Mitral Valve Repair for Mitral Regurgitation in Patients With Marfan Syndrome.

BACKGROUND: There is concern about the durability of mitral valve repair (MVr) for mitral regurgitation (MR) in Marfan patients due to limited long-term data. Furthermore, a detailed time course of changes in cardiac function after MVr in Marfan patients has not been reported. We examined repair techniques, postoperative cardiac function, and outcomes of MVr in Marfan patients. METHODS AND RESULTS: We retrospectively reviewed 29 Marfan patients (mean [±SD] age 27.4±14.8 years) who underwent MVr at The University of Tokyo Hospital from 2010 to 2022. The mean follow-up period was 5.2±3.2 years. The causes of MR were isolated anterior leaflet prolapse in 25% of patients, isolated posterior leaflet prolapse in 11%, and bileaflet prolapse in 64%. Echocardiographic findings showed significant decreases in left ventricular (LV) diastolic and left atrial diameters 1 week after MVr. LV systolic diameter was significantly decreased 3 years after MVr, and LV ejection fraction initially declined before subsequently increasing. The in-hospital and 30-day mortality rates were 0%. At 5 years, the overall survival rate was 94% and the rate of freedom from MR was 84%. CONCLUSIONS: The mid- to long-term outcomes after MVr in Marfan patients were satisfactory, supporting the durability of MVr in these patients. Postoperative cardiac reverse remodeling occurred in a phased manner in Marfan patients, similar to that in patients with degenerative MR.

Orthotopic heart transplantation in patient with situs inversus and pectus excavatum: a case report.

BACKGROUND: Heart transplantation in patients with situs inversus is challenging, especially in terms of reconstruction of the systemic venous return. Several rerouting techniques have been presented but are associated with vulnerability to external compression, which might cause hemodynamic instability, especially in the presence of chest deformity. In this study, we report a rare case of successful heart transplantation in the presence of situs inversus and pectus excavatum. CASE PRESENTATION: A 55-year-old man, with a history of surgeries for corrected transposition of the great arteries with ventricular septal defect, was registered for heart transplantation owing to progression of heart failure. Subsequently, he had undergone a left ventricular assist device implantation; 14 years after registration, he underwent transplantation of the heart with normal anatomy. The inferior vena cava was reconstructed by anastomosing the left atria with a counterclockwise rotation of the donor heart and by lengthening the recipient inferior vena cava with a conduit made of the residual right atrial tissue. The superior vena cava was reconstructed using a donor innominate vein harvested with sufficient length. After successful weaning from cardiopulmonary bypass, the chest could not be closed because the heart was compressed owing to chest deformity, resulting in hemodynamic instability. Therefore, to exclude the left lung, a left pericardial screen was created using a bovine pericardium, allowing the chest to be closed with acceptable hemodynamics. The patient suffered postoperatively from a higher venous pressure, suggesting an obstruction of venous return early after surgery. The obstruction gradually resolved, and the patient was transferred for rehabilitation. CONCLUSIONS: Heart transplantation in the presence of situs inversus is challenging; moreover, the presence of pectus excavatum further complicates the procedure. The paradoxically larger left lung and chest deformity compressed and impaired reconstructed systemic venous return. Although intrathoracic exclusion of the left lung was effective, an intraoperative or early postoperative thoracoplasty for pectus excavatum was also a viable option. Patient-specific management is mandatory, depending on the anatomy.

Vaccine Therapy for Heart Failure Targeting the Inflammatory Cytokine Igfbp7.

