Concomitant Mitral Regurgitation in Severe Aortic Stenosis　- Insights From the CURRENT AS Registry-2.

BACKGROUND: Data on concomitant mitral regurgitation (MR) in patients with severe aortic stenosis (AS) are scarce.Methods and Results: We investigated the risk of concomitant MR in patients with severe AS in the CURRENT AS Registry-2 according to initial treatment strategy (transcatheter aortic valve implantation [TAVI], surgical aortic valve replacement [SAVR], or conservative). Among 3,365 patients with severe AS, 384 (11.4%) had moderate/severe MR (TAVI: n=126/1,148; SAVR: n=68/591; conservative: n=190/1,626). The cumulative 3-year incidence for death or heart failure (HF) hospitalization was significantly higher in the moderate/severe than no/mild MR group in the entire population (54.6% vs. 34.3%, respectively; P<0.001) and for each treatment strategy (TAVI: 45.0% vs. 31.8% [P=0.006]; SAVR: 31.9% vs. 18.7% [P<0.001]; conservative: 67.8% vs. 41.6% [P<0.001]). The higher adjusted risk of moderate/severe MR relative to no/mild MR for death or HF hospitalization was not significant in the entire population (hazard ratio [HR] 1.15; 95% confidence interval [CI] 0.95-1.39; P=0.15); however, the risk was significant in the SAVR (HR 1.92; 95% CI 1.04-3.56; P=0.04) and conservative (HR 1.30; 95% CI 1.02-1.67; P=0.04) groups, but not in the TAVI group (HR 1.03; 95% CI 0.70-1.52; P=0.86), despite no significant interaction (Pinteraction=0.37). CONCLUSIONS: Moderate/severe MR was associated with a higher risk for death or HF hospitalization in the initial SAVR and conservative strategies, while the association was less pronounced in the initial TAVI strategy.

Mycotic pulmonary artery pseudoaneurysm following total arch replacement: a case report.

BACKGROUND: Although the true prevalence and incidence are not clearly known, mycotic pulmonary artery aneurysm is a potentially devastating condition that leads to high mortality, over 60% if untreated. Among them, mycotic pulmonary artery pseudoaneurysm, which occurs in relatively central areas, has rarely been reported. We report an extremely rare case of a late complication with a mycotic pulmonary artery pseudoaneurysm, presumably due to infective endocarditis, in a 68-year-old woman 4 months after total arch replacement. CASE PRESENTATION: A 68-year-old woman was referred to our department for 2 weeks with fever of unknown origin. She had a history of emergency total arch replacement for an acute type A aortic dissection 4 months earlier and chronic rheumatoid arthritis on monthly subcutaneous tocilizumab treatment for several years. Blood culture was positive for Enterococcus faecalis. Transthoracic and transesophageal echocardiography revealed a left ventricular ejection fraction of 58%, severe mitral regurgitation with a 15-mm diameter vegetation on the anterior mitral leaflet, and severe aortic insufficiency with string-like structures. Contrast computed tomography showed a focal saccular outpouching from the right pulmonary artery. On 18F-fluorodeoxyglucose (FDG) positron emission tomography, focal uptake of FDGs was observed along the same lesion of the pulmonary artery and ascending-arch graft. The patient eventually recovered after the surgical intervention of mitral and aortic valve replacement, re-total arch replacement, pulmonary artery repair, application of omental flap, and antibiotics without any evidence of re-infection after 1 year. CONCLUSIONS: We report a successful surgical repair of mycotic pulmonary artery pseudoaneurysm 4 months after total arch replacement for acute type A aortic dissection. This report describes an effective treatment for an extremely rare postoperative condition.

Clinically significant incidental noncardiac findings on Preprocedural computed tomography in patients with aortic stenosis undergoing aortic-valve replacement.

