Fenestrated Fontan-like circulation under durable left-ventricular assist device support in fulminant myocarditis.

Fulminant myocarditis is a fatal development from profound biventricular heart failure and often requires both right- and left-ventricular assistance to maintain hemodynamics, even at the risk of increased mortality and morbidity. Here, we present a 42-year-old female with profound biventricular failure due to fulminant myocarditis, resolved by an isolated durable left-ventricular assist device support under a fenestrated, Fontan-like circulation and managed low-pulmonary vascular resistance.

Changes in the Quality of Life of Patients with Left Ventricular Assist Device and their Caregivers in Japan: Retrospective Observational Study.

Left ventricular assist devices (LVAD) improve quality of life (QOL) in many patients with end-stage severe heart failure, but not in some patients. In addition, the burden on caregivers is expected to increase after LVAD patients are discharged. Our study aimed to investigate the impact of LVAD on the QOL of patients and caregivers. Thirty-two LVAD patients were assessed for changes in QOL, mental status, and activity level using the Euro QOL (EQ-5D-5L), Short Form 12 (SF-12), Minnesota Living with Heart Failure Questionnaire, Hospital Anxiety and Depression Scale (HADS), and Frenchay Activities Index. Twenty-four caregivers were assessed for changes in QOL, mental status, and burden of care using the EQ-5D-5L, SF-12, HADS, and Burden Index of Caregiver (BIC-11). The LVAD patients and caregivers responded contemporaneously regarding two points: pre-and post-LVAD. Patients' physical and mental QOL was significantly improved, but not social QOL and activity level. Caregivers' QOL and burden of care did not change, and anxiety was reduced (p = 0.028). The patients were divided into two groups based on whether EQ-5D-5L was improved: twelve patients in the unimproved group (UG) and twenty patients in the improved group (IG). In the UG, 50% had LVAD-related strokes (p = 0.001, IG: 0%), and their social QOL decreased (p = 0.023). The activity levels improved in the IG. Multi-dimensional analyses on the QOL in LVAD patients yielded mixed results. Anticipated benefits derived from LVAD therapy may be limited by LVAD-related complications such as stroke that negatively impacts on the QOL.

A Case of an Increase in Prothrombin Time-International Normalized Ratio by Interaction Between Warfarin and Baloxavir Marboxil in a Patient on Implantable Ventricular Assist Device.

BACKGROUND: Baloxavir marboxil (BM) is a novel drug with a cap-dependent endonuclease inhibitory action for influenza A or B; it is highly safe and requires just a single oral dose. Patients with severe heart failure use implantable ventricular assist device (iVAD) until transplantation, but they have an increased risk of thrombosis development. Their warfarin is administered based on point-of-care testing (POCT) with a strict control of prothrombin time-international normalized ratio (PT-INR). CASE REPORT: Here, we report a case of a patient with iVAD whose PT-INR was significantly increased from the target range after BM administration. The patient was a 45-year-old man and transplanted with iVAD; warfarin treatment was started when his PT-INR target range was 3.0-3.5. At home, he frequently self-measured PT-INR by POCT and precisely controlled the warfarin dose. He had a fever, was diagnosed with influenza A and was administered BM 40 mg. Thereafter, his PT-INR continued to increase, reaching 4.8 on day 12 of BM administration, exceeding his target range; warfarin was skipped for 1 day. In this case, based on the history of BM administration and clinical course, the increase in PT-INR could be due to BM. Considering the interaction between warfarin and BM, we suspected a possibility of competition for protein-binding sites. Increased PT-INR in the patient was detected early by POCT and thus severe bleeding was avoided. CONCLUSION: Strict monitoring of PT-INR when using BM in patients taking warfarin is of clinical importance.

Aortic Insufficiency Causes Symptomatic Heart Failure during Left Ventricular Assist Device Support.

