[Selective Sinus Replacement for Aortic Root Disease].

BACKGROUND: Selective sinus replacement seems a reasonable option in cases requiring replacement of one or two sinuses of Valsalva, especially with acute aortic dissection and high bleeding risk. METHODS: Six patients (average age 58±17 years;five males) underwent selective replacement of the right sinus of Valsalva with right coronary artery bypass grafting (n=5) in 2015-2023. Five patients developed acute aortic dissection and one developed aneurysm of the right sinus of Valsalva. RESULTS: All patients survived the operation, and there were no cases requiring re-exploration for bleeding. Intraoperative transesophageal echocardiography showed trivial or less aortic regurgitation (AR) in all patients. Cardiopulmonary bypass time, aortic cross-clamping time, and lower body circulatory arrest time were 214±28 min, 159±22 min, and 31±6 min (n=5), respectively. During follow-up of 55±44 (4-104) months, all patients were asymptomatic. AR was mild or less in four patients, mild-moderate in one patient, and severe in one patient. All patients had normal cardiac function without left ventricular enlargement, and so no reoperation was required. CONCLUSIONS: Although this method appears to be relatively safe and effective, some patients developed late AR. Long-term follow-up of larger numbers of patients will be necessary to confirm its effectiveness.

What does complete revascularization mean in 2021? - Definitions, implications, and biases.

PURPOSE OF REVIEW: Coronary revascularization is known to be an excellent treatment for coronary artery disease. However, whether incomplete myocardial revascularization compromises long-term outcomes, as compared to complete revascularization (CR), remains contentious. Herein, we review the concept of and evidence on CR/incomplete revascularization (ICR) and discuss future perspectives. RECENT FINDINGS: When possible, achieving CR in coronary artery bypass grafting is desirable; nonetheless, ICR is also a reasonable option to balance the therapeutic benefits against the risks. SUMMARY: Although angiography-based assessment currently remains the standard of care, fractional flow reserve guidance may reduce the number of lesions requiring revascularization, which may be helpful for an appropriate surgical revascularization strategy. In particular, utilizing this approach may refine hybrid revascularization procedures, especially among high-risk patients.

New hemostatic technique with combined use of Hydrofit® and Surgicel®: an in vitro and in vivo study.

We developed an effective hemostatic technique using Hydrofit® and Surgicel® simultaneously. The aim of this study was to demonstrate the hemostatic efficacy of the Hydrofit® and Surgicel® combination technique through an in vitro experiment and to elucidate mid-term consequences of the combined components through an in vivo experiment. For the in vitro experiment, a closed circuit using a heparin-coated cardiopulmonary bypass circuit and a prosthetic graft was created. The amount of bleeding from the prosthetic graft was measured, and the following three hemostatic methods were applied: only gauze compression in control group, Hydrofit® application in Hydrofit group, Surgicel® spread Hydrofit® application in Hydrofit and Surgicel (HS) group, respectively. In the in vivo experiment, Hydrofit® and/or Surgicel® were implanted under skin on the back of rats (n = 10) at 4 points. In the control group, only an incision was made; in the Hydrofit, Surgicel, and HS groups, Hydrofit® and/or Surgicel® was implanted. One and three months later, each of the five rats were killed and in each section histopathologic examination was carried out. In the in vitro experiment, the amount of bleeding was 7.84 ± 1.08, 2.26 ± 1.02, and 0.87 ± 0.38 ml in the control, Hydrofit, and HS groups, respectively. The amount of bleeding in the HS group was more suppressed than in the Hydrofit group (p = 0.012). In the in vivo experiment, the maximal depth diameter of each remaining hemostatic sealant was measured. After 3 months, the diameter was 0, 2289.0 ± 768.2, 3850.3 ± 935.8 µm in Surgicel, Hydrofit and HS groups, respectively. The diameter was significantly increased in the HS group compared with the Surgicel and Hydrofit groups (p < 0.001, respectively,). In conclusion, the combination of Hydrofit® and Surgicel® was effective in achieving hemostasis. The remnants of Hydrofit® and Surgicel® were present for a long time in the tissues which could compress the surrounding tissue.

