Significance of End-Diastolic Forward Flow in Patients With Repaired Tetralogy of Fallot　- Its Interaction With the Left Ventricular Property and End Organ Damage.

BACKGROUND: Although right ventricular (RV) enlargement may affect RV diastolic dysfunction assessed by end-diastolic forward flow (EDFF) in patients with repaired tetralogy of Fallot (TOF), EDFF may also be modified by left ventricular (LV) hemodynamics. We hypothesized that EDFF is affected by LV hemodynamics, not limited to RV diastolic stiffening.Methods and Results: Among 145 consecutive patients with repaired TOF who underwent catheterization, hemodynamic properties in 47 with consistent EDFF and 75 without EDFF were analyzed. Compared with patients without EDFF, those with EDFF had a large RV volume with a high regurgitant fraction. Although cardiac index and central venous pressure (CVP) were similar, contrast injection augmented CVP and LV end-diastolic pressure (EDP) in patients with vs. those without EDFF, suggesting compromised diastolic reserve. In patients with EDFF, the velocity-time integral (VTI) of EDFF was positively correlated with LVEDP and systemic vascular resistance, in addition to RV EDP. EDFF-VTI was correlated with hepatic venous wedge pressure and markers of hepatic dysfunction. Subanalysis of the older (≥6 years) half of the study cohort revealed that EDFF was associated with bi-atrial enlargement independent of RV volume, highlighting the pronounced role of EDFF on the diastolic property in the aged cohort. CONCLUSIONS: EDFF-VTI in patients with repaired TOF reflects RV diastolic dysfunction, affected by the left heart system. EDFF-VTI indicates blood stagnation, which may be attributed to end-organ damage.

Ruptured Abdominal Aortic Aneurysm Repair Using Open Proximal Anastomosis Under Deep Hypothermic Circulatory Arrest.

Proximal aortic clamping under normothermia is generally adequate for operative repair of abdominal aortic rupture; however, the hypothermic circulatory arrest (HCA) technique is not as common. Proximal exposure and clamping are sometimes difficult due to the risk of bleeding, rerupture, and ischemia. We present a successful case of a ruptured abdominal aortic aneurysm (AAA) that was repaired using cardiopulmonary bypass with HCA. A 75-year-old man presented with sudden back pain and was diagnosed with a ruptured AAA using computed tomography. The aneurysm had a maximal diameter of 100 mm and protruded anteriorly just below the renal arteries. The rupture site was close to the renal arteries, and thus, there was a high risk of bleeding and shock during proximal exposure. Cardiopulmonary bypass was established by cannulation of the right axillary artery and right femoral vein, following which open laparotomy was performed. Proximal exposure and anastomosis could be safely performed using HCA. This cardiopulmonary bypass with HCA technique may be useful as a surgical strategy for ruptured juxta-renal AAAs.

[Valve Re-replacement after Aortic Valve Replacement with Starr-Edwards Ball Valve Forty-five Years Ago:Report of a Case].

The patient was a 67-year-old man. At 22 years of age, he underwent aortic valve replacement with Starr-Edwards ball valve. At 67 years of age, he complained of fatigue of the New York Heart Association (NYHA) class Ⅲ condition. He was diagnosed with mitral regurgitation, tricuspid regurgitation, ascending aortic aneurysm and chronic atrial fibrillation. Transthoracic and transesophageal echocardiograms showed a mobile, elongated echogenic mass attached to the valve cage and floating downstream. We performed Bentall procedure, ascending aortic replacement, mitral valve replacement, tricuspid annuloplasty and left atrial appendage closure. Explanted ball valve showed extensive cloth destruction and partial cloth tear. Mild pannus formation was observed beneath the valve. Despite 45 years after initial operation, significant valve dysfunction was not observed.

Twenty-year experience following aortic valve replacement in patients younger than 60 years of age.

