bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 668: The Role of IL-27 Receptor Signaling in the Development of Abdominal Aortic Aneurysm
Authors: Peshkova Iuliia , Makhov Petr , Hou Vivianly , Koltsova Ekaterina
Published: July 2021

Abdominal aortic aneurysm (AAA) is a cardiovascular disease, which is characterized by aortic wall dilation with subsequent rupture and internal bleeding. Inflammatory reactions in the vessel wall are likely essential for AAA pathogenesis, just like they are important for the development of another vascular pathology- atherosclerosis, which can predispose to AAA formation in a context-dependent manner. While inflammatory cytokines were shown to promote atherosclerosis and AAA, little is known about contribution of anti-inflammatory cytokines with regard to their ability to control vascular inflammation. Interleukin (IL)-27 signaling is required to suppress atherosclerosis development but its function in AAA remains unknown.

We utilize Angiotensin II (AngII) model to evaluate the role of IL-27R signaling in pathogenesis of AAA. AngII containing pumps were surgically implanted into Il27ra-/- x Ldlr-/-; Il27ra -/- x Apoe-/- and Il27ra+/- littermate controls and AAA progression was analyzed 4 weeks later.

Surprisingly, we found attenuated AAA progression in Il27ra-/- mice compared to Il27ra+/- and wt counterparts. The latter developed large AAA with visual hemorrhage into the artery wall, while Il27ra-/- mice developed small AAA with fewer myeloid cells and T cells. Moreover, opposite to aortic arches, T cells in abdominal aortas of Il27ra-/- mice produced less inflammatory IL-17A, while IFNγ production was unchanged. Interestingly, we found enhanced production of “Th2-like” cytokines IL-4 and IL-13, by NK cells and Type 2 Innate lymphoid cells (ILC2) in Il27ra deficient mice, which correlated with the protection from AAA.

Overall, we conclude that immunoregulatory cytokine IL-27 can differentially control atherosclerosis and AAA development by regulating innate and adaptive immune cell recruitment and cytokine production in the aortic wall.
Abstract 683: Serum Myeloperoxidase/Paraoxonase 1 Ratio Predicts Recurrent Coronary Artery Disease
Authors: Tsuda Shigeyasu , Toh Ryuji , Mori Kenta , Nagao Manabu , Tanaka Nobuaki , Mori Takeshige , Monguchi Tomoko , Nakajima Hideto , Honjo Tomoyuki , Shinohara Masakazu , Nishimura Kunihiro , Ishida Tatsuro , Hirata Ken-ichi
Published: July 2021

Objective:
Myeloperoxidase (MPO) is known as major leukocyte enzyme that oxidizes lipoproteins. High density lipoprotein (HDL) contains paraoxonase 1 (PON1), which hydrolyzes oxidized phospholipids. HDL requires PON1 to attenuate accumulation of lipid peroxides in LDL. We recently reported that serum MPO/PON1 ratio could be used as a useful marker for dysfunctional HDL and showed elevated ratios in patients undergoing recurrent percutaneous coronary intervention (PCI). However, it remains obscure whether serum MPO/PON1 ratio can predict relapsing coronary atherosclerotic lesions after PCI.

Methods and Results:
Total 111 patients who had a history of successful PCI were enrolled. Their serum MPO mass and PON1 activities were measured at the time point of enrollment, and they had angiographical follow-up evaluation. Fourteen patients needed repeat-PCI due to restenosis and/or de novo lesions during the follow up period (143±730 days). With the established cut off value of 1.59 based on our previous work, Kaplan-Meier analysis showed significantly higher recurrence rate of coronary lesions which required PCI treatment in patients with higher MPO/PON1 ratio at enrollment than that in patients with lower MPO/PON1 ratio (66.7% vs. 6.0%, p<0.001). High MPO/PON1 ratio was independently associated with recurrent coronary atherosclerotic lesions in multivariate Cox regression analysis after adjusting for age, gender, hypertension, diabetes mellitus, dyslipidemia, and smoking (Hazard ratio 15.8, 95% CI 4.20-59.07, p <0.001), while conventional lipid profiles failed to show any statistical relationships to disease recurrence. In addition, C-index of MPO/PON1 ratio was significantly larger than that of MPO alone, indicating that combination of MPO and PON1 provides greater improvement than single application of MPO in predicting coronary lesions (0.787 vs. 0.719, p<0.05).

Conclusions:
This study demonstrated that higher MPO/PON1 ratio (>1.59) could predict future recurrence of coronary lesions after PCI. This ratio could be useful marker for secondary prevention of coronary artery disease.
Abstract 696: Surgical Injury Induces Local and Distant Adipose Tissue Browning
Authors: Longchamp Alban , Tao Ming , Bartelt Alexander , Ding Kui , Lynch Lydia , Hine Christopher , Corpataux Jean-Marc , Kristal Bruce , Mitchell James , Ozaki Charles Keith
Published: July 2021

Objective:
Adipose tissue quantity and quality are strong predictors of vascular function. The adipose organ, which comprises brown, white and beige adipocytes, possesses remarkable plasticity in response to feeding and cold exposure. While surgical procedures constantly traumatize adipose tissue, its impact on adipocyte phenotypes remains to be established.

Approach and Results:
We studied the effect of trauma on adipocyte phenotypes one day after sham, incision control, or surgical injury to the left inguinal adipose compartment. We included caloric restriction to control for surgery-associated body temperature changes and weight loss. The cellular and molecular changes in subcutaneous, visceral, interscapular, and perivascular adipose tissue using histology, immunohistochemistry, gene expression and flow cytometry analysis. After one day, surgical trauma stimulated adipose tissue browning at the site of injury (
Figure 1
) and, importantly, in the contralateral inguinal depot. Browning was not present after incision only, and was independent of surgery-associated body temperature and weight loss. Adipose trauma rapidly recruited monocytes to the injured site and promoted alternatively activated macrophages. Conversely, PDGF receptor-positive beige progenitors were reduced. Finally, eight hours after adipose injury, mice had increased levels of circulating norepinephrine, which correlated with reduced lipid content and adipocytes size.

