bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2223: Carotid Intima Media Thickness Progression is Modest in Statin-Treated Familial Hypercholesterolemia Patients - Results from a Patient Level Meta-Analysis of 1257 Patients
Authors: Vergeer Menno , Zhou Rong , Duivenvoorden Raphael , Koglin Joerg , Mitchel Yale B , Huijgen Roeland , Sapre Aditi , Bots Michiel L , Pasternak Richard C , Gagné Claude , Marais A D , Ballantyne Christie M , Isaacsohn Jonathan L , Stalenhoef Anton F , Kastelein John J
Published: July 2021

In the past, patients with heterozygous familial hypercholesterolemia (HeFH) were believed to be an ideal population to study changes in carotid intima media thickness (cIMT) based on their aggressive lipid disorder and high incidence of atherosclerotic events. However, following publication of recent cIMT trials in this population, the feasibility of demonstrating a reduction of cIMT progression in statin-treated HeFH patients has come under scrutiny. To inform future study designs, we evaluated cIMT progression and baseline predictors of cIMT progression (change in mean cIMT for all segments and common carotid artery (CCA) cIMT over 1 and 2 years), in merged data of 1257 patients from the statin arms of the ASAP, RADIANCE 1, CAPTIVATE and ENHANCE studies and performed backward regression analyses with prespecified co-variates. Based on this analysis, bootstrap analyses were performed to estimate cIMT progression for various hypothetical in- and exclusion criteria. For all studies combined, 2-year mean cIMT progression was 0.0102 ± 0.1348 mm. Positive predictors of this progression were prior use of high dose statins and use of other lipid-modifying therapy. Positive predictors of 1-year mean cIMT progression and 1 & 2 year CCA cIMT progression were age, history of hypertension, Framingham risk score, female gender, high dose statin use and history of CAD; negative predictors were screening LDL-C and ApoA-I. In simulations, HeFH patients previously taking statin and over 50 years of age had an estimated 2-year mean cIMT progression of 0.0216 ± 0.155 mm (based on n = 380). Two year progression for patients with a history of CAD or a Framingham risk score ≥ 10 would be estimated at 0.0197 ± 0.158 mm (based on n = 334). This study shows that cIMT progression in a contemporary HeFH patient population is substantially lower than anticipated, limiting the usefulness of cIMT studies to test new therapies in this population. While focus on individual subgroups characterized by population-specific predictors of cIMT progression results in slightly higher cIMT progression, the current analysis suggests that other patient populations should be considered for future cIMT studies.
Abstract 2231: Thoracic Aortic Calcification and Coronary Heart Disease Events: the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Budoff Matthew J , Nasir Khurram , Katz Ronit , Takasu Junichiro , Carr J Jeffrey , Wong Nathan D , Allison Matthew , Lima Joao A , Detrano Robert , Blumenthal Roger S , Kronmal Richard
Published: July 2021

Background:
The presence of coronary artery calcium (CAC) is an independent marker of cardiovascular disease (CVD) events and mortality. However, the predictive value of thoracic aorta calcification (TAC), which can be additionally examined without further scanning during assessment of CAC, in predicting coronary heart disease (CHD) events in asymptomatic women and men, is not well-established.

Methods:
We collected data on risk factors and performed scanning for both TAC and CAC in a multi-ethnic population-based cohort of 6809 individuals (62±10 years, 47% males). Using the same images for each participant, TAC and CAC were computed using the Agatston method. The study subjects had no clinical cardiovascular disease at entry and were followed for a median of 4.1 years.

Results:
The mean age of the study population was 62±10 years (47% males). At baseline 1904 (28%) participants had detectable TAC, whereas 3392 (50%) had CAC>0. During the follow-up interval, 189 (2.78%) and 108 (1.59%) participants suffered any CHD and hard CHD event, respectively. Table

below provide the hazard ratio (95% CI) for coronary events with presence of TAC. Overall TAC was a stronger predictor of CHD risk in women than in men. .

Conclusion:
Our study result suggests that TAC imparts independent prognostic power to predict future coronary events in women and may provide rationale for more intensive risk factor modification.

Hazard Ratios (95% CI) of All CHD and Hard CHD Events with TAC (TAC>0 vs. TAC=0)
Abstract 2235: Prognostic Value of 64 Slices Computed Tomography Coronary Angiography in Patients with Suspected Coronary Artery Disease
Authors: Sozzi Fabiola B , Civaia Filippo , Iacuzio Laura , Russek Stephan , Rossi Philipe , Bourlon Francois , Marco Jean , Danzi Gian Battista , Dor Vincent
Published: July 2021

To assess the value of 64-slice computed tomography (CT) coronary angiography for the risk stratification in patients with suspected coronary artery disease (CAD). The prognostic value of 64-slice CT is still unknown. A total of 205 patients (129 men [63%], age 61±10 years) who were referred for further cardiac evaluation due to suspicion of CAD underwent 64-slice CT to evaluate the presence and severity of CAD. It was determined weather the lesion was obstructive or not using a threshold of 50% luminal narrowing. Plaques were classified in calcificed, soft and mixed based on type. End-point during follow-up was hard cardiac events (non-fatal myocardial infarction, unstable angina requiring hospitalization, myocardial revascularization). Coronary plaques were detected in 150 (73%) patients. During a mean follow-up period of 30 months, 83 events occurred in 44 patients. Event-free survival curves in patients with obstructive and non-obstructive lesions respectively and in patients with normal lumen are presented in figure

. In patients with normal coronary arteries, the 30-month event rate was 0% versus 46% in patients with significant obstructions (≥50% luminal narrowing) (p <0.001), and 9% in patients with non-significant lesions (<50% luminal narrowing). In multivariate analysis, significant predictors of cardiac events were age, hypercholesterolemia, presence of CAD, obstructive CAD, number of segments with obstructive plaques and obstructive soft plaques. 64-slice CT coronary angiography provides independent prognostic informations over baseline clinical risk factors in patients with suspected CAD.
Abstract 2236: Usefulness of 64-Slice Computed Tomography in Patients Undergoing Percutaneous Coronary Intervention of Chronic Total Occlusion
Authors: Ohanessian Alice , Lefévre Thierry , Sastry Sanjay , Louvard Yves , Dumas Pierre , Morice Marie-Claude
Published: July 2021

Background.
Despite constant technical advances, percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) remains a challenge with procedural success ranging from 65 to 85% in high volume center. MSCT provides information which cannot be obtained with conventional coronary angiography such as: plaque constitution, calcifications and distribution, route and distal run off. A better knowledge of these parameters may influence the approach to such complex PCI, optimize procedural strategy and success. The aim of our study was to evaluate the usefulness of cardiac CT before PCI of CTO.