BACKGROUND: There is a scarcity of data on the prevalence of abnormal findings on preprocedural computed tomography (CT) before aortic valve replacement (AVR) in patients with aortic stenosis (AS). METHODS: Among consecutive 593 patients with severe AS who were planned to undergo AVR, we evaluated the prevalence of clinically significant incidental noncardiac findings on preprocedural CT. Clinically significant incidental noncardiac findings were defined as newly detected abnormalities that required therapy, consultation for expert, further investigation, or clinical follow-up. RESULTS: The mean age was 82.0 years and 39.5 % of the patients were men. Of those, 78.4 % of the patients were treated with transcatheter aortic valve implantation (TAVI) and 21.6 % of the patients were treated with surgical AVR (SAVR). There were 271 clinically significant incidental noncardiac findings in 227 patients (38.3 %) including 2.5 % of malignancy. The prevalence of clinically significant incidental noncardiac findings were higher in the TAVI group than in the SAVR group (40.2 % versus 31.3 %). The prevalence of clinically significant incidental noncardiac findings were lower in patients under 60 years of age (10.0 %) than in patients over 60 years of age (60-69 years: 40.0 %, 70-79 years: 34.3 %, 80-89 years: 39.7 %, and ≥90 years: 42.1 %). CONCLUSIONS: Clinically significant incidental noncardiac findings were newly identified on preprocedural CT in approximately 40 % of patients with severe AS undergoing AVR including 2.5 % of malignancy.

Surgical treatment for a child with traumatic ventricular septal rupture and ventricular aneurysm.

A five-year-old boy was diagnosed with the ventricular septal rupture and ventricular aneurysm after blunt chest trauma in child abuse. Because of the intractable heart failure, he underwent operation in subacute period. Postoperative course was uneventful. The blunt cardiac injury in children can be caused by mild trauma and can be lethal. Surgical intervention should be considered when the clinical condition is unstable.

Two cases of pararenal artery aortic aneurysm treatment after pancreaticoduodenectomy and abdominal aortic aneurysm stent grafting.

BACKGROUND: Acute pancreatitis caused by surgical procedures may occur less frequently in surgeries for aortic aneurysm involving the abdominal branch. However, in such cases, the associated mortality rate increases significantly. There have been few reports on abdominal aortic aneurysm surgery after pancreatoduodenectomy; as such the incidence of postoperative pancreatitis remains unclear. CASE PRESENTATION: Two cases of pararenal artery aortic aneurysm after pancreaticoduodenectomy and endovascular aneurysm repair (EVAR) for an abdominal aortic aneurysm are reported. In the first case, a 74-year-old man was diagnosed with abdominal aortic aneurysm and duodenal cancer 6 years earlier and underwent pancreaticoduodenectomy after EVAR. Subsequently, the abdominal aorta expanded to 58 mm at the level of the renal artery proximal to the EVAR site. Graft replacement was performed through a left thoraco-retroperitoneal incision. However, the patient died from acute pancreatitis, believed to be caused by intraoperative manipulation. Given this initial experience, in the second case, a 77-year-old man had undergone a pancreaticoduodenectomy for a gastrointestinal stromal tumor 17 years earlier and EVAR for an abdominal aortic aneurysm 10 years earlier. The abdominal aorta had expanded to 50 mm immediately below the right renal artery on the proximal side of the EVAR. Subsequently, hematuria was noted, and he was diagnosed with right ureteral cancer. Autologous transplantation of the left kidney and EVAR was performed avoiding manipulation of the area around the pancreas and achieved good results. Combined right renal and ureteral resections were performed 20 days after EVAR. CONCLUSIONS: While performing aortic surgery after pancreaticoduodenectomy, surgeons should avoid manipulating tissues around the pancreas.

Transarterial Embolization of Type 2 Endoleak Post Thoracic Endovascular Aortic Repair (TEVAR) Using a Triaxial System With a 1.3-F Microcatheter: A Case Report.

Although transarterial embolization is recognized as a treatment for type 2 endoleaks, it can occasionally be challenging. We report the case of an 86-year-old man who presented with an enlarging thoracoabdominal aortic aneurysm following thoracic endovascular aortic repair. Using a triaxial system with a 1.3-F microcatheter, transarterial embolization of a type 2 endoleak was successfully performed through a long and tortuous arterial route comprising the thoracodorsal and ninth intercostal arteries. The postoperative clinical course was uneventful, and computed tomography obtained six days later showed no endoleak in the thoracoabdominal aortic aneurysm. This case suggests the usefulness of a triaxial system with a 1.3-F microcatheter for transarterial embolization of type 2 endoleaks.

18F-FDG PET/CT in left atrial undifferentiated pleomorphic sarcoma with osteosarcomatous differentiation.