Aortic Insufficiency Causes Symptomatic Heart Failure during Left Ventricular Assist Device Support.

De novo aortic insufficiency is often documented during long-term left ventricular assist device (LVAD) support, despite the absence of aortic insufficiency at the time of LVAD implantation. However, whether aortic insufficiency affects long-term mortality and symptomatic heart failure in LVAD-supported patients remains controversial. We aimed to examine whether aortic insufficiency development influenced mortality and symptomatic heart failure following LVAD implantation. Fifty-three patients who underwent durable LVAD implantation between January 1, 2008 and April 31, 2017 were retrospectively examined in a single center institute. After discharge, we performed the echocardiographic examination in accordance with the Japanese registry for the mechanically assisted circulatory support protocol. Aortic insufficiency was graded on an interval scale (severe = 4, moderate = 3, mild = 2, trivial or none = 1). Kaplan-Meier estimates for long-term mortality at the follow-up were generated. We used a logistic regression model to identify risk factors for symptomatic heart failure. The overall median duration of LVAD support was 856.3 ± 430.8 days (range, 12-1,744 days). We did not observe a significant difference in long-term mortality in patients with aortic insufficiency ≥ 3 grade compared with patients with aortic insufficiency < 3 grade (P = 0.767; log-rank). Aortic insufficiency was associated with an increased risk for heart failure event after discharge (odds ratio, 4.12; confidence interval, 1.48-16.93; P = 0.005). Aortic insufficiency was an independent risk factor for symptomatic heart failure and was not associated with long-term mortality. Aortic insufficiency progression was associated with symptomatic heart failure.

Perioperative use of the intra-aortic balloon pump: where do we stand in 2018?

PURPOSE OF REVIEW: Intraaortic balloon pump (IABP) has been the most widely used device to help patients recover from circulatory disorder mainly because of cardiogenic shock; however, no evidence-based clinical benefit derived from IABP support has been reported in recent clinical trials. This review provides an overview of the current outcomes and challenges in perioperative IABP use for cardiogenic shock patients. RECENT FINDINGS: Although IABP support yielded no significant difference in mortality for myocardial infarction complicated by cardiogenic shock, perioperative IABP use generated beneficial clinical outcomes for high-risk patients undergoing coronary revascularization. The latest technology such as optical fiber sensor incorporated into the devices provides some beneficial effects on hemodynamics and reduces device-related complications. SUMMARY: Perioperative IABP use is reasonable for cardiogenic shock patients as a bridge to further surgical intervention, to wean from cardiopulmonary bypass, and to postoperative recovery. Over the next years, a revolutionary technology will overcome the currently limited IABP therapy. Larger and longer term clinical investigations are also required to identify ideal patients for IABP use and to establish the position of IABP therapy.

Evidence of Pulmonary Vascular Reverse Remodeling After Pulmonary Artery Banding Performed in Early Infancy in Patients With Congenital Heart Defects.

BACKGROUND: Histomorphometric evidence of the effect of pulmonary artery banding (PAB) in infancy on pulmonary vascular reverse remodeling has not been fully described.Methods and Results:We retrospectively reviewed 34 patients who underwent serial lung biopsies before and after PAB.Index of pulmonary vascular disease (IPVD) as a measure of the degree of progression of pulmonary arteriopathy significantly decreased after PAB (1.22±0.25 at 1st and 1.13±0.21 at 2nd biopsy, P=0.04). Additionally,DR=100 µmas an indicator of medial thickness of pulmonary arteries significantly decreased after PAB (15.6±3.7 at 1st and 11.4±2.6 at 2nd biopsy, P<0.0001). Patients were divided into 3 groups by age at PAB: <3 months (Group 1), between 3 and 6 months (Group 2), and >6 months (Group 3). The average secondDR=100 µmof groups 1 and 2 was significantly lower than that of group 3 (11.1±2.2 and 9.8±2.0 vs. 14.9±2.8, respectively; P<0.0001). Additionally, the second IPVD was also significantly lower in groups 1 and 2 than in group 3 (1.1±0.2 and 1.1±0.2 vs. 1.3±0.4, respectively; P=0.02). CONCLUSIONS: Histomorphometric evidence of post-PAB pulmonary vascular reverse remodeling is robust. The magnitude of vascular reversibility is pronounced when PAB is performed before 6 months of age.