OBJECTIVE: Reports on long-term outcomes of surgical aortic valve replacement (AVR) for patients aged < 60 years are scarce in Japan. Hence, we aimed to evaluate these outcomes in patients aged < 60 years. METHODS: Between March 2000 and December 2020, 1477 patients underwent aortic valve replacement. In total, 170 patients aged < 60 years who underwent aortic valve replacement were recruited. Patients aged < 18 years were excluded. Patient data collected from the operative records and follow-up assessments were reviewed. RESULTS: The mean age was 49 ± 9 years, and 64.1% of patients were male. One-hundred-and-fifty-two patients (89.4%) underwent aortic valve replacement with a mechanical valve and 18 (10.6%) with a bioprosthetic valve. The mean follow-up period was 8.1 ± 5.5 years. No operative mortality occurred, and in-hospital mortality occurred in one patient (0.6%). Ten late deaths occurred, with seven cardiac-related deaths. The overall survival rate was 95.4 ± 1.7%, 93.9 ± 2.3%, 90.6 ± 3.9%, and 73.2 ± 11.8% at 5, 10, 15, and 20 years, respectively. Freedom from major bleeding was 96.4 ± 1.6% at 5, 10, and 15 years, and 89.0 ± 7.3% at 20 years. Freedom from thromboembolic events was 98.7 ± 1.3%, 97.3 ± 1.9%, 90.5 ± 4.5%, and 79.0 ± 11.3% at 5, 10, 15, and 20 years, respectively. Freedom from valve-related reoperation was 99.4 ± 0.6% at 5 years, 97.8 ± 1.7% at 10 and 15 years, and 63.9 ± 14.5% at 20 years. CONCLUSIONS: Patients aged < 60 years undergoing aortic valve replacement with a high mechanical valve implantation rate had favorable long-term outcomes.

Patterns of collateral arteries to the spinal cord after thoraco-abdominal aortic aneurysm repair.

OBJECTIVES: Our goal was to evaluate postoperative patterns of collateral arteries to the spinal cord during occlusion of the segmental arteries supplying the artery of Adamkiewicz (AKA). METHODS: Between April 2011 and December 2022, a total of 179 patients underwent thoraco-abdominal aortic aneurysm repair; 141 had an identifiable AKA on preoperative multidetector computed tomography scans, 40 underwent thoraco-abdominal aortic aneurysm replacement (TAAR) and 101 underwent thoracic endovascular aortic repair (TEVAR). New postoperative collateral blood pathways invisible on preoperative contrast-enhanced computed tomography scans were identified in 42 patients (10 patients who had TAAR vs 32 patients who had TEVAR) who underwent preoperative and postoperative multidetector computed tomography scanning for AKA identification. RESULTS: The thoracodorsal and segmental arteries were the main collateral pathways in both groups. Th9-initiated collaterals were the most common. Collaterals from the internal thoracic artery were observed in the TEVAR group but not in the TAAR group. One patient in the TEVAR group experienced postoperative paraparesis, which was not observed in the TAAR group. Postoperative paraplegia was more common in the non-Th9-origin group, but this difference was not significant. CONCLUSIONS: Thoracodorsal and segmental arteries may be important collateral pathways after TEVAR and TAAR. For thoracodorsal arteries, preserving the thoracodorsal muscle during the approach would be crucial; for segmental arteries, minimizing the area to be replaced or covered would be paramount. An AKA not initiated at the Th9 level poses a high risk of postoperative paraplegia.

A case of severe ureteral injury repaired by renal autotransplantation with an iliac vein patch using bovine pericardium.

Introduction: Renal autotransplantation is considered a surgical procedure for extensive ureteral defects. Herein, we report a case of severe ureteral injury repaired by laparoscopic nephrectomy and renal autotransplantation with an iliac vein patch using bovine pericardium. Case presentation: A 56-year-old woman who had previously undergone gynecological surgery complained of right-sided abdominal pain. She was then later diagnosed with a right middle ureteral injury with a 5-cm long defect. We performed retroperitoneal laparoscopic nephrectomy and renal autotransplantation. As the iliac vein was fragile, venous patching using bovine pericardium was performed. The patient's renal function was well preserved after surgery. Conclusion: Laparoscopic nephrectomy and renal autotransplantation is an effective method for repairing severe ureteral injury with the preservation of renal function. A venous patch using bovine pericardium might be considered as a replacement for a fragile vein.

Successful Atrial Septal Defect Closure Subsequent to Medical Pulmonary Preconditioning in an Infant With Severe Pulmonary Hypertension Associated With Bronchopulmonary Dysplasia.