Primary cardiac sarcomas are rare and sometimes difficult to discern from benign tumors and intracardiac thrombi. We describe the ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT findings in a case of left atrial undifferentiated pleomorphic sarcoma with osteosarcomatous differentiation, presenting with severe mitral regurgitation and pulmonary hypertension. The tumor presented as a broad-base mass protruding into the cardiac lumen, accompanied by punctate calcification-like high attenuation on CT. 18F-FDG PET/CT revealed high 18F-FDG uptake in the mass. Severe mitral regurgitation, a rare manifestation, was caused by tumor extension to the mitral valve leaflets and subvalvular tissue, which was best visualized on transesophageal echocardiography. This case illustrates the importance of multimodal diagnostic approaches including 18F-FDG PET/CT, which can facilitate accurate diagnosis and timely initiation of curative treatment, ultimately saving the patient's life. Learning objective: Firstly, cardiac sarcomas, particularly those with calcification/ossification, are rare and may mimic benign tumors and chronic intracardiac thrombi. Multimodal imaging approach, including 18F-FDG PET/CT, may be helpful in the accurate diagnosis of malignancies. Second, left atrial undifferentiated pleomorphic sarcoma has the potential to extensively spread along the endocardium and can extend to involve the valve leaflets, resulting in mitral regurgitation and pulmonary hypertension.

Modeling mutation-specific arrhythmogenic phenotypes in isogenic human iPSC-derived cardiac tissues.

Disease modeling using human induced pluripotent stem cells (hiPSCs) from patients with genetic disease is a powerful approach for dissecting pathophysiology and drug discovery. Nevertheless, isogenic controls are required to precisely compare phenotypic outcomes from presumed causative mutations rather than differences in genetic backgrounds. Moreover, 2D cellular models often fail to exhibit authentic disease phenotypes resulting in poor validation in vitro. Here we show that a combination of precision gene editing and bioengineered 3D tissue models can establish advanced isogenic hiPSC-derived cardiac disease models, overcoming these drawbacks. To model inherited cardiac arrhythmias we selected representative N588D and N588K missense mutations affecting the same codon in the hERG potassium channel gene KCNH2, which are reported to cause long (LQTS) and short (SQTS) QT syndromes, respectively. We generated compound heterozygous variants in normal hiPSCs, and differentiated cardiomyocytes (CMs) and mesenchymal cells (MCs) to form 3D cardiac tissue sheets (CTSs). In hiPSC-derived CM monolayers and 3D CTSs, electrophysiological analysis with multielectrode arrays showed prolonged and shortened repolarization, respectively, compared to the isogenic controls. When pharmacologically inhibiting the hERG channels, mutant 3D CTSs were differentially susceptible to arrhythmic events than the isogenic controls. Thus, this strategy offers advanced disease models that can reproduce clinically relevant phenotypes and provide solid validation of gene mutations in vitro.

Pleurodesis using OK-432 for persistent pleural effusion after cardiac surgery in the neonatal period or early infancy.

OBJECTIVE: To evaluate the efficacy of pleurodesis using OK-432 after cardiac surgery in the neonatal period or early infancy. METHODS: We retrospectively reviewed the data of 11 consecutive patients who underwent cardiac surgery in the neonatal period or early infancy and pleurodesis using OK-432 for persistent postoperative pleural effusion in two institutions. RESULTS: The median age at surgery was 8 days (interquartile range [IR], 2-18) with a body weight of 2.84 kg (IR, 2.30-3.07). The maximum amount of pleural drainage before pleurodesis was 94.7 (IR, 60.2-107.7) ml/kg/day. Pleurodesis was initiated at postoperative day 20 (IR, 17-22) and performed in bilateral pleural spaces in seven patients and unilateral in four. The median numbers of injection were 4 (IR, 3-6) times per patient and 3 (IR, 2-3) times per pleural space. In 10 patients, pleural effusion was decreased effectively, and drainage tubes were removed without reaccumulation within 15 (IR, 12-28) days after initial pleurodesis. However, in one patient, with severe lymphedema, pleural effusion was uncontrollable, resulting in death due to sepsis. Adverse events were observed in nine patients; temporal deterioration of lung compliance and arterial blood gas occurred in two, insufficient drainage requiring new chest tube(s) in five, temporal atrial tachyarrhythmia in one, and lymphedema in four. CONCLUSIONS: Pleurodesis using OK-432 is effective and reliable for persistent postoperative pleural effusion in neonates and early infants. Most of the complications, which derived from inflammatory reactions, were temporary and controllable. However, severe lymphedema is difficult to control.

