Advance care planning in the treatment of implantable left ventricular assist device: a republication of the review published in Japanese Journal of Artificial Organs.

Advance care planning (ACP) is essential in managing serious and chronic illnesses to ensure that patients receive care aligned with their personal values, goals, and preferences. This review focuses on integrating ACP in the treatment of patients receiving implantable left ventricular assist devices (VADs). The heart failure palliative care team developed a unique advance directive form and pamphlet to facilitate ACP discussions, emphasizing not only medical treatment preferences but also patients' values and life goals.The study highlights the distinction between bridge to transplantation (BTT) and destination therapy (DT) in VAD patients, with different goals and considerations for ACP. The use of decision aids developed especially for DT candidates as a communication tool helps in sharing patients' wishes and facilitates shared decision-making, particularly in the complex decisions surrounding DT therapy.Challenges in implementing ACP, such as time constraints due to urgent medical conditions, difficulties in patient communication, and the recent COVID-19 pandemic, are addressed. The need for a comprehensive healthcare system capable of supporting patients' ACP wishes, especially in the community setting, is also pointed out.Future directions include not only developing materials to ease ACP discussions and ensuring that ACP content is shared among healthcare providers to foster collaborative and detailed planning, but also a call for widespread adoption of ACP in Japan.This is a translation of a paper written in Japanese Journal of Artificial Organs (Vol. 52, No. 1, pp. 89-92) with additions and corrections.

Left ventricular assist device temporary explantation as a strategy for infection control in a pediatric patient.

We report a case of temporary Berlin Heart EXCOR® explantation in a pediatric patient with idiopathic dilated cardiomyopathy who suffered an uncontrollable inflow cannulation site infection while on bridge-to-transplantation. Despite failure to thrive and catheter-related infections, once free of the device, the patient was cured of infection using systemic antibiotics and surgical debridement. The patient underwent EXCOR® reimplantation after four months, and is awaiting heart transplantation in stable condition. A life-threatening ventricular assist device-related infection may require device explantation under conditions that may not fulfill conventional explantation criteria despite risks. Temporary explantation can be an effective strategy if isolated systolic dysfunction is managed carefully.

The usefulness of chest drain and epicardial pacing wire culture for diagnosing mediastinitis after open-heart surgery.

PURPOSE: Culture of extracted drains or epicardial pacing wires is an easy and noninvasive method for detecting mediastinitis after open-heart surgery, although studies on its sensitivity and specificity are limited. We, therefore, investigated the usefulness of this approach for diagnosing mediastinitis. METHODS: We retrospectively studied the culture results of drains and epicardial pacing wires extracted from 3308 patients. Prediction models of mediastinitis with and without culture results added to clinical risk factors identified by a logistic regression analysis were compared. RESULTS: The incidence of mediastinitis requiring surgery was 1.89% (n = 64). Staphylococcus was the causative bacterium in 64.0% of cases. The sensitivity, specificity, and positive and negative predictive values of positive culture results were 50.8%, 91.8%, 10.7%, and 99.0%, respectively. Methicillin-resistant Staphylococcus aureus had the highest positive predictive value (61.5%). A multivariate analysis identified preoperative hemodialysis (OR 5.40 [2.54-11.5], p < 0.01), long operative duration (p < 0.01), postoperative hemodialysis (OR 2.25 [1.01-4.98], p < 0.05), and positive culture result (OR 10.2 [5.88-17.7], p < 0.01) as independent risk factors. The addition of culture results to pre- and postoperative hemodialysis and a lengthy operative time improved the prediction of mediastinitis. CONCLUSIONS: A culture survey using extracted drains and epicardial pacing wires may provide useful information for diagnosing mediastinitis.

How should cardiac xenotransplantation be initiated in Japan?