While atrial septal defect (ASD) may contribute to right ventricular decompression in patients with severe pulmonary hypertension (PH), the pulmonary vasculature might be compromised by increased pulmonary blood flow, even though pulmonary vasodilators successfully reduce resistance. ASD closure is a treatment option that may ameliorate PH symptoms associated with bronchopulmonary dysplasia (BPD) in infants. However, the feasibility of ASD closure is obscure in patients with BPD-PH causing right-to-left shunting. Here, we present an eight-month-old girl with ASD complicated by BPD-PH, in which the pulmonary pressure exceeded the systemic pressure; the ASD was successfully closed after pulmonary preconditioning with dexamethasone and high-dose diuretics. Our patient was delivered as the third baby in triplets at a gestational age of 25 weeks, with a birth weight of 344 g. She was diagnosed with BPD at three months of age (37 weeks of postmenstrual age) with a body weight of 1.4 kg. Mild pulmonary hypertension was identified at the age of five months, and oral sildenafil was initiated. While her atrial septal defect was small at the time of PH diagnosis, it became hemodynamically significant when she grew up to 3.4 kg of body weight, at seven months after birth. Her estimated right ventricular pressure was apparently more than the systemic pressure, and oxygen saturation fluctuated between 82% and 97% under oxygen supplementation due to bidirectional interatrial shunt with predominant right-to-left shunting. Pulmonary preconditioning lowered the estimated right ventricular pressure to almost equal the systemic pressure and elevated arterial oxygen saturation while also suppressing right-to-left shunting. Cardiac catheterization after preconditioning revealed a ratio of pulmonary blood pressure to systemic blood pressure ratio (Pp/Ps) of 0.9, pulmonary resistance of 7.3 WU-m2, and a pulmonary to systemic blood flow ratio (Qp/Qs) of 1.3 (approximately 1.0 in the normal circulation without significant shunt), with the cardiac index of 2.8 L/min/m2. The acute pulmonary vasoreactivity test against the combination of 20 ppm nitric oxide and 100% oxygen was negative, although the patient had consistently high pulmonary flow with makeshift improvements after preconditioning. Despite the high pulmonary resistance even after preconditioning, aggressive ASD closure was performed so that pulmonary flow could be consistently suppressed regardless of the pulmonary condition. Her Pp/Ps under 100% oxygen with 20 ppm nitric oxide was 0.7 immediately after closure. After two years of follow-up, her estimated right ventricular pressure was less than half of the systemic pressure with the use of three pulmonary vasodilators, including sildenafil, macitentan, and beraprost. A strategy to temporarily improve PH and respiratory status aimed at ASD closure could be a treatment option for the effective use of multiple pulmonary vasodilators, by which intensive treatment of BPD can be achieved.

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.].

Autonomic function is associated with health-related quality of life in patients with end-stage renal disease: a case-control study.

OBJECTIVE: In the present study, we assessed the associations among fatigue, quality of life (QOL), clinical parameters, and body mass index (BMI) with autonomic function in end-stage renal disease (ESRD) patients undergoing hemodialysis as well as fatigue-free healthy subjects. DESIGN AND METHODS: This was a case-control study. This study compared autonomic function in ESRD patients (n = 192) to that of healthy subjects (n = 282) and evaluated its association with fatigue, QOL, and clinical parameters such as glucose, albumin, cholesterol, and BMI. Fatigue was evaluated by a recently established fatigue questionnaire and performance status, and QOL was evaluated with the kidney disease QOL questionnaire. With regards to autonomic function, spontaneous beat-to-beat variations were measured, according to time- (standard deviation of all normal a-wave intervals [CVa-a%]) and frequency domains (low frequency [LF] power, high frequency [HF] power, and LF/HF ratio) with acceleration plethysmography. RESULTS: CVa-a%, LF power, HF power, and LF/HF ratio were significantly lower in ESRD patients than healthy subjects. There were significant inverse correlations between these factors and age in healthy subjects, but not in ESRD patients. Although the fatigue score was not associated with any autonomic parameters, ESRD patients with impaired performance status exhibited a significantly lower LF/HF ratio. Moreover, in ESRD patients, the LF/HF ratio was significantly and positively associated with several components of QOL, including physical functioning and role emotional, independent of other clinical parameters and BMI. CONCLUSIONS: Impaired autonomic function is significantly associated with fatigue and impaired QOL in dialysis patients.

Hepatic-to-azygos vein redirection after a failed bifurcated graft Fontan conversion.

A successful hepatic-to-azygos vein redirection was performed in a patient with absent inferior vena cava using a long vascular graft to address a pulmonary arterio-venous fistula after a failed Fontan conversion. No exacerbation was observed 5 years postoperatively.

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.

Patterns of sheath elongation, cell proliferation, and manganese(II) oxidation in Leptothrix cholodnii.