BACKGROUND: The heart comprises many types of cells such as cardiomyocytes, endothelial cells (ECs), fibroblasts, smooth muscle cells, pericytes, and blood cells. Every cell type responds to various stressors (eg, hemodynamic overload and ischemia) and changes its properties and interrelationships among cells. To date, heart failure research has focused mainly on cardiomyocytes; however, other types of cells and their cell-to-cell interactions might also be important in the pathogenesis of heart failure. METHODS: Pressure overload was imposed on mice by transverse aortic constriction and the vascular structure of the heart was examined using a tissue transparency technique. Functional and molecular analyses including single-cell RNA sequencing were performed on the hearts of wild-type mice and EC-specific gene knockout mice. Metabolites in heart tissue were measured by capillary electrophoresis-time of flight-mass spectrometry system. The vaccine was prepared by conjugating the synthesized epitope peptides with keyhole limpet hemocyanin and administered to mice with aluminum hydroxide as an adjuvant. Tissue samples from heart failure patients were used for single-nucleus RNA sequencing to examine gene expression in ECs and perform pathway analysis in cardiomyocytes. RESULTS: Pressure overload induced the development of intricately entwined blood vessels in murine hearts, leading to the accumulation of replication stress and DNA damage in cardiac ECs. Inhibition of cell proliferation by a cyclin-dependent kinase inhibitor reduced DNA damage in ECs and ameliorated transverse aortic constriction-induced cardiac dysfunction. Single-cell RNA sequencing analysis revealed upregulation of Igfbp7 (insulin-like growth factor-binding protein 7) expression in the senescent ECs and downregulation of insulin signaling and oxidative phosphorylation in cardiomyocytes of murine and human failing hearts. Overexpression of Igfbp7 in the murine heart using AAV9 (adeno-associated virus serotype 9) exacerbated cardiac dysfunction, while EC-specific deletion of Igfbp7 and the vaccine targeting Igfbp7 ameliorated cardiac dysfunction with increased oxidative phosphorylation in cardiomyocytes under pressure overload. CONCLUSIONS: Igfbp7 produced by senescent ECs causes cardiac dysfunction and vaccine therapy targeting Igfbp7 may be useful to prevent the development of heart failure.

Posttraumatic aortic regurgitation and root pseudoaneurysm following blunt chest trauma: a case report.

BACKGROUND: The simultaneous diagnosis of severe aortic regurgitation and aortic root pseudoaneurysm resulting from traffic injury is extremely rare. This report presents the case of a patient with Marfan syndrome who experienced aortic root pseudoaneurysm and subacute severe aortic regurgitation following a traffic accident. CASE PRESENTATION: A 64-year-old woman was diagnosed with Marfan syndrome 16 years ago and is undergoing ongoing follow-up at an outpatient clinic. Eight years previously, the patient underwent total arch replacement combined with J-graft open stent graft® (JGOS; Japan Lifeline Co., Tokyo, Japan) deployment for acute type A dissection. Five months before presentation, the patient suffered a left rib fracture in a traffic accident and received conservative management at a local hospital. The patient presented to the emergency room with worsening shortness of breath and orthopnea. Echocardiography revealed severe aortic regurgitation and moderate tricuspid regurgitation. Computed tomography revealed new-onset pseudoaneurysm at the aortic root. Surgical repair was successfully performed using a modified Bentall procedure with a bioprosthetic valve and tricuspid annuloplasty. Intraoperative findings revealed pseudoaneurysm with perforation of the right sinus of Valsalva. Although the left and right aortic valve leaflets were normal, the noncoronary leaflet exhibited a ruptured fibrous strand of a cusp fenestration, resulting in acute aortic regurgitation. CONCLUSIONS: This case report highlights the rare occurrence of aortic root pseudoaneurysm and subacute aortic regurgitation following a traffic accident. In cases of blunt chest trauma, particularly in patients with Marfan syndrome, frequent examination is crucial to assess the possibility of posttraumatic aortic regurgitation and aortic injury.

Current issues of destination therapy in Japan: to achieve 5-year or even longer survival.

In April 2021, destination therapy (DT) was finally approved in Japan. Since DT does not aim at heart transplantation (HT), our goal is to have a patient safely remain on an implantable ventricular assist device (VAD) for the rest of his/her life. To achieve this goal, similarly to bridge-to-transplant (BTT) patients, the authors believe the following six aspects are even more crucial in DT patients: (1) to appropriately assess risks before implantation, (2) to carefully determine the ability to manage the device by multidisciplinary discussions, (3) to prevent complications by improving the quality of care, (4) to expand the number of facilities that can take care of DT patients by improving collaboration among the facilities, (5) to reduce the burden of caregivers by utilizing social resources, and (6) to establish a home palliative care system based on advance care planning. In addition, for elderly DT patients to live happy and long lives, it is essential to help them to find a purpose of life and to keep activities of daily living, such as employment, schooling, and participation in social activities, just like the general elderly population. Our goals are not only to do our best for the patients just in front of us, but also to establish a system to follow up our DT cohort, same as BTT one, by all-Japan manner. In the present review, we discuss the current state of DT in Japan and what we need to focus on to maintain or improve its long-term performance.

Predictors of long-term success after successful explantation of continuous flow left ventricular assist device support.