Conclusions:
In this study, we identify adipose trauma as an unexpected driver of adipose tissue browning, holding important implications for the biologic response to injury.
Abstract 709: Aging Determines Different Osteochondrogenic Protein Expression Profile Associated With Increased Calcification and Elastocalcinosis in Diabetic Patients Submitted to Amputation
Authors: Farias-Silva Elisangela , de Almeida Mendes Cynthia , Andrade Maria Claudina C , Carmo Luciana S , Wolosker Nelson , Liberman Marcel
Published: July 2021

Peripheral artery disease (PAD) frequently occurs in diabetes mellitus (DM) and associates with limb ischemia and amputation. Vascular calcification, which is very prevalent both in DM and in the elderly, contributes to PAD pathophysiology and further increases amputation risk. Our objectives were to quantify vascular calcification, elastic and collagen fiber content, besides osteochondrogenic protein expression in arteries from 2 diabetic patients at the extremes of age. Femoral and dorsalis pedis artery from a 92-year-old male (O) and a 40-year-old male (Y), both with DM, were harvested at the time of amputation caused by limb ischemia. Other cardiovascular risk factors were similar among patients. Specimens were fixed in buffered formaldehyde, processed and stained for hematoxylin-eosin, Verhoeff-van-Gieson and Masson’s trichrome. Immunohistochemical analysis was performed to assess osteogenic protein expression such as RUNX2, alkaline phosphatase (ALP) and Osterix (OSX), which are upregulated during vascular smooth muscle cell reprogramming to an osteogenic phenotype, responsible for hydroxyapatite deposition. Arteries from 92-year-old patient showed markedly architectural changes of the vascular wall in comparison with the younger patient sample, such as decreased collagen (O=0.8±0.2%
versus
Y=33.5±5.2% area/field, p<.05) and elastic fibers (O=1.6±0.4% vs. Y=7.8±1.5% area/field, p<.05) content. Coincidently, we demonstrated increased vascular calcification (O=209.7±27.5mm
2
/field vs. Y=30.6±6.3 mm
2
/field). Osteochondrogenic protein expression also showed opposing results: OSX stained around large calcification nuclei, mostly in the older, but not in the younger patient samples. Furthermore, RUNX2 and ALP expression, which determines early osteoblastic cell differentiation, occurred around small calcium deposits, mainly in the 40-year-old patient. We demonstrated that age and time-length exposure to diabetes are predictive of collagen and elastic fibers content associated with increased calcification area. Moreover, osteochondrogenic protein expression profile favors RUNX2 and ALP in the younger vs OSX in the older patient respectively, implying different stages of the disease.
Abstract 712: Screening of Thrombolytic Agents in vivo Using a Novel Zebrafish Model of Ischemic Stroke Induced by Photochemical Thrombosis
Authors: Hsu Jia-Wen , Lee I-Ju , Chang Wei-Tien , Chuang Yung-Jen , Liau Ian
Published: July 2021

Background:
Timely thrombolytic therapy for acute ischemic stroke is important for improving neurological prognosis. Screening of thrombolytic agents on contemporary animal models of focal ischemic stroke is generally difficult as they require sophisticated surgical procedures such as induction of cerebral artery occlusion through mechanical ligation. Herein we seek to develop a novel zebrafish (Danio rerio) model of acute ischemic stroke for screening of thrombolytic drugs.

Methods:
All experiments were performed on a modified confocal optical microscope, which allows the induction of thrombosis at a selected blood vessel of larval zebrafish and the imaging of thrombotic and thrombolytic processes in real time. To initiate photochemical thrombosis, a 532-nm laser was focused at a blood vessel of a larva (4 dpf) that had been injected with a photosensitizer (rose bengal). To test the thrombolytic activity of tPA, we injected tPA to the blood vessel of a larval with a thrombus that partially occluded the blood flow.

Results:
Through photochemical means, we induced endothelial injury at selected blood vessel which subsequently triggered thrombosis. We show that an occlusion at the 1st branch of central artery drastically diminished the hemodynamics and cardiac function of larval zebrafish and impaired their capability to maintain balance during swimming whereas that at the basilar artery resulted in a high death rate. Immunofluorescent imaging shows that the photochemically induced thrombus comprised fibrins and platelets. After the injection of tPA to a larval with a partially occluded blood vessel, the fibrin mesh on the thrombus appeared sparse and limp which eventually led to the restoration of blood flow.

Conclusions:
Our zebrafish model of ischemic stroke is convenient to adapt and is highly reproducible. This model can potentially become an effective platform that benefits the screening of thrombolytic agents and the optimization of their dose.
Abstract 713: Effects of Demographics and Clinical Risk Factors on Human Femoropopliteal Artery Histopathology
Authors: Kamenskiy Alexey , Nusz Sheridan , Hunter William , Desyatova Anastasia , Ruhlman Melissa , Pipinos Iraklis , MacTaggart Jason
Published: July 2021

Introduction:
Disease of the femoropopliteal artery (FPA) is associated with significant morbidity and quality of life impairment. End-stage lesions may be too advanced to determine how demographics and clinical risk factors impact arterial wall damage and lesion development; therefore we investigated the influence of these patient characteristics on various stages of human FPA histopathology.