Is Trisomy 21 a Risk Factor for Rapid Progression of Pulmonary Arteriopathy?　- Revisiting Histopathological Characteristics Using 282 Lung Biopsy Specimens.

BACKGROUND: Pulmonary hypertension (PH) is more progressive in trisomy 21 patients. However, pulmonary arteriopathic lesions in these patients have not been fully characterized histopathologically.Methods and Results:A retrospective review of a lung biopsy registry identified 282 patients: 188 patients with trisomy 21 (Group D) and 94 without (Group N). The mean age at lung biopsy was 3 and 7 months (P<0.0001). Pulmonary arterial pressure (PAP) and pulmonary vascular resistance were similar between the 2 groups. There were no significant differences in the proportion of patients with irreversible intimal lesions or the index of pulmonary vascular disease (IPVD; a measure of the degree of pulmonary arteriopathy progression) between the 2 groups. In addition, after propensity score matching for patient background (n=43 in each group), there were no significant differences in IPVD (P=0.29) or the ratio of irreversible intimal changes between the D and N groups (P=0.39). Multivariate analysis identified age (P<0.0001) and PAP (P=0.03) as the only risk factors for progression of pulmonary arteriopathy. CONCLUSIONS: Histopathologically, early progression of pulmonary arteriopathy in patients with trisomy 21 was not proved compared with patients without trisomy 21. Although we cannot exclude the possibility of bias in the Group D and N patients who were slated for lung biopsy, factors other than pulmonary arteriopathy may affect the marked progression of clinical PH in trisomy 21 patients.

Histopathological examination by lung biopsy for the evaluation of operability and postoperative prognosis in patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: To evaluate the prognosis after pulmonary thromboendarterectomy (PTE) in patients with chronic thromboembolic pulmonary hypertension (CTEPH), a lung biopsy was performed in 34 patients with central CTEPH and in 7 patients with peripheral CTEPH during PTE. METHODS AND RESULTS: Postoperative prognosis was classified from A to E based on the postoperative hemodynamic parameters and clinical condition, and was compared with the index of occlusion (IOCTEPH), which indicates the degree of occlusion in the small pulmonary arteries. Criteria of (A-E) were established only for central CTEPH. Category (A) corresponded to an IOCTEPH from 1.0 to 1.4, (B) from 1.5 to 1.7, (C) from 1.8 to 2.0, and (D) from 2.1 to 2.4. One patient with an index of 3.0 was rated as (E). This patient had collateral vessels around the obstructed small pulmonary arteries and died postoperatively. In all 12 patients who underwent PTE after the criteria were established, postoperative hemodynamic parameters and clinical conditions were consistent with the IOCTEPH. One patient with a high degree of medial atrophy in their small pulmonary arteries died after PTE. CONCLUSIONS: These results indicate that a lung biopsy during PTE is useful for prognostication in patients with CTEPH.

Corrigendum: Use of the index of pulmonary vascular disease for predicting longterm outcome of pulmonary arterial hypertension associated with congenital heart disease.

[This corrects the article DOI: 10.3389/fcvm.2023.1212882.].

Longitudinal Outcomes Following Surgical Repair of Primary Mitral Regurgitation.

Degenerative mitral valve (MV) disease is the most common cause of organic mitral regurgitation (MR) in developed countries. Surgical mitral valve repair is the gold standard treatment for primary MR. Surgical mitral valve repair is associated with excellent outcomes in terms of survival and freedom from recurrent MR. As well, innovations in surgical repair techniques, including thoracoscopically and robotically assisted approaches, further reduce morbidity. Emerging catheter-based therapies may also provide advantages in select patient groups. Although the outcomes following surgical mitral valve repair are well described in the literature, longitudinal follow-up is heterogenous. Indeed, longitudinal follow-up and long-term data are vital to better advise treatment and counsel patients.

Use of the index of pulmonary vascular disease for predicting long-term outcome of pulmonary arterial hypertension associated with congenital heart disease.

