bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11008: Hypoglycemia in Stemi is Associated with Higher Mortality and Morbidity, Irrespective of the Presence of Diabetes
Authors: Humos Basel , DARGHAM SOHA , Al suwaidi Jassim , Jneid Hani , Abi Khalil Charbel
Published: March 2022

Introduction:
Hyperglycemia in patients admitted for STEMI is associated with a worse outcome

Hypothesis:
We hypothesized that hypoglycemia in patients hospitalized for STEMI is also associated with a higher morbidity and mortality.

Methods:
We used data from the National Inpatient Sample (2005-2017) to identify adult patients admitted with STEMI as the primary diagnosis. Secondary diagnosis was hypoglycemia. We compared cardiovascular and socio-economic outcomes between STEMI patients with and without hypoglycemia and assessed temporal trends.

Results:
Hypoglycemia tends to complicate 0.117% of all cases hospitalized for STEMI. The mean age of STEMI patients hospitalized with hypoglycemia has been slightly trending down, from 67.40 ± 15 in 2005 to 63.86 ± 12 in 2017 (p=0.046). Mortality was stable with time, but the prevalence of ventricular tachycardia (VTach) and ventricular fibrillation (Vfib) decreased, total charges and length of stay (LOS) increased. Compared to non-hypoglycemic patients, those with developed hypoglycemia were older, more also likely to be males (64.4%) and whites (72.1%), only 6.7% had a history of diabetes as compared to 28.5% in STEMI patients (p=0.001). Cardiovascular events were more likely to occur in the presence of hypoglycemia: mortality risk increased by almost 4-fold (4.490 [4.174 - 5.848]. There was also a higher risk of cardiogenic shock (OR= 1.718 [21.387 - 2.127], VFib (OR=1.799 [1.406 - 2.301]), AF (OR=1.28 [1.025 - 1.607]), acute renal failure (OR= 2.355 [1.902 - 2.917] but not stroke (all ORs were adjusted, including on the presence of diabetes). Patients who developed hypoglycemia were less likely to have PCI (OR= 0.488 [0.417 - 0.571] but more likely to have CABG (OR= 2.259 [1.814 - 2.814]. They had a longer in-hospital stay and cost more than non-hypoglycemia patients. Sensitivity analysis though propensity-score matching confirmed our findings.

Conclusions:
Hypoglycemia was found to complicate 0.117% of all patients hospitalized with STEMI. Patients with hypoglycemia were found to have higher odds of mortality and cardiovascular complications during their hospital stay compared to patients without hypoglycemia, irrespective of the presence of diabetes at baseline.
Abstract 11010: Aryl Hydrocarbon Receptor Plays an Essential Role in the Pathogenesis of Pulmonary Arterial Hypertension
Authors: Okazawa Makoto , Masaki Takeshi , Asano Ryotaro , Inagaki Tadakatsu , Ishibashi Tomohiko , Yamagishi Akiko , Ishibashi-Ueda Hatsue , Ogo Takeshi , Nakaoka Yoshikazu
Published: March 2022

Introduction:
Pulmonary arterial hypertension (PAH) is a devastating disease characterized by arteriopathy in the small to medium-sized distal pulmonary arteries, often accompanied by infiltration of inflammatory cells. Aryl hydrocarbon receptor (AHR), a nuclear receptor/transcription factor, detoxifies xenobiotics and regulates the differentiation and function of various immune cells. However, the role of AHR in the pathogenesis of PAH is largely unknown.

Hypothesis:
We hypothesized that AHR has a role in PAH pathogenesis both in human and animal models.

Methods:
Wild type (WT) and
Ahr
-knockout (
Ahr
-/-
) rats were either treated with AHR agonists or VEGFR2 inhibitors or fed a diet containing a Chinese herbal drug Qing-Dai, which may cause drug-induced PAH, in combination with hypoxia, and then subjected to hemodynamic analysis. Histological characteristics were analyzed in the lungs of these rats and patients with idiopathic PAH. RNA-seq and qRT-PCR were performed on specimens from SU5416/Hypoxia (SuHx) rats, including lungs and the peripheral blood mononuclear cells (PBMCs), and PBMCs of PAH patients. AHR agonistic activity in serum was judged by luciferase reporter assay.

Results:
WT rats treated with the potent endogenous AHR agonist (6-formylindolo[3,2-b]carbazole) in combination with hypoxia, developed severe pulmonary hypertension (PH) with plexiform-like lesions, whereas WT rats treated with the potent VEGFR2 inhibitors (KI8751 and TAK-593) did not.
Ahr
-/-
rats did not develop PH in the SuHx rats. A diet containing Qing-Dai in combination with hypoxia led to development of PH in
Ahr
+/+
rats, but not in
Ahr
-/-
rats. Several inflammatory signaling pathways were up-regulated in endothelial cells and PBMCs, which led to infiltration of CD4
+
IL-21
+
T cells and MRC1
+
macrophages into vascular lesions in an AHR-dependent manner. AHR agonistic activity in serum was significantly higher in PAH patients than in healthy volunteers and was associated with poor prognosis of PAH. The expression of several AHR-related genes were changed in PBMCs of PAH patients.

Conclusions:
AHR plays crucial roles in the development and progression of PAH, indicating that this receptor is a potential target for both diagnosis and treatment of PAH.
Abstract 11012: Cognitive Dysfunction Among Patients Referred for Transcatheter Aortic Valve Implantation: Results of the Montreal Cognitive Assessment and Clinical Impact at 6 Months
Authors: Monnin Charles , Besutti Matthieu , Ecarnot Fiona , Guillon Benoit , Chatot Marion , Chopard Romain , Yahia Mohamed Chouaib , Meneveau Nicolas , Schiele Francois
Published: March 2022

Introduction:
Detection of Cognitive Dysfunction (CD) is not routinely performed among patients undergoing Transcatheter Aortic Valve Implantation (TAVI).

