no significant reduction in dilator response to papaverine. The changes in dilator response with PA versus control were not different between LMA and AA.

Conclusions:
Acute exposure to PA induced endothelial dysfunction in human leptomeningeal arterioles suggesting a potential mechanism for vascular dysfunction that could contribute to AD. Similarity in response to saturated fatty acid between LMA and AA suggests that AA, which is easier to obtain, may be a novel surrogate human model to study brain microvascular function.
Abstract 18266: Overactive Tgfβ Signaling in Smooth Muscle Cells Induces Hypertension in Mice Through Increased Myogenic Tone and is Responsible for Increased Myogenic Tone in Resistance Vessels of Hypertensive Patients
Authors: Carnevale Daniela , Casaburo Manuel , Bizzotto Dario , Cugino Daniela , Selvetella Giulio , Innocenzi Gualtiero , Bressan Giorgio , Lembo Giuseppe
Published: July 2021

Emilin1 (E1) is a protein of the extracellular matrix that regulates TGFβ activity through proteolysis of the proTGFβ. E1 KO mice are hypertensive, with increased TGFβ activation. As E1 is expressed in blood vessels starting from embryonic life to adulthood, is still unknown whether the E1 KO phenotype results from a developmental defect or lack of a homeostatic role exerted in the adult. To dissect this issue, we inactivated E1 in smooth muscle cells (VSMCs) of adult mice, by the use of floxed E1 and CreERT2 [a tamoxifen (TAM) inducible Cre recombinase] under the control of the smooth muscle myosin heavy chain (Smmhc) promoter. When Smmhc-CreERT2 E1fl/fl mice were given TAM, blood pressure significantly increased (124±1 vs basal condition 106±1 mmHg) as well as myogenic response in resistance arteries (16.3±0.7 vs basal condition 11.4±0.1 % at 125 mmHg).

In order to evaluate the relevance of our findings in the human pathology, we enrolled 20 hypertensive and 20 normotensive patients that underwent neurosurgical intervention for primary lumbar hernia repair and dissected out resistance vessels from skeletal muscle biopsies. We analyzed the myogenic tone of human peripheral resistance vessels in a pressure myograph and randomized vessels to receive vehicle, a neutralizing antibody anti-TGFβ or a preimmune non relevant IgG. As first, we found that hypertensive patients had significantly increased myogenic tone as compared to normotensive (16.6±2.1% vs 10.5±0.4% at 125 mmHg). Moreover, the pretreatment of vessels with anti-TGFβ antibody normalized the myogenic tone of hypertensive patients (10.8±0.6%) to the levels of normotensives (11.8±1.3%). A pretreatment with the non relevant IgG did not modify the myogenic tone of hypertensives (17±0.6%), thus demonstrating that the effect was dependent of an increased TGFβ signaling in vessels of hypertensive patients.

Overall, our results suggest that the TGFβ pathway in VSMC, is crucial for the myogenic tone of resistance arteries and is linked to the regulation of blood pressure. The data obtained in peripheral resistance vessels from hypertensive patients, that display an increased myogenic tone dependent on overactive TGFβ signaling, highlight the translational potential of our findings to the human pathology.
Abstract 18269: Regional Longitudinal Deformation Improves Prediction of Ventricular Tachyarrhythmias in Heart Failure Patients With Reduced Ejection Fraction - A MADIT-CRT Sub-Study
Authors: Biering-Sørensen Tor , Knappe Dorit , Pouleur Anne-Catherine , Clagett Brian , Moss Arthur J , Solomon Scott D , Kutyifa Valentina
Published: July 2021

Background:
Abnormalities of regional function are known predictors of ventricular arrhythmia. We assessed whether measures of regional longitudinal deformation by speckle tracking echocardiography improve prediction of ventricular tachyarrhythmias over clinical, echocardiography parameters, or biomarkers.

Methods:
We studied 1064 patients enrolled in MADIT-CRT with speckle-tracking data available. Peak longitudinal strain was obtained for the septal, lateral, anterior and inferior myocardial walls. The endpoint was the first event of ventricular tachycardia (VT) or fibrillation (VF).

Results:
During the median follow-up of 2.9 years, 254 (24%) patients developed VT/VF. Patients with VT/VF had significantly lower LVEF (28.3% vs 29.5%, p<0.001) and longitudinal strain in all myocardial walls compared to patients without VT/VF (Figure). After multivariate adjustment for clinical and conventional echocardiographic predictors of VT/VF, only longitudinal strain in the anterior and inferior myocardial walls remained independent predictors of VT/VF (anterior: HR 1.08 [1.03; 1.13], p=0.001; inferior: HR 1.08 [1.04; 1.12], p<0.001; per 1% increase for both). After including BNP in the model, only a decreasing myocardial function in the inferior myocardial wall predicted VT/VF (HR 1.05 [1.00; 1.10], p<0.05) (Figure). Additionally, only strain in the inferior myocardial wall provided incremental prognostic information on the risk of VT/VF when added to a model already including clinical parameters and LVEF, determined by a significant increase in the Harrell’s C-statistic (0.70 vs 0.67, p=0.002).