The world's first clinical cardiac xenotransplantation, using a genetically engineered pig heart with 10 gene modifications, prolonged the life of a 57-year-old man with no other life-saving options, by 60 days. It is foreseeable that xenotransplantation will be introduced in clinical practice in the United States. However, little clinical or regulatory progress has been made in the field of xenotransplantation in Japan in recent years. Japan seems to be heading toward a "device lag", and the over-importation of medical devices and technology in the medical field is becoming problematic. In this review, we discuss the concept of pig-heart xenotransplantation, including the pathobiological aspects related to immune rejection, coagulation dysregulation, and detrimental heart overgrowth, as well as genetic modification strategies in pigs to prevent or minimize these problems. Moreover, we summarize the necessity for and current status of xenotransplantation worldwide, and future prospects in Japan, with the aim of initiating xenotransplantation in Japan using genetically modified pigs without a global delay. It is imperative that this study prompts the initiation of preclinical xenotransplantation research using non-human primates and leads to clinical studies.

Multiphoton-driven Photocatalytic Defluorination of Persistent Perfluoroalkyl Substances and Polymers by Visible Light.

Perfluoroalkyl substances (PFASs) and fluorinated polymers (FPs) have been extensively utilized in various industries, whereas their extremely high stability poses environmental persistence and waste treatment. Current decomposition approaches of PFASs and FPs typically require harsh conditions such as heating over 400°C. Thus, there is a pressing need to develop a new technique capable of decomposing them under mild conditions. Here, we demonstrated that perfluorooctanesulfonate (PFOS), known as a "persistent chemical," and Nafion, a widely utilized sulfonated FP for ion-exchange membranes, can be efficiently decomposed into fluorine ions under ambient conditions via the irradiation of visible LED light onto semiconductor nanocrystals (NCs). PFOS was completely defluorinated within 8-h irradiation of 405-nm LED light, and the turnover number of the C-F bond dissociation per NC was 17200. Furthermore, 81% defluorination of Nafion was achieved for 24-h light irradiation, demonstrating the efficient photocatalytic properties under visible light. We revealed that this decomposition is driven by cooperative mechanisms involving light-induced ligand displacements and Auger-induced electron injections via hydrated electrons and higher excited states. This study not only demonstrates the feasibility of efficiently breaking down various PFASs and FPs under mild conditions but also paves the way for advancing toward a sustainable fluorine-recycling society.

What voltage-sensing phosphatases can reveal about the mechanisms of ion channel regulation by phosphoinositides.

Many membrane proteins including ion channels and ion transporters are regulated by membrane phospholipids such as phosphoinositides in cell membranes and organelles. Voltage-sensing phosphatase, VSP, is a voltage-sensitive phosphoinositide phosphatase which dephosphorylates PI(4,5)P2 into PI(4)P. VSP rapidly reduces the level of PI(4,5)P2 upon membrane depolarization, thus serving as a useful tool to quantitatively study phosphoinositide-regulation of ion channels and ion transporters using a cellular electrophysiology system. In this review, we focus on the application of VSPs to Kv7 family potassium channels, which have been important research targets in biophysics, pharmacology and medicine.

Staged left ventricular assist device reimplantation via the left anterior wall approach for a patient with severe pump pocket infection.

Pump pocket infection (PPI) is a refractory condition that can cause lethal complications in patients with a left ventricular assist device (LVAD). We report a case of PPI after LVAD implantation for ischemic cardiomyopathy that was successfully treated with staged pump reimplantation into the left ventricular anterior wall with the pedicled omental transfer. Major modification of the pump implantation site might be a useful strategy for local infection control of severe PPI.

Photochromism of colloidal ZnO nanocrystal powders under ambient conditions.