Methods:
FPAs were obtained from 14-80 year-old human tissue donors (
n
=120). Proximal segments of the arteries were mechanically tested and labeled with Verhoeff-Van Gieson stains. FPA intimal-medial damage severity was assessed and correlated with histology, mechanical properties, subject demographics, risk factors, and physiological stresses and stretches using Pearson correlation
r
with two-tailed significance levels.

Results:
Age correlated strongest (
r
=0.664, p<0.01) with the degree of FPA intimal-medial damage, explaining 50% of the variation alone. Primarily due to medial calcification, more damaged FPAs were stiffer and demonstrated lower physiological circumferential stretch (
r
=-0.510, p<0.01), circumferential stress and longitudinal stress (
r
=-0.355,
r
=-0.379, p<0.01). More damage was associated with larger arterial radii (
r
=0.470, p<0.01), thickened arterial walls (
r
=0.238, p<0.01), decreased
in situ
longitudinal pre-stretch (
r
=-0.537, p<0.01), less elastin in the arterial wall (
r
=-0.432, p<0.01), thinner individual elastin fibers (
r
=-0.571, p<0.01), and thinner, less dense, and more discontinuous external elastic laminae (
r
=-0.252,
r
=-0.456,
r
=0.588, p<0.01). Damage was positively associated with male gender (
r
=0.265, p<0.01), higher BMI (
r
=0.224, p=0.01), hypertension (
r
=0.266, p<0.01), diabetes (
r
=0.265, p<0.01) and coronary artery disease (
r
=0.375, p<0.01), but not with dyslipidemia (
r
=0.117, p=0.161) or smoking history (
r
=0.041, p=0.626).

Conclusions:
More severely damaged FPAs demonstrate elastin loss, medial calcification and increased stiffness compared to less damaged arteries. FPA damage correlates with most classical cardiovascular risk factors, but not with dyslipidemia or tobacco history, suggesting possible unique pathophysiological mechanisms that require further investigation.
Abstract 714: Lipid Disorders Might Be Affected to Develop Critical Limb Ischemia in PAD Patients
Authors: Miyama Noriyuki , Sakashita Hideki , Shindo Shunya , Komai Hiroyoshi
Published: July 2021

Introduction:
Critical limb ischemia (CLI) is manifested by rest pain, non-healing ulcer and gangrene. Intermitted claudication (IC) is a representative initial symptom in patients with peripheral arterial disease (PAD), and CLI is a very severe condition of PAD. However, only 1-2% of PAD cases result in CLI, and some patients suddenly present with the symptoms of CLI, without a history of IC. We assessed the hypothesis that patients with CLI had different characteristics regarding lipid disorders and comorbidities, compared to patients with only IC.

Methods:
131 patients with PAD, including 38 CLI and 93 IC patients, were included. The levels of serum small-dense LDL (sd-LDL), malondialdehyde Modified LDL (MDA-LDL), leptin, and adiponectin, all of which were related with atherosclerosis, were measured. Data were also analyzed regarding the association between CLI and patient characteristics, including a history of hypertension, diabetes mellitus, hyperlipidemia, chronic obstructive pulmonary disease (COPD), coronary arterial disease (CAD), and hemodialysis. Univariate and multivariate analyses were performed.

Results:
CLI patients showed lower sd-LDL (p< .0001), lower MDA-LDL (p=.0003), higher leptin (p=.015), and higher adiponectin (p=.0012), compared to IC patients. CLI was associated with a history of CAD (p<.0001), hemodialysis (p<.0001), diabetes mellitus (p=.040), and without hyperlipidemia (p=.040) in univariate analysis. In multivariate logistic analysis, low sd-LDL, a history of CAD and hemodialysis were significantly associated with CLI.

Conclusions:
CLI patients had different characteristics regarding lipid disorders and comorbidities, compared to IC patients. These data suggested that CLI patients had some lipid or metabolism disorders, potentially affected to presentation of CLI.
Abstract 715: Cytochrome P450 1B1 Gene Disruption Prevents Neointimal Growth in Wire-Injured Carotid Artery of Male Mice
Authors: Mukherjee Kamalika , Yaghini Fariborz A , Estes Anne M , Buckley Tyler H , Gonzalez Frank J , Malik Kafait U
Published: July 2021

We have previously reported that cytochrome P450 1B1 (CYP1B1), a heme-thiolate monooxygenase expressed in cardiovascular tissues, contributes to the development of hypertension and its associated pathogenesis in various experimental animal models. The current study was conducted to determine the contribution of CYP1B1 in neointimal growth following wire injury of carotid artery in 8 week-old male Cyp1b1+/+ and Cyp1b1-/- mice. The left carotid artery was injured with a metal wire and denudation of the endothelial layer was confirmed by the absence of von Willebrand factor staining cells, 1 day after the injury in both Cyp1b1+/+ and Cyp1b1-/- mice. After 14 days of injury, the mice were sacrificed, and both injured and uninjured contralateral carotid arteries were collected for histological and immunohistochemical analysis. The wire injury caused neointimal growth as indicated by increased intimal area, intima/media ratio and elastin disorganization in carotid arteries of Cyp1b1+/+ mice; these changes were minimized in the carotid arteries of Cyp1b1-/- mice. Vascular smooth muscle cells (VSMCs) were found to be the major cellular component of these neointima, as evident by positive staining for α-smooth muscle actin. We also found increased infiltration of inflammatory and immune cells as indicated by expression of CD68+ macrophages and CD3+ T-cells, respectively, in the wire-injured carotid arteries of Cyp1b1+/+ mice but not Cyp1b1-/- mice. Administration of 4-Hydroxy-2, 2, 6, 6-tetramethylpiperidine 1-oxyl (TEMPOL), a superoxide dismutase mimetic, in drinking water (2 mmoles/l), attenuated the neointimal growth in wire-injured carotid arteries of Cyp1b1+/+ mice. Furthermore, in vitro studies showed significant reduction of angiotensin II-induced migration, proliferation and protein synthesis in VSMCs from Cyp1b1-/- compared to Cyp1b1+/+ mice. These data suggest that Cyp1b1-dependent oxidative stress contributes to the neointimal growth caused by wire injury of carotid arteries of male mice. Therefore, inhibitors of Cyp1b1 could be useful in the treatment of restenosis caused by vascular injury including balloon angioplasty, atherosclerosis and diabetes in males.
Abstract 721: More Severe Brain Damage Found in Cholesterol-embolic Stroke Compared with Clot-embolic Stroke
Authors: Yang Shu , Dong Honglin , Yao Luyu , Gu Xin , Shi Runhua , Yao Kai , Zhao Cynthia , Tan Tze-Woei , Zhang Wayne
Published: July 2021