Conclusion:
In MADIT-CRT, assessment of regional longitudinal myocardial deformation in the inferior myocardial wall provided incremental prognostic information over clinical, conventional echocardiographic risk factors, or biomarkers in predicting ventricular tachyarrhythmias.
Abstract 18321: Analysis of a Consanguineous Cohort to Identify and Characterize Human Knockouts
Authors: Saleheen Danish , Nataranjan Pradeep , Zhao Wei , Rasheed Asif , Khetarpal Sumeet , Lander Eric , Gabriel Stacey , Daly Mark , Frossard Philippe , Danesh John , Rader Daniel , Kathiresan Sekar
Published: July 2021

Background:
Experimental disruption of both gene copies (“knockout”) in model organisms has proven useful to understand gene function. Identification of “human knockouts” (i.e., individuals in which null mutations disrupt both copies of a given gene) should therefore provide valuable insights to a gene function that could be of direct relevance to humans.

Objective and Methods:
We leverage naturally-occurring null mutations and consanguinity in the human population in order to: 1) identify humans knocked out for genes; and 2) characterize the phenotypic consequences of complete gene disruption. We performed whole-exome sequencing in 7,078 individuals living in Pakistan, a region of the world with high levels of consanguinity, and tested whether knockouts differed from wild-type participants across a range of >200 cardiometabolic traits.

Results:
Median length of genome-wide homozygosity among Pakistani participants was 6-7 times higher than participants of European (CEU, TSI), East Asian (CHB, JPT, CHD) and African ancestries (YRI, MKK), respectively. In Pakistanis, we were able to enumerate 47,656 mutations predicted to be null (nonsense, frameshift, or canonical splice-site); variants were further filtered based on MAF, transcript position, splice sites, and conservation to identify 36,850 “high-confidence” null mutations across 12,131 autosomal genes. Across all participants, 961 distinct genes were completely disrupted by homozygous null mutations. 1,306 participants (18.4%) had at least one gene knocked out. In a phenotypic screen, homozygosity for null mutations at
APOC3
was associated with absent plasma apolipoprotein C-III levels; at
PLAG27
, with absent enzymatic activity of lipoprotein-associated phospholipase A2 in the blood; at
CYP2F1
, with higher plasma interleukin-8 concentrations; and at either
A3GALT2 or NRG4
, with markedly reduced plasma insulin C-peptide concentrations. After physiologic challenge with oral fat,
APOC3
knockouts, when compared to wild-type family members, displayed marked blunting of the usual post-prandial rise in plasma triglycerides.

Conclusion:
These observations provide a roadmap to understand the consequences of complete disruption of a large fraction of genes in the human genome.
Abstract 18329: Aortic Pulse Wave Velocity Improves Following Moderate-intensity Continuous Training but not High-intensity Interval Training in Older Men and Postmenopausal Women
Authors: Kim Han-Kyul , Hwang Chueh-Lung , Yoo Jeung-Ki , Hwang Moon-Hyon , Handberg Eileen M , Nichols Wilmer W , Christou Demetra D
Published: July 2021

Introduction:
Aortic pulse wave velocity (AoPWV), a measure of arterial stiffness, increases with age and is an independent predictor of cardiovascular disease. Higher levels of habitual physical activity are associated with reduced AoPWV, but the effect of well-controlled aerobic training interventions in healthy older adults remains unclear. We hypothesized that moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) will both improve AoPWV in healthy older adults.

Methods:
Thirty five sedentary older men and postmenopausal women, free of overt cardiovascular disease (age, 65±1 yrs, body mass index, 27.7±0.8 kg/m
2
; systolic and diastolic blood pressures, 116±2 and 69±1 mmHg, respectively; mean±SE) participated in this intervention. Subjects were randomized to MICT (n=13), HIIT (n=12) or non-exercise control group (CONT; n=10). Isocaloric MICT and HIIT were performed on Airdyne bicycles 4 days/week for 8 weeks under supervision. MICT consisted of 47 min of cycling at 70% of maximal heart rate, while HIIT consisted of 40 min of cycling at alternating intensities of 90% and 70% of maximal heart rate. AoPWV, aortic systolic and diastolic blood pressures were evaluated using applanation tonometry (SphygmoCor) before and after the intervention.

Results:
AoPWV improved by 0.52 m/s in MICT (9.26±0.39 vs. 8.75±0.35 m/s, pre- vs. post-intervention; P<0.05), but did not change in HIIT (9.29±0.29 vs. 9.16±0.38 m/s, P>0.05) or CONT (8.82±0.75 vs. 9.26±0.70 m/s, P>0.05). Aortic systolic blood pressure (MICT: 106±2 vs. 107±3 mmHg; HIIT: 115±3 vs. 113±4 mmHg; CONT: 109±5 vs. 110±4 mmHg) and diastolic blood pressure (MICT: 69±2 vs. 69±2 mmHg; HIIT: 70±2 vs. 70±2 mmHg; CONT: 68±2 vs. 69±2 mmHg) did not change with the intervention (P>0.05). Body mass index remained unchanged in all groups (P>0.05).