Zinc oxide (ZnO) nanocrystals (NCs) exhibit photochromic reactions under specific conditions upon ultraviolet light irradiation. Since the color is originated from the excited electrons at the conduction band of ZnO NCs, the photoinduced absorption is observed only in the solution with hole acceptors under inert conditions. ZnO is earth-abundant and less toxic than many other substances, and has been widely used in various industrial fields. If the photochromic reaction of ZnO can be observed consistently under ambient conditions, the material may pave the way for large-scale photochromic applications such as in pigments, windows, and building materials in addition to conventional photochromic applications. In this study, we synthesize hydrophilic ZnO NCs and observe the solid-state photochromic reactions in the visible to mid-infrared regions even in humid-air conditions. We reveal that the coloration of powders of ZnO NCs under ambient conditions originates mainly from two factors: (1) charge separation induced by hole trapping by water molecules adsorbed on the surface of NCs, and (2) deceleration of the reactions involving the electrons in the conduction band of ZnO NCs with molecular oxygen and the adsorbed water molecules.

Effect of Diabetes Mellitus on Outcomes in Patients With Left Ventricular Assist Device　- Analysis of Data From a Japanese National Database.

BACKGROUND: The objective of this study is to investigate the effect of preoperative diabetes on all-cause mortality and major postoperative complications among patients with continuous-flow left ventricular assist device (LVAD) by using data from a national database.Methods and Results: The 545 study patients who underwent primary HeartMateII implantation between 2013 and 2019 were divided into 2 groups according to their diabetes mellitus (DM) status; patients with DM (n=116) and patients without DM (n=429). First, the on-device survival and incidence of adverse events were evaluated. Second, after adjusting for patients' backgrounds, the change of laboratory data in the 2 groups were compared. Overall, on-device survival at 1, 2, and 3 years was almost equivalent between the 2 groups; it was 95%, 94%, and 91% in patients without DM, and 93%, 91%m and 91% in patients with DM (P=0.468) The incidence of adverse events was similar between 2 groups of patients, except for driveline exit site infection in the adjusted cohort. Cox proportional hazards regression analysis revealed younger age (HR: 0.98 (95% confidence interval (CI): 0.97-0.99, P=0.001) and presence of DM (HR: 1.83 (95% CI: 1.14-2.88), P=0.016) as significant predictors of driveline infection. Laboratory findings revealed no differences between groups throughout the periods. CONCLUSIONS: The clinical results after LVAD implantation in DM patients were comparable with those in non-DM patients, except for the driveline exit site infection.

Short-Term Outcomes of Magnetically Levitated Left Ventricular Assist Device in Advanced Heart Failure　- The Japanese Cohort.

BACKGROUND: The superiority of a fully magnetically levitated centrifugal-flow left ventricular assist device (LVAD) in terms of overall survival, stroke events and pump thrombosis has been demonstrated in previous international analyses, so we evaluated a Japanese cohort for the same.Methods and Results: This retrospective observational study was conducted at Osaka University Medical Hospital and the National Cerebral and Cardiovascular Center in Japan. A total of 75 consecutive patients who underwent HeartMate3 (HM3) implantation were included. The primary endpoint was on-device survival, and the secondary endpoint was the incidence of LVAD-related complications at 2 years. All parameters were compared with those of the previously performed HeartMate II (HMII) implantation in 197 cases. The on-device survival rates were 94.7% and 92.3% in the HM3 and HMII groups, respectively, at the 2-year follow-up (P=0.62). The rehospitalization-free rate after implantation was 61.8% in the HM3 group, which was significantly higher than that in the HMII group (relative risk, 0.35; 95% confidence interval [CI], 0.23-0.55; P<0.0001). Event-free survival rates from cerebral cerebrovascular events and pump thrombosis in the HM3 group were significantly higher than those in the HMII group, at 97.2% and 100%, respectively (relative risk, 0.14; 95% CI 0.03-0.58); P=0.0015 and relative risk, not calculated; P=0.049, respectively). CONCLUSIONS: Satisfactory short-term outcomes were observed after HM3 implantation in a Japanese cohort.

Long-term outcomes of autologous skeletal myoblast cell-sheet transplantation for end-stage ischemic cardiomyopathy.

