bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 635: The Proximal AV Bundle in the Human Heart and Related Morbidity
Authors: Racker Darlene K 
Published: July 2021

INTRODUCTION: The proximal AV bundle (PAVB) has been shown to be the only input to the AV node (AVN) in the canine heart in anatomoelectrical reports over the past 20 years. The anatomic studies utilized photographic correlations of epi- and endocardial aspects of whole hearts through blocking, and serial histologic parallel, perpendicular and transverse plane Goldner Trichrome stained sections of the flattened heart; Karnovsky’s fixative at pH 7.2 and sucrose buffer rinses; direct 3D and stereotaxic analysis. Electrical studies, under direct observation of in-vitro superfused hearts, delineated unique wire, catheter, and micropipet electrode potentials via high K, transections, Lucifer Yellow iontophoresis and photoablations during spontaneous and paced SA node rhythms and with simultaneous SA node, atrionodal bundles, PAVB, AVN and distal AV bundle recordings.
HYPOTHESIS: The PAVB exists in the human heart.

METHODS AND RESULTS: Explanted normal human hearts, deemed unsuitable for transplantation, processed as above with transverse sections, revealed that the AVN (Figs. A–C

) is joined by the PAVB at a 90-degree angle (Figs. B, C

). These “normal” hearts from older patients (57– 80 yr) had atrophic or absent atrial myocardium. In Figure C

, most of the right medial atrial wall myocardium, but not the left atrium (LA), had been replaced by fat.

CONCLUSIONS: PAVB is the only AVN input in the human heart. As in the canine heart, PAVB also runs away from the annulus and is apposed to LA. Knowledge of the PAVB should be helpful in decreasing morbidity associated with clinical procedures. Care must be taken in ablating the fast superior atrionodal bundle pathway input to the PAVB.

Figures

A
and
B
are from the same 60 yr and
C
is from a 71 yr old heart. AVN (A) is apposed to the left ventricular outflow tract (LVOFT and dotted line) along with the PAVB (
B and C
). But as seen in
C
, PAVB assumes a position apposed to LA, And, as in the dog heart, thereafter (not shown here) PAVB is completely apposed to LA.
Abstract 843: Restrictive Cardiomyopathy Linked cTnI Mutation (K178E) Causes Severe Heart Failure and Early Mortality
Authors: Jean-Charles Pierre-Yves , Du Jianfeng , Li Yuejin , Gobara Nariman , Huang Xupei 
Published: July 2021

Multiple mutations in cardiac troponin I (cTnI) have been linked to the development of restrictive cardiomyopathy (RCM) in human patients. Among them, K178E mutation has the worst clinical phenotype. K178E mutation may influence the inhibitory function through actin binding since previous studies have shown that amino acids number 173–181 bind to actin and increase the inhibitory effect of TnI. We modeled the mutation of lysine 178→glutamate (K178E) in human cTnI by cardiac specific expression of the mutated protein (cTnI
179Glu
in mouse sequence) in transgenic mice. Multiple lines were generated with varying degrees of expression to establish a dose relationship. Increased resting tension in isolated cardiac myocytes and decreased myofibrillar compliance were the main manifestations in cellular function measurements. In vivo cardiac function measured by high-resolution ultrasonic imaging and Doppler echocardiography revealed a significant diastolic dysfunction characterized with decrease of left ventricular end diastolic dimension (LVEDD), decreased cardiac ejection fraction (EF) and left ventricular faction of shortening (FS) as well as a decreased cardiac output (CO). Doppler measurements showed a restrictive left ventricular filling pattern, i.e. reversed E/A ratio; decreased deceleration time (DT); decreased isovolumic relaxation time (IVRT). Enlarged left and right atria was a dramatic sign, which was observed in most of the transgenic mice, and was developed early and fast (at age of 2–3 weeks). Severely affected lines developed a pathology similar to that observed in human restrictive cardiomyopathy patients who carry the same mutation and with a high early mortality. Our data indicate the causality of this mutation for diastolic dysfunction and heart failure and provide a useful animal model for further understanding the thin filament structure-function relationships and the physiological function of triponin in cardiac contraction and relaxation.

(Supported by NIH GM073621 and AHA0715116B)
This research has received full or partial funding support from the American Heart Association, AHA Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico & Tennessee).
Abstract 951: Femoral Plaques Confound the Association of Circulating Oxidized Low-density Lipoprotein with Carotid Atherosclerosis in a General Population Aged 35–55 Years (Asklepios Study).
Authors: Rietzschel Ernst , Langlois Michel , De Buyzere Marc , De Bacquer Dirk , Bekaert Sofie , Blaton Victor , De Backer Guy , Gillebert Thierry 
Published: July 2021