De novo aortic insufficiency is often documented during long-term left ventricular assist device (LVAD) support, despite the absence of aortic insufficiency at the time of LVAD implantation. However, whether aortic insufficiency affects long-term mortality and symptomatic heart failure in LVAD-supported patients remains controversial. We aimed to examine whether aortic insufficiency development influenced mortality and symptomatic heart failure following LVAD implantation. Fifty-three patients who underwent durable LVAD implantation between January 1, 2008 and April 31, 2017 were retrospectively examined in a single center institute. After discharge, we performed the echocardiographic examination in accordance with the Japanese registry for the mechanically assisted circulatory support protocol. Aortic insufficiency was graded on an interval scale (severe = 4, moderate = 3, mild = 2, trivial or none = 1). Kaplan-Meier estimates for long-term mortality at the follow-up were generated. We used a logistic regression model to identify risk factors for symptomatic heart failure. The overall median duration of LVAD support was 856.3 ± 430.8 days (range, 12-1,744 days). We did not observe a significant difference in long-term mortality in patients with aortic insufficiency ≥ 3 grade compared with patients with aortic insufficiency < 3 grade (P = 0.767; log-rank). Aortic insufficiency was associated with an increased risk for heart failure event after discharge (odds ratio, 4.12; confidence interval, 1.48-16.93; P = 0.005). Aortic insufficiency was an independent risk factor for symptomatic heart failure and was not associated with long-term mortality. Aortic insufficiency progression was associated with symptomatic heart failure.

The incidence, risk factors, and outcomes of gastrointestinal bleeding in patients with a left ventricular assist device: a Japanese single-center cohort study.

Continuous flow-left ventricular assist devices (CF-LVADs) have become a therapeutic option in the management of advanced heart failure. Several studies show that patients with CF-LVAD are at an increased risk of gastrointestinal bleeding (GIB). However, few reports have presented the characteristics of GIB in Japanese populations. We investigated the incidence, etiology, and outcome of GIB in patients with CF-LVAD. Records of adult patients who received CF-LVADs between October 2008 and January 2017 were reviewed. GIB was defined as detection of bleeding sites by any type of diagnostic imaging. 54 patients received CF-LVAD, of which eight (14%) presented with overt GIB (12 events). GIB patients are significantly older (p = 0.04) and their pre-operative inferior vena cava diameter was larger (p = 0.02). Multivariate analysis revealed that the use of Jarvik 2000 (p = 0.003) was a risk factor for GIB. In total, 85.8% of patients were free from GIB at 1 year. The most common site was the small intestine (67%). The most common cause was angiodysplasia (50%). Six patients required blood transfusion (nine events) and four underwent endoscopic clippings (five events); however, no patients needed surgeries. The incidence of GIB in our cohort was similar to the global registry data. Double balloon endoscopy is useful for diagnosis and treatment of small intestinal lesions. Future efforts to further understand the incidence of GIB in Japanese populations by multicenter data are needed.

[Effects of Olmesartan Medoxomil on Patients with Thoracic and Thoracoabdominal Aortic Aneurysm;Evaluation of Anti-hypertensive Effect and Possible Suppression of Aneurysmal Dilation( OLM 40 Study)].

We evaluated the blood pressure( BP) lowering effect and possible suppression of aortic enlargement by olmesartan (OLM) in patients with thoracic and thoracoabdominal aortic aneurysm. In this single center prospective, forced titration study, 50 patients were registered between 2008 and 2011. After all patients received any of OLM 10, 20, and 40 mg/day as an initial dose, the dosage of OLM was titrated up to 40 mg as needed during follow-up period. Home BP (HBPs), aortic aneurysm size assessed by computed tomography (CT) scan, indices of renal function were recorded at 3- and 6-months follow-up. Depending on whether 40 mg/day of prescription was continued for more than 4 months or not, the patients were divided into 2 groups:less than 40 mg (<40 mg) and 40 mg groups. Morning HBPs tended to decrease in both groups, and the percent changes in BPs were essentially the same regardless of dosage. The absolute value of aortic diameter tended to slightly enlarge only in <40 mg group. Also in the <40 mg group, the absolute differences in aortic diameter between those at the time of study registration and each follow-up were 0.5±1.8 mm at 3-month and 1.2±2.3 mm at 6-month (p=0.047),whereas the percent changes were 0.9±3.3% and 2.2±4.5% at 3 and 6 months, respectively( p=0.058). As for 40 mg group, the absolute differences and percent changes did not reach statistically significant increase during the follow-up period. No severe renal dysfunction related to OLM 40 mg prescription was observed. Our results imply that OLM 40 mg may suppress aortic aneurysmal dilation independently of blood pressure lowering effect. Further study with larger number of sample size is warranted to assure this observation.