Aims: Limited data exist on risk factors for the long-term outcome of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH). We focused on the index of pulmonary vascular disease (IPVD), an assessment system for pulmonary artery pathology specimens. The IPVD classifies pulmonary vascular lesions into four categories based on severity: (1) no intimal thickening, (2) cellular thickening of the intima, (3) fibrous thickening of the intima, and (4) destruction of the tunica media, with the overall grade expressed as an additive mean of these scores. This study aimed to investigate the relationship between IPVD and the long-term outcome of CHD-PAH. Methods: This retrospective study examined lung pathology images of 764 patients with CHD-PAH aged <20 years whose lung specimens were submitted to the Japanese Research Institute of Pulmonary Vasculature for pulmonary pathological review between 2001 and 2020. Clinical information was collected retrospectively by each attending physician. The primary endpoint was cardiovascular death. Results: The 5-year, 10-year, 15-year, and 20-year cardiovascular death-free survival rates for all patients were 92.0%, 90.4%, 87.3%, and 86.1%, respectively. The group with an IPVD of ≥2.0 had significantly poorer survival than the group with an IPVD <2.0 (P = .037). The Cox proportional hazards model adjusted for the presence of congenital anomaly syndromes associated with pulmonary hypertension, and age at lung biopsy showed similar results (hazard ratio 4.46; 95% confidence interval: 1.45-13.73; P = .009). Conclusions: The IPVD scoring system is useful for predicting the long-term outcome of CHD-PAH. For patients with an IPVD of ≥2.0, treatment strategies, including choosing palliative procedures such as pulmonary artery banding to restrict pulmonary blood flow and postponement of intracardiac repair, should be more carefully considered.

Preventive effect of low-dose landiolol on postoperative atrial fibrillation study (PELTA study).

OBJECTIVE: To investigate the efficacy of prophylactic administration of low-dose landiolol on postoperative atrial fibrillation (POAF) in patients after cardiovascular surgery. METHODS: Consecutive 150 patients over 70 years of age who underwent cardiovascular surgery for valvular, ischemic heart, and aortic diseases were enrolled in this single-center prospective randomized control study from 2010 to 2014. They were assigned to three treatment groups: 1γ group (landiolol at 1 µg/kg/min), 2γ group (landiolol at 2 µg/kg/min), or control group (no landiolol). In the two landiolol groups, landiolol hydrochloride was intravenously administered for a period of 4 days postoperatively. Electrocardiography was continuously monitored during the study period, and cardiologists eventually assessed whether POAF occurred or not. RESULTS: POAF occurred in 24.4% of patients in the control group, 18.2% in 1γ group, and 11.1% in 2γ group (p = 0.256). Multivariate logistic regression analysis showed that the incidence of POAF tended to decrease depending on the dose of landiolol (trend-p = 0.120; 1γ group: OR = 0.786, 95% CI 0.257-2.404; 2γ group: OR = 0.379, 95% CI 0.112-1.287). Subgroup analysis showed a significant dose-dependent reduction in POAF among categories of female sex, non-use of angiotensin II receptor blockers (ARBs) before surgery, and valve surgery (each trend-p = 0.02, 0.03, and 0.004). CONCLUSIONS: These findings indicate that prophylactic administration of low-dose landiolol may not be effective for preventing the occurrence of POAF in overall patients after cardiovascular surgery, but the administration could be beneficial to female patients, patients not using ARBs preoperatively, and those after valvular surgery.

Agonist-induced internalization of histamine H2 receptor and activation of extracellular signal-regulated kinases are dynamin-dependent.

