bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 5863: Rate and Correlates of Aortic Regurgitation Progression in a Cohort of 4128 Patients with Mild or Mild to Moderate Aortic Regurgitation
Authors: Patel Reena , Kamath Ashvin , Varadarajan Padmini , Krishnan Srikanth , Pai Ramdas G
Published: July 2021

Background
: Though the natural history of aortic stenosis is well studied, rate of progression of aortic regurgitation (AR) is not clear. This information is valuable for clinical decision making in patients with milder degrees of AR undergoing non aortic valve cardiac surgery.

Methods
: Our echocardiographic database between the years 1993 and 2007 was screened for patients with 1 or 2+ AR who had follow up echocardiograms at least 3 months later. AR severity was graded 1–4 based on standard criteria. A change in AR grade was annualized.

Results
: Of the 4128 patients, 3266 had 1+ and 862 had 2+ AR on the initial echocardiogram: age was 67±15 years, duration of follow up 4.2±2.7 years. Of those with 1+ AR on the initial echocardiogram, 95% had no change over a mean interval of 4.2 years and 2% increased the grade by ≥1+ per year. The average increase in AR grade was 0.04 per year. Of those with 2+ AR on initial echo, 90% had no change over this period and 2% increased the grade by ≥1+ per year. The average increase in grade was 0.07 per year. In the whole cohort, the AR progression correlated positively with age (p=0.03), ventricular septal thickness (p<0.0001), stroke distance (p=0.0003), increased transaortic velocity (p=0.01) and gradient (0.01) and initial AR severity (p<0.0001).

Conclusions
:

The rate of AR progression is extremely slow and prophylactic aortic valve replacement during non aortic surgery may not be indicated in those with 1 or 2+ AR.

AR progression seems to be higher in the elderly and those with aortic stenosis, higher cardiac output and greater AR severity.

On the average, it would take 25 years to progress from grade 1+ to 2+ AR and 14 years to progress from grade 2+ to 3+ assuming linear progression.
Abstract 5864: In Vivo Aortic Valve Thermal Heterogeneity In Patients With Non-rheumatic Aortic Valve Stenosis: First In Vivo Experience In Humans
Authors: Toutouzas Konstantinos , Drakopoulou Maria , Synetos Andreas , Tsiamis Eleftherios , Agorogiannis George , Kavantzas Nikolaos Kavantzas Nikolaos , Patsouris Eustratios , Iliopoulos Dimitris , Theodoropoulos Stergios , Yacoub Magdi , Stefanadis Christodoulos
Published: July 2021

Background:
Histological studies have demonstrated a potential role of inflammation and neoangiogenesis in aortic valve stenosis (AVS). Inflammatory activation may generate heat. We investigated in vivo in patients with AVS whether there is:

thermal heterogeneity within the valve leaflets,

temperature difference between the leaflets and the ascending aortic wall and

a possible correlation between heat production, inflammation and neoangiogenesis.

Methods:
We examined 96 leaflets from 32 patients scheduled for aortic valve replacement. Seventy-five leaflets were from 25 patients with AVS and 21 from 7 patients with aortic valve insufficiency (AVI) (control group). Temperature measurements were performed right before the hypothermic cardioplegia. Temperature difference (ΔT) was assigned as the mean temperature of each aortic leaflet minus the temperature of the aortic wall.

Results:
Histological, immunohistological analysis for inflammatory cells and vascular endothelial growth factor (VEGF) immunoreactivity was performed. Significant thermal heterogeneity was recorded within the leaflets of AVS, compared AVI (1.52±1.35°C vs 0.13±0.11°C, p<0.01). In AVS ΔT was 1.09±1.16°C for the non-coronary (NC), 1.24±1.03°C for the right and 1.53±1.23°C, for the left leaflet. ΔT was lower in AVI (0.10±0.10°C for the NC, 0.02±0.19°C for the right and 0.05±0.19°C, for the left leaflet, p<0.01 for all comparisons). Leaflets of AVS had increased inflammatory cell infiltration, calcium deposit, and anti-VEGF expression compared to AVI (p<0.01).

Conclusions:
Thermal heterogeneity is increased in AVS and correlates with inflammatory mononuclear cell infiltration, expression of pro-inflammatory cytokines and neoangiogenic factors. Future studies need to be performed to investigate possible prognostic and therapeutic implications.
Abstract 5787: Macrophage Infiltration and Apoptosis can be Imaged Utilizing
18
F-fdg and
99m
Tc-annexin A5: Potential Indicators of Plaque Vulnerability
Authors: Zhao Yan , Kuge Yuji , Zhao Songji , Strauss H. W , Blankenberg Francis G , Tamaki Nagara
Published: July 2021

Objectives:
Vulnerability of atheroma is associated with activated macrophage infiltration and apoptosis of foam cells. Activated macrophages have a high metabolic rate, and utilize exogenous glucose as their energy source. The oxidized lipid content of foam cells, is toxic and often results in apoptosis of these cells. Nuclear imaging provides at least two potential indicators to identify vulnerable plaques:
18
F-FDG as a marker of macrophage metabolism and
99m
Tc-annexin A5 (
99m
Tc-AN5) as a marker of apoptosis. This study compared the macrophage infiltration and lesion histology to the uptake of each tracer in apolipoprotein E knockout (ApoE−/−) mice.

Methods:
Male apoE−/− mice (n=4 –5/group) were maintained on a high-fat diet after the age of 5 wks. At the age of 25 and 35 wks,
14
C-FDG and
99m
Tc-AN5 were administered and aortas were harvested. Dual-tracer autoradiography, Movat pentachrome staining and Mac-2 staining were performed on serial cryostat sections (n=5– 6/mouse). Regional tracer uptake levels (ID%×kg/mm
2
) were evaluated in relation to the morphological lesion characteristics (AHA lesion phenotypes) and degree of macrophage infiltration (Mac-2 positive areas).