Conclusions:
MICT Airdyne exercise leads to arterial destiffening, however, HIIT does not lead to improved arterial stiffness in healthy older men and postmenopausal women.
Abstract 18353: A Real-world Study Evaluating the Utility of an Innovative Digital Health Feedback Device in Patients With Uncontrolled Hypertension
Authors: DiCarlo Lorenzo , Naik Ravin , Macey Neil , West Richard J , Godbehere Peter , Thurston Stephen C , Fox Robin , Singh Indy , Xiang Weina , Kim Yoona
Published: July 2021

Introduction:
For patients with uncontrolled blood pressure (BP), differentiation of pharmacological resistance from inadequate or improper medication use is key to clinical management. A digital health feedback device (DHFD) has been developed, utilizing an Ingestible Sensor (IS) and Wearable Sensor (WS) to passively record medication taking and timing, and measure physiological and behavioral metrics such as heart rate, step count, activity and rest patterns. This study evaluated DHFD use in diagnosing the cause of persistent BP elevation.

Methods:
Patients with a history of BP (≥140/90) on ≥2 anti-hypertensives (AHs) at 6 primary care centers in the United Kingdom were prescribed the DHFD for 14 days. Patients co-ingested the IS along with their prescribed BP medications while continuously wearing the WS. BP was assessed on days 1 and 14.

Results:
A total of 151 patients were enrolled; 38% were taking ≥3 AHs at baseline; 144 patients (95%) completed the 2 planned weeks of DHFD use. Root cause of treatment unresponsiveness was identified by DHFD in 100% of completers; 58% had pharmacological resistance, and 42% had inadequate AH use. During DHFD use, mean systolic BP decreased significantly by -10±17 (p<0.001) and mean diastolic BP decreased significantly by -5±9 mmHg (p<0.001); 38% of subjects achieved BP control on their current therapy. Subsequent management included: medicines reviews and/or adherence counselling with no AH changes in 81%, medication changes in 13%, referrals to specialists in 1%, and no additional actions were taken in 6%. Majority of practices (75%) found the DHFD added value, and 83% of patients expressed a positive experience. Side effects were minimal, consisting of mainly minor skin irritation (8%), or gastrointestinal symptoms (3%). Two patients withdrew due to possibly-related adverse events.

Conclusions:
In subjects using the DHFD for uncontrolled BP while prescribed AHs, all received a more informed therapeutic intervention from their providers following DHFD use. BP control was achieved in 38% within 2 weeks. DHFD can facilitate evidence-based progression through the BP treatment pathway by differentiating which patients can achieve treatment goals with prescribed therapy from those who may require AH changes.
Abstract 18360: Predictors of Physician Under-recognition of Angina in Outpatients With Stable Coronary Artery Disease
Authors: Grodzinsky Anna , Kosiborod Mikhail , Beltrame John , Gosch Kensey , Jones Philip G , Spertus John A , Alexander Karen P , Shafiq Ali , Arnold Suzanne V
Published: July 2021

Background:
Under-recognition of angina by physicians may result in under-treatment with revascularization or medications that could improve patients’ quality of life. Patient and physician characteristics associated with under-recognition have never been described.

Methods:
Outpatients with stable CAD in a 24-site US registry completed the Seattle Angina Questionnaire (SAQ) and their physicians independently quantified patients’ angina in the month prior to their clinic visit. Angina frequency was categorized as none, monthly, and daily/weekly. Among patients who reported angina, under-recognition was defined as the physician reporting a lower frequency of angina than the patient. A hierarchical (for site and physician) logistic model examined patient and physician factors associated with under-recognition of angina. Physician variability was assessed with a median odds ratio (MOR), which compares the likelihood of 1 physician at 1 random site under-recognizing angina vs. another physician at another site.

Results:
Among 1203 patients with stable CAD, 304 patients reported angina in the prior month, of whom 122 (40%) were under-recognized by their physician. Physicians were more likely to under-recognize the frequency of angina in patients with heart failure and among patients with less frequent angina (Figure). No other patient or physician factors were associated with under-recognition. There was significant variability across physicians (MOR 2.6), indicating that some physicians were better than others at recognizing angina.

Conclusions:
Under-recognition of angina is common in routine clinical practice and was largely unrelated to standard patient and physician characteristics. The large variation across physicians suggests that a more systematic approach is needed to assess angina from patients with CAD. The use of a validated tool, such as the SAQ, should be tested for improving angina recognition and outcomes.
Abstract 18377: Prospective, Multi-center Trial to Determine the Effect of Viewing a 60-second Video on Emergency Department Patients and Their Companions Willingness to Perform Compression-only Cardiopulmonary Resuscitation
Authors: Dall Tanya , Tainsh Valerie , Carlberg David , Garcia Olga E , Konieczny Jaime , Goyal Munish
Published: July 2021

Introduction:
Bystander CPR is uncommonly performed in out-of-hospital cardiac arrest patients transported to our ED. Previous studies suggest adults without formal CPR training can retain compression-only CPR skills with a single viewing of a 60 second, AHA training video. We sought to determine the impact of viewing this video on the willingness of ED patients and their companions to perform compression-only CPR.