Hypothesis:
We sought to determine whether CD has an impact on the clinical course of these patients, during hospitalization at the time of TAVI and up to 6 months afterwards.

Methods:
The MoCA was performed before TAVI by an experienced operator in an unselected population of patients referred for TAVI. CD was defined according to the MoCA score: No CD if score ≥26, mild CD if score 18-25, moderate if 10-17 and severe if <10. Multivariate Cox logistic regression analysis was used to determine the impact of CD on procedural success of TAVI, length of stay, 6 month survival, re-admission, and change in clinical status (changes in NYHA class and/or functional status).

Results:
MoCA was performed in 83 consecutive patients. TAVI was performed using femoral access and local anesthesia in all patients. There were no procedural deaths, and 2 deaths at 6 months. The median age was 85 years, and median Euroscore I was 11.62. The median MOCA score was 22, CD was excluded in 17(20%), mild in 50 (60%), moderate in 15 (18%) and severe in one patient. No difference was observed in rate of procedural success, 6 month mortality, re-admission, degree of dyspnea by NYHA between the different cognitive groups. Length of stay after the TAVI procedure was lower in patients without CD, compared to those with CD at any level: 3±1 days versus 4.3±1 days, p=0.045, and p=0.02 by multivariate analysis (figure).

Conclusions:
Among patients referred for TAVI, mild or moderate CD was observed in 80% of patients. Patients without CD had a shorter length of stay at the time of TAVI, but CD was not associated with worse prognosis or clinical status at 6 months.
Abstract 11016: Long-Term Outcomes of Bovine versus Porcine Mitral Valve Replacement - A Multi-Center Analysis
Authors: Robich Michael P , Westbrook Benjamin M , DiScipio Anthony , Ramkumar Niveditta , Hirashima Fuyuki , Kramer Robert S , Quinn Reed D , Ross Cathy S , Iribarne Alexander ,   The Northern New England Cardiovascular Disease Study Group
Published: March 2022

Introduction:
Recent national guidelines recommending mitral valve replacement (MVR) for severe secondary mitral regurgitation have resulted in increased utilization of mitral bioprostheses. We examined long-term survival and risk of re-operation between patients having bovine vs porcine MVR.

Methods:
A retrospective analysis of MVR or MVR+CABG from 2001 - 2017 among seven hospitals reporting to a prospectively maintained clinical registry was conducted. The analytic cohort included 1,308 patients undergoing MVR (811 bovine and 497 porcine). Baseline comorbidities were balanced using 1:1 propensity score matching with 432 patients in each group. . The primary end point was all-cause mortality. Secondary end points included in-hospital morbidity, 30-day mortality, length of stay, and risk of reoperation.

Results:
In the analytic cohort, patients receiving porcine valves were more likely to have diabetes (19% bovine vs. 29% porcine; P<.001), COPD (21% bovine vs. 27% porcine; P=.01), dialysis or creatinine >2 mg/dL (4% bovine vs. 7% porcine; P=.03) and coronary artery disease (65% bovine vs. 76% porcine; P<.001). In the overall cohort there was no difference in long-term survival (porcine HR 1.17 [95% CI 1.00-1.37; P=0.050]) or reoperation (porcine HR 0.56 [95% CI 0.23-1.32; P=0.19).

In the propensity-matched cohort, the bovine valve patients were less likely to return to the OR for bleeding (6% vs. 9.3%; absolute standardized difference 0.12), but were more likely to have a stroke (3.7% vs. 1.9%; absolute standardized difference 0.11). There was no difference in in-hospital and 30-day mortality. After 1:1 propensity score matching, there was no difference in long-term survival (porcine HR 0.97 [95% CI 0.81-1.17; P=0.76]) or risk of reoperation (porcine HR 0.54 [95% CI 0.20-1.47; P=0.23).

Conclusions:
In this multicenter analysis of patients undergoing bioprosthetic MVR there was no difference in long-term survival, and risk of reoperation.
Abstract 11018: Prognosis Difference of Disproportional Mr According to Disease Etiology
Authors: Bak Minjung , KIM Jihoon , Park Sung-ji
Published: March 2022

Introduction:
After concept of disproportional MR (mitral regurgitation) is raised, investigators focused on whether disproportional MR could predict prognosis of secondary MR. But subgroup analysis of secondary MR according to etiology is limited until now.

Hypothesis:
We assessed the hypothesis that prognosis of disproportional MR is different according to etiology.

Methods:
We collected total 395 patients with severe secondary MR with reduced ejection fraction from January 2000 to October 2020 in one medical center, in South Korea. Only patients with DCMP (dilated cardiomyopathy) or ICMP (ischemic cardiomyopathy) were included. Criteria of disproportional MR was over 0.17 of RV (regurgitant volume)/EDV(end diastolic volume) in this study. We analyzed 1) the prognosis of disproportional MR according to etiologies and compared 2) predictive performance for mortality of disproportional MR with other MR measurements, RV and EROA (effective regurgitant orifice area), in each group.

Results:
In analysis based on etiology, disproportional group showed significantly higher all death risk (HR 10.08, 95% CI [1.237 - 82.07], p value = 0.031) in only DCMP group. There was no meaningful difference of mortality in ICMP group according to disproportionality (HR 1.265, 95% CI [0.556 - 2.882], p value = 0.575) (figure 1). When compare predictive performance of MR measurements for mortality, RV/EDV has highest value of C index than other methods in DCMP group and not in ICMP (figure 2).