Leptothrix cholodnii is a Mn(II)-oxidizing and sheath-forming member of the class ß-Proteobacteria. Its sheath is a microtube-like filament that contains a chain of cells. From a chemical perspective, the sheath can be described as a supermolecule composed of a cysteine-rich polymeric glycoconjugate, called thiopeptidoglycan. However, the mechanism that controls the increase in sheath length is unknown. In this study, we attempted to detect sheath elongation through microscopic examination by using conventional reagents. Selective fluorescent labeling of preexisting or newly formed regions of the sheath was accomplished using combinations of biotin-conjugated maleimide, propionate-conjugated maleimide, and a fluorescent antibiotin antibody. Epifluorescence microscopy indicated that the sheath elongates at the terminal regions. On the bases of this observation, we assumed that the newly secreted thiopeptidoglycan molecules are integrated into the preexisting sheath at its terminal ends. Successive phase-contrast microscopy revealed that all cells proliferate at nearly the same rate regardless of their positions within the sheath. Mn(II) oxidation in microcultures was also examined with respect to cultivation time. Results suggested that the deposition of Mn oxides is notable in the aged regions. The combined data reveal the spatiotemporal relationships among sheath elongation, cell proliferation, and Mn oxide deposition in L. cholodnii.

A spatial relationship between sheath elongation and cell proliferation in Sphaerotilus natans.

Sphaerotilus natans is a filamentous sheath-forming bacterium. A method of selective fluorescent-labeling of its sheath using conventional reagents was developed. Terminal expansion of the sheath was confirmed by this method. In addition, ubiquitous cell growth was revealed by sequential phase-contrast microscopy of a filament. Based on this and earlier reports, a model of the sheath formation is proposed.

Distal arch replacement for aortic aneurysm associated with pseudocoarctation through the L-incision approach.

We report the case of a 16-year-old boy in whom we successfully repaired a distal aortic arch aneurysm associated with pseudocoarctation using double aortic cannulation and antegrade selective cerebral perfusion through the L-incision approach. This approach provided excellent exposure from the ascending aorta to the descending aorta, which enabled total body perfusion. We avoided cardiac arrest and hypothermic circulatory arrest during the surgery. The L-incision approach could be a better alternative for aortic arch surgery in adolescents.

Intrapulmonary artery septation for unilateral absence of the pulmonary artery.

We describe a seven-month-old boy with tetralogy of Fallot and an absent left pulmonary artery. Due to the diminutive size of the left pulmonary artery, we performed a native tissue left pulmonary artery reconstruction and intrapulmonary artery septation procedure with a left modified Blalock-Taussig shunt. After confirming left pulmonary artery growth, the patient underwent tetralogy of Fallot repair, removal of septation patch, and division of the Blalock-Taussig shunt. Nine months post-surgery, we confirmed his balanced lung perfusion (R/L ratio 6:4). The intrapulmonary artery septation procedure would be suitable for both the resuscitation and reconstruction of the hypoplastic absent pulmonary artery.

Effect of Minocycline Pleurodesis in Infants With Refractory Chylothorax After Palliative Surgery for Complex Congenital Heart Disease.

Chylothorax is a critical complication after surgery for congenital heart disease, which markedly compromises the postoperative course with increased mortality. As the cardiovascular load additively causes stagnation of the thoracic duct, chylothorax after palliative cardiac surgery can be highly refractory to the therapies. Here we report a case of two patients with refractory chylothorax attributed to hemodynamic load which was successfully treated with minocycline pleurodesis. In combination with congenital heart disease, extremely low birth weight coupled with prematurity in case 1 and venous obstruction with excessive volume load due to additional aortopulmonary shunt in case 2 additively increased resistance to the therapies, including fasting with total parenteral nutrition (TPN), XIII factor supplementation, octreotide infusion, as well as the use of steroids. As pleural effusion was sustained at more than 50 ml/kg/day, the condition of both patients deteriorated severely; pleurodesis using minocycline was urgently introduced. Pleural effusion declined at every session and both cases were in remission in a few sessions without unfavorable acute reaction. No symptoms suspecting chronic adverse effects were observed during follow-up, including respiratory dysfunction, pulmonary hypertension, tooth staining, or abnormal bone mineralization. Although the application of minocycline for children should be minimized, minocycline pleurodesis can be an option for patients with refractory and life-threatening chylothorax.

Transcriptional control of tight junction proteins via a protein kinase C signal pathway in human telomerase reverse transcriptase-transfected human pancreatic duct epithelial cells.