Objectives:
The nature and feature between cholesterol and blood clot emboli are significantly different. The aim of this study was to investigate if any difference in ischemic brain damage caused by cholesterol emboli vs. clot emboli.

Methods:
Embolic stroke model was created using Sprague-Dawley rats. They were randomly divided into control (Ctrl), cholesterol emboli (ChE), and clot emboli (ClE) groups. Plaques and blood samples were collected from the patients who underwent carotid endarterectomy. Plaques were rinsed and heated at 100
o
C for 60 minutes to denature protein. Plaques and blood clots were broken into 0.30 - 0.35mm and diluted into a final concentration of 1,000 fragments per 100μL. Normal saline, the cholesterol emboli and blood clot emboli suspensions (300μL) were separately injected, according to different groups, into rat brains via left internal carotid artery. The animals were sacrificed at 24 hours post injection and brain ischemia was assessed using pathological H/E staining. Neuropathologic injury in hippocampus (CA1, CA2, CA3, and DG) was scored from 1 to 5 (Figure 1).

Results:
The brain injury scores of the three groups were analyzed using Student-Newman-Keuls Test. Both ClE and ChE groups had significant higher injury scores compared to Ctrl group (p<0.05, respectively). The Injury score of ChE group was significantly higher than that of ClE group (p<0.05) (Figure 1).

Conclusions:
The findings suggest that cholesterol embolization results in more severe damage in rat brain, compared to blood clot embolization. It may imply that clinical presentations and treatment outcomes of embolic strokes can be affected by different sources of emboli.
Abstract 9: Smooth Muscle Cells Are Crucial for Vascular Stem Cell Migration and Vasculogenesis via Keratinocyte Cell-derived Chemokine
Authors: Yu Baoqi , Wong Mei M , Potter Claire , Hu Yanhua , Wang Wen , Xu Qingbo
Published: July 2021

Introduction:
Recently, a population of stem/progenitor cells have been identified within the adventitia of vessel walls. While existing data indicate their capacity of differentiation into specific vascular lineages, their migratory roles within vascular diseases remain unknown. Interestingly, smooth muscle cells (SMCs) have been shown to reside within close proximity with the progenitors within the medial layer and thus may have a putative role on the motility of progenitor cells.

Hypothesis:
We hypothesize that mouse adventitia-derived resident progenitor cells will migrate in response to SMCs via their secretion of specific chemokine(s).

Methods and Results:
In vitro
transwell and wound healing migration assays showed significant increases in Sca-1
+
vascular progenitor cell migration in response to both SMCs and SMC-conditioned medium (CM). A chemokine ELISA array revealed that keratinocyte cell-derived chemokine (KC) level was markedly increased in SMC-CM. Exogenous recombinant KC significantly increased progenitor cell migration and KC knockdown in SMC-CM using siRNA markedly inhibited progenitor migration. The expression of its receptor, CXCR2, was upregulated following treatment with SMC-CM and treatment with a CXCR2 antagonist was found to significantly inhibit SMC-mediated progenitor migration. Furthermore, we found that the p38 MAP kinase pathway was involved in SMC-mediated migration; the phosphorylation of p38 in response to SMC-CM was partially reduced following knockdown with KC SiRNA. The migration of progenitor cells was also significantly decreased following treatment with a p38 inhibitor. Using a matrigel plug angiogenesis assay
in vivo
, we found that the KC induced Sca-1
+
progenitors migration and enhanced markedly vasculogenesis after 2 weeks. The functional knockdown of KC in C57BL/6 mice using a KC morpholino system potentially reduces Sca-1
+
progenitor cell migration compared to corresponding controls (n≥4 per group).

Conclusion:
In conclusion, SMCs can induce Sca-1
+
progenitor cell migration via the release of KC and subsequent activation of p38 MAPK signalling pathway via CXCR2. The lack of functional KC inhibited progenitor cell migration and vasculogenesis
in vivo
.
Pulmonary Autograft Versus Aortic Homograft for Rereplacement of the Aortic Valve
Authors: Carr-White Gerald S. , Glennan Sally , Edwards Sue , Ferdinand Francis D. , Desouza Anthony C. , Pepper John R. , Yacoub Magdi H.
Published: July 2021

Background
—The use of a pulmonary autograft for rereplacement of the aortic valve has both potential advantages and disadvantages. This study details the early results of a subset of patients enrolled in a prospective randomized trial comparing pulmonary autografts and aortic homografts who have had previous aortic valve replacements.