Hypothesis:
Watching a 60 second AHA CPR training video is associated with a 10% increase in willingness to perform CPR.

Methods:
A convenience sample of adults age 18-70 from two urban, academic EDs with socioeconomically diverse patient populations was recruited. Patients in hallways and non-english speakers were excluded. Subjects were asked to complete a pre-video survey to assess baseline knowledge and willingness to perform CPR on a stranger and on family/friends, watch a 60 second, previously validated AHA CPR instructional video, and then complete a post-training CPR survey. Willingness was scored as 1 (not at all likely) to 5 (extremely likely). An answer of 4 or 5 was considered “willing to perform CPR”. A sample size of 110 subjects from each hospital was determined necessary to detect at 10% absolute difference assuming 0.80 power and one-sided alpha level of 0.05. Sign and McNemar's tests were used to compare pre and post video measurements.

Results:
Between 1/1/15 to 6/7/15, 281 patients and their companions were approached about study participation, of which 229 (82%) consented; complete data were available for 216 subjects. Subjects were mean age 47, 66% female, 68% black, and 69% college educated. After watching the video, willingness to perform CPR on a stranger increased by 29%, from 57% to 86% (p< 0.001). Willingness to perform CPR on family/friends increased by 19%, from 75% to 94% (p<0.001). Among subjects whose willingness to perform CPR changed (110 on a stranger and 67 on family/friends, respectively), 98% (108) and 96% (64) changed from less willing to more willing.

Conclusion:
In adult patients and their companions in two diverse, academic EDs, watching a 60 second CPR training video was associated with a significant absolute increase in willingness to perform compression-only CPR on a stranger (29%) and on family/friends (19%).
Abstract 18395: Safety of Continuing Ivabradine Treatment During Hospitalization for Worsening of Heart Failure in the SHIFT Study
Authors: Borer Jeffrey , Swedberg Karl , Komajda Michel , Ford Ian , Tavazzi Luigi , Böhm Michael , Dominjon Fabienne , Wu Yuna , Depre Christophe , Maya Juan
Published: July 2021

Background:
Chronic medical treatment is usually adapted during hospitalizations for worsening heart failure (HWHF). Ivabradine, a heart rate (HR)-slowing agent that inhibits the funny current (If) in the sinus node, when added to standard of care reduced the relative risk of HWHF by 26% in the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT). Upon HWHF in SHIFT, ivabradine could be maintained even though patients were in acute/unstable HF. This post hoc exploratory analysis assessed the safety of continuing administration of ivabradine during HWHF in SHIFT.

Methods:
The safety of ivabradine within the 30 days following the first HWHF admission was assessed in patients receiving either ivabradine or placebo presenting with at least 1 adjudicated HWHF during the trial. The safety of ivabradine within the 30 days following the first HWHF admission in patients who continued study drug (CSD) versus those that discontinued study drug (DSD) during hospitalization within each treatment arm were compared.

Results:
Baseline characteristics of patients who were at least once HWHF were comparable between the ivabradine (n = 447) and placebo (n = 619) arms. During HWHF, study drug was continued in 70% of ivabradine- and 73% of placebo-treated patients. Within the 30 days following the first HWHF admission, serious adverse events were reported in 10.1% of ivabradine- (CSD: 11.1%, DSD: 7.6%) and 12.6% placebo-treated patients (CSD: 14.2%, DSD: 8.4%). Cardiovascular death was reported in 0.7% of ivabradine- (CSD: 0.6%, DSD: 0.8%) and 0.6% of placebo-treated patients (CSD: 0.9%, DSD: 0%).

Conclusions:
The safety profile of ivabradine in patients within 30 days following admission for HWHF was comparable to placebo, regardless of whether patients continued or discontinued study drug.
Abstract 18408: Cortical Spreading Depolarizations After Cardiac Arrest in an Asphyxial Rat Model
Authors: Hansen Frederik B , Secher Niels , Østergaard Leif , Skovgaard Morten , Tønnesen Else , Granfeldt Asger
Published: July 2021

Introduction:
Delayed neuronal cell death is observed following cardiac arrest (CA). The exact mechanisms remain unknown. Cortical spreading depolarization (CSD) is characterized by depolarization of neurons and glia cells, spreading as a wave that travels across the cortex. CSDs are known to occur in peri-infarct tissue and have been associated with poor outcome after stroke, and might contribute to the progression of neuronal injury after CA.

Objective:
To investigate if spontaneous CSDs occur during the post resuscitation period following CA, and to describe the characteristics of induced CSDs.