Small GTP-Binding Protein GDP Dissociation Stimulator Prevents Thoracic Aortic Aneurysm Formation and Rupture by Phenotypic Preservation of Aortic Smooth Muscle Cells.

BACKGROUND: Thoracic aortic aneurysm (TAA) and dissection are fatal diseases that cause aortic rupture and sudden death. The small GTP-binding protein GDP dissociation stimulator (SmgGDS) is a crucial mediator of the pleiotropic effects of statins. Previous studies revealed that reduced force generation in aortic smooth muscle cells (AoSMCs) causes TAA and thoracic aortic dissection. METHODS: To examine the role of SmgGDS in TAA formation, we used an angiotensin II (1000 ng·min-1·kg-1, 4 weeks)-induced TAA model. RESULTS: We found that 33% of Apoe-/- SmgGDS+/- mice died suddenly as a result of TAA rupture, whereas there was no TAA rupture in Apoe-/- control mice. In contrast, there was no significant difference in the ratio of abdominal aortic aneurysm rupture between the 2 genotypes. We performed ultrasound imaging every week to follow up the serial changes in aortic diameters. The diameter of the ascending aorta progressively increased in Apoe-/- SmgGDS+/- mice compared with Apoe-/- mice, whereas that of the abdominal aorta remained comparable between the 2 genotypes. Histological analysis of Apoe-/- SmgGDS+/- mice showed dissections of major thoracic aorta in the early phase of angiotensin II infusion (day 3 to 5) and more severe elastin degradation compared with Apoe-/- mice. Mechanistically, Apoe-/- SmgGDS+/- mice showed significantly higher levels of oxidative stress, matrix metalloproteinases, and inflammatory cell migration in the ascending aorta compared with Apoe-/- mice. For mechanistic analyses, we primary cultured AoSMCs from the 2 genotypes. After angiotensin II (100 nmol/L) treatment for 24 hours, Apoe-/- SmgGDS+/- AoSMCs showed significantly increased matrix metalloproteinase activity and oxidative stress levels compared with Apoe-/- AoSMCs. In addition, SmgGDS deficiency increased cytokines/chemokines and growth factors in AoSMCs. Moreover, expressions of fibrillin-1 ( FBN1), α-smooth muscle actin ( ACTA2), myosin-11 ( MYH11), MYLLK, and PRKG1, which are force generation genes, were significantly reduced in Apoe-/- SmgGDS+/- AoSMCs compared with Apoe-/- AoSMCs. A similar tendency was noted in AoSMCs from patients with TAA compared with those from control subjects. Finally, local delivery of the SmgGDS gene construct reversed the dilation of the ascending aorta in Apoe-/- SmgGDS+/- mice. CONCLUSIONS: These results suggest that SmgGDS is a novel therapeutic target for the prevention and treatment of TAA.

[Splenic Injury during Replacement of the Thoracoabdominal Aorta].

Extraperitoneal approach is commonly employed for thoracoabdominal aortic repair via Stoney incision. It is supposedly rare to encounter abdominal visceral bleeding during that procedure. However, the spleen may spontaneously adhere to the adjacent peritoneum, which could induce incidental injury to the spleen by its anterior mobilization during extraperitoneal approach. Unless we bare its potential risk in mind, bleeding from the spleen may be overlooked, which results in hemodynamic deterioration. We have experienced 3 cases of splenic injury that necessitated hemostatic maneuvers for bleeding during and just after the thoracoabdominal aortic repair.