Methods and Results
—A total of 47 patients who had undergone ≥1 previous aortic valve replacement were randomized to receive either a pulmonary autograft (24 patients aged 40±11 years) or an aortic homograft (23 patients aged 37±11 years) for rereplacement of the aortic valve. One early death occurred in the homograft group, and 1 late (7 months) death occurred in the autograft group. One patient who received a pulmonary autograft was reoperated on for inflammatory pulmonary stenosis. One patient in each group was reopened for bleeding (both within 24 hours). Two patients in the autograft group had postoperative neurological weakness; they fully recovered over 2 months. Hospital stay, blood loss, incidence of perioperative arrhythmia, and markers of coronary ischemia were similar between the 2 groups. At 6-month follow-up (range, 1 to 12 months), left ventricular end-diastolic diameter was similar in both groups (homografts, 5.0±0.9 cm; autografts, 5.2±0.6 cm;
P
=NS), and no patient in either group had significant aortic valve dysfunction.

Conclusions
—Rereplacement of the aortic valve with a pulmonary autograft is feasible and safe in patients aged 14 to 60, regardless of their preoperative diagnosis or clinical condition.
Comparison of Long-Term Outcomes of Atrial Repair of Simple Transposition With Implications for a Late Arterial Switch Strategy
Authors: Sarkar David , Bull Catherine , Yates Robert , Wright David , Cullen Seamus , Gewillig Marc , Clayton Rebecca , Tunstill Adelaide , Deanfield John
Published: July 2021

Background
—We report the single-institution, long-term results of 358 patients with simple transposition of the great arteries surviving >30 days after a Mustard (n=226, 1965 to 1980) or Senning (n=132, 1978 to 1992) procedure.

Methods and Results
—Outcome measures included late death, reintervention, ECG and ambulatory ECG rhythm, new arrhythmia, and functional status. Average follow-up was 13.4 (range 0.32 to 17.9) years for the Senning group and 11.7 (range 0.04 to 23.9) years for the Mustard group. The Senning group had a better survival rate at 5, 10, and 15 years (95% versus 86%, 94% versus 82%, and 94% versus 77%, respectively). In both groups, the majority of late deaths were sudden, without preceding ventricular dysfunction. Survival and survival free of reintervention were significantly better in the Senning group (relative risk [RR] 0.34,
P
=0.06 versus RR 0.39,
P
=0.027). Loss of sinus rhythm was comparable and unrelated to death. After era correction, the incidence of atrial flutter was similar and strongly associated with late death in both groups. Clinical systemic ventricular failure was uncommon, and at last follow-up, 92% of the Senning group and 89% of the Mustard group were in New York Heart Association class I. In a model exploring the implications of elective arterial switch conversion, this would only be beneficial if the hazard late after switch was markedly reduced and/or the hazard after the Senning procedure increased with time.

Conclusions
—Late outcomes after the Senning procedure are superior to those after the Mustard procedure. Both groups had late sudden deaths that were not associated with clinical systemic ventricular failure. Good functional status after the Senning procedure suggests that a strategy of elective switch conversion cannot be justified for patients with isolated transposition.
Ambulatory Care of Patients With Left Ventricular Assist Devices
Authors: Schmid Christof , Hammel Dieter , Deng Mario C. , Weyand Michael , Baba Hideo , Tjan Tonny D. T. , Drees Gabriele , Roeder Norbert , Schmidt Christoph , Scheld Hans H.
Published: July 2021

Background
—Left ventricular assist devices (LVAD) have revolutionized the treatment of patients with acute and chronic heart failure as they provide a high quality of life. We report on our experience with patients receiving ambulatory care after LVAD implantation.

Methods and Results
—Since July 1995, 46 patients with a mean age of 45±11 years underwent implantation of an electrically driven LVAD with portable controller and batteries. Sixteen (35%) patients bridged >30 days were treated in part on an outpatient basis. After LVAD implantation, they were treated in the hospital for 86±32 days (range 40 to 153 days). Afterward, they received ambulatory care for 74±76 days (range 2 to 301 days, total experience 1206 days). In 13 cases, the outpatient treatment was interrupted by 1.7±1.7 readmissions, for a total of 32±42 days (median 19 days). Reasons for readmission included systemic or drive line infections (incidence 0.0066 per outpatient day), suspected or true thromboembolic events (incidence 0.0066 per outpatient day), and suspected malfunction of the LVAD. One patient supported as alternative to transplantation died after cerebral bleeding after 244 days, 1 patient with a history of acute myocarditis had ventricular fibrillation during LVAD assist while being at home for 177 days and died in a low output state, 10 patients were given transplantation after a mean support interval of 206±88 days, and 4 patients currently await heart transplantation.

Conclusions
—Outpatient treatment after LVAD implantation is feasible, and severe complications are uncommon.
Predictors of Proximal Aortic Dissection at the Time of Aortic Valve Replacement
Authors: von Kodolitsch Yskert , Simic Ognjen , Schwartz Ann , Dresler Christoph , Loose Roger , Staudt Martin , Ostermeyer Jörg , Haverich Axel , Nienaber Christoph A.
Published: July 2021

Background
—Type I aortic dissection develops in 0.6% of patients late after aortic valve replacement (AVR), and 13% of patients with type I aortic dissections have a history of AVR. Predictors of aortic dissection at AVR, however, have not been characterized.