Methods
. All patients with CTO underwent 64-slice CT before the scheduled PCI. We used a scan protocol with 64±0.625mm slice collimation (pitch 0.2), 350 ms (General Electric Lihgtspeed VCT) and 420 ms (Philips Brillance) rotation time and simultaneous (ECG) gating. Patients with heart rates above 65 bpm received intravenous beta-blockade. All CT examinations were performed with retrospective electrocardiogram gating. Exclusion criteria were atrial fibrillation and creatinemia >140 μmol/l.

Results
. Sixty patients were included in the study. Mean age was 63.58.5 yrs, 90% were male. On MSCT, the occlusion length was 25.5mm16.5 (33.119.8 on angiography). Calcifications were evaluated as minimal in 42% (26% angio), moderate in 42% (54%) and severe in 1% (12%) of the cases. No calcification was found in 15% (8%). A possible coronary route was identified in 68% (18% on angio), the lumen was relatively visible in 77%, acceptable in 23% and eccentric in 98%. One side branch was observed in 62 %, two in 8% and none in 30% of the CTO. Procedural difficulty was assessed by angio using a scale of 1 (very easy) to 5 (extremely difficult) with a mean rate of 3.540.92 falling to 2.620.81 after reading the MSCT data. MSCT was deemed as extremely useful in 80%, useful in 18% and non useful in 2%. Overall procedural success was achieved in 79% of the CTOs.

Conclusion
. MSCT appears to be a new tool for optimising procedural strategy and increasing success rate in CTO angioplasty.
Abstract 2240: T2-Prepared Steady-State Free-Precession Blood Oxygenation Level-Dependent MRI in Patients with Coronary Artery Disease and Normal Volunteers: Validation against PET
Authors: Karamitsos Theodoros D , Recio-Mayoral Alejandro , Arnold Jayanth R , Leccisotti Lucia , Bhamra-Ariza Paul , Howells Ruairidh K , Searle Nick , Robson Matthew D , Rimoldi Ornella E , Camici Paolo G , Neubauer Stefan , Selvanayagam Joseph B
Published: July 2021

Blood oxygenation level-dependent (BOLD) MRI clinical studies at 1.5 Tesla (T) have been principally limited by low signal to noise. We sought to apply this method at 3T in patients with coronary artery disease (CAD) and normal volunteers, and validated it against perfusion measurements by PET. Twenty-two patients (age 62±8 yrs, 16 men) with CAD (at least 1 stenosis > 50% on quantitative coronary angiography-QCA) and 10 normal volunteers (age 52±7 yrs, 7 men) underwent 3T BOLD MRI and PET. For BOLD MRI a mid-ventricular slice was acquired every 30sec at rest and during adenosine stress (140 μg/kg/min). A set of 6 images was acquired at rest and at peak stress. Using PET with oxygen-15 labelled water, myocardial blood flow (MBF) was measured at baseline and during adenosine hyperemia. The BOLD short-axis view was divided into 6 segments, according to the mid-ventricular segments of the 17-AHA segment model, and mean signal intensities (SI) were calculated using QMass (Medis) software. PET images were analyzed with MATLAB software (MathWorks Inc.) and registered with the BOLD short-axis image using anatomical landmarks. Taking QCA as the gold standard, cut-off values for stress MBF (< 2.57ml/min/g - AUC 0.79) and BOLD SI change (< 4.75% -AUC 0.78) were determined to define ischemic segments. Rest MBF, stress MBF, coronary flow reserve and BOLD-SI change of ischemic (n=69), remote to ischemia (n=73) and normal segments (n=60) are shown in table

. BOLD MRI and PET agreed on the presence or absence of ischemia in 18 of the 22 patients (82%), and in all normals. With regards to per segment analysis: taking PET as the gold standard and by applying the cut-off values for stress MBF and BOLD SI, BOLD MRI had only moderate sensitivity (61%) but good specificity (88%) for the identification of ischemia. T2-prepared SSFP 3T BOLD imaging is feasible in the clinical setting and has good agreement with PET perfusion measurements for the detection of myocardial ischemia.
Abstract 2307: Contemporary Perioperative Results of Isolated Aortic Valve Replacement for Aortic Stenosis: Implications for Transcatheter Aortic Valve Implantation
Authors: Malaisrie S C , McCarthy Patrick M , McGee Edwin C , Lee Richard , Rigolin Vera , Davidson Charles J , Rajamannan Nalini M , Bonow Robert O
Published: July 2021

Transcatheter aortic valve implantation (AVI) is compelling for some high-risk patients with aortic stenosis (AS). However, comparison of procedure outcomes with older surgical series may overestimate operative risk. We therefore analyzed our contemporary series of isolated aortic valve replacement (AVR) for AS. From April 2004 to January 2008, 642 patients underwent AVR with or without concomitant cardiac procedures. Of these patients, 175 patients had an isolated AVR, and 140 patients underwent isolated AVR for AS. The characteristics were age 68, male gender 56%, ejection fraction 57%. Sixty-four percent had a minimally-invasive AVR and 18% were reoperations. Twenty percent were 80 years old or greater, 35% were in NYHA functional class III-IV, and 4% had an estimated operative mortality of 10% or greater using the Society of Thoracic Surgery (STS) risk calculator. Thirty-day mortality was 0%, but there was one in-hospital death (0.7%) from complications of an esophageal perforation. Reoperation for bleeding occurred in 5.7%, cerebrovascular accident (CVA) in 0%, acute renal failure (ARF) in 2.9%, myocardial infarction (MI) in 0%. Bioprosthetic valves were used in 98.6% and mechanical in 1.4%. Mean gradient decreased from 48 mmHg to10 mmHg. Actuarial survival was 97% and 90% at 1 and 3 years. Patients >80 years (n=28) were more likely to have an increased length of hospital stay (9.8 versus 6.3 days, p=0.01) and less likely to be discharged to home (48% versus 86%, p<0.01) as compared to patients <80 years. Today, AVR for AS can be performed in many high-risk patients with low operative mortality and morbidity, although patients over 80 years are at greater risk of prolonged recovery. Transcatheter AVI should be compared to this high threshold.
Abstract 2316: Ranolazine, a Late Sodium Current Inhibitor, as an Adjunct to Cardioplegia Further Reduces Contracture during Ischemia and Reperfusion
Authors: Hwang Hyosook , Arcidi Joseph M , Hale Sharon L , Simkhovich Boris Z , Belardinelli Luiz , Dhalla Arvinder , Shryock John C , Kloner Robert A
Published: July 2021