Evidence of Pulmonary Vascular Reverse Remodeling After Pulmonary Artery Banding Performed in Early Infancy in Patients With Congenital Heart Defects.

BACKGROUND: Histomorphometric evidence of the effect of pulmonary artery banding (PAB) in infancy on pulmonary vascular reverse remodeling has not been fully described.Methods and Results:We retrospectively reviewed 34 patients who underwent serial lung biopsies before and after PAB.Index of pulmonary vascular disease (IPVD) as a measure of the degree of progression of pulmonary arteriopathy significantly decreased after PAB (1.22±0.25 at 1st and 1.13±0.21 at 2nd biopsy, P=0.04). Additionally,DR=100 µmas an indicator of medial thickness of pulmonary arteries significantly decreased after PAB (15.6±3.7 at 1st and 11.4±2.6 at 2nd biopsy, P<0.0001). Patients were divided into 3 groups by age at PAB: <3 months (Group 1), between 3 and 6 months (Group 2), and >6 months (Group 3). The average secondDR=100 µmof groups 1 and 2 was significantly lower than that of group 3 (11.1±2.2 and 9.8±2.0 vs. 14.9±2.8, respectively; P<0.0001). Additionally, the second IPVD was also significantly lower in groups 1 and 2 than in group 3 (1.1±0.2 and 1.1±0.2 vs. 1.3±0.4, respectively; P=0.02). CONCLUSIONS: Histomorphometric evidence of post-PAB pulmonary vascular reverse remodeling is robust. The magnitude of vascular reversibility is pronounced when PAB is performed before 6 months of age.

Is Trisomy 21 a Risk Factor for Rapid Progression of Pulmonary Arteriopathy?　- Revisiting Histopathological Characteristics Using 282 Lung Biopsy Specimens.

BACKGROUND: Pulmonary hypertension (PH) is more progressive in trisomy 21 patients. However, pulmonary arteriopathic lesions in these patients have not been fully characterized histopathologically.Methods and Results:A retrospective review of a lung biopsy registry identified 282 patients: 188 patients with trisomy 21 (Group D) and 94 without (Group N). The mean age at lung biopsy was 3 and 7 months (P<0.0001). Pulmonary arterial pressure (PAP) and pulmonary vascular resistance were similar between the 2 groups. There were no significant differences in the proportion of patients with irreversible intimal lesions or the index of pulmonary vascular disease (IPVD; a measure of the degree of pulmonary arteriopathy progression) between the 2 groups. In addition, after propensity score matching for patient background (n=43 in each group), there were no significant differences in IPVD (P=0.29) or the ratio of irreversible intimal changes between the D and N groups (P=0.39). Multivariate analysis identified age (P<0.0001) and PAP (P=0.03) as the only risk factors for progression of pulmonary arteriopathy. CONCLUSIONS: Histopathologically, early progression of pulmonary arteriopathy in patients with trisomy 21 was not proved compared with patients without trisomy 21. Although we cannot exclude the possibility of bias in the Group D and N patients who were slated for lung biopsy, factors other than pulmonary arteriopathy may affect the marked progression of clinical PH in trisomy 21 patients.

Application of actuator-driven pulsed water jet for coronary artery bypass grafting: assessment in a swine model.

Actuator-driven pulsed water-jet (ADPJ) dissection is an emerging surgical method for dissecting tissue without heat and mechanical injury to vessels. We elucidated the mechanical properties of the piezo ADPJ and evaluated its usefulness and safety in coronary artery bypass grafting procedures. The relationship between the input voltage (10-100 V) and peak pressure of the pulsed water jet was evaluated. The tissue strengths of swine internal thoracic and coronary arteries and the surrounding tissues were measured to assure tissue-selective dissection. Internal thoracic arteries were harvested by conventional electric cautery and the water jet in four swine, and eight coronary arteries surrounded by myocardium were attempted to be exposed with the water jet. The dissected specimens were histologically evaluated. The peak pressure of the pulsed water jet was positively correlated with the input voltage (R 2 = 0.9984, P < 0.001). The breaking strengths of the target vessels (internal thoracic and coronary arteries) and the surrounding tissues were significantly different (P = 0.002 and P < 0.001, respectively). Histologic examination revealed that internal thoracic arteries were isolated with less heat damage using the pulsed water jet (P = 0.002) compared with electric cautery, and coronary arteries also were dissected without apparent histologic damage. ADPJ has the possibility of assuring tissue selectivity among the internal thoracic and coronary arteries. The results also indicated that the use of ADPJ may enhance safe procedures to harvest grafts during coronary artery bypass grafting.