Conclusions:
In conclusion, prognostic implication of disproportional MR was different according to disease etiology.
Abstract 11021: The Relationship Between TAPSE and HR During Exercise in Heart Failure of Any LVEF: A CPET Imaging Study
Authors: Guazzi Marco , Sugimoto Tadafumi , Generati Greta , Losito Maurizio , Bandera Francesco , alfonzetti eleonora
Published: March 2022

Introduction:
The relationship between TAPSE vs heart rate (HR) during physical exercise may well represent the force-frequency relationship of the right ventricular (RV) whose impact on exercise performance and hemodynamics may translate in interesting insight.

Aims:
to phenotype heart failure (HF) patients based on the response in TAPSE vs HR.

Methods:
A total of 164 patients with HF and 32 healthy subjects with normal RV to pulmonary circulation (Pc) coupling, left atrium (LA) size and reservoir function (LA volume index <34 ml/m
2
and LA-strain >23%) underwent cardiopulmonary exercise testing combined with exercise Echo. TAPSE/HR slope was assessed using (peak TAPSE - rest TAPSE)/(peak HR - rest HR) ratio. According to the 95% confidence interval of TAPSE/HR slope (0.03 - 0.13, median 0.06) in healthy subjects, HF patients were divided into 2 groups: responders (TAPSE/HR ≥0.03, n=108) and non-responders (<0.03, n=56) (figure).

Results:
There was no significant difference in age (65±12 vs 68±13 years), sex (70 vs 63% male), peak VO
2
(14±4 vs 13±4 ml/kg/min), and VE/VCO
2
slope (32±8 vs 33±10) between responder and non-responder group. However, responders exhibited a higher LA-strain at rest (21±12 vs 17±10%) and exercise (21±12 vs 17±10%), and a lower LA volume index (43±21 vs 52±27 ml/m
2
) and mitral E/e’ (18±10 vs 22±11) than non-responders, respectively (P<0.05). Non-responders exhibited a lower peak TPASE/pulmonary artery systolic pressure (PASP) ratio (0.34±0.18 vs 0.45±0.16, P<0.001) than responders, although similar PASP (36±12 vs 34±15 mmHg) and TAPSE (19±5 vs 18±4 mm) were observed at rest in the 2 groups. Beta-blocker therapy was not a determinant of TAPSE/HR relationship.

Conclusions:
The RV force-frequency relationship may be impaired in HF. Especially in non-responders the lack of adaptive RV performance combines with worse RV to Pc coupling and atrial dysfunction. These data may offer additional insights in the concepts of exercise limitation in HF.
Abstract 11023: Assessment of Cognitive Dysfunction Using the Montreal Cognitive Assessment Test: Rate, Severity and Comparison with the Clock Test Alone in a Population of Patients Referred for TAVI
Authors: Monnin Charles , Besutti Matthieu , Ecarnot Fiona , Guillon Benoit , Chatot Marion , Chopard Romain , Yahia Mohamed Chouaib , Meneveau Nicolas , Schiele Francois
Published: March 2022

Introduction:
Although not recommended in routine practice, the detection and quantification of Cognitive Dysfunction (CD) in older patients might have an impact on clinical decisions.

Hypothesis:
We assessed the rate and severity of CD in an unselected population of patients referred for Transcatheter Aortic Valve Implantation (TAVI) using the Montreal Cognitive Assessment (MoCA) and using the Clock Drawing Test (ClockT) alone.

Methods:
The MoCA was performed before TAVI by an experienced operator. The ClockT was scored out of 10 points according to the Rouleau rating scale. CD was defined according to the MoCA score: No CD if score ≥26, mild CD if score 18-25, moderate if 10-17 and severe if <10. Inter-observer reliability of scoring on the ClockT was estimated with the Bland-Altman method. Agreement between MoCA scores and the ClockT for ruling out and for detecting CD were measured with the Kappa coefficient.

Results:
MoCA was performed in 83 consecutive patients referred for TAVI, median age 85 years. The mean time required for assessment was 11±2 min for the MoCA and 3±2 min for the ClockT. The mean MoCA score was 21± 4.5: CD was excluded in 17(20%) pts, mild CD was found in 50(60%), moderate in 15(18%) and severe in one (1%). The median ClockT score was 8 (interquartile 6; 9), with excellent inter-observer concordance (Kappa= 0.84). Overall, 51% of the variance of the MoCA score was explained by the ClockT alone according to multiple regression. A ClockT <7 detected a group with significantly lower MoCA score, compared to pts with higher ClockT scores (figure).

Conclusions:
Among patients referred for TAVI, CD can be excluded using the MoCA test in 20%, while moderate or severe CD is observed in 18%. The ClockT alone is faster to implement, reliable to interpret and enabled detection of patients with moderate CD when Rouleau scoring was <7.
Abstract 11025: Markers of Heart Rate Variability Represent Strong and Independent Predictors of All-Cause Death in Heart Failure - Results from the Myovasc Study
Authors: Zeid Silav , Buch Gregor , Velmeden David , Soehne Jakob , Schulz Andreas , Schuch Alexander , Troebs Sven-Oliver , Heidorn Marc , Mueller Felix , Coboeken Katrin , Lackner Karl J , Gori Tommaso , Muenzel Thomas , Prochaska Juergen H , Wild Philipp
Published: March 2022

Introduction:
Although different measures of heart rate variability (HRV) have been proposed as markers of autonomic dysfunction (AD) in heart failure (HF), evidence on their clinical relevance is limited.

Methods:
Data from the MyoVasc study (NCT04064450; N=3,289), a prospective cohort study on chronic HF, were analyzed. Study participants received a highly standardized, 5-hour examination including 24-hour Holter ECG recording. RR intervals were extracted to evaluate HRV markers from time and frequency domain analyses, and non-linear markers derived via phase space reconstruction, phase-rectified signal averaging, and entropy analyses. HRV markers of interest were selected using a systematic literature screen, and a random survival forest model predicting cardiac death. Reference values were determined in a healthy subsample. To evaluate clinical relevance, HRV markers were investigated in multivariable Cox regression analyses for their relationship to all-cause death considering potential confounders and mediators.