Results:
Plaque size and intimal thickness were increased with lesion progression. Macrophage infiltration was increased from early (type I-II) to atheromatous lesions (type III-IV) but decreased in fibroatheromatous lesions (type V).
99m
Tc-AN5 showed higher uptake levels in atheromatous lesions (0.49±0.20 %IDxkg/mm
2
) than early (0.40±0.17) or fibroatheromatous (0.30±0.13) lesions, being concordant with macrophage infiltration.
14
C-FDG uptake was also the highest in atheromatous lesions (3.1±1.5 in atheromatous, 2.8±1.5 in early, and 2.3±1.4 in fibroatheromatous lesions). The uptakes of both
99m
Tc-AN5 (r=0.65, p<0.01) and
14
C-FDG (r=0.44, p<0.001) were positively correlated with the degrees of macrophage infiltration.

Conclusion:
Each tracer showed a higher uptake in atheromatous lesions (AHA type III-IV) than other more stable lesions, directly corresponding to the degree of macrophage infiltration. Unstable plaques can be imaged utilizing
18
F-FDG and
99m
Tc-annexin A5, due to the presence of metabolically active and apoptotic macrophages.
Abstract 5788: VCAM-1 Targeted PET-CT Detects Inflammatory Atherosclerotic Plaques
Authors: Nahrendorf Matthias , Keliher Edmund , Panizzi Peter , Zhang Hanwen , Hembrador Sheena , Libby Peter , Kelly Kimberly , Weissleder Ralph
Published: July 2021

Hybrid PET-CT imaging of VCAM-1 expression and vascular anatomy may facilitate simultaneous assessment of atherosclerotic lesion biology and morphology, and enhance risk assessment in individual patients. We used combined in vitro/in vivo screening of candidate affinity ligands and developed a PET reporter for imaging VCAM-1 expression with high sensitivity, specificity and translational potential. Three different phage display-derived VCAM-1 affinity peptides were tested using immobilized VCAM-1, VCAM-1 expressing cells and apoE−/− mice. A compound with a linear peptide and arborising tetrameric design showed high affinity (86.6 nM) and specificity for VCAM-1 (97% inhibition with soluble VCAM-1). This lead compound was derivatized with 18Fluorine to synthesize the clinically viable PET agent 18F-4V. In vivo PET-CT imaging showed robust uptake of 18F-4V in plaque laden arterial sections from 8 apoE−/− mice, significantly higher than in 4 wild type mice and attenuated by atorvastatin treatment (p<0.05). 18F-4V uptake was confirmed in excised aortas, colocalized with atherosclerotic plaques delineated by Oil Red O staining and correlated with mRNA levels of VCAM-1 measured by quantitative RT-PCR (R2=0.62, p=0.03). 18F-4V allows noninvasive PET-CT imaging of VCAM-1 in atheromata, has sufficient dynamic range to quantify treatment effects, and correlates with inflammatory gene expression. This approach lends itself to seamless translation to human PET-CT imaging.
Abstract 5885: Impacts of Renal Insufficiency on the Prevalence of Heart Failure With Preserved Ejection Fraction in Hypertensive Patients
Authors: Ohtani Tomohito , Mano Toshiaki , Sakata Yasushi , Nishio Mayu , Takeda Yasuharu , Kamimura Daisuke , Tamaki Shunsuke , Omori Yosuke , Yamamoto Kazuhiro
Published: July 2021

Renal insufficiency is a predictor of hospitalization for heart failure in hypertensive patients. However, the onset of heart failure in patients with kidney diseases is principally attributed to left ventricular systolic dysfunction induced by myocardial infarction or long-term hypertension, and the effects of renal insufficiency on the prevalence of symptomatic heart failure stage without systolic dysfunction remain unclear. This study aimed to assess the effects of renal insufficiency on the prevalence of heart failure with preserved ejection fraction. Out of 650 hypertensive outpatients with ejection fraction≥50%, 191 patients met the Framingham heart failure criteria. The multiple logistic regression analysis revealed that obese, female, estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m
2
and a ratio of transmitral E velocity to early diastolic mitral annular velocity (E/E′) >15 were independent predictors of the prevalence of heart failure (Table

). To assess the effect of the renal insufficiency, the patients were divided into three groups as follow; CKD-A: eGFR≥75 (n=158), CKD-B: 60≤eGFR<75 (n=207), CKD-C: eGFR<60ml/min/1.73m
2
(n=285). The patients in CKD-B group represented higher E/E′ ratio and lower E′ velocity than those in CKD-A group. These indices were not different between the patients in CKD-B and CKD-C group. Hemoglobin concentration was significantly decreased and brachial-ankle pulse wave velocity was significantly elevated in the patients in CKD-C group compared to the other groups. Left ventricular diastolic dysfunction and renal insufficiency are independent risk factors for the prevalence of heart failure with preserved ejection fraction in hypertensive patients. Renal insufficiency exerts its effects through the modulation of extracardiac factors such as anemia and arterial stiffening rather than through the promotion of diastolic dysfunction.

Table.

Multivariate analysis of determinants of heart failure with EF≥50%
Abstract 5907: Development of Left Ventricular Dysfunction During Progression of Infant Right Ventricular Hypertrophy
Authors: Kitahori Kazuo , He Huamei , Cowan Douglas B , Friehs Ingeborg , Nido Pedro J , McGowan Francis X
Published: July 2021

Background: Progressive left ventricular (LV) dysfunction can be a major late complication in patients with chronic right ventricular (RV) pressure overload (e.g. tetralogy of Fallot). The mechanisms remains unclear. We therefore examined LV function (serial echocardiography and ex vivo Langendorff) and histology in a model of infant pressure-load RV hypertrophy (RVH).

Methods and Results: Ten-day-old rabbits (N=6 per time point, total =48) underwent pulmonary artery banding (PAB), were sacrificed at 2–8 weeks after PAB, and compared to age-matched sham controls. Both RV and LV performance (myocardial performance index, MPI; fractional area change, FAC), measured by echocardiography, decreased during the progression of RVH (Table

). In addition, RVH caused significant septal displacement, reduced septal contractility, and decreased LV end-systolic (LVDs) and diastolic (LVDd) dimensions. Significant septal and LV free wall apoptosis (myocyte-specific TUNEL and activated caspase-3), fibrosis (Masson’s Trichrome), and reduced capillary density (CD31 immunostaining) occurred in the left ventricles of the PAB group after 6 – 8 wks (all p<0.05).