OBJECTIVES: Predictors and evaluations of continuous flow left ventricular assist device (cf-LVAD) explantation in recovered patients remain under discussion due to lack of evidence on long-term safety and efficacy. This study summarized our experiences regarding cf-LVAD explantation in non-ischaemic dilated cardiomyopathy patients and estimated a predictor for sufficient myocardial recovery allowing left ventricular assist device explant. METHODS: We retrospectively identified 135 adult patients with cf-LVAD therapy as bridge to heart transplant due to non-ischaemic dilated cardiomyopathy. Of those, 13 patients underwent device explantation (recovery group) after myocardial recovery. Twelve (92%) of the explanted patients were evaluated using our weaning protocol and underwent surgical explantation. Meanwhile, the remaining 122 continued with cf-LVAD therapy (non-recovery group). RESULTS: Multivariate logistic regression analysis revealed time interval between the first heart failure event and cf-LVAD implantation as an independent predictor for successful explantation. The optimal time interval cutoff value to predict cf-LVAD explantation was 7 months, with a sensitivity of 91.0% and specificity of 84.6%. Echocardiography in patients with successful cf-LVAD explantation showed significant improvement of left ventricular function and dimensions at 6 months postoperatively. The 13 explanted patients are currently alive at a median of 30 (interquartile range; 18-58) months after explantation. The survival rate free from rehospitalization due to heart failure following explantation was 100%. Left ventricular function and remodelling after explantation were also preserved. CONCLUSIONS: In non-ischaemic dilated cardiomyopathy patients with a short interval between the first heart failure event and cf-LVAD therapy, left ventricular myocardium may recover in an early phase after device implantation.

A leadless pacemaker implantation for a patient with systemic right ventricle under ventricular assist device support.

Patients with congenitally corrected transposition of the great arteries (ccTGA) often develop complete atrioventricular block and heart failure due to the abnormal disposition of atrioventricular node and disadvantage of systemic right ventricle. These issues are managed with a pacing system and a ventricular assist device (VAD), respectively. While technological advances offer new treatment strategies, the simultaneous deployment of a leadless pacemaker and a VAD in cases of ccTGA remains unexplored. Here, we present a case of leadless pacemaker implantation for a VAD-supported ccTGA patient. The safety of a leadless pacemaker for a subpulmonary left ventricle and electromagnetic interference between devices are major concerns when implanting a leadless pacemaker; however, the current case overcomes these obstacles. There were no perioperative complications, and both devices were functioning without problems during a one-year follow up. We expect that, even in patients with cardiac complexity such as systemic right ventricle under VAD support, a leadless pacemaker could become the treatment of choice if the indication is appropriate, although careful and close follow up is needed. Learning objective: Technological advances expand treatment strategies and provide significant benefits to patients with adult congenital heart disease (ACHD). However, discussion of the combination of a leadless pacemaker and a ventricular assist device (VAD) is rare. We demonstrated the efficacy of a leadless pacemaker for a subpulmonary left ventricle in a patient with systemic right ventricle on VAD. This approach could be an option even for ACHD patients.

[Surgical Replacement of Descending Aorta for Adult Aortic Coarctation by Using Three-dimensional Computer Graphics Reconstruction].

Aortic coarctation is diagnosed in approximately 5% of adult patients with congenital heart disease and is commonly diagnosed through the close examination of hypertension. Various surgical strategies for adult coarctation have been recently reported. Generally, aortic replacement may require blood transfusion in case of injury of the well-developed collateral vessels. Therefore, in order to secure an operative safety, we preoperatively used a medical image viewer to identify the abnormal vessels by three-dimensional computer graphics (3DCG) reconstruction. A 34-year-old male patient was referred to our hospital with hypertension and low ankle-brachial pressure index( ABI). Chest computed tomography( CT) scan showed aortic coarctation and development of abnormal collateral vessels. Descending aorta was replaced via a left third-fourth intercostal thoracotomy under partial extracorporeal circulation. As the image viewer depicted, anatomical abnormality of the collateral vessels was identified precisely, and surgically treated without any injury. The patient was discharged 10 days postoperatively without transfusion and with a normalized ABI.

The first case report of de novo Crohn's disease after heart transplantation successfully treated with ustekinumab.