We evaluated the cardiac function recovery following skeletal myoblast cell-sheet transplantation and the long-term outcomes after applying this treatment in 23 patients with ischemic cardiomyopathy. We defined patients as "responders" when their left ventricular ejection fraction remained unchanged or improved at 6 months after treatment. At 6 months, 16 (69.6%) patients were defined as responders, and the average increase in left ventricular ejection fraction was 4.9%. The responders achieved greater improvement degrees in left ventricular and hemodynamic function parameters, and they presented improved exercise capacity. During the follow-up period (56 ± 28 months), there were four deaths and the overall 5-year survival rate was 95%. Although the responders showed higher freedom from mortality and/or heart failure admission (5-year, 81% versus 0%; p = 0.0002), both groups presented an excellent 5-year survival rate (5-year, 93% versus 100%; p = 0.297) that was higher than that predicted using the Seattle Heart Failure Model. The stepwise logistic regression analysis showed that the preoperative estimated glomerular filtration rate and the left ventricular end-systolic volume index were independently associated with the recovery progress. Approximately 70% of patients with "no-option" ischemic cardiomyopathy responded well to the cell-sheet transplantation. Preoperative renal and left ventricular function might predict the patients' response to this treatment.

Sudden severe left ventricular assist device inflow cannula obstruction caused by huge thrombus after closure of mechanical aortic valve: case report.

Thrombus formation is a troublesome and sometimes lethal complication occurring in patients with severe heart failure and supported by a left ventricular assist device (LVAD). Appropriate treatment for pump thrombosis especially in emergency cases with severe pump failure is difficult to choose. Herein, we present important findings of a case of unexpected LVAD pump thrombosis that rapidly developed into serious pump failure and circulatory arrest due to total obstruction of the LVAD inflow tract by a huge thrombus.

Risk factors of gynecological bleeding in female patients with left-ventricular assist device.

Women with implantable left-ventricular assist devices (LVADs) experience gynecological bleeding (GYN-bleeding). However, a few studies have investigated female-specific problems. Therefore, this study aimed to identify the risk factors for adverse GYN-bleeding after LVAD implantation. We retrospectively analyzed 59 women (mean age: 41 ± 15 years) with long-term implantable LVAD support (≥ 6 months) at our institution between 2005 and 2018. The history of GYN-bleeding before implantation was defined as abnormal utero-ovarian bleeding, excessive menstruation, uterine fibroids, and endometrial lesions. GYN-bleeding after implantation was defined as a requirement of emergency outpatient visits and/or hospitalization, blood transfusions, hormonal therapy, and/or surgery. Additionally, risk factors for GYN-bleeding were identified using the Cox regression model. Twenty-four GYN-bleeding cases were seen in 15 patients (two times: five patients, three times: two patients, 0.18 events per patient-year). The 1- and 2-year GYN-bleeding-free rates were 84% and 73%, respectively. Twelve patients (17 events) required RBC ≥ 4 units, and five patients (7 events) required FFP ≥ 4 units. Seven patients required pseudomenopausal treatment after blood transfusion, and four patients required surgical treatment. Fifteen patients with GYN-bleeding after implantation were significantly younger than the remaining 44 patients without GYN-bleeding (34 ± 12 years vs. 43 ± 16 years, P = 0.02). Multivariable risk analysis showed a history of GYN-bleeding before implantation was a significant risk factor (hazard ratio 3.7 [1.2-10.6], P = 0.004). Patients with a history of GYN-bleeding before LVAD implantation have a high risk of developing GYN-bleeding after implantation. We should identify the high-risk population and prepare for the management of GYN-bleeding.

Impella 5.0 support as a bridge to the exchange of an infected left ventricular assist device.

A pump infection is a fatal complication specific to left ventricular assist devices. Infection recurrence is a major concern when device exchange is indicated for pump infection. In the present case, we used the Impella 5.0 to maintain proper hemodynamics and to treat the infection in the absence of an implantable device. We demonstrate that the Impella 5.0 can serve as an effective bridge for device exchange by controlling infection and minimizing organ dysfunction, despite prolonged management.