Conclusion: This study for the first time shows that pressure overload resulting in RVH causes LV dysfunction by both mechanical and molecular effects upon the septum and LV myocardium. In particular, the development of RVH is associated with septal and LV apoptosis, pathologic LV remodeling, and reduced LV capillary density. Potential mediators and mechanisms (e.g. paracrine vs. circulating stimuli) merit further investigation

LV performance during the progression of RVH
Abstract 5918: Length of Stay for Acute Heart Failure: Effects of Cohorting Patients on Variability
Authors: Saltzberg Mitchell , Albert Maria , Mahoney Donna , Bouffard Lynne , Weintraub William
Published: July 2021

Background: Quality metrics for heart failure (HF) are increasingly utilized as an indicator of quality care. Mean length of stay (LOS) is a commonly utilized metric that is made available to the public but variability in LOS is not reported. Efforts to cohort HF pts in the hospital improve quality of care but the effect on LOS is less well defined.

Methods: As part of an ongoing performance improvement project at ChristianaCare, LOS was evaluated using standard descriptive statistics. A LOS distribution was also generated monthly to visualize LOS variability. Comparisons were made for HF pts cohorted on a dedicated HF unit (HFU) vs. all other units (Other) and by inclusion/exclusion of HF pts with prolonged LOS > 10 days to reduce the effects of outliers.

Results: 71 % of all HF patients were discharged in < 5 days, 82 % in < 10 days. Mean LOS (March 07–March 08) for HF was 6.63 days overall (6.1 HFU vs. 7.2 other; p = 0.05). After exclusion of long LOS HF pts, mean LOS fell to 4.4 days (4.3 HFU vs. 4.5 Other; p = 0.06). Median LOS for all HF patients was 5.0 days regardless of location. The standard deviation of LOS was significantly lower for HFU patients (4.5 vs. 11.5 days, p < 0.02) The LOS graph (Graph 1) highlights the wide variability in LOS and how mean statistics may be misleading.

Conclusions: Mean LOS can be misleading as a metric for quality of HF care provided as outliers significantly impact this value. Other statistics and graphical displays can more accurately reflect quality of care. In addition, cohorting of HF patients significantly reduces overall variability in LOS and suggests a more consistent approach to acute HF care.
Abstract 5926: Cardiac Electrical Resynchronization Therapy Combining HIS Bundle and Left Ventricular Pacing is Effective in the Treatment of Severe Heart Failure
Authors: Tung Stanley , Rajagopalan Kesava , Ignaszewski Andy , Affolter Jonathan
Published: July 2021

Introduction:
It is known that Cardiac Resynchronization Therapy (CRT) combining right ventricular (RV) apex pacing and left ventricular pacing (LVP) is ineffective in up to 35% of heart failure (HF) patients. Our hypothesis is that RV apical pacing bypasses the rapidly conducting right bundle and may further impede ventricular activation with LBBB hence a more physiological CRT is via HIS Bundle pacing (HBP) and LVP. We report of our early experience with Cardiac Electrical Resynchronization Therapy (CERT) incorporating HBP with LVP in patients with severe HF.

Methods:
Patients indicated for CRT were approached for CERT. In addition to an atrial and LV lead, patients also received a HBP lead. An active fixation lead (SelectSecure/Site® Medtronic) was used directly for HIS Bundle mapping and pacing. HBP implant thresholds, procedure and fluoroscopy times, pre and post implant QRS, PR interval, and NYHA class were collected. Student
t
-test was used for analysis.

Results:
15 patients (13 male, mean age 70yrs) referred for CRT underwent successful CERT with mean follow up of 3.5±4.3 months. The mean implant HBP threshold, procedure and fluoroscopy time were 1.6V/0.6ms, 150min, and 26min respectively. All patients had QRS shortening with a mean of 64±21ms (pre CERT 182ms, post CERT 118ms, p<0.0001, figure

) and mean PR shortening of 81±101ms (pre CERT 254ms, post CERT 173ms, p<0.05). 13 patients had improvement of at least one NYHA class.

Conclusions:
HBP with LVP is effective in achieving electrical resynchronization, and has resulted in early improvement of HF symptoms. Evidence of reverse remodeling is pending. CERT needs to be further validated before considering for wide adoption.
Abstract 5932: The Differences of Echocardiography and MRI Findings in Patients with Constrictive Pericarditis According to the History of Chest Radiation
Authors: Kim Kye Hun , Feng DaLi , Glockner James , Martinez Matthew , Edwards William D , Syed Imran S , Araoz Philip , Julsrud Paul R , Bree Jerome F , Williamson Eric , Oh Jae K
Published: July 2021

Background:
Radiation therapy (RT) to the chest may induce various combined cardiac problems such as constrictive pericarditis (CP), restrictive myocardial disease, and coronary artery disease. Therefore, it was hypothesized that the MRI and transthoracic echocardiographic (TTE) findings in patients with CP may differ according to the history of RT.

Methods:
A total of 68 patients with CP who performed both TTE and MRI study at Mayo Clinic from 2002 to 2008 were reviewed and divided into two groups according to the history of RT; RT group (group I, n=13, 53.6±9.8 years, 8 males) versus no RT group (group II, n=55, 59.0±14.8, 45 males).

Results:
The results of TTE study were summarized in table

. Early diastolic velocity of septal mitral annulus (E′) and deceleration time (DT) of mitral inflow was significantly lower, and the ratio of early diastolic mitral inflow velocity (E) to E′ is significantly higher in group I than in group II. Left atrial volume index (LAVI) was significantly lower and LA area and left ventricular end-diastolic dimension (LVEDD) was significantly smaller in group I than in group II. Delayed enhancement of pericardium was the only significant finding in MRI and significantly prevalent in group I than in group II (100.0% in group I vs 63.6% in group II, p=0.012). The other MRI findings including pericardial thickness, left ventricular and right ventricular ejection fraction, and the presence of pericardial and pleural effusion were not different between the groups.