Although cardioplegia (CP) protects myocardium during ischemic cardiac arrest, cardioplegic preservation can be suboptimal for increasingly complex cardiac surgical patients. Ranolazine (Ran), a novel antianginal agent, was recently shown to mitigate ischemia-induced Ca
2+
overload via its inhibitory effects on the late Na
+
current, but the benefit of Ran during cardioplegic arrest is not known. The purpose of the study was to investigate the therapeutic potential of Ran as an adjunct to CP. Hearts isolated from female Sprague-Dawley rats were Langendorff-perfused and exposed to normothermic global ischemia for 40 min followed by 30-min reperfusion (I/R). Three groups were studied: control buffer (n = 10); crystalloid CP (Fremes, n = 12); CP supplemented with Ran (n = 12). CP was bolus-injected with or without Ran at the time of ischemia. End-diastolic pressure (EDP), developed pressure, dP/dt
min
, and dP/dt
max
were measured throughout the study. CP significantly delayed onset of ischemic contracture (defined as a time to 20 mmHg of EDP), compared to control (25 ± 2 min in CP alone vs. 12 ± 1 min in control, p < 0.05). Ran added to CP further delayed the time to contracture (34 ± 2 min in Ran, p < 0.05 compared to CP alone). Consistent with these findings, the area under the diastolic pressure curve during the entire period of ischemia was significantly smaller in CP + Ran versus CP alone (p < 0.05). I/R caused dramatic elevations in EDP during reperfusion. CP lessened the extent of the reperfusion contracture (32 ± 3 mmHg in CP alone vs. 76 ± 3 mmHg in control, p < 0.05). Addition of Ran to CP further lessened the contracture (17 ± 2 mmHg in Ran, p < 0.05 compared to CP alone). I/R severely depressed systolic cardiac contractile function. The impairment in contractile function was significantly reduced by CP, as well as CP + Ran, but there was no statistical difference between the two groups. While CP alone reduced the onset of cardiac contracture in this model of I/R, addition of Ran to CP further enhanced the cardioprotection. These results suggest the potential therapeutic efficacy of Ran as an adjunct to CP and further support the protective role of late Na
+
current inhibition.
Abstract 2360: Central Sleep Apnea with Nocturnal Hypoxia Promotes Increased Circulating Erythropoietin in Heart Failure
Authors: Calvin Andrew D , Somers Virend K , Miller Jennifer M , Steensma David P , Olson Lyle J
Published: July 2021

Central sleep apnea (CSA) with nocturnal hypoxia is frequent in heart failure (HF). Hypoxia causes increased circulating erythropoietin (EPO) in healthy normals. EPO promotes increased vasoconstriction and exogenous EPO administration is associated with adverse cardiovascular events. No prior studies have related EPO concentration to apnea or hypoxia due to CSA. EPO is elevated in HF patients with nocturnal hypoxia due to CSA. Ambulatory, non-anemic HF patients (n = 29) with LVEF < 45% and healthy controls (n = 18) underwent polysomnography (PSG). Subjects with obstructive sleep apnea (OSA) were excluded. CSA was defined as apnea-hypopnea index (AHI) ≥ 15. Hypoxia was quantified as the proportion of sleep with arterial oxygen saturation < 90% (T90%). Blood for EPO was drawn post-PSG. Other clinical characteristics were summarized from the medical record. HF subjects and controls were similar age (54 vs 60 y, p = 0.09). CSA was present in 14 HF subjects; 13 were men compared to 8 of 15 without CSA (p = 0.04). HF subjects had 42% higher mean EPO than controls (p < 0.01) despite similar hemoglobin (13.9 vs 14.0 g/dL, p = 0.8). NYHA class III–IV HF subjects had 42% higher mean EPO than class I–II HF subjects (p = 0.05, figure

). EPO concentration was correlated with severity of nocturnal hypoxia by simple linear regression (r = 0.4; p = 0.02). By multivariate analysis, elevated EPO was associated with NYHA class III–IV HF and elevated AHI (p = 0.01 and 0.03, respectively; r = 0.6) after adjusting for age, gender, LVEF, renal function and hemoglobin. Nocturnal hypoxia due to CSA promotes increased endogenous EPO concentration in HF patients.
Abstract 2372: Clinical And Metabolic Effects Of Six Months Testosterone Treatment In Elderly Female Patients With Chronic Heart Failure
Authors: caminiti G , karam R , volterrani M , marazzi G , miceli M , massaro R , rosano G M
Published: July 2021

Background: Patients with chronic heart failure (CHF) show muscle mass wasting and decreased exercise capacity. Testosterone supplementation improves several clinical and metabolic parameters in male CHF subjects. No studies have evaluated the effects of long-term testosterone administration on female patients with CHF.

Aim: To assess the effect of a 6 months testosterone administration on exercise capacity, muscle strength, and insulin resistance in female patients with advanced CHF.

Methods: Thirty-two elderly female patients (pts) with stable CHF, mean age 68,6 ± 7, ejection fraction 32,9 ± 6, NYHA class III, were enrolled. Of these, 20 were randomized to receive testosterone therapy (T) (through transdermal patch) and 12 to receive placebo (P), both on top of maximal medical therapy. At baseline, at three and after 6 months patients underwent echocardiogram, cardiopulmonary test, 6-minute walking test (6MWT), quadriceps maximal isometric voluntary contraction(MVC) and peaktorque (PT) and HOMA index assesment.