Mixed-Valent Trinuclear CoIII-CoII-CoIII Complex with 1,3-Bis(5-chlorosalicylideneamino)-2-propanol.

A mixed-valent trinuclear complex with 1,3-bis(5-chlorosalicylideneamino)-2-propanol (H3clsalpr) was synthesized, and the crystal structure was determined by the single-crystal X-ray diffraction method at 90 K. The molecule is a trinuclear CoIII-CoII-CoIII complex with octahedral geometries, having a tetradentate chelate of the Schiff-base ligand, bridging acetate, monodentate acetate coordination to each terminal Co3+ ion and four bridging phenoxido-oxygen of two Schiff-base ligands, and two bridging acetate-oxygen atoms for the central Co2+ ion. The electronic spectral feature is consistent with the mixed valent CoIII-CoII-CoIII. Variable-temperature magnetic susceptibility data could be analyzed by consideration of the axial distortion of the central Co2+ ion with the parameters Δ = -254 cm-1, λ = -58 cm-1, κ = 0.93, tip = 0.00436 cm3 mol-1, θ = -0.469 K, gz = 6.90, and gx = 2.64, in accordance with a large anisotropy. The cyclic voltammogram showed an irreversible reduction wave at approximately -1.2 V·vs. Fc/Fc+, assignable to the reduction of the terminal Co3+ ions.

Sputum characteristics of patients with severe COVID-19: report of two cases with immunocytochemical detection of SARS-CoV-2 spike protein.

Patients with SARS-CoV-2 infection and with severe COVID-19 often have multiple coinfections, and their treatment is challenging. Here, we performed cytology analysis on sputum samples from two patients with severe COVID-19. The specimens were prepared using the rubbing method and stained with Papanicolaou stain. In both cases, several cells with frosted nuclei were observed, and the cytological findings per 100 cells were evaluated. The infected cells were mononuclear to multinuclear, showing chromatin aggregation at the nuclear margins, intranuclear inclusion bodies, eosinophilic cytoplasmic inclusion bodies, and mutual pressure exclusion of the nuclei. Immunocytochemical staining revealed that the cells were positive for AE1/AE3 and negative for CD68 expression, indicating their epithelial origin. Furthermore, infected cells with frosted nuclei were positive for surfactant protein A (SP-A) in Case 2, suggesting infection of type II alveolar pneumocytes or Clara cells. Moreover, in Case 2, the infected cells were positive for herpes simplex virus (HSV) I + II and SARS-CoV-2 spike protein, confirming double infection in these cells. In conclusion, sputum cytology is an important tool for determining the diversity of viral infection, and additional immunocytochemistry can be used for definitive diagnosis.

[Clinical Outcome of Heart Transplantation in Osaka University].

In this article, we analyzed 114 adult heart transplantation( HTx) cases from 1999 to 2021. Of these cases, 94% of patients underwent left ventricular assist device ( LVAD) implantation before HTx. The mean period of LVAD support was 3.0 ±1.2 years. Thirty-day mortality was 0.8% and the 10-year survival rate was 89% after HTx. Preoperative and postoperative renal function was the prognostic factors. Long LVAD support was not associated with the long-term survival after HTx.

Four-quadrant visualization of systemic circulatory equilibrium: right ventricular failure after left ventricular assist device implantation.

