M1 macrophage is the predominant phenotype in coronary artery lesions following Kawasaki disease.

Kawasaki disease (KD) is a systemic inflammatory process that affects the medium-sized arteries, causing various cardiovascular complications. However, it is not clear if the vascular sequelae following KD can predispose to the development of atherosclerosis later in life. Our aim was to examine the macrophage phenotypes in the coronary arteries forming giant aneurysms after KD to gain insight into the pathogenesis of vascular lesions in KD. We examined histological sections of the coronary arteries from five patients with KD who underwent coronary bypass grafting procedure as treatment for giant aneurysms and subsequent stenosis. Immunohistochemical expression of M1- and M2-macrophage markers was assessed to determine the macrophage phenotype of KD to compare with that of atherosclerosis in eight adult patients. All the KD specimens showed a mild to moderate degree of intimal thickening consisting of mature fibrous tissue and distortion of elastic fibers, mimicking the histological features of atherosclerosis. The total number of CD68 positive macrophages was higher in atherosclerosis than in KD specimens. Among the CD68 positive macrophages, the proportion of M1 phenotype, detected by CD86 or SOCS3, was higher in KD than in atherosclerosis. In contrast, the proportion of M2 phenotype, detected by CD163 or MRC1, was higher in patients with atherosclerosis. Despite similar histological features, KD and atherosclerosis appear to have a different immunological etiology for progression of the chronic vascular lesions. A further study enrolling a larger number of cases is required to delineate underlying mechanisms of vascular complications in KD.

[Coronary artery bypass grafting for cardiovascular sequelae in Kawasaki disease].

There are several issues regarding surgical revascularization for Kawasaki coronary disease including (1) the choice of conduits and (2) the optimal timing and correct indication for coronary artery bypass grafting(CABG). The internal thoracic artery(ITA) is the best conduit in terms of growth potential for pediatric CABG and for excellent long-term patency. The use of saphenous vein graft should be avoided unless an ITA is unavailable. The indication of CABG for Kawasaki coronary disease has not been established. In principle, coronary aneurysms should be observed continuously for 1 to 2 years under restrictive anticoagulation therapy, because regression of coronary aneurysm often occurs in 50 % within 1 to 2 years. The presence of severe ischemia in giant coronary aneurysms involving either the left main trunk or left anterior descending coronary artery is an absolute indicator for CABG. In addition, giant aneurysms with recurrent thrombosis under restrictive anticoagulation therapy or with severe delayed flow without significant localized stenosis may be an indication for CABG.

I-Composite Graft with Right Internal Thoracic Artery and Right Gastroepiploic Artery in Coronary Artery Bypass Grafting.

PURPOSE: When added to the internal thoracic artery (ITA), the right gastroepiploic artery (GEA) has been used as an in-situ graft or an I-composite right ITA-right GEA graft in coronary artery bypass grafting (CABG). We aimed to verify its potential. METHODS: We evaluated 104 patients who underwent first isolated CABG with this I-composite graft. The number of distal anastomoses, graft flow (GF) and pulsatility index (PI) during surgery, and graft patency in the early term regarding this I-composite graft were evaluated. RESULTS: The number of total distal anastomoses and distal anastomoses with arterial grafts were 4.17 ± 0.81 and 3.63 ± 0.81, respectively. This I-composite graft achieved 2.38 ± 0.69 distal anastomoses. GF tended to increase according to the increased number of distal anastomoses (p = 0.241), and the PI maintained a low score regardless of the number of distal anastomoses (p = 0.834). Graft patency was 95.5%; moreover, the number of distal anastomoses with this I-composite graft did not affect early-term graft patency. CONCLUSION: Right GEA utility was expanded as this I-composite graft in addition to in-situ graft. This I-composite graft has an adequate flow capacity for revascularization in non-left anterior descending coronary artery lesions.

15-year outcomes of the JOCRI study (JOCRIED study): a randomised comparison of off-pump and on-pump multiple arterial coronary revascularisation.

OBJECTIVE: The Japanese Off-Pump Coronary Revascularization Investigation (JOCRI) study reported a non-significant difference in early outcomes and graft patency between off-pump coronary artery bypass grafting and on-pump coronary artery bypass grafting in 2005. The JOCRIED study aimed to review the long-term outcomes of the JOCRI study participants. METHOD AND RESULTS: The JOCRIED study enrolled 123 of the JOCRI study participants completing the clinical follow-up between August 2018 and August 2020; 61 patients in the off-pump group and 62 patients in the on-pump group. The follow-up period was 13.8 ± 2.8 years. The groups were compared regarding mortality, the incidence of major adverse cardiac and cerebrovascular events and repeat revascularisation. The 15-year cumulative survival rate (off-pump vs on-pump, respectively; 77.7% vs 75.3%; p = 0.85), major adverse events-free survival rate (62.5% vs 55.6%; p = 0.27) and repeat revascularisation-free rate (84.8% vs 78.0%; p = 0.16) were not significantly different between the two groups. Revascularisation was the most common major adverse events in the JOCRIED participants. Although percutaneous coronary intervention was performed in 8 patients (13%) in the off-pump group and in 14 patients (23%) in the on-pump group (p = 0.23), no patients underwent redo coronary artery bypass grafting. CONCLUSIONS: Off-pump coronary artery bypass grafting provides comparable 15-year outcomes to on-pump coronary artery bypass grafting.