Results: VO2 and distance walked at 6MWT significantly improved in T group from baseline both at three (+20%; +36% respectively) and six months (+28%; 41% respectively) while were unchanged in the P group. At six months Patients of T group had a significantly higher increase of both MVC and PT than P group. HOMA-R was significantly reduced (− 15% vs +5%; p < 0.05) and HDL-cholesterol levels were increased (+22% vs p < 0.05).in T group respect to P. NYHA class improved (from III to II) in 7/20 pts of T group and 2/12 of P group. Increase in free testosterone levels were significantly related to improvement in VO2 peak (r 0,42; p 0.032). No significant echocardiographic changes were observed in both groups. No side effects were observed. Two patients of both group were hospitalizes for HF recurrence.

Conclusion: Testosterone supplementation improves exercise tolerance, muscle strength, and insulin resistance in women with advanced CHF. Testosterone seem to be an effective and safe therapy for CHF elderly female subjects.
Abstract 2373: The Effects of Statin Therapy on MMP Families in Patients with Acute Heart Failure
Authors: Shirakabe Akihiro , Asai Kunuya , Hata Noritake , Yokoyama Shinya , Akutsu Koichi , Shinada Takuro , Kobayashi Nobuaki , Kanemaru Katsuhiro , Mizuno Kyoichi
Published: July 2021

Introduction: It is known that increased matrix metalloprotease (MMP) accelerated cardiac remodeling in chronic heart failure (HF). Although roles of MMPs in acute HF have not been well clarified, we also found that MMPs increased in acute HF and decreased in the improvement of HF with conventional therapy. Pharmacological modification of MMPs may be beneficial for a treatment of acute HF. Therefore we assessed the hypothesis that a statin decreased MMPs in acute HF.

Methods: Serum levels of MMP-2,-3, and -9 were measured on admission (Day 1), Day 3, and Day 14 in 38 acute HF patients. The patients were randomized to either atorvastatin group (n = 20) or control group (n = 18). Atorvastatin (10 –20mg per day) was started within 12 hours after their admission and continued for two weeks. There was no limitation in HF treatment and the treatment was not different between the two groups except atorvastatin. Patient characteristics including an etiology of HF and cardiac function were also not different between the groups.

Results: There were no differences in serum levels of MMP-2, -3, and-9 on Day 1 between atorvastain group (1435.3 ± 292.6 ng/ml, 72.2 ± 40.4 ng/ml, 132.9 ± 85.5 ng/ml, respectively) and control group(1284.5 ± 399.6 ng/ml, 142.0 ± 139.7 ng/ml, 88.4 ± 51.2 ng/ml, respectively). MMP-2 significantly decreased in both atorvastatin and control group on Day 3 and Day 14. But, decreases of MMP-2 on Day 3 and Day 14 from Day 1 were significantly greater in atorvastatin group (− 581.3 ± 237.3 ng/ml and − 447.7 ± 228.3 ng/ml, respectively) than in control group (− 321.3 ± 257.8 ng/ml and − 275.0 ± 179.4 ng/ml, respectively). MMP-9 significantly decreased in atorvastatin group on Day 3 and Day 14 (132.9 ± 85.5 ng/ml on Day1, 71.4 ± 48.6 ng/ml on Day 3, 53.0 ± 28.5 ng/ml on Day 14; p < 0.05), but did not change significantly in control group. MMP-3 did not significantly change in both groups.

Conclusion: MMP-2 decreased with conventional HF treatment, but MMP-3 and -9 did not. Interestingly, early start of statin treatment significantly decreased both MMP-2 and -9, but not MMP-3 in acute HF. This is the first report demonstrating the effects of statin on MMPs in acute HF.
Abstract 2375: Regulation of Cardiac Myocyte Contractility by Phospholemman
Authors: Song Jianliang , Zhang Xue-Qian , Wang JuFang , Cheskis Ellina , Chan Tung O , Feldman Arthur M , Tucker Amy L , Cheung Joseph Y
Published: July 2021

Phospholemman (PLM) regulates cardiac contractility by modulating Na
+
/Ca
2+
exchanger (NCX1) and/or Na
+
-K
+
-ATPase activities. PLM, when phosphorylated at serine68, disinhibits Na
+
-K
+
-ATPase but inhibits NCX1. In this study, we first demonstrated that adult mouse cardiac myocytes cultured for 48 hours had normal surface membrane area and t-tubule appearance, and exhibited near normal contractility. Contractile differences between wild-type (WT) and PLM knockout (KO) myocytes were preserved after 48h of culture. Infection with adenovirus overexpressing GFP did not affect contractility at 48h. When WT PLM was overexpressed in PLM-KO myocytes, part of PLM was phosphorylated, both Na
+
-K
+
-ATPase current (I
pump
) and Na
+
/Ca
2+
exchange current (I
NaCa
) were depressed, and contractility and [Ca
2+
]
i
transients reverted back to those observed in cultured WT myocytes. Overexpressing PLMS68E mutant (phosphomimetic) in PLM-KO myocytes resulted in suppression of I
NaCa
but no effect on I
pump
. Contractility and [Ca
2+
]
i
transient amplitudes in PLM-KO myocytes overexpressing PLMS68E mutant were depressed when compared to PLM-KO myocytes overexpressing GFP. Overexpressing PLMS68A mutant (mimicking unphosphorylated PLM) in PLM-KO myocytes had no effects on I
NaCa
but decreased I
pump
. Contractility and [Ca
2+
]
i
transient amplitudes in PLM-KO myocytes overexpressing S68A mutant were similar to PLM-KO myocytes overexpressing GFP. Neither WT PLM nor its mutants had any effect on SR Ca
2+
uptake in KO myocytes. We conclude that at the single myocyte level, PLM affects cardiac contractility and [Ca
2+
]
i
homeostasis primarily by its direct inhibitory effects on Na
+
/Ca
2+
exchange.
Abstract 2385: Epidemiology of Incident Heart Failure in a Contemporary Elderly Population: The Health, Aging, and Body Composition (Health ABC) Study
Authors: Kalogeropoulos Andreas P , Georgiopoulou Vasiliki V , Kritchevsky Stephen , Psaty Bruce , Rodondi Nicolas , Smith Nicholas , Bauer Douglas C , Bibbins-Domingo Kirsten , Satterfield Suzanne , Smith Andrew L , Newman Anne B , Vasan Ramachandran , Harris Tamara B , Wilson Peter W , Butler Javed
Published: July 2021