Predictors of the need for pacemaker implantation after the Cox maze IV procedure for atrial fibrillation.

PURPOSE: The Cox maze IV (CMIV) procedure is being used increasingly frequently for surgical ablation of atrial fibrillation (AF). This study aimed to identify the risk factors of the need for postoperative pacemaker implantation (PMI) after CMIV. METHODS: Preoperative, intraoperative, and postoperative data were retrospectively collected from 67 consecutive patients who underwent CMIV at our institution; 7 (10.4%) required PMI (as a treatment of brady AF or sick sinus syndrome). RESULTS: Patients who needed PMI tended to have lower preoperative heart rates than those who did not on a 12-lead electrocardiogram (ECG; 68.7 ± 11.6 vs. 79.1 ± 18.5 bpm, p = 0.07) and a 24-h ECG (94,772 ± 9800 vs. 109,854 ± 19,078 beats/day, p = 0.03). A multivariate analysis identified a low amplitude of the fibrillatory wave on preoperative ECG as a risk factor of PMI necessity after CMIV [odds ratio = 14.7; 95% confidence interval (CI) 1.9-324.7; p = 0.007] and internal use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) as a negative risk factor (odds ratio = 0.16; 95% CI 0.02-0.99; p = 0.049). CONCLUSIONS: A low amplitude of the fibrillatory wave was identified as a risk factor of PMI necessity, whereas the internal use of ACEIs/ARBs diminished the need for PMI. These factors should be considered before CMIV is performed.

[Preliminary Results with Implantation of Extracorporeal Ventricular Assist System without Sternotomy Incision].

Temporary mechanical circulatory support device has been highly advocated for severe cardiogenic shock patient. However, standard ventricular assist device (VAD) implantation is invasive procedure for these sick patients. Less-invasive cardiac procedures are known to be generally associated with many beneficial effects such as reduction of trauma, blood loss and risk of infection, and relatively short intensive care unit stay. Here we describe an alternative technique for less invasive extracorporeal VAD implantation.

Intractable bleeding tendency due to acquired von Willebrand syndrome after Jarvik 2000 implant.

A 61-year-old man was implanted with a Jarvik 2000, a continuous axial flow type left ventricular assist device (LVAD), for end-stage heart failure due to dilated cardiomyopathy. One month later, his postoperative course was complicated with intractable oozing-type gastrointestinal bleeding from multiple small shallow ulcers and erosions in the colon. In addition, repeated bleeding episodes were encountered at around thoracentesis site for pleural effusion. Hematological examination showed that platelet counts and coagulation factors were kept within normal ranges. We, thereafter, revealed remarkable loss of the large multimers of von Willebrand factors (VWFs), which might be closely associated with his intractable bleeding tendency.

Hemodynamics of a functional centrifugal-flow total artificial heart with functional atrial contraction in goats.