Conclusion:
In CP patients with the history of RT compared to patients without history of RT, E′ and DT was significantly lower, LAVI and LVEDD were smaller, pericardial DE in MRI was invariably found. The lower E′ velocity and decreased chamber size and volumes may be explained by RT induced coexisting myocardial disease.

TTE findings of the patients
Abstract 5933: Reduced Number of Gap Junctions at the Intercalated Disc in the Ventricles of Boxer Dogs Afflicted with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
Authors: Oxford Eva M , Maass Karen , Moise N. Sydney , Delmar Mario
Published: July 2021

ARVC is an inherited myocardial disease associated with sustained monomorphic ventricular tachycardia, sudden cardiac death, and replacement of RV myocardium with fatty or fibro-fatty tissue. Lethal arrhythmias often occur in young patients, before apparent structural damage. It has been hypothesized that loss of Cx43 gap junctions (GJ) may act as a substrate for ventricular arrhythmias in these patients. An inherited form of ARVC is present in the boxer, with clinical symptoms and pathological features similar to those of humans. Here, we used transmission electron microscopy (TEM) to assess the ultrastructure of the intercalated disc (ID) in ARVC-afflicted boxers. Samples from the right and left ventricles (RV and LV) of 1 unafflicted beagle, and 3 ARVC afflicted boxers were examined by TEM. Samples from beagle tissue showed normal morphology, good alignment of the sarcomeres and myofibrils, and attachment of myofibrils to the ID. Samples from the ARVC-afflicted boxer lacked myofibril organization, with few attachments to the ID. Within RV and LV longitudinal sections from one afflicted and one control animal, three parameters were measured: ID length, individual GJ length, and number of GJ per ID. No significant differences were found in the length of IDs or of GJs from RV or LV samples of ARVC vs. control. ID length (μm) was 26.8 +/− 5.4 and 44.9+/− 10.6 in control RV and LV, respectively. ID length in afflicted samples was 31.2+/− 5.0 and 52.3+/−13.5 (pNS). GJ length (μm) was .5+/−.03 and .5+/.05 for RV and LV of the control group, and .4+/−.07 and .6+/−,13 in samples obtained from RV and LV of ARVC afflicted animals (pNS). However, our data indicated a significant (p<.01) decrease in the number of GJ per ID in the ARVC sample by over 80% (5.7+/−.4 RV, 5.8+/− 1.4 LV in control; 1.1+/−.16 RV, 1.5+/−.2 LV in ARVC). Our results suggest that ARVC, both in humans and in boxer dogs, associates with a loss of GJ, which may act as a substrate for lethal arrhythmias. In contrast to human ARVC, no desmosomal protein mutations have been linked to boxer ARVC. This suggests a different genetic basis and yet, a common molecular pathway for ARVC in both species. As such, boxers represent a valuable model to understand the mechanisms leading to malignant ventricular arrhythmias in ARVC patients.

This research has received full or partial funding support from the American Heart Association, AHA Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).
Abstract 5943: Electrical Dysynchrony Acutely Increases Interstitial Matrix Metalloproteinase Activity
Authors: Mukherjee Rupak , Zavadzkas Juozas A , Rivers William T , McLean Julie E , Chang Eileen I , Koval Christine N , Stroud Robert E , Spinale Francis G
Published: July 2021

Increased matrix metalloproteinase (MMP) abundance occurs with adverse LV remodeling in a number of cardiac disease states, including those induced by long-standing arrhythmias. However, whether regionally contained dyssynchronous electrical activation of the LV, with consequent dyskinesia, alter interstitial MMP activation remained unknown. Electrical activation of the LV of pigs (n=10, 30–35 kg) was achieved by pacing (120 bpm) at left atrial (
A
) and LV sites (
V)
such that normal
A-V
electrical activation (60 min) was followed by regional early
V
activation for 60 min
within 1.5 cm of the

V site

, and restoration of normal
A-V
pacing for 120 min. Regional shortening (piezoelectric crystals) and interstitial MMP activity (microdialysis with MMP fluorogenic substrate) at the
V
pacing site and a remote LV site were monitored at 30 min intervals. With early
V
activation, segmental shortening was reduced (8.4±0.6% vs 1.2±0.9%, p<0.05) at the
V
site, but not at the remote site (8.5±0.3%). Interstitial MMP activity was similar at remote and
V
sites during initial
A-V
pacing (1172±187 vs. 1332±87 fluoro units, resp). Dyssynchrony increased interstitial MMP activity at the
V
site compared to the remote region (Figure

). Restoration of
A-V
pacing normalized segmental shortening (8.5±0.4%), but MMP activity remained elevated. This study, for the first time, demonstrates that despite restoration of mechanical function, disturbances in electrical conduction - in and of itself - can directly cause regional MMP activation, and therefore, contribute to myocardial remodeling.
Abstract 5946: Ntprobnp Guided Treatment for Chronic Heart Failure: Results from the Battlescarred Trial
Authors: Richards A Mark , Lainchbury John G , Troughton Richard W , Strangman Kim , Frampton Christopher M , Pilbrow Anna , Yandle Tim G , Hamid Amjad , Nicholls M Gary
Published: July 2021