Inflammatory bowel disease (IBD) is a complex chronic inflammatory intestinal disease. The development of de novo IBD after solid organ transplantation with immunosuppressive agents has been rarely reported. We present the case of a 65-year-old man with repeated colitis after heart transplantation (HTx) who was diagnosed with Crohn's disease (CD). The patient underwent HTx due to non-ischemic dilated cardiomyopathy. Six months after HTx, he developed serious diarrhea and a transient fever, which persisted for about 6 months. Valganciclovir or any antibiotic agents were not effective for his symptoms and longitudinal ulcers in colonoscopy aggravated during the course, so that we made a diagnosis of CD. We started 5-aminosalicylic acid and found improvement in his symptoms and colonoscopic findings. However, 7 months after improvement, CD worsened. We started ustekinumab by which his condition successfully went into remission again. While oral immunosuppressive drugs are thought to suppress autoimmune diseases in general, IBD should be included in the differential diagnoses for recurring enterocolitis after HTx. Poorly controlled CD can lead to serious and potentially fatal complications, but in this case, ustekinumab has been used safely and effectively for the treatment of CD. Learning objective: Colitis is a common complication after heart transplantation (HTx). Although cytomegalovirus colitis or posttransplant lymphoproliferative disorder are observed commonly, de novo inflammatory bowel disease (IBD) should be considered when serious refractory colitis occurs. Not only 5-aminosalicylic acid but also ustekinumab, which is a monoclonal antibody to the p40 subunit of interleukin (IL)-12 and IL-23, may be a safe and effective treatment for de novo IBD after HTx.

Right Heart Reserve Function Assessed With Fluid Loading Predicts Late Right Heart Failure After Left Ventricular Assist Device Implantation.

BACKGROUND: A left ventricular assist device (LVAD) is an effective therapeutic option for advanced heart failure. Late right heart failure (LRHF) is a complication after LVAD implantation that is associated with increasing morbidity and mortality; however, the assessment of right heart function, including right heart reserve function after LVAD implantation, has not been established. We focused on a fluid-loading test with right heart catheterization to evaluate right heart preload reserve function and investigate its impact on LRHF. METHODS: Patients aged > 18 years who received a continuous-flow LVAD between November 2007 and December 2022 at our institution, and underwent right heart catheterization with saline loading (10 mL/kg for 15 minutes) 1 month after LVAD implantation, were included. RESULTS: Overall, 31 cases of LRHF or death (right heart failure [RHF] group) occurred in 149 patients. In the RHF vs the non-RHF groups, the pulmonary artery pulsatility index (PAPi) at rest (1.8 ± 0.89 vs 2.5 ± 1.4, P = 0.02) and the right ventricular stroke work index (RVSWi) change ratio with saline loading (0.96 ± 0.32 vs 1.1 ± 0.20, P = 0.03) were significantly different. The PAPi at rest and the RVSWi change ratio with saline loading were identified as postoperative risks for LRHF and death. The cohort was divided into 3 groups based on whether the PAPi at rest and the RVSWi change ratio were low. The event-free curve differed significantly among the 3 groups (P < 0.001). CONCLUSIONS: Hemodynamic assessment with saline loading can evaluate the right ventricular preload reserve function of patients with an LVAD. A low RVSWi change with saline loading was a risk factor for LRHF following LVAD implantation.

Effect of chitin-architected spatiotemporal three-dimensional culture microenvironments on human umbilical cord-derived mesenchymal stem cells.

Mesenchymal stem cell (MSC) transplantation has been explored for the clinical treatment of various diseases. However, the current two-dimensional (2D) culture method lacks a natural spatial microenvironment in vitro. This limitation restricts the stable establishment and adaptive maintenance of MSC stemness. Using natural polymers with biocompatibility for constructing stereoscopic MSC microenvironments may have significant application potential. This study used chitin-based nanoscaffolds to establish a novel MSC three-dimensional (3D) culture. We compared 2D and 3D cultured human umbilical cord-derived MSCs (UCMSCs), including differentiation assays, cell markers, proliferation, and angiogenesis. When UCMSCs are in 3D culture, they can differentiate into bone, cartilage, and fat. In 3D culture condition, cell proliferation is enhanced, accompanied by an elevation in the secretion of paracrine factors, including vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), Interleukin-6 (IL-6), and Interleukin-8 (IL-8) by UCMSCs. Additionally, a 3D culture environment promotes angiogenesis and duct formation with HUVECs (Human Umbilical Vein Endothelial Cells), showing greater luminal area, total length, and branching points of tubule formation than a 2D culture. MSCs cultured in a 3D environment exhibit enhanced undifferentiated, as well as higher cell activity, making them a promising candidate for regenerative medicine and therapeutic applications.

Prevalence of bleeding events in real-world Japanese registry for Percutaneous Ventricular Assist Device.