Methods and Results
—A study group of 33 patients with type I aortic dissection had aortic surgery 49±55 months after routine AVR. A group of 101 controls, who did not have morphological progression of aortic diameters ≥6 years after AVR, was used to identify predictors of postsurgical dissection. Multivariate analysis identified aortic regurgitation (
P
<0.002) and fragility (
P
<0.001) or thinning of the aortic wall (
P
<0.007) at AVR as predictors, associated with a 14%, 22%, and 7% probability of late aortic dissection, respectively. Clamping times, types of valve prostheses, concomitant coronary artery bypass grafting, and mean ascending aortic diameters of 43±10 mm at AVR did not predict late dissection. A separate analysis of 29 nondissecting aneurysms of the ascending aorta developing 104±64 months after routine AVR revealed younger age at AVR (
P
<0.003) and congenitally bicuspid aortic valves (
P
<0.03) as predictors of late aneurysm formation.

Conclusions
—Aortic regurgitation combined with fragile and thinned aortic walls in patients with moderate aortic dilation may reflect aortic root disease, with a high risk for postsurgical aortic sequelae if it is treated incompletely by isolated valve replacement.
Aortic Arch Reconstruction by Transluminally Placed Endovascular Branched Stent Graft
Authors: Inoue Kanji , Hosokawa Hiroaki , Iwase Tomoyuki , Sato Mitsuru , Yoshida Yuki , Ueno Katsuya , Tsubokawa Akiyoshi , Tanaka Terumitsu , Tamaki Shunichi , Suzuki Takahiko
Published: July 2021

Background
—Recently, thoracic aortic stent grafting has emerged as an alternative therapeutic modality for patients with thoracic aortic aneurysms and aortic dissections. However, its application has been limited to descending thoracic aortic aneurysms distal to the aortic arch. We report our initial clinical experience of endovascular branched stent graft repair for aortic arch aneurysms.

Methods and Results
—Endovascular grafting with Inoue branched stent grafts was attempted for 15 patients with thoracic aortic aneurysms and aortic dissections under local anesthesia (n=14) or general anesthesia (n=1). Single-branched stent grafts were used in 14 patients, and a triple-branched stent graft in one. The branched stent grafts were delivered through a 22F or a 24F sheath under fluoroscopic guidance and implanted across the aneurysmal aortic arch. In 2 patients, the single-branched stent graft did not pass through the 22F sheath used. Complete thrombosis of the aneurysm was ultimately achieved in 11 patients (73%). Of 4 persistent leaks, 1 minor leak spontaneously thrombosed and 1 major leak was successfully treated by additional straight stent graft placement. In 1 patient, the right external iliac artery ruptured during the withdrawal of the sheath and was successfully repaired by the implantation of a straight stent graft. One patient with severe stenosis of the aortic graft section was successfully managed by additional stent deployment. Peripheral microembolization to a toe occurred in 1 patient, and cerebral infarction occurred in 1 other patient. Two patients who had failed to receive endovascular stent grafts died during an average follow-up of 12.6 months, 1 of pneumonia and the other of rupture of a concomitant abdominal aortic aneurysm.

Conclusions
—This report demonstrates the technical feasibility of endovascular branched stent graft repair for aneurysms located at the aortic arch. Careful, longer follow-up and further extensive clinical trials are awaited toward establishing this technique as a recommendable alternative to surgical treatment of thoracic aortic aneurysms.
Recombinant Gene Transfer of Endothelial Nitric Oxide Synthase Augments Coronary Artery Relaxations During Hypoxia
Authors: Cable David G. , Vincent J. Pompili  , Timothy O’Brien  , Hartzell V. Schaff
Published: July 2021

Background
—Coronary arteries respond to hypoxia with transient relaxations, which increases coronary blood flow, in part, by release of nitric oxide. We hypothesized that increased expression of nitric oxide synthase might further augment blood vessel relaxation during hypoxia. The present study examined the effect of adenovirus-mediated transfer of bovine endothelial nitric oxide synthase (eNOS) on hypoxia-induced transient relaxations in canine coronary arteries.

Methods and Results
—Paired segments of coronary arteries were exposed to vehicle (phosphate-buffered saline with albumin) or an adenovirus encoding either
E coli
β-galactosidase (Ad.CMVLacZ, viral control; 10
10
pfu/mL) or eNOS (Ad.CMVeNOS; 10
10
pfu/mL) for 2 hours at 37°C. Immunohistochemistry with a monoclonal antibody specific for eNOS documented both endothelial and adventitial expression in Ad.CMVeNOS arteries, whereas vehicle and viral controls demonstrated only constitutive expression. Levels of cGMP were increased 5-fold in Ad.CMVeNOS arteries compared with controls. In arteries exposed to Ad.CMVeNOS, maximum contraction to prostaglandin F
2α
was reduced compared with viral controls, and this effect was eliminated by pretreatment with a competitive inhibitor of eNOS (
N
G
-monomethyl-
l
-arginine, 10
−3
mol/L). Hypoxia-induced transient relaxation (95% N
2
-5% CO
2
) in Ad.CMVeNOS arteries (45.2±8.8%, n=6) was augmented compared with vehicle (26.3±6.0%) or viral (27.2±7.1%) controls.

Conclusions
—Adenovirus-mediated gene transfer of nitric oxide synthase reduces receptor-dependent contractions and augments hypoxia-induced relaxations in canine coronary arteries; this method of augmentation of NO production might be advantageous for reduction of coronary artery vasospasm.
Right Ventricular Function After Pulmonary Autograft Replacement of the Aortic Valve
Authors: Carr-White Gerald S. , Kon Mark , Koh T. W. , Glennan Sally , Ferdinand Francis D. , De Souza Anthony C. , Pepper John R. , Pennell Dudley J. , Gibson Derek G. , Yacoub Magdi H.
Published: July 2021

Background
—The pulmonary autograft operation (the Ross procedure) involves excision of a portion of the right ventricular (RV) outflow tract, prolonged cross-clamp times, and insertion of a pulmonary homograft. There is concern about the effect of such operations on right ventricular function.