Objective. Previously reported associations of oxidized low-density lipoprotein (OxLDL) with non-invasive measures of atherosclerosis were inconsistent. Moreover oxLDL was not an independent predictor of future cardiovascular endpoints in models adjusting for lipid markers (total and HDL-cholesterol). Therefore, in the Asklepios Study cohort of 2524 asymptomatic subjects aged 35–55 years, we evaluated the multiple-adjusted association between circulating OxLDL and subclinical atherosclerosis in the carotid and femoral arteries (ultrasound based definitions).
Methods and results. Participants (mean age 45 years, 51.5% females) underwent a clinical examination, ultrasound protocol for determination of intima-media thickness (IMT) and plaques (Mannheim criteria) in the left and right carotid and femoral arteries, blood analysis for OxLDL (mAb-4E6) and other risk markers. They all completed a lifestyle variables study questionnaire. OxLDL concentrations were highest in subjects with femoral plaques (n=658). In the group of subjects with carotid plaques (n=476), elevated OxLDL concentrations were related to concomitant femoral plaques detected in 54% of these subjects. Stepwise multiple regression for oxLDL comprizing classical covariates demonstrated that non-HDL-cholesterol (beta 0.41), HDL-cholesterol (beta −0.34), femoral artery plaque (beta 8.97), ln(triglycerides) (beta 4.89), and gender (beta 2.79) were significant (p < 0.05) determinants. Full models including all appropriate anthropometric, hemodynamic, biochemical, and lifestyle variables confirmed that femoral plaques are independently related to OxLDL. Similar analyses demonstrated that femoral IMT, carotid IMT, or carotid plaques were not independently associated with OxLDL.
Conclusion. Circulating OxLDL is independently associated with femoral plaque and not with carotid artery wall damage.
Abstract 955: Vascular Function and Endothelial Progenitor Cells in Thromboangiitis Obliterans (Buerger’s Disease)
Authors: Nishioka Kenji , Higashi Yukihito , Umemura Takashi , Jituiki Daisuke , Goto Chikara , Nakamura Syuji , Hidaka Takayuki , Fujii Yuichi , Soga Jyunko , Hata Takaki , Idei Naomi , Fujimura Noritaka , Teragawa Hiroki , Kihara Yasuki 
Published: July 2021

Background: Buerger’s disease is associated with endothelial dysfunction. Several lines of evidence have shown that the circulating number and function of endothelial progenitor cells (EPCs) are surrogate biologic markers for cardiovascular diseases.
Methods and Results: The purpose of this study was to evaluate the role of EPCs in endothelial function in Buerger’s disease. We measured flow-mediated vasodilation (FMD), nitroglycerine (NTG)-induced vasodilation, circulating levels of EPCs, cell migration response to vascular endothelial growth factor (VEGF), and serum levels of VEGF in 25 patients with Buerger’s disease and 25 age- and sex-matched healthy subjects, and 25 patients with atherosclerosis obliterans (ASO). Vascular reactivity of brachial artery was measured by using high-resolution ultrasound. Circulating EPCs were quantified by flow cytometry. Cell migration assay was performed by the Boyden chamber technique. FMD was lower in both the Buerger’s group and the ASO group than in the control group (Buerger; 6.6±3.1%, ASO; 5.5±5.4%, vs. control; 10.6±3.3%, p<0.01, respectively). There was no significant difference in FMD between the Buerger’s group and ASO group. The number of circulating EPCs was similar in the Buerger’s group and control group, whereas the number of circulating EPCs was lower in the ASO group than in other groups (Buerger; 966±543/mL; control; 980±424/mL, vs. ASO; 466±339/mL, p<0.01, respectively). Cell migration to VEGF was similar in the Buerger’s group and control group, whereas cell migration was lower in the ASO group than in other groups (Buerger; 12.8±4.1/hpf; control; 13.2±3.5/hpf, vs. ASO; 4.2±1.1/hpf, p<0.01, respectively). Serum VEGF levels was higher in the Buerger’s and ASO groups than in the control group, whereas serum VEGF levels was similar in the Buerger’s group and ASO group.
Conclusions: These findings suggest that FMD was impaired in patient with Burger’s disease as well as patients with ASO compared with normal control subjects and that the number and function of EPCs were not decreased in patients with Burger’s disease. EPCs may be mobilized to restore endothelial function in Buerger’s disease. In patients with ASO, both the mobilizations of EPCs and endothelial function were impaired.
Abstract 2169: Chronic Intra-cardiac Parasympathetic AV-node Pacing In Goats With Chronic AF To Control Ventricular Rate
Authors: Kornet Lilian , Michels Koen , van Hunnik Arne , Verheule Sander , Scala Alberto Della , Cornelussen Richard 
Published: July 2021