Results:
Holter ECG recordings were available for analysis in 1,001 study participants (mean age 64.5±10.5 years; female sex: 35.4%). While the top 10 most frequently reported HRV markers in literature screen were from the time and frequency domains, the data-driven approach revealed predominantly non-linear HRV measures. Values outside reference ranges for SDANN, rMSSD, frequency bands (i.e., ULF, VLF, LF, total power, ULF
MED wavelet
), acceleration capacity (AC), deceleration capacity (DC), and time lag, were strong predictors of all-cause death in Cox regression analysis (median follow-up time: 6.1 [IQR 4.7/7.1] years) adjusted for age, sex, clinical profile and medication. In linear Cox regression analyses of the total sample, LF/HF (hazard ratio per SD (HR
SD
) 0.78 [95% confidence interval (CI) 0.62, 0.98], p=0.034), time lag (HR
SD
1.23 [95%CI 1.05, 1.44], p=0.0095), AC (HR
SD
: 1.57 [95%CI 1.24, 1.99], p=0.0002), and DC (HR
SD
0.67 [95%CI 0.53, 0.85], p=0.0012) were strong predictors for all-cause mortality independent of age, sex, clinical profile and medication.

Conclusions:
HRV markers reflecting AD are strong predictors of all-cause death in HF, suggesting clinical relevance and potential for intervention.
Abstract 11027: Short-and Long-Term Prognostic Value of Multiple Cardiac Biomarker Measurement in Patients Undergoing Elective Coronary Artery Bypass Graft Surgery
Authors: Thielmann Matthias , Cymorek Sebastian , WENDT Daniel , Oßwald Anja K , Ristau Wolfgang , Shehada Sharaf-Eldin , Schmack Bastian , Weymann Alexander , Kamler Markus , Kleinbongard Petra , Ruhparwar Arjang
Published: March 2022

Introduction:
Coronary artery bypass grafting (CABG) is associated with defined degree of myocardial injury reflected by perioperative rise of cardiac biomarkers. The present study aimed to evaluate multiple cardiac biomarkers and their association with short- and long-term outcome following CABG.

Methods:
In this prospective study, a total of 1030 patients with coronary artery disease (CAD) were enrolled between 07/2008 and 11/2018, undergoing elective, isolated, on-pump CABG. Perioperative cardiac troponin I and T (cTnI, cTnT) or ultra-sensitive (us-) cTnI were measured over 72hrs after surgery. Mean Follow-up was 5.5±2.7years with 100% completeness. Primary study endpoint was in-hospital mortality (IHM) and major adverese cardiac and cerebrovascular event (MACCE) rate at 30 days, as well as mortality in the long-term, defined as death from any cause.

Results:
Patients were 67.6±9.4years of age, 81.8% male, presenting 3-vessel CAD in 82% and/or left-main disease in 38%. Log EuroSCORE-I was 4.3±3.7%. Perioperative serum concentrations of cTnI (
P
=0.05), us-cTnI (
P
=0.02), but not cTnT (
P
=0.79) differed significantly between survivors and non-survivors and cTnI (
P
<0.001) and us-cTnI (
P
<0.001) between patients with and without MACCE within the first 30 days after surgery (2-way ANOVA). Kaplan-Meier analysis for time to event variables, clearly showed poor long-term prognosis in patients with high perioperative cTnI, having a 1-, 5- and 10-years survival of 93.5%, 81.3% and 54.5%, as compared to patients with medium or low cTnI (
P
=0.03). Multivariable logistic regression analyses revealed cTnI, but not cTnT and us-cTnI, as a strong and independent predictor for IHM (
P
<0.001) and MACCE (
P
=0.02). In a receiver operating curve (ROC) analysis, cTnI of 9.2ng/mL with an area under curve (AUC) of 0.72 (
P
=0.02) was identified as an optimal cut-off value for predicting IHM and a cut-off value of 6.38ng/mL with an AUC of 0.85 (
P
<0.001) for the prediction of MACCE.

Conclusion:
Serial perioperative cTnI measurment and/or its ultra-sensitive isoform allows for identifying patients with worse clinical short- and long-term outcomes following CABG. CTnT however, failed to identify patients at risk and was inferior in predicting short- and long-term outcomes.
Abstract 11032: Compound A, a Ginger Extract, Significantly Suppresses Pressure Overload-Induced Systolic Dysfunction in Mice
Authors: Kawase Yuto , Shimizu Kana , Funamoto Masafumi , Sunagawa Yoichi , Katanasaka Yasufumi , Shimizu Satoshi , Miyazaki Yusuke , Hasegawa Koji , Morimoto Tatsuya
Published: March 2022

Introduction:
Cardiac remodeling induced by hypertrophic stresses such as hypertension is a compensatory mechanism associated with cardiomyocyte hypertrophy and cardiac fibrosis. As cardiac remodeling eventually leads to chronic heart failure (HF), there is an urgent need for compounds that can effectively suppress both cardiomyocyte hypertrophy and cardiac fibrosis. In this study, we used a natural compound library to screen for compounds that suppress these two mechanisms with cultured cardiomyocyte and cardiac fibroblasts, and identified compound A, a ginger extract, as a candidate for HF therapy. The purpose of this study is to investigate the effect of compound A on cardiomyocyte hypertrophy and cardiac fibrosis
in vitro
and on the development of HF
in vivo
.