[Does Japanese coronary artery bypass grafting qualify as a global leader?].

Since the introduction of coronary artery bypass graft (CABG) surgery, Japanese cardiothoracic surgeons have made significant contributions to the continuing evolution of the procedure, particularly to progress in arterial conduits. In 1988, Kitamura et al. described the internal thoracic artery (ITA) as a "live" conduit for pediatric patients requiring CABG. Since then, the physiological and clinical characteristics of the ITA graft have been investigated and reported by numerous Japanese surgeons. Since the development of the use of the right gastroepiploic artery as a graft by Suma, Japanese surgeons have contributed significantly to its clinical usage worldwide. In the 21st century, energetic Japanese surgeons have been making every effort to improve their surgical outcomes by performing off-pump CABG. While only 15% of surgeons in Europe and North America use the off-pump technique, more than 60% of surgeons in Japan do so. Despite a much smaller surgical volume, Japanese surgeons have achieved comparable outcomes to those abroad. This also is attributable to the medical insurance system in Japan. In conclusion, CABG in Japan now qualifies as a global leader.

Prognosis of Coronary Artery Bypass Grafting in Preschool-Aged Patients with Myocardial Ischemia Due to Giant Aneurysm of Kawasaki Disease.

Coronary artery bypass grafting (CABG) for severe cardiac sequelae of Kawasaki disease (KD) complicated by myocardial ischemia is feasible even in childhood. However, no report has summarized the prognosis of CABG in preschool-aged children. Therefore, we evaluated the outcomes of seven preschool-aged children who underwent CABG for the cardiac sequelae of KD in our hospital. The median age at KD onset and CABG was 36 and 59 months, respectively. The median period from KD onset to CABG was 12 months. The median post-operative observation period was 108 months. CABG between the left internal thoracic artery and left anterior descending artery was performed in all patients. In all patients, postoperative cardiac catheter examination revealed good graft patency and no anastomotic stenosis. Further, pre-operative abnormality of coronary flow reserve returned to normal after CABG. Currently, only one patient is taking warfarin. Regarding school-life management, no patient has exercise limitations, except for one patient who had acute myocardial infarction before CABG. Further, the risk of graft stenosis or occlusion was evaluated in the included patients. However, no accidents have been reported to date, and myocardial ischemia and school-life management have improved. Thus, CABG is an effective treatment in preschool-aged children.

Surgical venous thrombectomy for Japanese patients with acute deep vein thrombosis: a review of 5 years' experience.

OBJECTIVE: Deep vein thrombosis (DVT) is a major risk factor for pulmonary thromboembolism (PTE). We carefully selected patients for surgical thrombectomy to treat acute-phase thrombosis and obtained favorable results. METHODS: Over the past 5 years, we have performed surgical thrombectomy via a minimum femoral skin incision in 11 patients. Surgery was considered for patients with persistent phlegmasia cerulea dolens, despite thrombolytic therapy. All of our patients underwent surgery within 14 days of the onset of symptoms. During the operation, the patients were kept in the supine anti-Trendelenburg position to prevent PTE, and general anesthesia was maintained with positive-pressure mechanical ventilation. Blood flow to the inferior vena cava was occluded with a blocking catheter, and thrombectomy was performed with a thrombectomy catheter inserted parallel to the blocking catheter. A cell separator device was used effectively for autologous blood transfusion. To prevent reocclusion and promote collateral perfusion, we constructed an arteriovenous fistula for an iliac venous spur. RESULTS: There were no major postoperative complications, such as PTE or peritoneal bleeding, and no cases of postthrombotic syndrome after an average 38.4 months of follow-up. CONCLUSION: This surgical technique for venous thrombectomy is minimally invasive and safe for Japanese patients; surgical thrombectomy should be considered a treatment option for DVT in Japan.

Ceritinib in Japanese patients with anaplastic lymphoma kinase (ALK)+ non-small cell lung cancer: interim analysis results of a post-marketing surveillance study.