Histamine H2 receptor (H2R) is a member of G protein-coupled receptor family. Agonist stimulation of H2R results in several cellular events including activation of adenylate cyclase and phospholipase C, desensitization of the receptor, activation of extracellular signal-regulated kinases ERK1/2, and receptor endocytosis. In this study, we identified a GTPase dynamin as a binding partner of H2R. Dynamin could associate with H2R both in vitro and in vivo. Functional analyses using dominant-negative form of dynamin (K44E-dynamin) revealed that cAMP production and the following H2R desensitization are independent of dynamin. However, the agonist-induced H2R internalization was inhibited by co-expression of K44E-dynamin. Furthermore, activation of extracellular-signal regulated kinases ERK1/2 in response to dimaprit, an H2R agonist, was attenuated by K44E-dynamin. Although H2R with truncation of 51 amino acids at its carboxy-terminus did not internalize after agonist stimulation, it still activated ERK1/2, but the degree of this activation was less than that of the wild-type receptor. Finally, K44E dynamin did not affect ERK1/2 activation induced by internalization-deficient H2R. These results suggest that the agonist-induced H2R internalization and ERK1/2 activation are partially dynamin-dependent. Furthermore, ERK1/2 activation via H2R is likely dependent of the endocytotic process rather than dynamin itself.

CLIC4 interacts with histamine H3 receptor and enhances the receptor cell surface expression.

Histamine H3 receptor (H3R), one of G protein-coupled receptors (GPCRs), has been known to regulate neurotransmitter release negatively in central and peripheral nervous systems. Recently, a variety of intracellular proteins have been identified to interact with carboxy (C)-termini of GPCRs, and control their intracellular trafficking and signal transduction efficiencies. Screening for such proteins that interact with the C-terminus of H3R resulted in identification of one of the chloride intracellular channel (CLIC) proteins, CLIC4. The association of CLIC4 with H3R was confirmed in in vitro pull-down assays, coimmunoprecipitation from rat brain lysate, and immunofluorescence microscopy of rat cerebellar neurons. The data from flowcytometric analysis, radioligand receptor binding assay, and cell-based ELISA indicated that CLIC4 enhanced cell surface expression of wild-type H3R, but not a mutant form of the receptor that failed to interact with CLIC4. These results indicate that, by binding to the C-terminus of H3R, CLIC4 plays a critical role in regulation of the receptor cell surface expression.

Reconsideration of frailty in relation to surgical indication.

Given that an increasing number of elderly patients are undergoing surgical procedures for a diversity of indications, the concept of frailty is currently being examined in more depth in clinical medicine. Established surgical risk scores designed to predict mortality are mainly focused on general demographic information and clinical factors; however, these do not account for the frailty condition. With vulnerability and low resiliency in the frail elderly, these conventional scores are unable to accurately predict postoperative outcomes including adverse complications, disability, the need for additional rehabilitation, and prolonged length of hospitalization. Over the last decade, it has been demonstrated that frailty is an independent risk factor of surgery and strongly associated with adverse postoperative outcomes and mortality. It is essential today that surgeons assimilate the concept of frailty and the relationship between frailty and surgical outcomes. A preoperative frailty assessment can assist in determining surgical indication and optimal perioperative management, ultimately impacting the postoperative functional state and quality of life. Here we review the validity of preoperative frailty assessments for surgical intervention, possible treatments for frailty, and indicate future directions in this field.

Intravenously injected human multilineage-differentiating stress-enduring cells selectively engraft into mouse aortic aneurysms and attenuate dilatation by differentiating into multiple cell types.

OBJECTIVES: Aortic aneurysms result from the degradation of multiple components represented by endothelial cells, vascular smooth muscle cells, and elastic fibers. Cells that can replenish these components are desirable for cell-based therapy. Intravenously injected multilineage-differentiating stress-enduring (Muse) cells, endogenous nontumorigenic pluripotent-like stem cells, reportedly integrate into the damaged site and repair the tissue through spontaneous differentiation into tissue-compatible cells. We evaluated the therapeutic efficacy of Muse cells in a murine aortic aneurysm model. METHODS: Human bone marrow Muse cells, isolated as stage-specific embryonic antigen-3+ from bone marrow mesenchymal stem cells, or non-Muse cells (stage-specific embryonic antigen-3- cells in mesenchymal stem cells), bone marrow mesenchymal stem cells, or vehicle was intravenously injected at day 0, day 7, and 2 weeks (20,000 cells/injection) after inducing aortic aneurysms by periaortic incubation of CaCl2 and elastase in severe combined immunodeficient mice. RESULTS: At 8 weeks, infusion of human Muse cells attenuated aneurysm dilation, and the aneurysmal size in the Muse group corresponded to approximately 62.5%, 55.6%, and 45.6% in the non-Muse, mesenchymal stem cell, and vehicle groups, respectively. Multiphoton laser confocal microscopy revealed that infused Muse cells migrated into aneurysmal tissue from the adventitial side and penetrated toward the luminal side. Histologic analysis demonstrated robust preservation of elastic fibers and spontaneous differentiation into endothelial cells and vascular smooth muscle cells. CONCLUSIONS: After intravenous injection, Muse cells homed and expanded to the aneurysm from the adventitial side. Subsequently, Muse cells differentiated spontaneously into vascular smooth muscle cells and endothelial cells, and elastic fibers were preserved. These Muse cell features together led to substantial attenuation of aneurysmal dilation.