Despite the increasing elderly population and rising heart failure (HF) burden, epidemiology of incident HF in the elderly is not well described. We studied 2934 elderly participants without prevalent HF enrolled in the Health ABC study (aged 73.6 ± 2.9 years, 47.9% men, 58.6% white, 41.6% black) and assessed incidence rates, population attributable risk (PAR) for independent risk factors, and outcomes of incident HF. After 7.1 year median follow-up, 258 (8.8%) participants developed HF requiring hospitalization (annual rate: 13.6 per 1000 participants). Men and blacks were more likely to develop HF than women and whites: annual rate was 16.3/1000 in blacks vs. 11.9/1000 in whites [hazard ratio (HR) 1.41, 95% confidence interval (CI), 1.11–1.80, p = 0.006]; and 15.8/1000 in men vs. 11.7/1000 in women (HR 1.34, 95% CI, 1.05–1.71, p = 0.021). Coronary heart disease and uncontrolled blood pressure had the highest PAR ( > 20% each) both in whites and blacks (Table 1

); a substantial proportion of incident HF was attributable to metabolic and cardio-renal risk factors. The fraction of incident HF cases attributable to modifiable risk factors was higher in blacks vs. whites (68% vs. 49%). No significant sex-based differences were observed in risk factors and PAR. Participants who developed HF had a considerably higher annual mortality than HF-free participants (18.0% vs. 2.7%). Survival after HF did not differ between whites and blacks; however, rehospitalization rates were two-fold higher in blacks compared to whites (62.1 vs. 30.3 per 100 patient-years, p < 0.001), due to a higher rate of HF related readmissions in blacks. Incident HF is common in the elderly and is associated with poor outcomes. A large proportion of incident HF risk was attributed to modifiable risk factors. Significant racial differences in PAR for risk factors and hospitalization rates after incident HF need to be accounted for future prevention and treatment efforts.

Table 1.

Adjusted rate ratios and population attributable risk for the modifiable risk factors of incident heart failure in the Health ABC study
Abstract 2387: Sex Differences in the Relationship between Echocardiographic Parameters and Clinical Outcomes in Chronic Stable Angina: Data from the ACTION trial
Authors: Ky Bonnie , Kirwan Bridget-Anne , de Brouwer Sophie , Lubsen Jacobus , Poole-Wilson Philip , Otterstad Jan-Erik , Kimmel Stephen E , Sutton Martin St. John
Published: July 2021

Objectives:
To elucidate how the association between clinical outcomes and echocardiographic parameters of size and function differ by sex in chronic stable angina.

Background:
Whether men and women with stable coronary disease and similar ejection fraction (EF) have equivalent cardiac risk is unknown.

Methods:
Baseline EF and end-diastolic (EDV) and end-systolic (ESV) volumes were calculated from 7016 patients in the ACTION study (A Coronary disease Trial Investigating Outcomes with Nifedipine GTS). All-cause and cardiac mortality and cardiovascular events were assessed over a mean of 4.9 years. Univariate and multivariable Cox proportional hazard models were used to determine the interaction between gender and echocardiographic parameters and clinical outcomes.

Results:
There was significant effect modification by sex on the association between EF < 45% and all-cause and cardiac mortality. Relative to those with an EF ≥ 55%, women with an EF < 45% demonstrated a greater increased risk of these two endpoints (HR 4.78, 95%CI 2.16–10.57; HR 22.44, 95%CI 3.07–164.27, respectively) as compared to men (HR 1.99, 95%CI 1.42–2.79; HR 2.77, 95%CI 1.73– 4.43, respectively; interaction unadjusted p = 0.03, adjusted p = 0.06 – 0.07) (Table 1

). There was also significant effect modification by gender on the association between an EDV > 175ml and risk of coronary procedures (unadjusted, adjusted p = 0.02) and ESV > 100ml and risk of heart failure (unadjusted p = 0.03, adjusted p = 0.26).

Conclusions:
EF demonstrates significant effect modification by sex on the hazard ratio for all-cause and cardiac mortality. Gender also significantly modifies the relationship between EDV and coronary procedures, and ESV with heart failure. Men and women with chronic stable angina and similar EF likely do not have equivalent risk. Gender-specific echocardiographic definitions may be of incremental benefit in the identification of high-risk women.

Table 1:

Unadjusted Hazard Ratios for Clinical Outcomes by Gender and Ejection Fraction
Abstract 2397: Morbidity and Mortality of Transthyretin (TTR) Amyloid Cardiomyopathy (ATTR-CM): Transthyretin Amyloidosis Cardiac Study (TRACS) a Prospective Evaluation
Authors: Ruberg Frederick L , Skinner Martha , Kim Antony Y , Zeldenrust Steven , Judge Daniel , Maurer Mathew , Falk Rodney H , Tripp Kenneth J , Packman Jeff , Grogan Donna
Published: July 2021

Background:
ATTR-CM is believed to have a relatively indolent course, with a median survival of ~5 years from heart failure symptoms; however, no data exist as to the rate of progression after disease diagnosis. ATTR-CM is associated with genetic variants, including V122I (present in ~ 3.5% of African Americans), or wild-type TTR (senile systemic amyloidosis - SSA). While there is no effective treatment other than heart transplantation, therapies designed to slow or halt amyloid deposition are in development. The purpose of this study was to characterize the natural history of ATTR-CM to support future therapeutic trials.

Methods:
Patients with ATTR-CM due to V122I (n = 11) and SSA (n = 18), were enrolled 10.4 ± 11.9 months after diagnosis (range: 0 – 60 months) and assessed every 6 months for up to two years by echocardiography and cardiac magnetic resonance imaging (CMR), with functional capacity assessed by 6-minute walk, and biochemical profile including cardiac troponins and NT-pro-B-type natriuretic peptide (BNP). Baseline data from the full cohort (n = 29), and available data from those completing the 12 month assessment (n = 15) are presented for this on-going study.