Methods & Results:
First, primary cultured cardiomyocytes were treated with 1 μM of compound A and stimulated with phenylephrine (PE). The results of immunofluorestaining showed that the compound significantly suppressed a PE-induced increase in the surface area of the cells. Quantitative PCR analysis demonstrated that the compound significantly suppressed PE-induced increases in the mRNA levels of hypertrophic response genes such as ANF and BNP. Next, primary cultured cardiac fibroblasts were treated with 1 μM of compound A and then stimulated with transforming growth factor-beta (TGF-β). The results of measurement of L-proline incorporation showed that the compound significantly suppressed TGF-β-induced incorporation. Quantitative PCR and western blotting demonstrated that the compound significantly suppressed TGF-β-induced mRNA and protein levels of α-smooth muscle actin (α-SMA). Finally, C57BL/6J mice were subjected to transverse aortic constriction (TAC) surgery, and were then given a daily oral administration of 1 mg/kg of compound A for 8 weeks. Echocardiographic analysis showed that the compound prevented TAC-induced increases in posterior wall thickness and systolic dysfunction. The compound also suppressed a TAC-induced increase in HW/BW ratio.

Conclusions:
Compound A suppressed TAC-induced development of HF via the suppression of cardiomyocyte hypertrophy and cardiac fibrosis. These findings suggest that compound A may be an effective agent for HF therapy.
Abstract 11042: New-Onset Atrial Fibrillation After Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis
Authors: Ryan Tammy , Jinah Rehman , Grindal Alexander , Pandey Avinash , Vadakken Maria , Jaffer Iqbal , Healey Jeff S , Belley-cote Emilie P , McIntyre William
Published: March 2022

Background:
New-onset atrial fibrillation (NOAF) is a common complication after transcatheter aortic valve replacement (TAVR), though estimates of the precise incidence are variable. We sought to quantify the incidence of NOAF after TAVR, explore the associated outcomes and identify predictors for this complication.

Methods:
Using a broad strategy, we searched Medline, EMBASE and the Cochrane database from 2015-2020 for articles that reported any outcomes of TAVR. We extracted data for studies published prior to 2015 from a previous systematic review (22 studies in total). Reviewers performed screening and data extraction in duplicate. We pooled data using a random effects model with Mantel-Haenszel weighting.

Results:
We identified 183 studies with 296,986 total participants that reported NOAF from 2008 to 2020. The pooled incidence of NOAF after TAVR was 9.9% (95%CI 8.1-12%). NOAF after TAVR was associated with longer index hospitalization (MD 2.66 days, 95% CI 1.05-4.27), higher risk of stroke (RR 1.65, 95% CI 1.09-2.5) and 30-day mortality (RR 1.76, 95%CI 1.12-2.76). NOAF after TAVR was also associated with increased risk of major or life-threatening bleeding (RR 1.60, 95%CI 1.39-1.84) and new permanent pacemaker implantation (RR 1.12, 95%CI 1.05-1.18). Risk factors for the development of NOAF after TAVR included trans-apical access, pulmonary hypertension, chronic kidney disease, peripheral vascular disease, and severe mitral regurgitation.

Conclusions:
NOAF is common after TAVR and associated with a longer hospital stay, a higher risk of stroke, major bleeding, mortality and permanent pacemaker implantation. Whether this risk is modifiable requires further study.
Abstract 11048: Serotonin Transporter Deficiency Leads to a Specific Fibrotic Pattern in Valvular and Myocardial Tissue
Authors: Castillero Estibaliz , D'Angelo Alex , Kurade Mangesh , LEVY Robert , Ferrari Giovanni
Published: March 2022

Introduction:
Increased serotonin (5HT) levels can lead to heart valve disease. This mechanism is observed in patients with 5HT-secreting carcinoid tumors and after treatment with the diet drug Dexfenfluoramine, which acts as a 5HT receptor (HTR)-2B agonist and as an inhibitor of the 5HT transporter (SERT). SERT internalizes 5HT, limiting HTR signaling (Figure 1A). We showed that SERT reduction on human mitral valve (MV) contributes to the progression of MV regurgitation. We investigated the impact of SERT deficiency on cardiac substructures in a SERT-/- murine model.

Methods:
SERT-/- and wild type (WT) C57BL/6J mice (n≥8/group) were sacrificed at 16 weeks of age, after echocardiography (Fig. 1B). Cardiac substructures (left ventricle (LV) apex, MV leaflets, aortic valve (AV) leaflets and aortic-mitral (AM curtain) were isolated in three animals/group (Fig. 1E).

Results:
Ventricular dimensions were significantly larger in SERT-/- mice vs. WT at end-systole and end-diastole (Fig. 1C). Fractional shortening was significantly reduced in SERT-/- mice vs. WT. Pricosirius staining of collagen showed that SERT-/- mice had increased MV leaflet fibrosis, MV and AV sub-valvular fibrosis at leaflet attachment points (AM curtain, Fig. 1D), and epicardial fibrosis. PCR (Fig. 1F) showed significantly increased COL1A1 expression in the LV myocardium, MV, AV and AM curtain in SERT-/- mice vs. WT. Fibrosis marker alpha smooth muscle actin (αSMA) was significantly increased in the myocardium and AM curtain of SERT-/- mice, but not in the valve leaflets. HTR2B expression was significantly increased in the MV and AM curtain of SERT-/- mice.

Conclusions:
SERT-/- mice have decreased cardiac function, and cardiac fibrosis that is associated with HTR2B upregulation in the MV leaflets and valve leaflet attachment points. Our results support the hypothesis that decreased 5HT clearance by SERT downregulation may increase HTR2B signaling in the MV leading to remodeling and regurgitation.
Abstract 11050: Sex Differences in Culprit Plaque Characteristics in Acute Coronary Syndromes
Authors: Seegers Lena M , Araki Makoto , Nakajima Akihiro , Yonetsu Taishi , Soeda Tsunenari , kurihara osamu , Higuma Takumi , Kimura Shigeki , Minami Yoshiyasu , Ako Junya , Adriaenssens Tom , Nef Holger , Lee Hang , McNulty Iris , Sugiyama Tomoyo , Kakuta Tsunekazu , Jang Ik-kyung
Published: March 2022

Introduction:
Despite the significant decline in cardiovascular mortality in women over the past few decades, sex differences in the underlying mechanisms remain poorly understood. Previous postmortem studies have demonstrated differences between men and women in coronary plaque characteristics with a higher prevalence of plaque erosion in young women, but more plaque rupture (PR) in older women after menopause. However,
in vivo
data are limited.