Three hundred and sixty four (364) patients satisfying Framingham and ESC criteria for symptomatic heart failure were randomized 1:1:1 (with prospective sub-stratification according to age ≤ or > 75 years) to Usual Care (UC), Intensive Clinical Management (CC) or Hormone Guided Care (HGC) incorporating serial measurement of NTproBNP levels into the treatment algorithm. The 3 treatment strategies were applied for 2 years. Minimum follow-up was 12 months with median follow-up 2.8 years. The primary end-points were all-cause mortality and death+/− admission with decompensated Heart Failure (HF). Groups were matched for age (median 76–77years); LVEF (37%) and baseline NTproBNP (medians 235–239 pmol/L ie 1997–2021 pg/ml). All-cause mortality at 12 months was halved by both intensive strategies (18.9, 9.1 and 9.1% respectively for UC, CC and HGC respectively; (P=0.028 overall and P=0.029 for pairwise (UC vs CC and UC vs HGC) intergroup comparisons). At 2 and 3 years follow-up mortality rates did not differ overall but significant treatment effects were observed in those aged ≤75years (P<0.025 for interaction between age and management strategy at all time points). At 1, 2 and 3 years, in those ≤ 75 years, cumulative all-cause mortality was 1.7, 7.3 and 15.5% in HGC; 7.3, 20.0, and 30.9% in CC and 20.3, 23.4 and 31.3% in UC. HGC significantly reduced cumulative mortality below that in UC throughout follow-up (P=0.001 and P=0.021 at 1 and 3 years respectively) and also below that in CC by 3 years follow-up (P=0.048) whereas CC conferred no advantage over UC after one year of follow-up (P=0.04 and ns at 1 and 3 years respectively). The composite end-point of death+/− admission with HF was reduced only in younger patients receiving HGC (P<0.05 at 1, 2 and 3 years follow-up compared with UC). Total days “alive and not in hospital with HF” over 3 years of follow-up, averaged 206 days more in this subgroup than in their peers within the UC group (P<0.05). No benefits were observed in those aged > 75 years. Intensive management of chronic HF reduces one-year mortality compared to usual care. Over long-term follow-up hormone guided therapy may offer an additional mortality advantage over otherwise similarly intensive specialist clinic-based care particularly in those aged ≤ 75 years.
Abstract 5955: Role of Bradykinin and Chymase in Cardiorenal Function Under Long-Term ACE Inhibition in Heart Failure
Authors: Wada Atsuyuki , Matsumoto Takehiro , Ohnishi Masato , Fujii Masanori , Tsutamoto Takayoshi , Horie Minoru
Published: July 2021

Renal insufficiency is relatively common in patients with heart failure (HF) and patients with chronic kidney disease are known to have a significant increase in cardiovascular morbidity and mortality. Angiotensin (Ang) II plays an important role in water and sodium (Na) balance and renal injury. Although ACE inhibitors (ACEIs) suppress the formation of Ang II and are useful in the treatment of HF, the agents also prevent the breakdown of bradykinin (BK), which exerts its vasodilative action through BK type 2 (B2) receptors. On the other hand, over 50% of renal Ang II formation in HF is mediated by ACE independent chymase pathway. The roles of BK and chymase in the cardiorenal function under chronic treatment of ACEI has not been fully elucidated as yet. We therefore evaluated the cardiorenal effects of a specific B2 receptor antagonist, FR173657 (FR, 0.3mg/kg/day) or a specific chymase inhibitor, (ChyI, 100mg/kg/day) with an ACEI, enalapril (1mg/kg/day) compared to those of enalapril alone in dogs with tachycardia induced HF (22days). Cardiac contractile function markedly deteriorated and body fluid retention and impaired renal function accompanied with upregulation of renal ACE and chymase mRNA levels after the induction of severe HF. However, enalapril significantly improved the ejection fraction (vehicle 19% vs. enalapril 36%, p<0.01) and increased urine excretion (vehicle 0.36 vs. enalapril 0.55 ml/min, p<0.05) associated with increases in the glomerular filtration rate (GFR) and renal plasma flow (RPF) (vehicle 24 vs. enalapril 60 ml/min, and 74 vs. 169 ml/min, respectively p<0.05) in HF. There were no differences observed in blood pressure and LV ejection fraction among three treatment groups. FR did not statistically affect urinary Na excretion, GFR and RPF compared to the ACE inhibition alone, however, the chymase inhibition has more significantly increased water and Na excretion rate (0.70 vs. 0.55 ml/min and 56 vs. 26 μEq/min, respectively p<0.05) and GFR (70 vs. 59 ml/min, p<0.05) compared to the ACE inhibition alone. In conclusion, endogenous BK does not likely contributes to the renoprotective effects of ACEI, however, combining ACE and chymase inhibition has greater therapeutic potential in the amelioration of renal function in HF.
Abstract 5992: Comparison of 4 Years Efficacy and Durability of Sirolimus-Eluting Stent and Paclitaxel- Eluting Stent Deployment in Patients with Very Long Coronary Lesions: Multicenter Registry in Asia
Authors: Nakamura Sunao , Ogawa Hisao , Bae Jang-Ho , Cahyadi Yeo Hans , Udayachalerm Wasan , Tresukosol Damras , Tansuphaswadikul Sudaratana
Published: July 2021

Aim
: The aim of this study is to compare the 4 years safety and durability of Sirolimus-eluting stent (SES) and Paclitaxel-eluting stent (PES) deployment on the outcome of patients with very long coronary lesions (VLL).

Methods
: A prospective analysis of 656 patients 730 lesions (male 70.4%, mean age 66.9 yrs) with very long coronary lesion (≥40mm) (368 SES and 288 PES) in five high volume Asian centers after successful stenting in VLL was performed. Lesion locations of VLL were LAD 48.2% (SES 50.2%, PES 45.7%), LCX 18.5%, RCA 33.3%. Complete clinical follow-up to 4 years is being analyzed for all patients.

Results
: The baseline clinical characteristics between 2 groups were similar. At 4 years overall cardiac events of SES (16.3%) were lower than PES (24.0%) (p=0.03). See table

for clinical results.

Conclusion
: The use of SES and PES in patients with very long coronary lesion was safe and feasible with low acute complication and low incidence of restenosis. SES showed lesser incidence of cardiac events (death, myocardial infarction, CABG and PCI) at 4 years clinical follow-up. SAT (sub acute stent thrombosis), LAST (late stent thrombosis: ~1year), VLAST (very late stent thrombosis: 1year~ 4years) MACE (death, myocardial infarction, CABG and PCI).
Abstract 6016: Pathology Of Hypersensitivity In Late Drug Eluting Stent Thrombosis
Authors: Ladich Elena , Nakazawa Gaku , Cook Stephane , Windecker Stephan , Burke Allen , Kolodgie Frank , Virmani Renu
Published: July 2021

Background: Localized hypersensitivity (HS) has been reported as a pathologic risk factor for late DES thrombosis (DES-LST). The objectives of the study were to examine the pathologic features of HS in DES-LST and correlate with stent characteristics, underlying plaque morphologies and patient risk factors.