Right ventricular failure (RVF) is a serious adverse event after left ventricular assist device (LVAD) implantation but difficult to be characterized. This study aimed to visualize the dynamic circulatory equilibrium of acute RVF after LVAD implantation using a new four-quadrant diagram constructed by 1) cardiac function with central venous pressure (CVP) and cardiac index (CI) axes, 2) arterial vascular resistance with CI and mean blood pressure (mBP) axes, 3) pressure-diuretic function with mBP and net urinary sodium output (net U-Na) axes, and 4) venous compliance with net U-Na and CVP axes. Twenty LVAD patients were stratified into two groups, group S (≤10 days) and group L (>10 days), according to duration of postoperative inotropic support. The preoperative equilibrium loops were small in both groups. In the early postoperative phase, the loop in group S became dramatically enlarged to the left and upward, indicating increased CVP and CI by LVAD support. In group L, however, augmentation of CI was smaller despite similarly increased CVP, and net U-Na was decreased despite increased mBP. In the late postoperative phase, the equilibrium loop in group L recovered as similar to that seen in group S. Thus, acute RVF, as shown in group L, was characterized by the shape of the loop constructed by marked increased CVP, a relatively small increase in CI, and concomitant impairment of pressure natriuresis. In conclusion, the novel four-quadrant presentation of systemic circulatory equilibrium provides clear visualization of RVF after LVAD implantation, thus serving as a useful guide for prompt and optimal management.NEW & NOTEWORTHY Systemic circulatory dynamics are regulated by various negative feedback systems, including cardiac, arterial, venous, and renal functions, as well as autonomic nervous systems. The present novel four-quadrant presentation of their functions allows clear visualization of dynamic organ-to-organ interactions that can lead to a new circulatory equilibrium after therapeutic intervention. This new system physiological framework can serve as a useful guide for prompt and optimal management of circulatory malfunction.

Bilateral Internal Thoracic Artery Grafting Improves Survival for Severe Left Ventricular Dysfunction and Diabetes.

BACKGROUND: In patients with severe left ventricular (LV) dysfunction requiring coronary artery bypass grafting (CABG), the association between diabetic status and outcomes after surgery, as well as with survival benefit following bilateral internal thoracic artery (ITA) grafting, remain largely unknown.Methods and Results:Patients (n=188; mean [±SD] age 67±9 years) with LV ejection fraction ≤40% who underwent isolated initial CABG were classified into non-diabetic (n=64), non-insulin-dependent diabetic (NIDM; n=74), and insulin-dependent diabetic (IDM; n=50) groups. During follow-up (mean [±SD] 68±47 months), the 5-year survival rate was 84% and 65% among non-diabetic and diabetic patients, respectively (P=0.034). After adjusting for all covariates, both NIDM and IDM were associated with increased mortality, with hazard ratios (HRs) of 1.9 (95% confidence interval [CI] 1.0-3.7; P=0.049) and 2.4 (95% CI 1.2-4.8; P=0.016), respectively. Among non-diabetic patients, there was no difference in the 5-year survival rate between single and bilateral ITA grafting (86% vs. 80%, respectively; P=0.95), whereas bilateral ITA grafting increased survival among diabetic patients (57% vs. 81%; P=0.004). Multivariate analysis revealed that bilateral ITA was significantly associated with a decreased risk of mortality (HR 0.3; 95% CI 0.1-0.8; P=0.024). CONCLUSIONS: NIDM and IDM were significantly associated with worse long-term clinical outcome after CABG for severe LV dysfunction. Bilateral ITA grafting has the potential to improve survival in diabetic patients with severe LV dysfunction.

Complex HeartWare left ventricular assist device infection treated with pump exchange: clinical alert for the driveline location.

Infection is a major complication in patients with a left ventricular assist device (LVAD). Once a driveline exit-site infection (DLI) reaches the LVAD component, LVAD exchange may become necessary for radical treatment, although clinical results are not satisfactory. In this report, we describe two cases of LVAD infection successfully treated with pump exchange. During LVAD support, the DLI extended into the pump pocket and the outflow graft despite aggressive surgical debridement and negative pressure wound therapy. These two patients required LVAD exchange for radical treatment, because the estimated waiting period for heart transplantation was at least more than 1 year. The LVAD exchange was performed through median re-sternotomy, and the infected HeartWare ventricular assist device (HVAD) was completely removed under cardiopulmonary bypass. Then, a new LVAD covered with the omentum flap was implanted. These two patients were successfully bridged to heart transplantation after 10 months and 2 years of support without recurrence of infection. These two cases may suggest that the driveline of the HVAD needs to be kept away from the outflow graft to prevent refractory outflow graft infection.