Methods:
This study included 1368 patients with acute coronary syndrome undergoing pre-intervention optical coherence tomography (OCT) imaging from a multicenter international registry. The culprit plaque was categorized as plaque rupture, plaque erosion or calcified plaque, and stratified by age. Plaque microstructures at culprit lesion were also analyzed.

Results:
Sex differences were found in the underlying mechanisms of the culprit lesion: In women a significant ascending trend with age (P<0.001) was observed in PR and plaque vulnerability with lipid rich plaque (P<0.001) and thin cap fibroatheroma (TCFA) (P=0.005), whereas this trend was not obvious in men. In multivariate analysis, age was identified as an independent predictor for PR (odds ratio (OR) 1.039; 95% CI, 1.015-1.062,
P
<0.001) and for lipid rich plaque (OR 1.054; 95% CI 1.030-1.079, P<0.001) in women.

Conclusions:
An increasing trend in the prevalence of PR and plaque vulnerability with age was observed only in women but not in men.
Abstract 11052: The Association Between Left Ventricular Mass and Coronary Artery Calcium Score in Retired National Football League Players
Authors: Smith Genevieve E , Fernandez Camilo , Stewart Gregory W
Published: March 2022

Introduction:
Literature suggests that increased left ventricular mass (LVM) is a predictor of coronary heart disease and mortality in the general population, and that increased LVM is associated with higher CAC. However, the association between LVM and subclinical atherosclerosis as indicated by absolute CAC has not been widely explored in retired elite athletes, who may have had or still have increased LVM as a result of exercise adaptation. Thus, we sought to investigate this association in a cohort of retired National Football League (NFL) players.

Methods:
This cross-sectional study included 632 retired NFL players aged 40 and older (mean age 56.4 ± 9.7 yrs; 51.3% Black) that participated in NFL Player Care Foundation health screenings. Two-dimensional echocardiogram was used to determine LVM according to American Society of Echocardiology guidelines and indexed to height to obtain left ventricular mass index (LVMI, g/m
2.7
). LVH was considered as LVMI > 49.2 g/m
2.7
. Multi-variable logistic regression models were utilized to determine the association of LVM with the highest quintile of CAC (CAC = 264-6239) after adjusting for traditional cardiometabolic risk factors.

Results:
The mean LVM of study participants was 220.8 ± 56.6 g and the prevalence of LVH 16.9%. LVM was highest in the 2
nd
quintile of CAC, with LVM in the highest quintile of CAC significantly lower than that of the first and second quintiles and not significantly different from that of the 3
rd
or 4
th
quintiles. Multi-variable logistic regression models revealed that increasing LVM was associated with decreased odds for the highest quintile of CAC (odds ratio [OR]: 0.99, 95% confidence interval [CI] 0.99 - 1.00,
p
= 0.0486), with no such association for LVH (OR: 0.72, 95% CI 0.37-1.41,
p
= 0.3429).

Conclusion:
Odds for increased atherosclerotic cardiovascular disease risk, as indicated by the highest quintile of CAC, are decreased by augmented LVM within physiological range in this cohort of retired NFL players, possibly reflective of a potential protective effect of high lifetime exercise dose. These results suggest that there may be lingering or carryover effect of early life cardiovascular fitness, even in middle-aged retired athletes.
Abstract 11055: Length of Anticoagulation Treatment in Provoked VTE - Lessons from the Maqi
2
Collaborative
Authors: Joyce Elizabeth , Haymart Brian , Kong Xiaowen , Ali Mona , Kaatz Scott , Kline-rogers Eva M , Kozlowski Jay , Froehlich James B , Carrigan Mara , Barnes Geoffrey
Published: March 2022

Introduction:
Anticoagulation (AC) with warfarin or direct oral anticoagulants (DOAC) is the core of VTE treatment. Due to lower risk of VTE recurrence, American College of Chest Physicians (ACCP) recommends three months AC in patients with provoked VTE and without other indication for long-term AC. We aimed to assess how closely “real world” practice followed guideline recommendations.

Hypothesis:
We hypothesize most patients taking warfarin or DOAC for provoked VTE receive no more than three months AC. Patients who get prolonged AC are more likely to be taking DOAC than warfarin.

Methods:
We identified patients who initiated warfarin or DOAC from a six center AC clinic registry between 2008-20. Provoked VTE was defined as VTE after a transient risk factor: surgery, lower extremity cast/immobilization, childbirth, or OCPs. AC duration was categorized as <80, 80-120, or >120 days. Appropriate treatment window was defined as 80-120 days to adjust for variability in clinic scheduling. Median AC length for DOAC vs. warfarin was compared with a two-sample test. Prevalence of extended AC was compared using chi-square test. Variables increasing risk of extended AC were analyzed with logistic regression, adjusted for baseline demographic and clinical characteristics.

Results:
At six centers, we identified 488 patients with provoked VTE on warfarin and 302 on DOAC. Average AC length was 137 days for warfarin and 180 days for DOAC (p<0.0001). 266 (54.5%) patients on warfarin and 215 (71.2%) on DOAC got >120 days of AC (p<0.001). Variables increasing risk of >120 days AC include recurrent VTE (OR 2.11; CI 1.34,3.32), prior MI (OR 4.09; CI 1.37,12.2), and DOAC use (OR 2.34; CI 1.69, 3.23) (Figure 1).