Materials and methods: From a registry of 153 DES patients, 33 patients with DES-LST were identified. LST was defined as platelet-rich thrombus in a coronary stent implanted > 30 days. Stented arteries were serially sectioned at 2–3 mm intervals and stained with H&E, Movat stain, Luna stain (eosinophils), and UCHL (T-lymphocytes). Localized HS was defined as an inflammatory cell infiltrate composed predominantly of eosinophils and T-lymphocytes limited to the arterial wall surrounding the stent. Patient data, risk factors, stent characteristics, and underlying plaque morphology were compared between two groups: hypersensitivity (HS), and non-hypersensitivity LST (NHS).

Results: Of the 33 DES-LST cases with occlusive thrombus, 6 (4 men, 2 women) demonstrated HS histologically (18%). The mean age was 54 years (range 40 – 62 years). All 6 had Cypher stents (mean stent length=24 mm), 4 had >1 stent, 2 with overlapping stents. The mean stent duration was 624 days (range 112 to 990 days). Three patients were on ASA and clopidogrel, 2 ASA only, 1 discontinued ASA/clopidogrel prior to non-cardiac surgery. Patient risk factors included hyperlipidemia (n=6), hypertension (n=5) and smoking (n=4). All demonstrated underlying fibroatheroma with stent struts penetrating necrotic core in 3 and 2 with previous rupture sites. Stent malapposition was present in 5 (83%). Twenty-seven patients demonstrated NHS-LST (Cypher=7, Taxus=20). Mean stent duration was 326 days (range 31–1200 days). Malapposition was identified in 10 (37%). Compared to NHS, the HS LST group was more likely to demonstrate stent malapposition (p=0.04) and longer implant times (p=0.049).

Conclusions: DES-LST is related to HS in 18% of cases, is associated with Cypher stents, malapposition and longer implantation time. Localized HS with stent thrombosis is a clinically important problem that may occur late after stenting and warrants further pathologic study.
Abstract 6022: The Effect of Pre-Hospital Tirofiban on Early Stent Thrombosis in STEMI Patients Undergoing Primary PCI
Authors: Heestermans Ton , Klinieken Isala , van Werkum Wouter , ten Berg Jurrien , Giannitsis Evangelos , Dill Thorsten , Dambrink Jan-Henk , Klinieken Isala , Hamm Christian , van ’t Hof Arnoud W
Published: July 2021

Objective
The aim of this analysis was to assess the effect of pre-hospital initiation of high-dose (HD) tirofiban on the incidence of early stent thrombosis (ST) in patients undergoing primary PCI for acute myocardial infarction.

Methods
Patients were randomized to HD tirofiban or no tirofiban in the ambulance on top of 600 mg clopidogrel, 500 mg aspirin and 5000 IU unfractionated heparin. ST was defined according to the Academic Research Consortium definitions of
“definite”
and
“probable”
stent thrombosis.

Results
A total of 1073 out of 1398 patients (76.8%) underwent primary PCI with stent implantation. Overall,
“definite”
or
“probable”
ST occurred in 39 patients (3.6%) at 30 days. The incidence in the no tirofiban or placebo group was 5.2% (28/537; 27 definite and 1 probable) versus 2.1% (11/536; 10 definite and 1 probable) in the HD tirofiban group (p=0.006). In univariate analysis, predictors of ST were no pre-hospital initiation of HD tirofiban (p=0.006), previous myocardial infarction (p=0.016), TIMI risk score >3 (p=0.027) and TIMI major bleeding (p=0.002). By multivariate analysis, no pre-hospital initiation of HD tirofiban (Odds ratio [OR] 2.54, 95% confidence interval [CI] 1.21–5.32; p=0.013), previous myocardial infarction (OR 3.32, 95%-CI 1.35– 8.18; p<0.01), and TIMI major bleeding (OR 8.40, 95%-CI 2.24 –31.46; p=0.002) were independent predictors of early ST. Thirty day mortality was significantly higher in those with ST (10.3% versus 1.7%, p<0.001).

Conclusion
Pre-hospital initiation of high dose tirofiban reduces the 30-day incidence of stent thrombosis in STEMI patients treated with primary PCI. Early stent thrombosis was associated with poor outcome.
Abstract 5799: Fine-Cell Detector Computed Tomography with 0.3mm-Collimation Improves Quantitative Assessment of Coronary Artery Stenosis: Experimental Study with Coronary Phantom
Authors: yamada Minoru , Jinzaki Masahiro , Sato Kozo , Tanami Yutaka , Ueno Akihisa , Imai Yasuhiro , Nukui Masatake , Ishihara Yotaro , Sasaki Kosuke , Kuribayashi Sachio
Published: July 2021

The purpose of this study was to evaluate whether the prototype fine-cell detector computed tomography (FDCT) could improve smaller coronary artery stenosis measurement compared with 64-slice multidetector-row CT (MDCT).

Method and Materials:

We developed coronary phantoms of 2mm in diameter with 0%, 25%, 50%, 75% stenosis. Each stenotic part was made by Acrylonitrile-Butadiene-Styrene (ABS: 50 Hounsfield Unit (HU)) and lumen was filled with diluted iodine (380 HU). These coronary phantoms put into the water tank were scanned by both prototype FDCT and 64-slice MDCT. Configuration of FDCT was 32-row*0.3125mm detector collimation with 0.35mm smaller X-ray tube focal spot width, and that of 64-slice MDCT was 16-row*0.625mm detector collimation and 0.7mm X-ray focal spot. All axial images were reconstructed using Standard kernel with 96mm display field-of-view. Minimum lumen diameter and degree of stenosis in these data sets were automatically measured using the Vessel Analysis software (GE Healthcare).