INTRODUCTION Drug therapy to reduce the ventricular rate during atrial fibrillation (AF) is effective in only 50% of the patients and limited by side effects. Currently available pacing algorithms are even less effective. The aim of this study was to test the feasibility of chronic AV-Node Inhibition (AVNI) by intra-cardiac parasympathetic nerve stimulation. Our ultimate goal is to develop a pacemaker device with a feature to inhibit AV node function to decrease ventricular rate during AF.
METHODS Leads were implanted in the right atrial appendage and right ventricular apex and connected to a pacemaker for AF induction. In addition, an atrial lead (’AVNI lead’) connected to an implantable high frequency neurostimulator was implanted at a site with a strong prolongation of the PQ-time. Immediately after implantation optimal settings, optimal location, acute effects of AVNI on ventricular rate and the possible pro-arrhythmic effects of AVNI were assessed. The ’safety window’ for AVNI was defined as the difference between the output at the AVNI lead that produced atrial capture and the output that produced AVNI. One week after implantation, AF was maintained for one week by burst pacing via the lead in the right atrial appendage. After this 2 week period, the chronic effects of AVNI were assessed weekly for periods ranging from 3 weeks to 7 months.
RESULTS In total, 5 goats were studied . The optimal location for AVNI was located at the junction of the coronary sinus and inferior vena cava. Optimal AVNI was found at a stimulation frequency of 30Hz and pulse width of 180 μs in each animal. During the implant procedure “a safety window” appeared to be present. However, it became smaller after a longer period of AVNS. The acute effect of AVNI (averaged over the experiments) was a prolongation of the median R-R interval of 37 % (SD = 21%), which was not significantly different from the chronic effect at the end of the study (average = 32% (SD = 18%).
CONCLUSIONS Chronic intra-cardiac AV-node inhibition to reduce the ventricular rate during AF is feasible. Atrial pro-arrhythmic effects can be avoided by optimization of the stimulus parameters and location.
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 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 2542: Effect of Lipid Lowering Therapy on Progression of Coronary Fibroatheroma Evaluated by Virtual Histology Intravascular Ultrasound
Authors: Nasu Kenya , Tsuchikane Etsuo , Katoh Osamu , Kimura Masashi , Ehara Mariko , Kinoshita Yoshihisa , Matsuo Hitoshi , Asakura Yasushi , Matsubara Tetsuo , Terashima Mitsuyasu , Suzuki Takahiko 
Published: July 2021

Background: The aim of this study is to asses the effect of 12 month treatment with Fluvastatin (60 mg daily) on progression of fibroatheroma in a non-culprit vessel.
Methods: This prospective study was performed at 2 centers and designed to enroll 80 patients. Patients were randomized to receive lipid-lowering therapy by Fluvastatin or a lipid lowering diet. All patients with high low-density lipoprotein-cholesterol level (> 140 mg/dl) were included in the Fluvastatin group. Non-culprit vessels were imaged with a 20 MHz phased-array intravascular ultrasound (IVUS) catheter with motorized pull-back system at 0.5 mm/s. Virtual Histology-derived fibroatheroma (VHD-FA) was defined as 1) percent necrotic core area >20%; 2) percent plaque plus media cross-sectional area >40%. For each image, the area of vessel and each plaque component were calculated. At 12-month followup repeat IVUS measurements were performed.

Results: A total of 44 VHD-FAs in the Fluvastatin group and 47 VHD-FAs in the control group were detected at baseline. In the Fluvastatin group, fibrous and fibro-fatty areas are significantly decreased, necrotic core did not increase, and there was a significant reduction in atherogenic lipoproteins. In the control group, fibrous, necrotic core and dense calcium areas significantly increased (table

).

Conclusion: Lipid-lowering therapy with Fluvastatin prevented progression of coronary fibroatheroma.

Laboratory data and IVUS measurements
Abstract 2570: The Unrestricted Use Of Paclitaxel-eluting Stents: Five-year Results Of The Research Registry
Authors: Onuma Yoshinobu , Kukreja Neville , Garcia-Garcia Hector M , Daemen Joost , van Domburg Ron , Serruys Patrick W 
Published: July 2021

Objectives: Although the safety of drug-eluting stents (DES) has been under scrutiny, limited follow-up data up to 5 years are available, particularly among real-world patients. Therefore, we evaluated the 5-year clinical event rates in patients from the The Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital (RESEARCH) registry to establish the safety and efficacy of sirolimus-eluting stent (SES) in an unselected all-comer population.
Methods: On April 16, 2002, our institution commenced the use of SES (Cypher; Cordis Corporation, Miami Lakes, Florida) as the default strategy for all percutaneous coronary interventions at our institution. In the first 6 months of enrollment, 508 patients with de novo lesions were treated exclusively with SES (the SES group) and compared with a group of 450 consecutive patients treated with BMS for de novo lesions in the preceding 6 months (the pre-SES group), matched for stent diameter. Survival data was acquired from municipal civil registries. Health questionnaires have been sent to all living patients to obtain data on adverse clinical events were collected. Medical records will be reviewed and family doctors or referring cardiologists contacted as necessary. The primary end-point was composite major adverse events (MACE: all-cause death, myocardial infarction or target vessel revascularization [TVR]). Secondary endpoints included all-cause death, TVR and stent thrombosis. A propensity score-adjustment will be performed to compensate for differences in baseline characteristics between the groups.
Findings: Survival data is currently available for 94% of the patients after 5 years. The 5-year all-cause mortality rates were 14.0% for SES and 13.4% for BMS (p=0.9). Data on the other 5-year endpoints is currently being collected and will be presented at the time of the meeting.
Conclusions: There is no difference in the 5-year survival rates in the real-world unselected patients treated with SES, compared with BMS.