In-hospital outcomes after SAVR or TAVI in patients with severe aortic stenosis.

There were no data comparing the in-hospital outcomes after transcatheter aortic valve implantation (TAVI) with those after surgical aortic valve replacement (SAVR) in Japan. Among consecutive patients with severe AS between April 2018 and December 2020 in the CURRENT AS Registry-2, we identified 1714 patients who underwent aortic valve replacement (TAVI group: 1134 patients, and SAVR group: 580 patients). Patients in the TAVI group were much older (84.4 versus 73.6 years, P < 0.001) and more often had comorbidities than those in the SAVR group. In-hospital death rate was numerically lower in the TAVI group than in the SAVR group (0.6% versus 2.2%). After excluding patients with dialysis, in-hospital death rate was very low and comparable in the TAVI and SAVR groups (0.6% versus 0.8%). The rates of major bleeding and new-onset atrial fibrillation during index hospitalization were higher after SAVR than after TAVI (72% versus 20%, and 26% versus 4.6%, respectively), while the rate of pacemaker implantation was higher after TAVI than after SAVR (8.1% versus 2.4%). Regarding the echocardiographic data at discharge, the prevalence of patient-prosthesis mismatch was lower in the TAVI group than in the SAVR group (moderate: 9.0% versus 26%, and severe: 2.6% versus 4.8%). In this real-world data in Japan, TAVI compared with SAVR was chosen in much older patients with more comorbidities with severe AS. In-hospital death rate was numerically lower in the TAVI group than in the SAVR group.

Activation of the pentose phosphate pathway in macrophages is crucial for granuloma formation in sarcoidosis.

Sarcoidosis is a disease of unknown etiology in which granulomas form throughout the body and is typically treated with glucocorticoids, but there are no approved steroid-sparing alternatives. Here, we investigated the mechanism of granuloma formation using single-cell RNA-Seq in sarcoidosis patients. We observed that the percentages of triggering receptor expressed on myeloid cells 2-positive (TREM2-positive) macrophages expressing angiotensin-converting enzyme (ACE) and lysozyme, diagnostic makers of sarcoidosis, were increased in cutaneous sarcoidosis granulomas. Macrophages in the sarcoidosis lesion were hypermetabolic, especially in the pentose phosphate pathway (PPP). Expression of the PPP enzymes, such as fructose-1,6-bisphosphatase 1 (FBP1), was elevated in both systemic granuloma lesions and serum of sarcoidosis patients. Granuloma formation was attenuated by the PPP inhibitors in in vitro giant cell and in vivo murine granuloma models. These results suggest that the PPP may be a promising target for developing therapeutics for sarcoidosis.

Minimal access aortic surgery.

Recently, there have been significant advances in small incisions through right thoracic cavity including robotic surgery. We have been performing aortic surgery through a partial sternotomy for ascending, arch, and aortic root replacement. In this article, we would like to provide tips for small incision aortic surgery at our institution by showing surgical videos of two cases. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-023-01578-5.

Overview of acute type A dissection in Japan.

Acute type A aortic dissection is a relatively uncommon but devastating disease and usually requires emergency surgery. Based on the several database projects, a large amount of perioperative patient data has now been accumulated and is expected to be useful in clinical practice. Especially in Japan, the number of surgeries for acute type A aortic dissection has been gradually increasing recently, and the overall mortality rate has stabilized at less than 10%. One of the keys to further improvement in outcomes will be to improve the results of aortic root replacement. In addition, strategies need to be established for very elderly patients, comatose patients, and patients with malperfusion as preoperative conditions. The use of a relatively new device, the frozen elephant trunk, is also increasing and might be changing the surgical outcome. In this report, we describe the current status of acute type A aortic dissection in Japan, with reference to recent guidelines and literature.

[Operation for the Shaggy Aorta Syndrome].