Results:

Measured coronary lumen at 0%, 25%, 50%, 75% stenosis of 2mm-diameter phantom (corresponding to 2.0mm, 1.5mm, 1.0mm, 0.5mm) were 2.2mm, 1.8mm, 1.4mm, 0.7mm in FDCT, whereas those were 2.5mm, 2.0mm, 1.5mm, 1.4mm in 64-slice MDCT, respectively. Each degree of stenosis was calculated 21%, 38%, 69% in FDCT, while 20%, 38%, 44% in 64-slice MDCT. Measured value of 75% stenosis in FDCT was significantly improved compared with 64-slice MDCT.

Conclusion:

FDCT improves the accuracy of smaller coronary artery stenosis measurement compared with 64-slice MDCT. Superior spatial resolution of FDCT could be promising for more accurate assessment of the coronary artery stenosis.
Abstract 6048: An Indirect Comparison of the Efficacy and Safety of Factor Xa Inhibitors with Thrombin Inhibitors nn Preventing Venous Thromboembolism after Hip or Knee Surgery
Authors: Karthikeyan Ganesan , Eikelboom John W , Yusuf Salim , Hirsh Jack
Published: July 2021

Introduction
Selective factor Xa inhibitors and thrombin inhibitors are effective in the prevention of venous thromboembolism (VTE) after hip or knee surgery, but they have not been compared directly against each other. We performed an indirect comparison of the relative efficacy and safety of these two classes of inhibitors, from meta-analyses of randomized controlled trials (RCTs) of these agents, in which a low molecular heparin (LMWH) was used as a common comparator.

Methods
Relevant RCTs were identified by searching MEDLINE (Ovid MEDLINE® 1950 to March week 1, 2008), EMBASE (1980 to 2008, week 10) and the Cochrane Central Register of Controlled Trials (1
st
quarter 2008), supplemented by hand searching and screening meeting websites. We restricted our search to the five agents (ximelagatran, dabigatran, fondaparinux, idraparinux and rivaroxaban) that have been evaluated in phase III trials. Trials were included if the study drug was compared against a LMWH and was administered in the pre- and/or postoperative (12–24hrs from surgery) period, to patients undergoing elective, hip or knee replacement surgery. The outcomes assessed were total VTE, symptomatic VTE, major bleeding and the need for blood transfusions. We obtained summary estimates (RR and 95% CI) for each outcome for the Xa and thrombin inhibitor studies, using a random-effects model. We then performed indirect comparisons between these estimates using standard statistical methods.

Results
We included 12 trials (18110 patients) of factor Xa inhibitors (fondaparinux, rivaroxaban) and 10 trials (17777 patients) of thrombin inhibitors (ximelagatran, dabigatran). These agents were compared with enoxaparin, except in two studies where dalteparin was the control agent. On indirect comparison, factor Xa inhibitors were significantly better than thrombin inhibitors in preventing total VTE (RR 0.54, 95% CI 0.40 – 0.75) and symptomatic VTE (RR 0.49, 95% CI 0.25– 0.97). There was no difference in the risk of major bleeding (RR 1.17, 95% CI 0.71–1.93) or the number of transfusions (RR 1.02, 95% CI 0.94–1.11).

Conclusion
Based on this indirect comparison, selective factor Xa inhibitors appear to be more effective than thrombin inhibitors, for the prevention of VTE after elective hip or knee surgery.
Abstract 6054: Immersing Feet in CO
2
-Rich Water-Bath Improves Ulcer Healing on Ischemic Limb after Infrainguinal Bypass Surgery
Authors: Hayashi Hisae , Kumada Yoshitaka , Furuhashi Kyuichi , Takahashi Hiroshi , Toriyama Takanobu , Ishii Hideki , Yamada Sumio , Murohara Toyoaki
Published: July 2021

Background
: We have shown that immersion of feet in warmed water enriched with carbon dioxide (CO
2
immersion) improves subcutaneous microcirculation in critical limb ischemia (CLI) with ischemic ulcer/gangrene. Using an animal model, other group has reported that the CO
2
immersion enhances collateral blood flow in ischemic limb via mobilization of endothelial progenitor cells and activation of NO-cGMP system. For CLI patients with ulcer/gangrene, infrainguinal bypass surgery is the standard therapy. However, ulcer healing and prevention of amputation still remain suboptimal. In order to know whether the CO
2
immersion improves the clinical efficacy, here we performed the CO
2
immersion after infrainguinal bypass surgery.

Methods
: This study was designed as a prospective controlled trial. Fifty-five patients with ischemic ulcer/gangrene underwent the standard care including successful infrainguinal bypass surgery were enrolled and were randomly divided into the two groups; patients underwent standard care added CO
2
immersion (CO
2
group, 27 patients with 30 limbs) and patients received standard care alone (control group, 28 patients with 30 limbs). The patients in the CO
2
group immersed their feet in CO
2
enriched water (depth of 20 –30 cm, 37–38°C, duration for 10 minutes) twice a day. Primary endpoint was defined as complete healing of ischemic ulcers.

Results
: Baseline demographical data, traditional risk factors, surgical procedure, ankle pressure and transcutaneous oxygen pressure (tcPO
2
) were comparable between the two groups. Rate of the complete ulcer healing after 1-year was much higher in the CO
2
group than in the control group (43.3% vs. 20.0%, HR 2.72, 95%CI 1.03–7.17, p=0.043). Cox multivariate analysis revealed that CO
2
immersion (HR 4.13, 95%CI 1.09 –15.75, p=0.038), diabetes (HR 0.020, 95%CI 0.01–.303, p=0.005) and tcPO
2
(HR 1.04, 95%CI 1.00 –1.09, p=0.050) were independent predictors for complete ulcer healing. In contrast, rates of 1-year mortality, graft patency and limbs salvage showed no significant differences between 2 groups (p=0.55, p=0.47 and p=0.16, respectively).