Methods and Results
—Twenty-five patients undergoing either pulmonary autograft or homograft replacement of the aortic valve as part of a prospective randomized trial had echocardiographic RV long-axis measurements performed before surgery and 6 months (range 3 to 12 months) after surgery. In all patients, systolic excursion (SE) and both shortening and lengthening rates (SR and LR, respectively) were reduced postoperatively (
P
<0.05) (homografts: SE 1.5±0.4 versus 2.3±0.6 cm, SR 6.8±2.1 versus 9.6±3.1 cm/s, LR 6.0±1.8 versus 8.9±3.0 cm/s; autografts: SE 1.4±0.4 versus 2.2±0.4 cm, SR 5.8±3.0 versus 8.2±3.0 cm/s, LR 5.7±1.9 versus 8.5±3.7 cm/s). There were no differences between the 2 groups. Eighteen patients who had undergone either aortic homograft or pulmonary autograft surgery were studied between 6 and 35 months after surgery. RV volumes were assessed with the use of MRI in addition to echocardiographic RV long-axis measurements. Global volumes were increased to a similar amount in both groups (homografts: end-diastolic volume 145±34 mL, end-systolic volume 78±23 mL; autografts: end-diastolic volume 157±33 mL, end-systolic volume 89±25 mL;
P
=NS), whereas stroke volumes were maintained in both groups (homografts 67±15 mL, autografts 67±16 mL;
P
=NS). RV SE was depressed in both groups to a similar degree to that seen with the previous group (homografts 1.5±0.3 cm, autografts 1.4±0.2 cm).

Conclusions
—Aortic valve replacement with either a pulmonary autograft or an aortic homograft leads to a degree of persistent RV longitudinal dysfunction that is not more pronounced in those undergoing the Ross procedure. The mechanisms and long-term effects of these changes must be further studied.
Peroxynitrite, the Breakdown Product of Nitric Oxide, Is Beneficial in Blood Cardioplegia but Injurious in Crystalloid Cardioplegia
Authors: Ronson Russell S. , Thourani Vinod H. , Ma Xin-Liang , Katzmark Sara L. , Han David , Zhao Zhi-Qing , Nakamura Masanori , Guyton Robert A. , Vinten-Johansen Jakob
Published: July 2021

Background
—Peroxynitrite (ONOO
−
) has been implicated as a primary mediator in the deleterious effects of nitric oxide (NO) in crystalloid solutions, possibly due to a lack of detoxification mechanisms, leading to the formation of ·OH. In contrast, ONOO
−
may exert cardioprotective effects in blood environments secondary to detoxification and the subsequent formation of NO-donating nitrosothiols. This dichotomy in physiological effects of ONOO
−
may exist between crystalloid and blood cardioplegia (BCP) environments. In the present study, we tested the hypothesis that ONOO
−
is cardiotoxic in crystalloid cardioplegia but cardioprotective in BCP in ischemically injured hearts.

Methods and Results
—In anesthetized dogs on cardiopulmonary bypass, global 37°C ischemia was imposed for 30 minutes, followed by 60 minutes of intermittent 4°C hyperkalemic crystalloid (Plegisol) or BCP with (+) or without (−) 5 μmol/L authentic ONOO
−
. After 2 hours of reperfusion, left ventricular (LV) function (end-systolic pressure-volume relations, in percent of baseline) was 56±3% in Plegisol−, which was further reduced in Plegisol+ to 40±4%.* In contrast, postischemic systolic function was better in BCP+ groups than in BCP− groups (96±2%* versus 82±2%, respectively). Differences in functional recovery could not be attributed to differences in hemodynamics. LV end-diastolic stiffness was significantly increased with the addition of ONOO
−
in both Plegisol (298±26% versus 466±30%*) and BCP (201±22% versus 267±13%*) groups. Consistent with increased LV chamber stiffness, myocardial edema was increased in BCP+ compared with BCP− (78.9±0.3% versus 76.4±0.3%*) and in Plegisol+ compared with Plegisol− (81.1±0.3% versus 79.6±0.4%*). Creatine kinase activity was significantly increased in Plegisol+ (48±6) compared with that in Plegisol− (31±6) but was unchanged in BCP− (14±2) relative to BCP+ (18±1). Nitrotyrosine (ng/mg protein) accumulation in LV myocardial biopsy samples confirmed myocardial exposure to ONOO
−
or its metabolites (Plegisol− 1.2±0.1, Plegisol+ 3.31±0.3*, BCP− 1.4±0.2, BCP+ 2.9±0.2*).

Conclusions
—We conclude that (1) the postcardioplegic cardiodynamic effects of ONOO
−
depend on its environment and (2) ONOO
−
in crystalloid solution impairs postcardioplegia systolic and diastolic functional recovery, whereas (3) ONOO
−
in BCP increases functional recovery. This environment-dependent dichotomy in the effect of ONOO
−
may affect the benefits of NO-related adjuncts to crystalloid or BCP solutions (*
P
<0.05 versus group without ONOO
−
). :II-384–II-391.)
Randomized Trial of Partial Versus Complete Chordal Preservation Methods of Mitral Valve Replacement
Authors: Yun Kwok L. , Sintek Colleen F. , Miller D. Craig , Schuyler Gregg T. , Fletcher Alden D. , Pfeffer Thomas A. , Kochamba Gary S. , Khonsari Siavosh , Zile Michael R.
Published: July 2021

Background
—The merits of retaining the subvalvular apparatus during mitral valve replacement for chronic mitral regurgitation have been demonstrated in numerous clinical and laboratory investigations. In this preliminary report, we analyzed the early effects of complete versus partial chordal preservation on left ventricular mechanics.

