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.

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.

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.

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.

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.

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.

[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.

Future perspective of cardioplegic protection in cardiac surgery.

"Depolarized arrest", induced by hyperkalemic (moderately increased extracellular potassium) cardioplegia is the gold standard to achieve elective temporary cardiac arrest in cardiac surgery. Hyperkalemic cardioplegic solutions provide good myocardial protection, which is relatively safe and easily and rapidly reversible. However, this technique has detrimental effects associated with ionic imbalance involving sodium and calcium overload of the cardiac cell induced by depolarization of the cell membrane. Hence, the development of an improved cardioplegic solution that enhances myocardial protection would be expected as an alternative to hyperkalemic cardioplegia. In this review, we assess the potential disadvantages of "depolarized arrest" and the suitability and clinical potential of "non-depolarized arrest". "Magnesium cardioplegia" and "esmolol cardioplegia" has been shown to exert superior protection with comparable safety profiles to that of hyperkalemic cardioplegia. These alternative techniques require further examination and investigation to challenge the traditional view that hyperkalemic arrest is best. Endogenous cardioprotective strategies, termed "ischemic preconditioning" and "ischemic postconditioning", may have a role in cardiac surgery to provide additional protection. The elective nature of cardiac surgery, with the known onset of ischemia and reperfusion, lends it to the potential of these strategies. However, the benefit of preconditioning and postconditioning during cardiac surgery is controversial, particularly in the context of cardioplegia. The clinical application of these strategies is unlikely to become routine during cardiac surgery because of the necessity for repeated aortic crossclamping with consequent potential for embolic events, but offers considerable potential especially if "pharmacological" preconditioning and postconditioning could be established.

Reentrant and focal activations during atrial fibrillation in patients with atrial septal defect.

BACKGROUND: Adult patients with atrial septal defect frequently experience atrial fibrillation. However, the electrophysiologic mechanism has not been directly examined, and the optimal surgical procedure has not been determined. METHODS: Ten patients undergoing operations for atrial septal defect and atrial fibrillation underwent intraoperative mapping by use of 253 epicardial electrodes. There were 7 men and 3 women, whose average age was 54 ± 11 years. Eight patients had a secundum defect and 2 a primum defect. There were 4 patients with paroxysmal atrial fibrillation and 6 with long-standing persistent atrial fibrillation. A modified biatrial Maze procedure was performed in 6 patients and pulmonary vein isolation with no other left atrial lesions in 4. RESULTS: The reentrant or focal activations driving atrial fibrillation were confined within the right atrium in all patients with paroxysmal atrial fibrillation, whereas multiple focal activations arising from the pulmonary veins or posterior left atrium and reentrant activations in the left atrium were observed in 5 of 6 patients with long-standing persistent atrial fibrillation. In 9 patients, sinus rhythm was restored postoperatively and 8 of those patients have been free of any atrial fibrillation during a follow-up period of 94 ± 45 months. CONCLUSIONS: The pattern of the atrial activation during atrial fibrillation correlated with the type of atrial fibrillation and varied from a simple right atrial reentry to complex reentrant and focal activations in the left atrium.

Preoperative evaluation of the saphenous vein by 3-D contrastless computed tomography.

Volume-rendering computed tomography (CT) without contrast medium has clearly demonstrated the 3-D mapping of the saphenous vein (SV). Contrastless volume-rendering CT was used to preoperatively evaluate the SV anatomy before coronary artery bypass grafting (CABG). This technique was useful for atypical anatomical variations, such as partial duplication of SV (Case 1) or varicose veins (Case 2). Volume-rendering CT may also help with redo CABG (to determine remaining SV) or during endoscopic SV harvesting with restricted view. Volume-rendering CT is an objective, less time-consuming modality to evaluate the SV preoperatively and may be less invasive in terms of avoiding unnecessary skin incision.

Open stent grafting with a trifurcated graft for an infected aortic arch aneurysm concomitant with severe calcified aorta.

An infected aortic arch aneurysm is a rare but life-threatening condition. Moreover, surgical treatment for patients with severe calcified aorta is challenging and needs a well-planned strategy. We report a patient with an infected aortic arch aneurysm concomitant with severe calcification of the aorta in whom good results were obtained with open stent grafting in combination with a trifurcated graft.

Overview: Japanese guidelines for myocardial revascularization to treat stable ischemic heart disease 2012.

Since its introduction in the early 1970s, coronary artery bypass grafting (CABG) has become an established surgical treatment for coronary artery disease (CAD). Percutaneous coronary intervention (PCI), first clinically applied in 1977, was promoted as an alternative to CABG during the mid-1980s. Along with the nationwide expansion of PCI, the ratio of PCI to CABG has exceeded 6-7:1. The Japanese Circulation Society (JCS) published "Guidelines on elective coronary intervention, including coronary artery bypass grafting (CABG), for ischemic heart disease in 2000" and "Guidelines on the selection of bypass conduits and operative procedures in coronary artery bypass grafting for ischemic heart disease". The society intended to revise these guidelines in 2010 and to issue two new guidelines specific either to PCI or CABG. They also planned to issue joint guidelines for myocardial revascularization and PCI/CABG, which are primary indications for patients with stable CAD, especially with those with more complex left main trunk disease and/or multi-vessel disease. The scientific committee of JCS established the "Council for myocardial revascularization" that consisted of experts including interventional and non-interventional cardiologists, cardiac surgeons and physicians specialized in diabetes or nephrology selected by medical and surgical societies. After over 10 rounds of meetings, the Council prepared primary guidelines for myocardial revascularization to treat stable CAD, PCI/CABG. These guidelines consist of (1) Statements about myocardial revascularization, (2) Interpretation of the statements and (3) Indications for PCI/CABG including a table.