Conclusion
: The CO
2
immersion after infrainguinal bypass surgery provided additional benefit for the ulcer healing in CLI patients with ulcer/gangrene.
Abstract 5804: Validation of a Body Mass Index Adapted Scanning Protocol for Low-Dose 64-Slice CT Coronary Angiography with Prospective ECG-Triggering
Authors: Tatsugami Fuminari , Husmann Lars , Herzog Bernhard A , Burkhard Nina , Valenta Ines , Gaemperli Oliver , Wyss Christophe A , Landmesser Ulf , Kaufmann Philipp A
Published: July 2021

As an increase in body mass index (BMI) confers a higher image noise in computed tomography coronary angiography (CTCA), we have validated a BMI-adapted scanning protocol for low-dose 64-slice CTCA with prospective electrocardiogram (ECG)-triggering. One-hundred-one consecutive patients underwent CTCA with prospective ECG-triggering, using a fixed contrast material protocol (80mL iodixanol, 50mL saline chaser, flow rate of 5mL/sec). Tube voltage and current were adapted to BMI (table

). Attenuation (Houndsfield units, HU) was measured and contrast-to-noise ratio (CNR) calculated for the proximal right coronary artery (RCA) and left main artery (LMA). Image noise was determined as the standard deviation of attenuation in the ascending aorta. Mean BMI was 25.7±4.3kg/m
2
(range 18.2–38.8kg/m
2
) the mean effective radiation dose was 2.1±0.7mSv (range 1.0 –3.2mSv). There was no significant correlation between BMI and image noise (r= 0.11,
P
= 0.284), indicating optimal protocol adjustment. However, BMI was inversely correlated to vessel attenuation (RCA: r=−0.45,
P
<0.001; LMA: r=−0.47,
P
<0.001), and CNR (RCA: r=−0.39,
P
<0.001; LMA: r=−0.37,
P
<0.001). The proposed BMI-adapted scanning parameters results in similar image noise regardless of BMI. Increased bolus dilution due to larger blood volume may have contributed to a decrease in CNR and vessel attenuation in higher BMI as a fixed contrast material bolus was used.

Table
Abstract 6091: A Simple TIMI Discharge Risk Score Post ACS Predicts CV Mortality at 2 Years
Authors: Forman Daniel E , Giugliano Robert P , Cannon Christopher P , Morrow David A , Qin Jie , Antman Elliott M , Braunwald Eugene
Published: July 2021

Improved risk stratification at hospital discharge may help guide better post-ACS management. We used data from 2 lipid-lowering trials post-ACS (PROVE IT-TIMI 22, A2Z) to derive a discharge score for predicting long-term CV mortality and validated the score in an external test set from MERLIN-TIMI 36 (ranolazine in nSTE-ACS). Univariate analyses of data from the index ACS admission were used to identify predictors of post-hospital CV mortality (avg 2 yr f/u). A multivariable model using backward selection was constructed to develop a simple mortality risk score with 1 point assigned to 11 independent risk predictors. 7290 pts (mean age 59 yrs; range 25–92), including 1681 women (23%), and 1538 pts age 70+ (21%) had complete data for all 11 variables. Stepwise increasing numbers of predictors corresponded to higher long-term CV mortality (c-stat 0.76) (FIG

). The 35% of pts with scores 0–2 had a 2-year CV mortality <0.7%, while the 18% with scores ≥5 had a 2-yr mortality of >8%. The score performed well in key subgroups such as women (c-stat 0.80), elderly (c-stat 0.77), and STEMI (c-stat 0.70), and in an older/sicker population (n=4222) from MERLIN-TIMI 36 (c-stat 0.73). Our score also discriminated risk of other endpoints including all-cause mortality (c-stat 0.74), death/CHF (c-stat 0.73). The GRACE postdischarge risk score yielded a c-stat of 0.74 in this dataset, despite its greater complexity and use of continuous variables. We developed a simple, convenient discharge risk score that discriminates high and low risk in post-ACS pts for long-term CV mortality, enabling long-term management priorities to be organized in proportion to risk.
Abstract 6102: Integration of Non-Contrast Cardiac Computed Tomography and Stress Myocardial Perfusion Imaging in the Emergency Department: Identifying Which Patients with Chest Pain Can be Safely Discharged Home
Authors: Nabi Faisal , Chang Su Min , Moye Lemuel A , Hust Robert G , Pratt Craig M , Mahmarian John J
Published: July 2021

Over 5 million emergency department (ED) visits occur annually for evaluation of chest pain. A rapid simple imaging algorithm is needed to identify patients with noncardiac chest pain so as to avoid unnecessary hospital admission. We conducted a prospective trial in 1031 low risk patients (60% women; mean age 54±13 years) admitted through the ED to our chest pain unit who had

no prior cardiac history,

a nondiagnostic ECG for ischemia, and

a normal initial troponin.

All patients had stress myocardial perfusion imaging (SPECT) with a coronary artery calcium score (CACS) by noncontrast cardiac computed tomography (CT) within 24 hours. Mean patient follow-up was 7.4±3.3 months. SPECT and CT studies were interpreted independently and the CACS quantified as an Agatston score. The mean TIMI risk score was 1.5±0.7. Cardiac events occurred in 29 patients (2.8%): acute myocardial infarction (N=4) or an acute coronary syndrome (ACS, N=21) during admission; or ACS following hospital discharge (N=4). Abnormal SPECT and cardiac events significantly increased with CACS (p<.001), with over a 40-fold increase in event rates for patients with a CACS>400 vs 0(Table

). Only 5 (0.8%) patients with CACS=0 had an abnormal SPECT and none had significant coronary artery disease by angiography. The 2 patients who had a CACS=0 and a cardiac event during their hospitalization both had a normal gated SPECT and no subsequent event in follow-up. The sensitivity of an abnormal CT was significantly higher than an abnormal SPECT for identifying patients with events (93% vs 65%, p<.01, respectively). A sizeable percentage (61%) of our low risk patient cohort had CACS=0 by CT which predicted both a normal SPECT and an excellent short-term outcome. Our data support that low risk patients with chest pain and a CACS=0 can be safely discharged home from the ED, with SPECT reserved for those with an abnormal CT result.