Results
: At baseline, both groups were similar in terms of gender, duration of disease from diagnosis, NYHA, troponin/NT-BNP, and echo or CMR-measured LV wall thickness. SSA patients were older (mean age 76 vs. 71y, P = 0.03), Caucasian (100% vs 0%, P < 0.001), with a history of atrial fibrillation (83% vs. 27%, p = 0.003). During a mean follow-up of 442 days (30–768), there have been 7 deaths (4 V122I; 3 SSA) and 1 cardiac transplantation (SSA), and 10 of 29 (34.5%) were hospitalized at least once (90% for cardiac reasons). For those subjects with a 12 month assessment, LV ejection fraction declined by echo (2.8 %) and CMR (12 %), with minimal changes in wall thickness. Increases were seen in NT-Pro-BNP (87%) and troponin (I: 186%; T: 70%). Worsening of NYHA class occurred in 43% of patients; 6-minute walk distance decreased by 19.2%.

Conclusions
: Despite reports of a relatively indolent course of ATTR-CM, preliminary data from this ongoing study are the first to demonstrate that quantifiable noninvasive parameters worsen over a 1 year follow up period and are associated with adverse clinical outcomes.
Abstract 2405: Acute Increase In Left Ventricular Filling Pressure Leads To Hyperventilation In Heart Failure Patients With Central But Not Obstructive Sleep Apnea Or Without Sleep Disordered Breathing
Authors: Oldenburg Olaf , Piper Cornelia , Bitter Thomas , Prinz Christian , Langer Christoph , Wiemer Marcus , Horstkotte Dieter
Published: July 2021

The pathohysiology of Cheyne-Stokes-respiration (CSR) in congestive heart failure (CHF) is not fully understood. Increase in pulmonary capillary wedge pressure (PCWP) may lead to stimulation of pulmonary J-receptors and consecutive hyperventilation. The present study investigates the influence of an acute increase in PCWP in CHF pts without sleep disordered breathing (SDB) compared to pts with central (CSR) and obstructive sleep apnea (OSA). Simultaneous left and right heart catheterizations were performed in 29 CHF pts (NYHA ≥ II, LVEF ≤ 40%). PCWP and arterial pCO
2
were measured under standardized settings at baseline and after left ventricular angio- and/or aortography resulting in an acute increase in intravascular volumes. Type and severity of SDB were determined by cardiorespiratory polygraphy the night before or thereafter. NT-proBNP concentration was measured and central CO
2
- receptor sensitivity determined by testing hypercapnic-hyperoxic-ventilatory response (HCVR) according to Read. CSR was diagnosed in 15 pts (apnea-hypopnoea-index [AHI] 32 ± 19/h; 59 ± 11 years; LVEF 32 ± 6%), OSA in 9 pts (AHI 27 ± 29/h; 64 ± 13 years; LVEF 33 ± 5%); 5 pts had no SDB (AHI 1 ± 2/h; 48 ± 13 years; LVEF 32 ± 7%). HCVR and NT-proBNP concentrations were significantly higher in CSR (5.6 ± 6.5l/min/mmHg and 5237 ± 6268pg/ml) compared to OSA (2.2 ± 0.6l/min/mmHg and 1127 ± 874pg/ml) or pts without SDB (1.6 ± 0.6l/min/mmHg and 197 ± 146pg/ml; p < 0.05). PCWP were elevated at baseline and increased significantly after angiography in all groups (CSR: 20.3 ± 6.6 mmHg to 22.9 ± 7.9 mmHg; OSA 22.8 ± 10 to 25.4 ± 11 mmHg; noSDB: 14.2 ± 10 to 17.4 ± 9mmHg; all p < 0.05). Arterial pCO
2
at baseline tended to be lower in pts with CSR. Only in CSR, not in OSA or pts without SDB increase in PCWP was accompanied by a further decrease in pCO
2
(CSR: 36.1 ± 5mmHg to 33.3 ± 5mmHg, p = 0.05; OSA: 38.7 ± 4mmHg to 40.1 ± 6mmHg, p = ns; noSDB: 39.6 ± 6mmHg to 39.7 ± 6mmHg, p = ns). In CHF pts with CSR but not in those without SDB or OSA, acute increase in PCWP stimulates ventilation, together with other factors like an increased central CO
2
- receptor sensitivity this may lead to hyperventilation and a consecutive decrease in pCO
2
below the apnea threshold. Moreover, the present data may explain why CSR in some pts reflects CHF severity.
Abstract 2407: Increased Arteriolar Resistance Of Heart Failure Is Associated With Rho-Independent Inhibition Of MLCP.
Authors: Azam Mohammed A , Hoefer Judith , Momen Mohammed Abdul , Bolz Steffen Sebastian , Husain Mansoor
Published: July 2021

Background: The clinical syndrome of heart failure (HF) is caused by decreased cardiac output, and is both compensated for and exacerbated by increased systemic vascular resistance (SVR). We posit that a mechanistic understanding of the vasomotor abnormalities that accompany HF may enable new diagnostic and therapeutic tools.

Objective: To determine the molecular mechanisms underlying increased resistance of mesenteric arteries (MAs) in a mouse model of HF.

Methods & Results: In a mouse left anterior descending (LAD)-ligation model of myocardial infarction (MI)-induced HF, echocardiography and hemodynamics documented markedly increased SVR. Isolated perfused MAs manifested dramatic, early (1 wk), and sustained (12 wk) increases in myogenic responses (MR). Vasoconstrictor responses to S1P and ET-1 were also increased in MAs of HF but not SHAM mice. At wk 6, aorta and MA were analyzed for levels and or activity of

Rho/GTP-Rho, a key mediator of enhanced vasoconstrictor responses. We also measured total and phosphorylated levels of:

MYPT1 (Thr850), the myosin targeting subunit of myosin light chain phosphatase (MLCP), an end-regulatory molecule of smooth muscle contraction;

CPI-17 (Thr38), an inhibitor of MLCP; and (iv) myosin light chain itself (MLC; Ser19).