In human pancreatic cancer, integral membrane proteins of tight junction claudins are abnormally regulated, making these proteins promising molecular diagnostic and therapeutic targets. However, the regulation of claudin-based tight junctions remains unknown not only in the pancreatic cancer cells but also in normal human pancreatic duct epithelial (HPDE) cells. To investigate the regulation of tight junction molecules including claudins in normal HPDE cells, we introduced the human telomerase reverse transcriptase (hTERT) gene into HPDE cells in primary culture. The hTERT-transfected HPDE (hTERT-HPDE) cells were positive for the pancreatic duct epithelial markers such as CK7, CK19, and carbonic anhydrase isozyme 2 and expressed epithelial tight junction molecules claudin-1, -4, -7 and, -18, occludin, JAM-A, ZO-1, ZO-2, and tricellulin. By treatment with fetal bovine serum or 12-O-tetradecanoylphorbol 13-acetate (TPA), the tight junction molecules were up-regulated at the transcriptional level via a protein kinase C (PKC) signal pathway. A PKC-alpha inhibitor, Gö6976, prevented up-regulation of claudin-4 by TPA. Furthermore, a PKC-delta inhibitor, rottlerin, prevented up-regulation of claudin-7, occludin, ZO-1, and ZO-2 by TPA. By GeneChip analysis, up-regulation of the transcription factor ELF3 was observed in both fetal bovine serum- and TPA-treated cells. Treatment with small interfering RNAs of ELF3 prevented up-regulation of claudin-7 by TPA. These data suggest that tight junctions of normal HPDE cells were at least in part regulated via a PKC signal pathway by transcriptional control.

Poly(I:C) reduces expression of JAM-A and induces secretion of IL-8 and TNF-α via distinct NF-κB pathways in human nasal epithelial cells.

Human nasal epithelium is an important physical barrier and innate immune defense protecting against inhaled substances and pathogens. Toll-like receptor (TLR) signaling, which plays a key role in the innate immune response, has not been well characterized in human nasal epithelial cells (HNECs), including the epithelial tight junctional barrier. In the present study, mRNAs of TLR1-10 were detected in hTERT-transfected HNECs, which can be used as an indispensable and stable model of normal HNECs, similar to primary cultured HNECs. To investigate the changes of tight junction proteins and the signal transduction pathways via TLRs in HNECs in vitro, hTERT-transfected HNECs were treated with TLR2 ligand P(3)CSK(4), TLR3 ligand poly(I:C), TLR4 ligand LPS, TLR7/8 ligand CL097, TLR8 ligand ssRNA40/LyoVec, and TLR9 ligand ODN2006. In hTERT-transfected HNECs, treatment with poly(I:C) significantly reduced expression of the tight junction protein JAM-A and induced secretion of proinflammatory cytokines IL-8 and TNF-α. Both the reduction of JAM-A expression and the induction of secretion of IL-8 and TNF-α after treatment with poly(I:C) were modulated by distinct signal transduction pathways via EGFR, PI3K, and p38 MAPK and finally regulated by a TLR3-mediated NF-κB pathway. The control of TLR3-mediated signaling pathways in HNECs may be important not only in infection by viral dsRNA but also in autoimmune diseases caused by endogenous dsRNA released from necrotic cells.

Identification and characterization of a mycobacterial (2R,3R)-2,3-butanediol dehydrogenase.

Bacterial strain B-009, capable of using racemic 1,2-propanediol (PD), was identified as a rapid-growing member of the genus Mycobacterium. The strain is phylogenetically related to M. gilvum, but has slightly different physiological characteristics. An NAD(+)-dependent enantioselective alcohol dehydrogenase, which acts on R-PD, was purified from the strain. The enzyme was a homodimer of a peptide coded by a 1047-bp gene (mbd1). A highly conserved sequence for medium-chain dehydrogenase/reductases with a preference for secondary alcohols was found in the gene. Hydroxyacetone was produced from R-PD by an enzymatic reaction, indicating that position 2 of the substrate was oxidized. The enzyme activity was highest for (2R,3R)-2,3-butanediol (R,R-BD), enabling the enzyme to be identified as (2R,3R)-2,3-butanediol dehydrogenase (R,R-BD-DH). A homology search revealed M. gilvum, M. vanbaalenii, and M. semegmatis to have ORFs similar to mbd1, suggesting the widespread distribution of genes encoding R,R-BD-DH among mycobacterial strains.

Coronary artery bypass grafting for an anomalous origin of the right coronary artery: is it a valid surgical procedure?

The right internal thoracic artery to the right coronary artery bypass with ligation of the proximal native vessel is a simple and reliable option for the treatment of an anomalous aortic origin of the right coronary artery arising from the left sinus of Valsalva without an intramural course. Coronary artery bypass grafting is an uncomplicated option for elderly patients, those with connective tissue diseases, and those for whom combined aortic valve procedures are planned. Herein, we present four cases of this anomaly that underwent right internal thoracic artery anastomosis to the distal right coronary artery along with proximal right coronary artery ligation using a surgical clip. There was no occurrence of complications such as hypoperfusion syndrome, graft occlusion, recurrent symptoms, or late cardiac events.