Echocardiography-Guided Intramyocardial Injection Method in a Murine Model.

Cardiac regenerative therapy has received attention as a potentially revolutionary approach for treating the damaged heart. The mouse model of myocardial infarction (MI) remains one of the most common tools for the evaluation of such new therapies. Typically, intramyocardial administration of cells or biomaterials in mice is performed by an open-chest surgical procedure, but less invasive delivery methods are becoming available. Echocardiography-based transthoracic myocardial injection is one such minimally invasive approach that can reliably deliver therapeutics to the target site with limited complications and quick recovery for the animal following the procedure. Here, we will describe the method of echocardiography-guided intramyocardial injection in a mouse MI model.

Optimizing the host substrate environment for cardiac angiogenesis, arteriogenesis, and myogenesis.

INTRODUCTION: The diseased host milieu, such as endothelial dysfunction (ED), decreased NO bioavailability, and ischemic/inflammatory post-MI environment, hamper the clinical success of existing cardiac regenerative therapies. Area covered: In this article, current strategies including pharmacological and nonpharmacological approaches for improving the diseased host milieu are reviewed. Specifically, the authors provide focus on: i) the mechanism of ED in patients with cardiovascular diseases, ii) the current results of ED improving strategies in pre-clinical and clinical studies, and iii) the use of biomaterials as a novel modulator in damaged post-MI environment. Expert opinion: Adjunct therapies which improve host endothelial function have demonstrated promising outcomes, potentially overcoming disappointing results of cell therapy in human studies. In the future, elucidation of the interactions between the host tissue and therapeutic agents, as well as downstream signaling pathways, will be the next challenges in enhancing regenerative therapy. More careful investigations are also required to establish these agents' safety and efficacy for wide usage in humans.

Methylglyoxal-Induced Endothelial Cell Loss and Inflammation Contribute to the Development of Diabetic Cardiomyopathy.

The mechanisms for the development of diabetic cardiomyopathy remain largely unknown. Methylglyoxal (MG) can accumulate and promote inflammation and vascular damage in diabetes. We examined if overexpression of the MG-metabolizing enzyme glyoxalase 1 (GLO1) in macrophages and the vasculature could reduce MG-induced inflammation and prevent ventricular dysfunction in diabetes. Hyperglycemia increased circulating inflammatory markers in wild-type (WT) but not in GLO1-overexpressing mice. Endothelial cell number was reduced in WT-diabetic hearts compared with nondiabetic controls, whereas GLO1 overexpression preserved capillary density. Neuregulin production, endothelial nitric oxide synthase dimerization, and Bcl-2 expression in endothelial cells was maintained in the hearts of GLO1-diabetic mice and corresponded to less myocardial cell death compared with the WT-diabetic group. Lower receptor for advanced glycation end products and tumor necrosis factor-α (TNF-α) levels were also observed in GLO1-diabetic versus WT-diabetic mice. Over a period of 8 weeks of hyperglycemia, GLO1 overexpression delayed and limited the loss of cardiac function. In vitro, MG and TNF-α were shown to synergize in promoting endothelial cell death, which was associated with increased angiopoietin 2 expression and reduced Bcl-2 expression. These results suggest that MG in diabetes increases inflammation, leading to endothelial cell loss. This contributes to the development of diabetic cardiomyopathy and identifies MG-induced endothelial inflammation as a target for therapy.