When phosphorylated, MYPT1 inhibits MLCP, limiting its dephosphorylation of MLC, and thus prevents relaxation. Given our results with respect to ET-1 and S1P, we were surprised to find significantly decreased levels of total and GTP-Rho in MAs and aorta of HF as compared to SHAM mice. By contrast, increased levels of phosphorylated-MYPT1, CPI-17 and MLC were found in HF.

Conclusion: These data implicate a heretofore unrecognized mechanism of ‘Rho-independent’ inhibition of MLCP in the increased SVR, MR, and vasoconstrictor responses observed in the MI model of HF in mice.
Abstract 2409: Parvovirus B19 and Cardiomyopathy - The New Coxsackievirus
Authors: Stewart Garrick C , Lipes Myra A , Anello Mary Susan , Pratibhu Parakash P , Gottumukkala Raju , Winters Gayle L , Towbin Jeffrey A , Baughman Kenneth L
Published: July 2021

Enteroviruses such as coxsackievirus have been long considered a common cause of viral myocarditis. More recently multiple cardiotropic viruses have been isolated from endomyocardial biopsies (EMBx) from patients with myocarditis and idiopathic ventricular dysfunction. To determine the prevalence of viral genomic material in EMBx from adult heart failure patients. EMBx were obtained from 100 consecutive patients (median ejection fraction 20%, range 15– 65%) presenting for cardiomyopathy evaluation (median duration of symptoms 6mos, range 2d-20yrs). Frozen EMBx were evaluated using PCR and RT-PCR for cardiotropic viruses using primers specific for adenovirus, cytomegalovirus, enteroviruses, Epstein-Barr virus, and parvovirus B19 (PVB19). Positive human DNA/RNA controls were performed. Formalin preserved EMBx were evaluated by light microscopy for the presence of myocarditis. PVB19 was the only cardiotropic virus isolated from EMBx tissue (n = 12). Viral sequencing revealed different strains of PVB19 in each subject. No PVB19 positive subject had anti-parvovirus IgM, but all had circulating IgG, suggesting chronic infection. No subject with a PVB19 positive EMBx had evidence of active or borderline myocarditis according to the Dallas criteria. There were no differences in the degree of myocyte hypertrophy or fibrosis in PVB19 positive versus negative EMBx. PVB19, a single-stranded DNA virus and common childhood infection, was the only virus isolated from EMBx samples in this series of adult heart failure patients from the United States. The relationship between between PVB19 viral persistence and the development of cardiomyopathy merits further study.
Abstract 2432: Effect of Left Ventricular Systolic Dysfunction on Wasted Left Ventricular Energy and Tension-Time Index
Authors: Denardo Scott J , Nichols Wilmer W
Published: July 2021

Information obtained from the aortic pressure waveform is affected by age, physical condition, systemic hypertension, diabetes mellitus and coronary artery disease. However, alterations in the aortic pressure waveform in patients (pts) with heart failure and left ventricular systolic dysfunction (LVSD) have not been fully described, including a description of the effect on wasted LV pressure energy and tension-time index. Non-invasive high-fidelity radial artery tonometry was used for data acquisition, and a mathematical transfer function used to generate aortic pressure waveforms (see figure

). Pulse wave analysis (PWA) of the aortic pressure waveform was used to obtain information associated with LV/vascular coupling in 23 pts age 55±9.5 yrs with LVSD (mean LV ejection fraction, 22±6%) and compared to data collected from 23 normal subjects matched for age, gender, height, weight and heart rate. Measurements obtained using PWA in heart failure pts with LVSD demonstrate decreased wasted LV energy and tension time index, consistent with poor LV mechanical performance, in addition to decreased unaugmented pressure, pulse pressure, ejection duration and augmentation index. Further standardization of these aortic pressure waveform findings in heart failure pts may allow for the clinical use of arterial PWA to non-invasively estimate LVSD.
Abstract 2435: The Role of Myocardial Longitudinal Strain in Monitoring Subclinical Heart Failure in Survivors of Childhood Cancer
Authors: Mavinkurve-Groothuis Annelies M , Groot-Loonen Jacqueline , Bellersen Louise , Feuth Ton , Bokkerink Jos P , de Korte Chris L , Kapusta Livia
Published: July 2021

Objectives:
Previous studies have demonstrated that myocardial longitudinal strain and strain rate is decreased in asymptomatic patients treated with anthracyclines. In this study, the relation between global myocardial longitudinal strain, conventional echocardiographic parameters, NT-pro-BNP levels, cumulative anthracycline dosage and follow up duration was investigated in a large group of asymptomatic long term survivors of childhood cancer.

Methods:
79 asymptomatic survivors (45% children) underwent a detailed echocardiographic examination for obtaining conventional parameters and global myocardial longitudinal strain values in 4-chamber view. In addition to this, we collected blood samples for NT-pro-BNP estimation.

Results:
the survivors had a mean age of 20 years (range: 6 –37 years), a mean follow up duration of 14 years (range 5–27 years) and a mean cumulative anthracycline dose of 240 mg/m
2
(range 50 –524 mg/m
2
). Reduced global myocardial longitudinal strain was significantly related to an EF<55% (p<0.001) and to reduced left ventricular posterior wall thickness in diastole indexed by body surface area (LVPWd/BSA) (p<0.003). Reduced myocardial global longitudinal strain was not related to abnormal NT-pro-BNP levels, follow up duration and cumulative anthracycline dosage.