Methods:
Isoflurane-anesthetized Sprague-Dawley rats were randomized into one control group observed for 90 min (n=8), and two CA groups observed for 90 min (CA90min, n=7) and 360 min (CA360min, n=7), respectively, before data collection started. Animals underwent 8 min of asphyxial CA. Electrophysiological recordings were obtained over the right hemisphere through a burr hole. Potassium chloride (KCL) was applied onto the cortex through a separate burr hole in order to induce CSDs. Direct current recordings were gathered using an AgCl glass electrode. Induced abnormal CSDs were defined as CSDs with prolonged duration, low peak value, altered propagation speed and/or epileptiform discharges. Data collection (210 min) was divided into two periods: 1) In the 1
st
period no stimulation was applied in order to detect spontaneous elicited CSDs. 2) In the 2
nd
period KCl was applied.

Results:
Spontaneous CSDs were observed in one CA360min animal with prolonged CPR and time to return of spontaneous circulation of 298 sec. Significantly fewer CSDs were induced following KCl application in CA animals when compared with healthy controls (median(IQR) Control: 6(5-7) CA90min: 2(1-4) CA360min: 1(1-3), p<0.05). Induced abnormal CSDs were seen in both CA groups but not in controls (control vs. CA90min p=0.004, control vs. CA360min p=0.054). KCl application elicited multiple CSDs in rapid succession in 50% of CA animals and none of the controls (p=0.052).

Conclusion:
CSDs can occur following prolonged CA and resuscitation, and may lead to additional neuronal injury. The appearance and number of induced CSDs were altered in CA animals in comparison with healthy controls.
Abstract 18420: Does Maximum 10-hour Daily Activity From Objective Activity Monitoring Correlate With Self-reported or Performance-based Function in Older Adults With Severe Aortic Stenosis?
Authors: Tang Yufei , Maurer Mathew , Lazarte Rosa , Rubin Jonathan , Hung Ming Y , Garcia Melissa , Kodali Susheel , Harris Tamara , Green Philip
Published: July 2021

Objectives:
In older adults with aortic stenosis, we evaluated whether accelerometer-measured physical activity provides distinct clinical information apart from self-reported surveys or performance-based function tests (PBFT).

Background:
Wearable accelerometers can objectively quantify and monitor activity counts over an extended period of time, making them an ideal tool for measuring physical activity in older adults with cardiovascular disease; however, the relationship between accelerometer-measured activity and self-reported surveys or PBFT is unknown.

Methods:
We employed wrist-mounted accelerometry in 54 subjects with severe aortic stenosis prior to TAVR. Daily daytime activity was estimated using the maximum 10 hours of daily accelerometer-measured activity (M10) reported in activity counts. Subjects completed baseline surveys (NYHA, SF12, KCCQ, EQ-5D, LOT-R, Life Space, Detailed Activity Form) and PBFT (short physical performance battery, 6 minute walk test, grip strength) to estimate functional status. Simple and multiple linear regression models were used to evaluate the relationship between accelerometer-measured activity and survey data and PBFT.

Results:
The mean age was 87 years, 61% were female. Median ejection fraction was 63% (IQR 12). Most were NYHA Class III (65%), none were Class IV. There was a weak negative association between M10 and SF-12 Mental Composite Score (R2=0.1970, P=0.04) and between M10 and grip strength (R2=0.1568, P=0.004). However, neither multiple linear regression of overall survey data (R2=0.6159, P=0.23) nor PBFT (R2=0.1743, P=0.10) predicted M10.

Conclusions:
Self-reported surveys and performance-based function tests did not correlate well with maximal 10 hours of daily accelerometer-measured activity in older adults with aortic stenosis. Further studies will evaluate the distinct utility of accelerometer-measured activity in older adults with aortic stenosis predicting outcomes of TAVR.
Abstract 18434: Coronary Artery Calcium Progression and Atrial Fibrillation: The Multi-ethnic Study of Atherosclerosis (MESA)
Authors: O'Neal Wesley T , Efird Jimmy T , Qureshi Waqas T , Yeboah Joseph , Alonso Alvaro , Heckbert Susan R , Nazarian Saman , Soliman Elsayed Z
Published: July 2021

Introduction:
Coronary artery calcium (CAC) measured at a single time point has been associated with an increased risk for atrial fibrillation (AF). It is currently unknown whether CAC progression over time carries a similar risk.

Methods:
A total of 5,612 study participants (mean age 62 ± 10; 52% women; 39% whites; 27% blacks; 20% Hispanics; 12% Chinese-Americans) from the Multi-Ethnic Study of Atherosclerosis (MESA) were included in this analysis. Phantom-adjusted Agatston scores for baseline and follow-up measurements were used to compute the change in CAC per year (1 to 100, 101 to 300, and >300 units/year) compared with participants with ≤0 change. The mean time between CT scan for study participants was 2.4 ± 0.84 years. AF was ascertained by review of hospital discharge records and from Medicare claims data through December 31, 2010. Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95%CI) for the association between CAC progression and AF and models were adjusted for socio-demographics, cardiovascular risk factors, and baseline CAC.