Surgical management of a deep femoral artery aneurysm.

Standard surgical methods for managing true aneurysms of the deep femoral artery have not been established because these aneurysms are rare. An 85-year-old man, who had a ruptured aneurysm of the deep femoral artery, underwent aneurysmectomy and distal reconstruction with a contralateral autologous vein graft. Three-dimensional computed tomography is a valuable diagnostic modality to evaluate synchronous aneurysms and peripheral arterial circulation for treatment planning. Because of their etiology, aneurysms of the deep femoral artery should be treated with revascularization when technically feasible, even if the superficial femoral artery is patent. A contralateral saphenous vein may be the preferred conduit because ipsilateral venous stasis is likely.

[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.

Intraoperative electroanatomic mapping.

PURPOSE: An electroanatomic mapping system using an electromagnetic navigation technology constructs a 3-dimensional structure of the heart with high geometric accuracy of the data that provides a precise localization of the substrates of arrhythmias. The system was tested for the feasibility and efficacy in intraoperative mapping. DESCRIPTION: The strength of the magnetic field is measured by a location sensor with three different frequencies generated by a location pad placed beneath the operating table, and the spatial location of the sensor is determined. By roving the catheter on the heart while the local electrogram is recorded simultaneously, the 3-dimensional figure of the heart is reconstructed and an activation or voltage map is generated. EVALUATION: The system was used in 19 patients with ventricular tachycardia or other arrhythmias. The focus or reentrant circuit of the tachycardia was precisely located and a map-guided procedure was successfully performed in all patients. Cardiopulmonary bypass allowed for the tachycardias to be mapped without any hemodynamic compromise. CONCLUSIONS: Intraoperative mapping using the electroanatomic mapping system enables a precise localization of the tachycardia substrate.

Morphological evaluation of areas of damage in blunt cardiac injury and investigation of traffic accident research.

PURPOSE: This study investigated the relation between the cause of blunt cardiac injury and areas of damage. For the purpose of injury prevention, we also examined traffic accident cases in a micro study using engineering-based medicine. METHODS: Among the 2673 patients transported to our facility within the 15-month period from February 2009 to April 2010, there were 12 cases of cardiac perforation. We studied these cases anatomically to evaluate the morphology of the damaged cardiac areas. We conducted a detailed micro-study in two cases regarding the circumstances surrounding the traffic accident and the vehicular damage. RESULTS: Subjects were nine men (mean age 64 years). The mean Injury Severity Score was 54.0 ± 19.6, and the probability of survival was 0.147. The actual survival rate was 16.7% (2 survivors, 10 deaths). Lesion sites in the 12 cases (21 sites in total) were the right atrium in 8 cases, superior and inferior vena cava in 5 cases, right ventricle in 4 cases, pulmonary artery and left atrium in 1 case each, and pulmonary vein in 2 cases, excluding the left ventricle and ascending aorta. In three cases, the aortic isthmus was also injured. CONCLUSION: Blunt cardiac injury was more common on the right side chamber. The survival rate was extremely close to the calculated survival probability. Proper seatbelt usage is important for the prevention of blunt cardiac injury due to traffic accidents. Increased severity of injury may be associated with accidents involving light motor vehicles.

Double potential mapping: a novel technique for locating the site of incomplete ablation.

OBJECTIVE: Double potential mapping using bipolar electrodes that straddle the ablation line should identify the site of incomplete ablation as a conduction gap without constructing the activation maps. METHODS: Bipolar electrograms were recorded during pacing using 11 custom-made bipolar electrodes straddling the ablation line created by a bipolar radiofrequency ablation device on the lateral right atrium in seven canines. A linear ablation was made with an ablation device, of which one jaw was inserted into the atrium through a purse-string suture. A 3-mm-wide tape was placed on both jaws 10 mm from the tip of the ablation electrode to intentionally create an incomplete ablation lesion. The activation times at each dipole across the ablation line were defined as the times of the maximum positive and negative derivatives of the double potentials, and the site of conduction gap was determined as the site of the earliest activation across the linear ablation. The lateral right atrium was mapped simultaneously with 45 different bipolar electrodes to construct the activation maps and the earliest activation site across the ablation line was determined. RESULTS: The double potential mapping located the conduction gap on a real-time basis without displaying any maps. There was no significant change in the accuracy between the different times after ablation and different pacing cycle lengths. CONCLUSIONS: Double potential mapping locates the conduction gap on a real-time basis and would be useful in beating-heart epicardial ablation in off-pump setting.