Ceritinib is a selective anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of patients with unresectable advanced and/or recurrent ALK fusion gene-positive non-small cell lung cancer (NSCLC). As per the approval condition in Japan, this post-marketing surveillance (PMS) study evaluated the clinical safety (including adverse events [AEs], adverse drug reactions [ADRs] and priority investigation items) and efficacy (including ORR and PFS) of ceritinib in Japanese patients. Interim analysis was conducted ~ 2 years after the start of this non-interventional, multicentre, uncontrolled, open-label, special drug-use investigation and results are reported from March 28, 2016 to April 28, 2018. Each patient was followed up for 1 year. Most patients started treatment with 750 mg ceritinib. Safety profile was similar to that observed at the time of approval. No new AEs or ADRs with incidences higher than that at approval were identified. The rate of gastrointestinal ADRs (nausea, vomiting and diarrhoea) was 73.64%. Meaningful efficacy was observed in both post-crizotinib and post-alectinib settings, with ORR of 29.55% (95% CI 20.29-40.22) and disease control rate of 53.41% (95% CI 42.46-64.12). No concerns regarding the safety and efficacy of ceritinib were identified. No new measures, including modification of the PMS study protocol, are considered necessary.

Electrophysiological and histological assessment of transmurality after epicardial ablation using unipolar radiofrequency energy.

BACKGROUND: The transmurality of the ablation lesions created on a beating heart has not been examined histologically or electrophysiologically. This study aimed to assess the feasibility of an atrial epicardial or endocardial ablation in an off-pump setting using unipolar radiofrequency (RF) energy. METHODS: A linear ablation lesion of 5 cm was made in the lateral left atrium using unipolar RF energy with a temperature-controlled algorithm in 16 canines either epicardially (n=8) or endocardially (n=8) on the beating heart without any cardiopulmonary bypass. The ablation depth and transmurality were examined histologically two hours after the ablation. A conduction block across the linear ablation lesion was tested by epicardial mapping in two animals four weeks after each epicardial and endocardial ablation. RESULTS: There was no significant difference in the ablation depth between the epicardial and endocardial ablations (2.5+/-0.7 mm vs. 3.0+/-1.4 mm, p=0.055) in the histological examination. However, the ablation lesion was transmural in only 14 of 30 (46.7%) evaluated points after the epicardial ablation, while in 28 of 30 (93.3%) after the endocardial ablation (p<0.0001). The thin atrial tissue adjacent to the endocardium survived after the epicardial ablation. The activation maps demonstrated a complete linear conduction block in all animals after the endocardial ablation, but in none after the epicardial ablation. CONCLUSIONS: Epicardial unipolar radiofrequency ablation on the beating heart does not necessarily create a complete linear conduction block. An alternative ablation device that creates a transmural lesion is needed, and intraoperative electrophysiologic assessment of the lesion should be crucial in off-pump AF surgery.

Nonocclusive mesenteric ischemia after aortic surgery in a hemodialysis patient.

We report a case of nonocclusive mesenteric ischemia (NOMI), which developed after grafting for a descending thoracic aortic aneurysm in a hemodialysis patient. On postoperative day 5, acute increases in serum enzyme levels developed. Emergency angiography revealed severe vasoconstriction in the superior mesenteric artery (SMA) and other splanchnic arteries. Therefore an infusion of papaverine hydrochloride was started into the SMA. Although serum enzyme levels decreased, metabolic acidosis occurred the next day. An emergency laparotomy revealed segmental diffuse necrotic small intestine and colon. Despite a resection of the small intestine and sigmoid colon, the patient died of septic shock several days later. NOMI is uncommon, but it is a catastrophic event that can occur after cardiovascular surgery. If intestinal gangrene is suspected, prompt mesenteric angiography and vasodilator therapy followed by exploratory laparotomy should be performed without delay.

Review: surgical treatment of giant coronary aneurysms in pediatric patients with Kawasaki disease.

In Kawasaki disease (KD), giant coronary aneurysms in the proximal segments of the coronary arteries have long been among the serious complications associated with acute myocardial infarction. To treat myocardial ischemia in children, Kitamura et al. first performed coronary artery bypass grafting in a pediatric patient using an autologous saphenous vein. In the early 1980s, they began to use the internal thoracic artery (ITA) as a bypass graft to the left anterior descending artery, which later was proven to improve long-term life expectancy with its favorable long-term patency, as well as growth potential. Thus, the excellent characteristics of the ITA have come to be widely known among pediatric cardiac surgeons, and a growing number of coronary bypass surgery procedures using the ITA are now being performed worldwide. Although a longer follow-up with more patients is necessary, downsizing reconstructive procedure may be a treatment of choice for giant aneurysms of non-LAD territories to improve coronary circulation. The efficacy of surgical treatment for giant coronary aneurysms in pediatric patients with Kawasaki disease is now well established. Pediatric coronary artery bypass grafting using the ITA, either single or bilateral, can be safe not only for patients with Kawasaki coronary disease but also for infants with congenital coronary lesions.