Results:
At baseline, 2,904 (52%) participants had no evidence of CAC and 2,708 (48%) had CAC values >0. The mean CAC progression for those with baseline CAC was 46.1 ± 85.2 units per year and for those without baseline CAC was 0.84 ± 4.8 units per year. Over a median follow-up of 5.6 years, a total of 203 (3.6%) incident AF cases occurred. Any CAC progression (>0/year) was associated with an increased risk for AF (HR=1.55, 95%CI=1.10, 2.19) and the risk increased with higher levels of CAC progression per year (≤0/year: HR=1.0 [reference]; 1 to 100/year: HR=1.47, 95%CI=1.03, 2.09; 101 to 300/year: HR=1.92, 95%CI=1.15, 3.20; >300/year: HR=3.23, 95%CI=1.48, 7.05). An interaction was observed by age with the association of CAC progression with AF being stronger for younger (<61 years: HR=3.53, 95%CI=1.29, 9.69) compared with older (≥61 years: HR=1.42, 95%CI=0.99, 2.04) participants (p-interaction=0.037).

Conclusion:
CAC progression during an average of 5-6 years of follow-up is associated with an increased risk for AF. The associated risk is greater in individuals with faster CAC progression.
Abstract 18437: Women and Ischemic Heart Disease: Which Role for Katp Channels?
Authors: Severino Paolo , Calcagno Simone , Pucci Mariateresa , De Marchis Maria Laura , Palmirotta Raffaele , Mancone Massimo , Fedele Francesco
Published: July 2021

Background:
In the last decades, scientists have been studying the pathophysiology of ischemic heart disease (IHD) in women. In fact, as it is well known, in women IHD differs in term of pathogenesis, symptoms and prognosis. Different risk factors and mechanisms of disease may be at work in women. Genetic polymorphisms (SNP) for coronary ion channels may be involved in IHD susceptibility. In particular, the SNP rs5215 for Kir6.2 subunit of ATP-dependent potassium (KATP) channels has been proposed as a protective factor in IHD susceptibility, mostly in women.

Aim and methods:
To confirm the preliminary encouraging results on the protective role SNP rs5215_GG in IHD susceptibility for women, we enrolled 460 consecutive patients (144 women) with an indication to undergo coronary angiography for suspected ischemic heart disease, performing intracoronary functional tests in patients showing anatomically normal arteries to evaluate coronary microvascular function. We analyzed SNPs relative to the Kir6.2 subunit of KATP channels.

Results:
Among 460 patients, 330 presented with CAD (72 women), 68 with microvascular dysfunction (39 women) and 62 with anatomically and functionally normal coronary arteries (33 women). The SNP rs5215_GG was found to be more frequent in women compared to men (21/144 -14.6%, vs. 36/316 -11.3%; p=0.36). In particular, rs5215_GG was more frequent in ladies with anatomically and functionally normal coronary arteries compared with women presenting CAD (9/33 -27.2% vs. 7/72 -9.7%; p=0.037), whereas there was no difference between men in normal and CAD groups.

Discussion and conclusion:
Our data validate the hypothesis that rs5215_GG could reduce susceptibility to IHD in women, since it is more frequent in ladies presenting anatomically and functionally normal coronary arteries. The results suggest that KATP channels with rs5215_GG could be protective against IHD. Our data endorse the prospect of associations between SNP encoding coronary ion channels and IHD, validating the idea that ion channels play in coronary homeostasis and that their polymorphisms act in IHD genesis.
Abstract 18475: Is There Any End in Sight to This Debate on the Optimal Duration of Dual Antiplatelet Therapy After Drug-eluting Coronary Stent Implantation?
Authors: Sheyin Olusegun , Perez Xavier , Pierre-Louis Bredy , Kurian Damian
Published: July 2021

Introduction:
There is no end in sight to the ongoing debate on the optimal duration of dual antiplatelet therapy (DAPT) following drug-eluting coronary stent (DES) implantation.

Hypothesis:
Short-term DAPT is less effective than long-term DAPT in preventing adverse cardiovascular and cerebrovascular outcomes following DES.

Methods:
MEDLINE, EMBASE, Scopus and CENTRAL were searched for eligible randomized controlled trials (RCTs) that compared short-term (≤ 6 months) DAPT with long-term (≥ 12 months) DAPT following DES implantation. The primary end point was a composite of all cause death, myocardial infarction, target vessel revascularization, stroke or major bleeding. The secondary outcome were the individual components of the primary outcome, cardiovascular death, stent thrombosis and any bleeding episode.