Although mortality and complication rates of cardiovascular surgery have been reduced, shaggy aorta, which is defined as an extensive severe atherosclerosis of the thoracic and abdominal aorta, is considered a risk factor for perioperative mortality and complications. The shaggy aorta often leads a poor prognosis, and a very high hospital mortality rate when embolization occurs in multiple organs. Therefore, it is important to prevent embolism through detailed evaluation of the disease with preoperative contrast-enhanced computed tomography (CT) scan and intraoperative transesophageal echocardiogram, appropriate individualized treatment decisions, and careful surgical manipulation.

Effects of peripheral artery disease on long-term outcomes after percutaneous coronary intervention versus coronary artery bypass grafting in patients with severe coronary artery disease.

BACKGROUND: There is a scarcity of data evaluating the effect of peripheral artery disease (PAD) on long-term mortality after percutaneous coronary intervention (PCI) relative to coronary artery bypass grafting (CABG) in patients with severe coronary artery disease in real-world practice. METHODS: Among 14,867 consecutive patients who underwent their first coronary revascularization with PCI or isolated CABG between 2011 and 2013 in the CREDO-Kyoto PCI/CABG registry Cohort-3, the current study population consisted of 3380 patients with three-vessel coronary artery disease or left main coronary artery disease. Long-term clinical outcomes were compared between PCI and CABG stratified by the presence or absence of PAD. Median clinical follow-up was 5.9 (IQR: 5.1-6.8) years. RESULTS: There were 461 patients with PAD (PCI: N = 307, CABG: N = 154), and 2919 patients without PAD (PCI: N = 1823, CABG: N = 1096). The cumulative 5-year mortality after coronary revascularization was 31.2 % in patients with PAD and 16.2 % in those without PAD (p < 0.0001). There was a higher risk of PCI relative to CABG for all-cause death in patients with and without PAD (adjusted HR, 1.59; 95%CI, 0.99-2.53; p = 0.054, and HR, 1.25; 95%CI, 1.01-1.56; p = 0.04) without interaction (p interaction p = 0.48); Nevertheless, there was no excess risk of PCI relative to CABG for cardiovascular death regardless of PAD. CONCLUSIONS: The long-term mortality after coronary revascularization was significantly higher in severe CAD patients with PAD than those without PAD. There was a higher mortality risk of PCI relative to CABG in patients with and without PAD without interaction, which was mainly driven by excess non-cardiovascular deaths.

Therapeutic potential of human induced pluripotent stem cell-derived cardiac tissue in an ischemic model with unloaded condition mimicking left ventricular assist device.

OBJECTIVE: This study aimed to explore the therapeutic potential of human induced pluripotent stem cell (hiPSC)-derived cardiac tissues (HiCTs) in the emerging approach of bridge to recovery for severe heart failure with ventricular assist devices. We used a rat model of heterotopic heart transplantation (HTx) to mimic ventricular assist device support and heart unloading. METHODS: HiCTs were created by inserting gelatin hydrogel microspheres between cell sheets made from hiPSC-derived cardiovascular cells. Male athymic nude rats underwent myocardial infarction (MI) and were divided into the following groups: MI (loaded, untreated control), MI + HTx (unloaded, untreated control), MI + HTx + HiCT (unloaded, treated), and MI + HiCT (loaded, treated). HiCTs were placed on the epicardium of the heart in treated groups. We evaluated HiCT engraftment, fibrosis, and neovascularization using histologic analysis. RESULTS: After 4 weeks, HiCTs successfully engrafted in 5 of 6 rats in the MI + HTx + HiCT group (83.3%). The engrafted HiCT area was greater under unloaded conditions (MI + HTx + HiCT) than loaded conditions (MI + HiCT) (P < .05). MI + HTx + HiCT had a significantly smaller infarct area compared with MI and MI + HTx. The MI + HTx + MiCT group exhibited greater vascular density in the border zone than MI and MI + HTx. HiCT treatment suppressed cardiomyocyte atrophy due to left ventricular unloading (P = .001). The protein level of muscle-specific RING finger 1, an atrophy-related ubiquitin ligase, was lower in the MI + HTx + HiCT group than in MI + HTx (P = .036). CONCLUSIONS: Transplanting HiCTs into ischemic hearts under unloaded conditions promoted engraftment, neovascularization, attenuated infarct remodeling, and suppressed myocyte atrophy. These results suggest that HiCT treatment could contribute to future advancements in bridge to recovery.