Methods and Results
—Fifty patients undergoing isolated surgical correction of mitral insufficiency were prospectively randomized to either total or partial chordal-sparing mitral valve replacement. Of the first 19 patients studied, 8 had preservation of the posterior leaflet only, and 11 had complete preservation of all chordal structures. A comparison group consisted of 6 patients who had primary mitral valve repair. Echocardiography was performed preoperatively and at discharge from the hospital to determine dimensions, wall stress, and ejection fraction. Preservation of the posterior leaflet only resulted in a reduction in end-diastolic volume, an increase in end-systolic volume (
P
=0.058), a rising trend in end-systolic stress, a decrease in long-axis fractional shortening, and a fall in ejection fraction from 0.68±0.16 to 0.46±0.19 (
P
=0.001). Although patients who had preservation of all chordal structures also had decreased end-diastolic volume, long-axis fractional shortening, and ejection fraction (0.60±0.13 to 0.52±0.07,
P
=0.01), end-systolic stress fell and end-systolic volume decreased instead of increased. Compared with the posterior leaflet preservation group, those in the group with completely preserved chordal structures had a larger decline in end-diastolic volume and smaller decreases in long-axis fractional shortening and ejection fraction. Changes in end-systolic volume and stress were also statistically different between the 2 cohorts. No differences were detected between the group with total preserved chordal structures and the mitral repair group in any of the measured parameters.

Conclusions
—Compared with posterior chordal preservation only, complete retention of the subvalvular apparatus during mitral valve replacement resulted in improved ejection performance and smaller chamber volumes due to reduced systolic wall stress. These hemodynamic advantages are comparable to those observed with primary mitral reconstruction.
Socioeconomic Status Is an Important Determinant of the Use of Invasive Procedures After Acute Myocardial Infarction in New York State
Authors: Philbin Edward F. , McCullough Peter A. , DiSalvo Thomas G. , Dec G. William , Jenkins Paul L. , Weaver W. Douglas
Published: July 2021

Background
—Patient and hospital characteristics influence the use of invasive cardiac procedures. Whether socioeconomic status (SES) has an influence that is independent of these other determinants is unclear. The purpose of the present study was to examine the influence of household income as a measure of SES on the use of invasive cardiac procedures among a large group of patients with acute myocardial infarction.

Methods and Results
—We analyzed administrative discharge data from 231 nonfederal acute care hospitals in New York State that involved 28 698 black or white inpatients with
International Classification of Diseases, Ninth Revision, Clinical Modification
code 410.XX in the principal diagnosis position between January 1 and December 31, 1995. Household income was derived from postal ZIP codes and census data. The use of cardiac catheterization, PTCA, CABG, and any revascularization procedure was examined across groups stratified by income. Patients who resided in lower-income neighborhoods were more often female or black, had a higher prevalence of coexistent illness, had a higher use of Medicaid insurance, and were less often admitted to urban hospitals or hospitals that provide on-site CABG and PTCA. Crude and adjusted odds ratios for catheterization, PTCA, CABG, and any revascularization procedure were related to income in a graded fashion. After adjustment, patients in the highest quintile of income were 22% more likely to undergo catheterization, 74% more likely to undergo PTCA, 48% more likely to undergo CABG, and 76% more likely to undergo any revascularization procedure than were patients in the lowest quintile. The difference in cardiac catheterization did not fully account for income-based differences in revascularization, because income remained a significant determinant of revascularization after accounting for whether a catheterization was performed. Even among patients treated in hospitals that provide on-site CABG and PTCA, income was a significant determinant of procedures.

Conclusions
—Lower-income patients hospitalized for acute myocardial infarction are more often female or black, have more coexisting illnesses, and are less often admitted to urban hospitals or hospitals that provide CABG and PTCA. Even after adjustment for these and other factors, lower income is a negative predictor of procedure use.
Tetralogy of Fallot
Authors: d’Udekem Y. , Ovaert C. , Grandjean F. , Gerin V. , Cailteux M. , Shango-Lody P. , Vliers A. , Sluysmans T. , Robert A. , Rubay J.
Published: July 2021

Background
—In tetralogy of Fallot, transannular patching is suspected to be responsible for late right ventricular dilatation.

Methods and Results
—In our institution, 191 patients survived a tetralogy of Fallot repair between 1964 and 1984. Transannular patching was used in 99 patients (52%), patch closure of a right ventriculotomy in 35, and direct closure of a right ventriculotomy in 55. Two had a transatrial-transpulmonary approach. To identify predictive factors of adverse long-term outcome related to right ventricular dilatation, the following events were investigated: cardiac death, reoperation for symptomatic right ventricular dilatation, and NYHA class II or III by Cox regression analysis. Mean follow-up reached 22±5 years. The 30-year survival was 86±5%. Right ventricular patching, whether transannular or not, was the most significant independent predictor of late adverse event (improvement χ
2
=16.6,
P
<0.001). In patients who had direct closure, the ratio between end-diastolic right and left ventricular dimensions on echocardiography was smaller (0.61±0.017 versus 0.75±0.23,
P
=0.007), with a smaller proportion presenting severe pulmonary insufficiency (9% versus 40%,
P
=0.005). There was no difference between right ventricular and transannular patching concerning late outcome (log rank
P
value=0.6), right ventricular size (0.70±0.28 versus 0.76±0.26,
P
=0.4), or incidence of severe pulmonary insufficiency (30% versus 43%,
P
=0.3).

Conclusions
—In tetralogy of Fallot, transannular patching does not result in a worse late functional outcome than patching of an incision limited to the right ventricle. Both are responsible for a similar degree of long-term pulmonary insufficiency and right ventricular dilatation.