PURPOSE: Bleeding complication is a critical risk factor for outcomes of acute heart failure patients requiring mechanical circulatory support (MCS), including percutaneous catheter-type heart pumps (Impella). The Japanese registry for Percutaneous Ventricular Assist Device (J-PVAD) is an ongoing, large-scale, real-world registry to characterize Japanese patients requiring Impella. Here we analyzed bleeding complication profiles in patients who received Impella. METHODS: All consecutive Japanese patients who received Impella from October 2017 to January 2020 were enrolled. The 30-day survival and bleeding complications were analyzed. RESULTS: A total of 1344 patients were included: 653 patients received Impella alone, 685 patients received a combination of veno-arterial extracorporeal membrane oxygenation and Impella (ECPELLA), and 6 patients had failed Impella delivery. Overall 30-day survival was 67.0%, with Impella alone at 81.9% and ECPELLA at 52.7%. Overall bleeding/hematoma adverse events with a relation or not-excluded relation to Impella was 6.92%. Among them, the rates of hematoma and bleeding from medical device access sites were 1.41% and 4.09%, respectively. There was no difference between etiologies for these events. CONCLUSION: This study represents the first 3-year survival and the safety profile focused on bleeding adverse events from the J-PVAD registry. The results show that the real-world frequency of bleeding adverse events for patients who received Impella was an expected range from previous reports, and future real-world studies should aim to expand this data set to improve outcomes and adverse events.

Impact of prolonged cardiopulmonary resuscitation on outcomes in heart transplantation with higher risk donor heart.

OBJECTIVES: To evaluate the influence of prolonged cardiopulmonary resuscitation (CPR) on outcomes in heart transplantation with higher risk donor hearts (HRDHs). METHODS: Patients transplanted in our hospital between May 2006 and December 2019 were divided into 2 groups, HRDH recipients and non HRDH recipients. HRDH was defined as meeting at least one of the following criteria: (1) donor left ventricular ejection fraction ≤ 50%, (2) donor-recipient predicted heart mass ratio < 0.8 or > 1.2, (3) donor age ≥ 55 years, (4) ischemic time > 4 h and (5) catecholamine index > 20. Recipients of HRDHs were divided into 3 groups according to the time of CPR (Group1: non-CPR, Group 2: less than 30 min-CPR, and Group 3: longer than 30 min CPR). RESULTS: A total of 125 recipients were enrolled in this study, composing of HRDH recipients (n = 97, 78%) and non HRDH recipients (n = 28, 22%). Overall survival and the rate of freedom from cardiac events at 10 years after heart transplantation were comparable between two groups. Of 97 HRDH recipients, 54 (56%) without CPR, 22 (23%) with CPR < 30 min, and 21 (22%) with CPR ≥ 30 min were identified. One-year survival rates were not significantly different among three groups. The 1-year rate of freedom from cardiac events was not also statistically different, excluding the patients with coronary artery disease found in early postoperative period, which was thought to be donor-transmitted disease. Multivariate logistics regression for cardiac events identified that the CPR duration was not a risk factor even in HRDH-recipients. CONCLUSION: The CPR duration did not affect the outcomes after heart transplantation in HRDH recipients.

Pre-Transplant Seroprevalence, Associated Factors, and Post-Transplant Incidence of Toxoplasma gondii Infection Among Heart Transplant Recipients in Japan.

BACKGROUND: Among solid organ transplant (SOT) recipients, heart transplant (HT) recipients are at a higher risk of Toxoplasma gondii infection. As Toxoplasma seroprevalence varies by geographic location, updated local epidemiology is essential to guide preventive and therapeutic strategies. However, the Toxoplasma seroprevalence and incidence of post-transplant toxoplasmosis among SOT recipients in Japan are unknown. METHODS: We performed a single-center retrospective observational study at an HT center in Tokyo, Japan. All HT recipients aged ≥18 years between 2006 and April 2019 were included. We reviewed patient charts and conducted a questionnaire survey to investigate the risk factors for infection. RESULTS: Among 105 recipients included in the study, 11 (10.5%) were seropositive before transplant. Ninety-five recipients (90.5%), including all pre-transplant seropositive recipients, answered the questionnaire. The recipients who had lived in Okinawa (odds ratio [OR] 7.5 [95% CI 1.42-39.61]; P = .032) and who reported raw-meat eating habits (OR 4.64 [95% CI 1.04-23.3]; P = .021) were more likely to be seropositive. None of the patients developed symptoms of toxoplasmosis. The post-transplant incidence of other major adverse outcomes was not significantly different according to the pre-transplant serostatus. CONCLUSIONS: About 10% of HT recipients at an HT center in Tokyo were seropositive for Toxoplasma pre-transplant, and none developed symptomatic toxoplasmosis post-transplant on trimethoprim-sulfamethoxazole. The history of raw meat consumption was associated with seropositivity; therefore, avoiding it might be recommended for HT recipient candidates.