Conclusion:
reduced global myocardial longitudinal strain is related to subclinical heart failure, e.g. abnormal EF and reduced LVPWd/BSA in asymptomatic survivors of childhood cancer. The role of myocardial strain in the early detection of anthracycline-induced cardiotoxicity needs to be explored by further longitudinal prospective studies.
Abstract 2468: Chronic Treatment Of Hypertensive Patients With The At1 Receptor Blocker Losartan Results In Sufficient Serum Levels Of The Metabolite Exp3179 Exhibiting Pparγ-stimulating Properties
Authors: Kappert Kai , Tsuprykov Oleg , Kaufmann Jan , Ott Ingo , Goebel Matthias , Bähr Ilse Nirmala , Häβle Paul-Laszlo , Gust Ronald , Fleck Eckart , Unger Thomas , Stawowy Philipp , Kintscher Ulrich
Published: July 2021

The losartan metabolite EXP3174 exhibits angiotensin II receptor 1 (AT1R)-blocking properties, whereas the metabolite EXP3179 potently induces the activity of the insulin-sensititzing peroxisome proliferator-activated receptor γ (PPARγ) as a partial agonist in vitro.. We investigated, whether hypertensive patients chronically treated with losartan exhibit sufficient plasma levels of EXP3179 to activate PPARγ in monocytes derived from losartan-treated patients. Hypertensive patients (n=9) treated with losartan (100mg/daily during at least the past two months), and control patients (n=7) with no chronic AT1R-blocking therapy were included. Blood was taken from all individuals and serum was prepared. Monocytes were extracted by negative isolation using a Dynal Monocyte Kit, followed by RNA-isolation and measurement of PPARγ target gene expression (CD36, ABC transporter G1 (ABCG1)) by quantitative real-time RT-PCR. Losartan-treated patients received 100mg orally, and serum was prepared 2, 4, and 6h after drug ingestion for HPLC-based determination of losartan and losartan metabolites (EXP3174/ EXP3179) in serum. Serum levels were standardized to measurements of purified compounds. Chronic treatment with losartan resulted in basal levels (24h after drug intake) of losartan, EXP3174 and EXP3179 of 382,5ng/ml, 97,0ng/ml and 164,2ng/ml, respectively. Levels of both, EXP3174 and EXP3179 were time-dependently enhanced in serum with a maximum 2h after drug intake (2619,6ng/ml, 980,9ng/ml, respectively). In order to evaluate the possible agonistic property of chronic EXP3179 serum levels on PPARγ, we determined the transcript levels of CD36 and ABCG1 as known PPARγ target genes. Gene expression was significantly upregulated in patients chronically treated with losartan by 5.26±1.55- and 188.54±56.92-fold for CD36 and ABCG1 (p=0.039, p=0.023 vs. control patients, respectively). This is the first clinical description of monocytic PPARγ-target gene regulation by chronic treatment with losartan, which likely is mediated by its metabolite EXP3179. Our data show that sufficient serum levels of EXP3179 are present under losartan treatment. PPARγ activation by AT1R-blockers may translate into synergistic beneficial actions in monocytes.
Abstract 2506: Coronary Spasm Occurs in Coronary Artery with Diffuse Intima Thickeing without Lipd and/or Calcification:Evaluation with Intravascular Optical Coherence Tomography
Authors: Morikawa Yoshinobu , Uemura Shiro , Ishigami Ken-ichi , Soeda Tsunenari , Okayama Satoshi , Takemoto Yasuhiro , Onoue Kenji , Somekawa Satoshi , Nishida Taku , Takeda Yukiji , Kawata Hiroyuki , Horii Manabu , Nakajima Tamio , Saito Yoshihiko
Published: July 2021

Coronary spasm (CS) plays an important role in the pathogenesis of many kinds of ischemic heart disease. However, morphological characteristics of coronary artery of CS remain unknown. We evaluated 37 patients with coronary spastic angina (CSA) who underwent diagnostic acetylcholine (ACh) provocation test, and 2 acute coronary syndrome patients suspected to have severe CS. The intravascular optical coherence tomography (OCT) was performed after complete dilatation of coronary artery in all patients and additionally performed during ACh-induced CS in 4 patients. Based on the ACh provocation test, 23 patients who developed CS and ischemic ECG changes were diagnosed as coronary spastic angina (CSA), and other 14 patients without CS were referred as CS-negative patients. CS-negative patients were further divided into 2 sub-groups according to the lipid and/or calcification content in coronary arterial wall by OCT findings. Intravascular OCT revealed most coronary segments with ACh-induced CS had homogenous intima thickening, and quantitative OCT analysis showed that CS-positive segments had significantly larger intima area compared with CS-negative segments without lipid and/or calcification (2.73±0.07 vs. 1.36±0.06 mm
2
, P<0.001). By contrast, CS-positive segments had significantly smaller intima area compared with CS-negative segments with lipid and/or calcification (2.73±0.07 vs. 4.51±0.17 mm
2
, P<0.001). During ACh-induced CS, lumen and total vascular area significantly decreased, whereas intima area did not change in comparison with complete vasodilatation. Furthermore, luminal surface of intimal layer formed markedly wavy configuration during CS. In CSA cases with acute coronary syndrome, we observed additional findings of intima injury as erosion and thrombus formation at spasm site. Coronary spasm occurs in coronary artery with diffuse intima thickening without lipid and/or calcification content but not in artery either without intima thickening or with lipid and/or calcification, and coronary spasm sometimes induces intimal injury by itself which may cause acute coronary event.
Abstract 2520: Drug-Eluting Stents for the Treatment of Chronic Total Occlusion: A Comparison with Sirolimus, Paclitaxel, Zotarolimus, EPC Capture and Everolimus-Eluting Stent: Multicenter Registry in Asia
Authors: Nakamura Sunao , Nakamura Shotaro , Ogawa Hisao , Bae Jang-Ho , Cahyadi Yeo Hans , Udayachalerm Wasan , Tresukosol Damras , Tansuphaswadikul Sudaratana
Published: July 2021

The aim of this study is to compare the safety and efficacy of Sirolimus (SES), Paclitaxel (PES), Zotarolimus (ZES), EPC capture (ECS) and Everolimus-eluting stent (EES) on the outcome of patients with chronic total occlusion (CTO). A prospective analysis of 1149 patients with 1183 CTOs (396 SES, 526 PES, 177 ZES, 41 ECS, 43 EES) in five high volume Asian centers after successful recanalization of CTO was performed. The study endpoints were 30 days and 9 months major adverse cardiac events (MACE), 9 months angiographic restenosis and target lesion revascularization (TLR). See table

for clinical results. The use of drug-eluting stents in patients with CTO was safe with low acute complication. Patients treated with SES and EES showed lesser rate of restenosis compared with other drug-eluting stents.