Results:
A total of 15,378 patients from 7 RCTs were studied. There was no statistically significant difference between the short-term and long-term DAPT groups with respect to the occurrence of the primary outcome {Risk ratio (RR) 1.017 (0.872-1.186), I2 = 0%}, all cause death {RR 0.896 (0.708-1.134)}, cardiovascular death {RR 0.924 (0.668-1.279)}, myocardial infarction {RR 1.139 (0.887-1.461)}, target vessel revascularization {RR 1.174 (0.916-1.505)}, stent thrombosis {RR 1.264 (0.786-2.032)} and stroke {RR 0.876 (0.685-1.611)}. However there was a statistically significant lower risk of major bleeding in the short-term DAPT group {RR 0.57 (0.36-0.90), p 0.02}. There was no statistically significant difference in the sub-group analysis of patients with diabetes and patients presenting with acute coronary syndrome, {RR 1.029 (0.745-1.421)} and {RR 1.062 (0.785-1.438)}, respectively.

Conclusion:
There was no difference in efficacy outcomes between short-term and long-term DAPT following DES, even among high-risk patients. Longer duration of DAPT was found to be associated with increased risk of major bleeding. These results are contrary to findings from the recently published DAPT trial. However, even though the DAPT trial reported a significant decrease in the incidence of stent thrombosis and major adverse cardiac and cerebrovascular events in the long-term DAPT group, there was a paradoxical increase in mortality.
Abstract 18492: Phase Analysis Detects Human Atrial Fibrillation Sources While Classical Activation Mapping May Not: Reconciling Classical and Computational Mapping
Authors: Zaman Junaid A , Lalani Gautam G , Baykaner Tina , Park Shirley , Krummen David E , Wang Paul J , Narayan Sanjiv M
Published: July 2021

Introduction:
The mechanisms maintaining human persistent AF are elusive. It is striking how most optical mapping studies in animal and recently human AF show rotors and focal sources, while most classical activation mapping studies of electrograms do not. We tested the hypothesis that sites in human persistent AF showing rotors by phase analysis may, due to precession (‘wobble’) and fibrillatory collision, rarely reveal sources in activation maps.

Methods:
We studied 25 patients with persistent AF (LA 47 mm, CHADS2=1.9), in whom phase-mapping of electrograms from 64 pole baskets revealed rotors/focal sources where ablation terminated AF. Electrograms (fig A) were annotated (Matlab) using minimum dV/dt (unipoles, fig B) and peak amplitude criteria (bipoles) to create contours (isochrones), that were classified into a) complete, b) partial or c) unresolvable sources.

Results:
In each case, ablation at phase-identified rotors/sources (4.0±5.7 mins) terminated persistent AF to sinus rhythm (fig C, 64%) or atrial tachycardia. Notably, isochrones detected sources in only 5/25 (20%) of cases (fig D), more easily in unipolar than bipolar signals. Isochrones revealed partial sources in 11 (44%) and were unresolvable in 9 (36%). Source detection in classical maps was obscured by low signal: noise, varying sequence (rotor precession), or electrode noise that phase analysis resolved by analyzing neighboring sites (fig E). The figure summarizes these steps for a case with perfect agreement between activation and phase maps.

Conclusions:
Rotors and focal sources for human persistent AF detected by phase analysis were mostly undetected in activation maps, due to rotor precession and fibrillatory conduction. These data may inform approaches to revise classical criteria to better map AF.
Abstract 18524: Heart Rate Variability and Cardiovascular Fitness are Lower in Non-hispanic Black versus Non-hispanic White Adolescents With Type 1 Diabetes
Authors: Faulkner Melissa S , Quinn Lauretta , Fritschi Cynthia
Published: July 2021

Type 1 diabetes mellitus (T1D) is growing worldwide with the incidence peaking at puberty. Current population projections indicate that the numbers will nearly triple by 2050 with the prevalence primarily among minority racial/ethnic groups. Future diabetes-related morbidity, mortality and health care expenditures associated with poor cardiovascular (CV) outcomes are of paramount concern. In adolescents with T1D, heart rate variability (HRV) is noted to be lower when compared with healthy control subjects. Current research also supports a level of physical activity for adolescents with T1D that does not meet American Heart Association guidelines of 60 minutes of moderate-to-vigorous intensity per day, leading to decreased levels of physical fitness and elevated HbA1c. T1D Exchange (a large national epidemiological study) found that only 14% of Non-Hispanic Black (NHB) versus 34% Non-Hispanic White (NHW) youth met the American Diabetes Association HbA1c targets of < 7.5%, potentially increasing the odds of poorer outcomes in NHB youth.The hypotheses were that HRV and CV fitness would be lower in NHB versus NHW adolescents with T1D and that those with poorer glycemic control would have lower HRV and CV fitness.