Conclusions:
In this multi-center analysis, most patients receive AC longer than guideline-recommended. DOAC use, recurrent VTE, and prior MI are associated with prolonged AC. Understanding the relationship between prior MI and AC duration in provoked VTE warrants future investigation.
Abstract 11058: Pooled Analysis of Six Randomized Trials Comparing Device Closure of Patent Foramen Ovale After Stroke to Medical Treatment: Overall Effects and Patient Selection Using a Causal Classification System
Authors: Kent David M , Saver Jeffrey L , Kasner Scott E , Nelson Jason , Carroll John D , CHATELLIER Gilles , Derumeaux Geneviéve , Furlan Anthony J , Herrmann Howard C , Juni Peter , Kim Jong S , Koethe Benjamin , Lee Pil Hyung , Lefebvre Bénédicte , Mattle Heinrich P , Meier Bernhard , Reisman Mark , Smalling Richard W , Soendergaard Lars , Song Jae-kwan , Mas Jean-Louis , Thaler David E
Published: March 2022

Introduction:
Patent foramen ovale (PFO)-associated strokes account for ~10% of ischemic strokes in adults aged 18-60. Despite overall beneficial effects of device closure on stroke recurrence risk, the best treatment option for any individual patient is often unclear.

Methods:
We pooled individual participant-level data from all 6 RCTs comparing PFO closure with percutaneous devices plus medical therapy vs medical therapy alone. The primary outcome was recurrent ischemic stroke. We used Cox proportional hazards models to estimate adjusted HRs, with study-specific baseline hazards and a fixed treatment effect. Pre-specified primary subgroup analyses used the Risk of Paradoxical Embolism (RoPE) Score (a 10 point score with higher scores reflecting younger age and absence of vascular risk factors) and the PFO-Associated Stroke Causal Likelihood (PASCAL) algorithm, a classification system that combines the RoPE Score with presence/absence of high risk PFO features (either atrial septal aneurysm or large-sized shunt) to group patients into 3 causal relatedness categories: Unlikely (RoPE< 7 and no high risk PFO feature); Possible (either RoPE
>
7 or any high risk PFO feature); or Probable (both RoPE
>
7 and any high risk PFO feature). The protocol was registered at PROSPERO.

Results:
A total of 121 recurrent strokes occurred in 3740 patients over median follow up of 57 months (IQR 24-64). The annualized incidence of stroke was lower with device vs medical therapy: 0.47% (0.34-0.65) vs 1.09% (0.87-1.36); adjusted HR 0.41 (0.27-0.60), p < 0.001.

The main results were robust to alternative analytic approaches. The primary subgroup analyses (Figure) showed statistically significant and clinically important interaction effects.

Discussion:
PFO closure reduces recurrent ischemic stroke in a robust manner. However, patients with neither a RoPE Score
>
7 or a high risk PFO feature (i.e. PASCAL Unlikely) do not appear to benefit, even in the well-selected trial population.
Abstract 11064: Intentional Weight Loss as a Novel Treatment for Heart Failure with Preserved Ejection Fraction
Authors: Hundertmark Moritz J , Burrage Matthew , Miller Jack , Watson William , Peterzan Mark , Rayner Jennifer , Neubauer Stefan , Valkovic Ladislav , Lewis Andrew J , Rider Oliver J
Published: March 2022

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is frequent in obesity and both conditions are projected to increase in prevalence. We sought to investigate if weight loss is an effective treatment for patients with HFpEF and obesity.

Hypothesis:
Intentional weight loss improves symptoms, serum markers and imaging markers in patients with HFpEF and obesity.

Methods:
12 obese HFpEF patients (BMI 33.5±5 kg/m
2
; NYHA I-III) were assessed before and after a very low energy diet (VLED; 800 calories per day) for 10 weeks and compared to 10 weight-matched, obese controls (BMI 31.8±1.5 kg/m
2
). We evaluated cardiac function using cardiovascular magnetic resonance (CMR) imaging, diastolic function with echocardiography and cardiac energetics (PCr/ATP) using
31
P-spectroscopy. Serum samples were drawn to measure N-terminal pro-brain natriuretic peptide (NTpro-BNP).

Results:
After 10 weeks of VLED, there was a highly significant reduction in body weight (BMI -2.7kg/m
2
± 0.38, p<0.001) paralleled by a significant drop in NTpro-BNP (-239pg/mL ± 149, p<0.05) and heart failure symptoms (NYHA median pre II vs. I post). Echocardiography revealed a significantly lower left atrial volume (-29mL ± 28, p<0.05) and a trend towards improved diastolic function (lateral E/E’ -0.68 ± 0.5, p=0.08). CMR demonstrated a significantly lower LV mass (-9g ± 2.9, p<0.05) but no changes in PCr/ATP at rest (Δ0.015±0.1, p=ns) or during dobutamine stress (Δ0.087±0.06, p=ns). Except NTpro-BNP, all parameters returned to comparative levels of obese weight-matched patients without HFpEF.

Conclusions:
In obese HFpEF, intentional weight loss improves prognostic serum markers for HF, decreases symptom severity, reduces atrial size and LV mass, and improves diastolic function. These findings underscore the potential for weight loss as an effective treatment for HFpEF and the need for larger trials.
Abstract 11067: ABCB10 Overexpression Prevents Acute Doxorubicin-Induced Cardiac Dysfunction
Authors: Smuder Ashley J , Doerr Vivian , Nguyen Branden L
Published: March 2022

Introduction:
Doxorubicin (DOX) is a highly effective chemotherapy agent used to treat solid tumor cancers and hematological malignancies. However, DOX treatment can cause adverse cardiac events, which can negatively affect patient outcomes by limiting cancer treatment and reducing overall survival. DOX-induced cardiotoxicity occurs due to its off-target accumulation within cardiomyocytes following administration. Within the heart, DOX predominantly localizes within the mitochondria where it promotes cellular injury via the production of reactive oxygen species (ROS). Currently, there is no clinically approved therapy to prevent this debilitating condition. Therefore, work is needed to identify therapeutic countermeasures to prevent DOX cardiotoxicity. In this regard, ABCB10 is a mitochondria-localized ATP-binding cassette transporter that is hypothesized to play a role in the maintenance of mitochondrial redox balance and iron homeostasis.