Early outcome of a randomized comparison of off-pump and on-pump multiple arterial coronary revascularization.

BACKGROUND: Previous randomized comparisons of off-pump and on-pump coronary artery bypass grafting (CABG) have yielded controversial results about the cardiac and neurological events and graft patency. In addition, these randomized studies were composed of CABG with a few arterial grafts. We performed a prospective randomized controlled study to compare off-pump and on-pump CABG with multiple arterial grafts. METHODS AND RESULTS: Between July, 2002, and September, 2004, 167 consecutive unselected patients referred for elective primary CABG were randomly assigned to undergo multiple arterial off-pump CABG (n=81) or on-pump CABG (n=86). The clinical outcomes and S-100 protein, neuron-specific enolase, and maximum creatine kinase-MB levels were compared. Early graft patency was examined within 3 weeks after the operation by angiography. The number of grafts performed per patient (3.5+/-1.0 for off-pump CABG and 3.6+/-0.9 for on-pump CABG) and the number of arterial grafts performed per patient (3.3+/-1.0 for off-pump CABG and 3.4+/-0.9 for on-pump CABG) were similar. Completeness of revascularization (completed grafts/planned grafts) was 98% in both procedures. There were no hospital deaths in either group. The operation time was significantly (P<0.001) shorter in the off-pump group than in the on-pump group (267+/-60 minutes versus 307+/-59 minutes). The incidence of perioperative complications was similar. The frequency of no need for transfusion was higher in the off-pump group than in the on-pump group (80% versus 55%, P<0.001). The S-100 protein levels at the admission into the intensive care unit were significantly (P<0.001) lower in the off-pump group than in the on-pump group (0.20+/-0.11 ng/mL versus 0.34+/-0.22 ng/mL). The neuron-specific enolase levels at the intensive care unit admission were significantly (P<0.001) lower in the off-pump group than in the on-pump group (10.4+/-9.0 ng/mL versus 16.9+/-6.9 ng/mL). Maximum creatine kinase-MB levels were significantly (P=0.046) lower in the off-pump group than in the on-pump group (17.1+/-16.7 IU/L versus 21.5+/-10.6 IU/L). The overall early graft patency rate with or without stenosis was the same (98%) in both groups, but the rate without stenosis was slightly worse in the off-pump group (93%) than in the on-pump group (96%) (P=0.093). The stenosis-free patency rate in the right coronary area was significantly (P=0.028) worse in the off-pump CABG group (90%) than in the on-pump group (99%). CONCLUSIONS: Off-pump CABG with multiple arterial grafts was as safe as the conventional on-pump CABG, with similar completeness of revascularization and early graft patency.

Surgical experience of subacute pulmonary thromboembolism with severe pulmonary hypertension.

Surgical treatment for subacute pulmonary arterial thromboembolism has previously been considered to be inappropriate. We undertook a pulmonary arterial thrombectomy and removal of a floating right heart thrombus in a patient who had been symptomatic for over a month. The pulmonary arterial pressure, which had been equal to the systemic pressure preoperatively, decreased gradually and almost normalized one month postoperatively. Pulmonary perfusion scintigraphy revealed a dramatic improvement and the patient returned to normal life activities.

Rupture of a normal-sized, non-dissected distal aortic arch in a Marfan patient.

We successfully repaired a rupture of a normal-sized, non-dissected distal aortic arch in a patient with Marfan syndrome. Six years previously she had undergone repair of the thoraco-abdominal aortic aneurysm with a 24-mm knitted Dacron graft for type B chronic aortic dissection. The rupture site was located at the back of the native distal aortic arch just 10 mm above the proximal anastomosis, and just below the left subclavian artery. This unexpected situation might be related to dilatation of the knitted Dacron graft up to 34 mm (142%), thus stretching out the fragile native aorta in this Marfan patient.

Sudden death in a case of cardiac amyloidosis immediately after pacemaker implantation for complete atrioventricular block.

We report a patient with cardiac involvement associated with primary amyloidosis presenting marked left ventricular (LV) wall thickening, severely decreased systolic and diastolic function, and complete atrioventricular block (CAVB), who died suddenly of cardiac arrest caused by electro-mechanical uncoupling occurring immediately after permanent pacemaker implantation. Post mortem examination showed no procedural complications such as cardiac or venous perforation. The heart was densely infiltrated with amyloid fibrils, especially in the extracellular tissues surrounding the papillary vessels.