Methods:
A sample of 96 adolescents with T1D (n = 67 NHW; n = 29 NHB) participated. Using 24-hour holter recordings, both spectral and time domain measures of HRV were obtained. Cardiovascular fitness (V02peak) using a graded exercise test was completed. HbA1c was obtained using the Siemens/Bayer DCA 2000. Findings: There were no significant differences in age (15.4 ± 1.9 vs. 15.0 ± 1.9 years) or duration of diabetes (6.6 ± 3.8 vs. 5.3 ± 3.4 years). Resting diastolic BP, recent and average HbA1c (values averaged over 1 year) were significantly higher (p < 0.05) and measures of HRV and fitness were significantly lower in NHB versus NHW adolescents (p < 0.001). While average HbA1c was associated with lower CV fitness in both NHB and NHW groups (r = -.44 vs. -.25, p < 0.05, respectively), lower measures of HRV were associated with poor glycemic control (HbA1c) only in NHBs (r = -.37 to -.43, p < 0.05). Conclusions: Findings support the importance of early identification of CV health disparities in adolescents with T1D, particularly variation experienced in NHB youth.
Abstract 18554: Patient, Cardiac Arrest and Hospital Characteristics That Predict Receipt of Coronary Angiography in Out-of-Hospital Cardiac Arrest Patients
Authors: Hanuschak Tasha , Brooks Steven , Morrison Laurie , Peng Paul , Zhan Cathy
Published: July 2021

Introduction:
Previous studies have suggested an association between coronary angiography and improved outcomes amongst post cardiac arrest patients. Our objective was to measure the association between patient and hospital-level characteristics and receipt of coronary angiography to generate hypotheses to inform a definitive trial.

Methods:
This was a population-based retrospective cohort study of data from 28 hospitals in Southern Ontario between March 1, 2010 and December 31, 2014. We included consecutive adult patients with atraumatic, OHCA, who achieved return of spontaneous circulation, and were alive 6 hours after hospital arrival. Multi-level logistic regression was used to measure the relationship between patient and hospital-level covariates and receipt of coronary angiography, adjusted for clustering and potential confounders.

Results:
During the period of study, 2678 consecutive patients met the inclusion criteria; mean age 66(±16), 68.3% male, 45.9% shockable initial rhythm, 84.2% comatose at hospital admission. Overall, 32.4% received coronary angiography and 21.8% received percutaneous coronary intervention (PCI). Coronary angiography use varied from 12.7% to 63.6% across the sites. Factors significantly associated with receiving coronary angiography included ST-elevation (OR=23.31, CI95 17.64-30.80), being comatose at hospital arrival (OR=0.15, CI95 0.10-0.23), shockable initial cardiac rhythm (OR=4.87, CI95 3.70-6.41), bystander AED use (OR=2.05, CI95 1.21-3.47), EMS-witnessed arrest (OR=1.80, CI95 1.16-2.78), initiation of therapeutic hypothermia (OR=1.96, CI95 1.38-2.79), initial admission to a PCI centre (OR=3.20, CI95 1.78-5.76), male sex (OR=1.43, CI95 1.07-1.90) and age (OR=0.98, CI95 0.97-0.99).

Conclusions:
There is significant variability in receipt of coronary angiography after cardiac arrest. We identified several patient and hospital-level factors that contribute to this variability. Future work should determine which post arrest patients will benefit most from urgent angiography and develop and evaluate knowledge translation strategies to ensure consistent delivery of best practices.
Abstract 18563: The Role of a Change in ECG Voltage on the Diagnosis and Prognosis in Cardiac Amyloidosis
Authors: Bagh Imad , Sperry Brett , Vranian Michael , Hanna Mazen
Published: July 2021

Background:
Low voltage on ECG may be caused by various medical conditions. In cardiac amyloidosis, low voltage in the limb leads is found in approximately 50% with AL and only 20-25% of ATTR, whether senile or familial. Despite not meeting low voltage criteria on ECG, a reduction of voltage over time may signify amyloid cardiomyopathy.

Methods:
The electrocardiograms of consecutive patients at the time of a diagnosis of cardiac amyloidosis at our institution were analyzed. Patients with ventricular paced rhythms were excluded. An additional ECG at least one year prior to the diagnosis was also analyzed. The sum of voltage in all limb leads and the Sokolow voltage (S wave in V1 plus R wave in V5 or V6) index were calculated. Low limb voltage was defined as ≤ 5 mm in all limb leads and low precordial voltage as ≤ 10 mm in all precordial leads. A Cox proportional hazards model was used to assess the correlation between decreasing ECG voltage and 3 year mortality.

Results:
A total of 338 patients (192 AL, 146 ATTR, age 68.7 +/- 12.1 years, obese 57%, HTN 54%) were identified. At the time of diagnosis, 167 patients (49.4%) met either low limb or low precordial voltage criteria. The limb lead voltage decreased in 63 of 73 patients (86.3%) and the Sokolow voltage decreased in 62 of 73 patients (84.9%). The mean overall decrease in limb lead voltage was 10.6 +/- 12.6 mm overall or 3.3 +/- 4.6 mm per year. The Sokolow voltage decreased 6.5 +/- 7.1 mm overall or 1.8 +/- 2.3 mm per year. On univariable analysis, the annualized decrease in Sokolow voltage showed a non-significant trend towards an increase in mortality.

Conclusion:
A decrease in voltage on serial ECG’s is more prevalent than low voltage in cardiac amyloidosis. There is a trend towards increased mortality in patients who have a greater decrease in voltage over time. The evaluation of serial ECG’s for changes in voltage is important to recognize in the diagnosis of cardiac amyloidosis and may have prognostic value.