Hypothesis:
We hypothesize that cardiac overexpression of ABCB10 would reduce DOX-induced oxidative damage and preserve cardiac function.

Methods:
Cause and effect were determined by overexpressing ABCB10 in the heart using an AAV9-MHCK7-ABCB10 construct. Acute effects of DOX (20 mg/kg i.p.) on the heart were assessed by echocardiography.

Results:
Our findings confirm that DOX treatment results in detriments to both cardiac and mitochondrial function 48-hours following administration. Importantly, cardiac overexpression of ABCB10 was sufficient to prevent the DOX-induced reduction in mitochondrial respiratory control ratio. In addition, both left ventricular fractional shortening percentage and myocardial performance index were preserved in ABCB10 overexpressing animals treated acutely with DOX.

Conclusions:
ABCB10 overexpression in the heart is an effective intervention to prevent cardiotoxicity and mitochondrial dysfunction acutely following DOX chemotherapy treatment.
Abstract 11069: Nutritional Risk Index is a Predictive Factor of Anthracycline-Induced Cancer Therapeutics-Related Cardiac Dysfunction
Authors: Yaegashi Daiki , Oikawa Masayoshi , Yokokawa Tetsuro , Misaka Tomofumi , KOBAYASHI ATSUSHI , Yoshihisa Akiomi , Nakazato Kazuhiko , Ishida Takafumi , Takeishi Yasuchika
Published: March 2022

Background:
It has been reported that nutritional risk index (NRI) is one of prognostic factors in cardiovascular diseases, but little is known about its relation to the onset of cancer therapeutics-related cardiac dysfunction (CTRCD).

Methods and Results:
Consecutive 202 cancer patients planed for anthracycline treatment were enrolled and followed up for 12 months in our hospital from February 2017 to June 2019. The patients were divided into 2 groups based on NRI value at 100 before chemotherapy (high NRI group, n=141, 110.5 [104.7-115.6]; low NRI group, n=61, 93.7 [89.6-97.6]). Baseline left ventricular end systolic volume index and left ventricular ejection fraction (LVEF) before chemotherapy were similar between two groups. After chemotherapy, the occurrence of CTRCD was higher in low NRI group than in high NRI group (14.8% vs. 3.5%, P=0.012). Furthermore, there was a correlation between the severity of NRI categories and the development of CTRCD. When we set the cut-off value of baseline NRI from ROC analysis at 100.8, sensitivity, specificity, and area under the curve to predict the occurrence of CTRCD were 71.4%, 70.7%, and 0.698, respectively. Multivariable logistic regression analysis revealed that baseline NRI value was an independent predictor of the development of CTRCD (odds ratio 0.935, 95% CI [0.881-0.992], P=0.026). The value of net reclassification index and integrated discrimination improvement for detecting CTRCD reached statistical significance when baseline NRI value was added to the regression model including known risk factors such as age, female gender, the presence of hypertension, chronic kidney disease, cumulative anthracycline dose, the usage of HER2 inhibitor, and radiation therapy; 0.872 (95% CI [0.421-1.323], P<0.001) for net reclassification index and 0.035 (95% CI [0.002-0.067], P=0.033) for integrated discrimination improvement.

Conclusion:
Baseline NRI is a novel parameter to predict anthracycline-induced CTRCD.
Abstract 11070: Antihypertensive Medication Challenges, Adherence, and Blood Pressure in African Americans with a History of Uncontrolled Hypertension
Authors: Cummings Doyle M , Adams Alyssa , Halladay Jacquie , Richman Erica , Cherrington Andrea , Anabtawi Muna , Ringel joanna , Soroka Orysya , Safford Monika M
Published: March 2022

Introduction:
African American adults with uncontrolled hypertension may have structural inequities in access to, intensity of, as well as greater challenges using antihypertensive medications, all of which may contribute to inadequate blood pressure (BP) control. Traditional self-reported measures of adherence suffer from social desirability bias and are not consistently correlated with BP control.

Hypothesis:
African Americans with higher systolic BP (SBP) experience more medication challenges (access, med taking) that are correlated with BP.

Methods:
Data at baseline are from a cluster randomized trial of patient-level coaching vs. practice level facilitation and the combination of the two interventions in 1596 adult African American patients (39% male; mean age 57 ± 12 yrs.) seen in rural primary care practices with a history of uncontrolled hypertension (average over the last year ≥ 140/90 mmHg). In bivariate and correlation analyses, we examined the cross-sectional association of self-reported medication adherence vs. self-reported medication challenges with SBP level at baseline. These relationships were further examined in a linear regression model with SBP as the outcome while controlling for age, gender, and annual income.

Results:
Patients were taking a mean of 2.4 antihypertensive medications. SBP level was significantly correlated with the number of antihypertensive medication challenges reported (p < 0.01). While those reporting lower medication adherence also reported significantly more medication challenges, mean SBP was not significantly different by self-reported medication adherence level. However, mean SBP was significantly higher in patients reporting 4 or more medication challenges (158 vs. 155mmHg, p=0.004). In linear regression analysis, age, income, and self-reported medication challenges (β = 0.3; .95% CI: 0.03 - 0.6; p = 0.028) were independently associated with SBP level while gender and self-reported medication adherence were not.

Conclusion:
African Americans with uncontrolled BP often require more intensive antihypertensive regimens. However, such regimens may be associated with more medication challenges that may adversely impact adherence and BP control.