Implantation of a total artificial heart (TAH) is one of the therapeutic options for the treatment of patients with end-stage biventricular heart failure. There is no report on the hemodynamics of the functional centrifugal-flow TAH with functional atrial contraction (fCFTAH). We evaluated the effects of pulsatile flow by atrial contraction in acute animal models. The goats received fCFTAH that we created from two centrifugal-flow ventricular assist devices. Some hemodynamic parameters maintained acceptable levels: heart rate 115.5 ± 26.3 bpm, aortic pressure 83.5 ± 10.1 mmHg, left atrial pressure 18.0 ± 5.9 mmHg, pulmonary pressure 28.5 ± 9.7 mmHg, right atrial pressure 13.6 ± 5.2 mmHg, pump flow 4.0 ± 1.1 L/min (left) 3.9 ± 1.1 L/min (right), and cardiac index 2.13 ± 0.14 L/min/m(2). fCFTAH with atrial contraction was able to maintain the TAH circulation by forming a pulsatile flow in acute animal experiments. Taking the left and right flow rate balance using the low internal pressure loss of the VAD pumps may be easier than by other pumps having considerable internal pressure loss. We showed that the remnant atrial contraction effected the flow rate change of the centrifugal pump, and the atrial contraction waves reflected the heart rate. These results indicate that remnant atria had the possibility to preserve autonomic function in fCFTAH. We may control fCFTAH by reflecting the autonomic function, which is estimated with the flow rate change of the centrifugal pump.

Poly-2-methoxyethylacrylate-coated cardiopulmonary bypass circuit can reduce transfusion of platelet products compared to heparin-coated circuit during aortic arch surgery.

Several coating techniques for extracorporeal circulation have been developed to reduce the systemic inflammatory response during cardiopulmonary bypass (CPB). We compared the clinical effectiveness and biocompatibility of poly-2-methoxyethylacrylate (PMEA)- and heparin-coated CPB circuits in total aortic arch replacement (TAR) with the prolonged use of the bypass technique. Twenty patients who underwent elective TAR were divided randomly into two equal groups: group P (n = 10) to use PMEA-coated circuits and group H (n = 10) to use heparin-coated circuits. Clinical outcomes, hematological variables, and acute phase inflammatory response were analyzed perioperatively. Demographic, CPB, and clinical outcome data were similar for both groups. Hemoglobin and platelet count showed similar time-course curves. However, the amount of platelet products transfused intraoperatively was significantly larger in group H (group P 26.0 ± 7.0 units; group H 33.0 ± 6.7 units, p = 0.04). Total protein, and albumin levels were significantly higher in group P during and after the operation (total protein, p = 0.04; albumin, p = 0.02). The use of PMEA-coated circuit is associated with retainment of perioperative plasma proteins levels and may help to reduce transfusion of platelet products in TAR in comparison with the heparin-coated circuit.

Graft placement with an omental flap for ruptured infective common iliac aneurysm in a patient with a continuous flow left ventricular assist device: alternative surgical approach avoiding driveline injury and pathogen identification by 16S ribosomal DNA gene analysis.

Patients supported by mechanical circulatory support have to wait for longer periods for heart transplantation in Japan. Infective events are a major complication and influence survival. Here, we present the case of a patient with an implantable left ventricular assist device for 6 months who had the complication of ruptured infective common iliac aneurysm. Graft placement with an omental flap was successfully performed via the alternative surgical approach to avoid percutaneous driveline injury. In samples of aortic specimens, 16S ribosomal DNA gene analysis identified Helicobacter cinaedi. Complete removal of the infected tissue and correct pathogen identification may have been relevant to the good clinical course.

Management of three cardiogenic pulmonary edemas occurring in a patient scheduled for left ventricular assist device implantation: indicators for determining left ventricular assist device pump speed.

A male patient with Marfan syndrome underwent aortic root replacement and developed left ventricular (LV) failure. Four years later, he underwent aortic arch and aortic valve replacement. Thereafter, his LV failure progressed, and cardiogenic pulmonary edema (CPE) appeared, which we treated with extracorporeal LV assist device (LVAD) placement. Three months later, the patient developed aspiration pneumonia, which caused hyperdynamic right ventricle (RV) and CPE. We treated by changing his pneumatic LVAD to a high-flow centrifugal pump. A month later, he underwent thoracoabdominal aortic replacement. After four weeks, he developed septic thrombosis and LVAD failure, which caused CPE. We treated with LVAD circuit replacement and an additional membrane oxygenator. Four months later, he underwent DuraHeart(®) implantation. During this course, pulmonary artery wedge pressure (PAWP) varied markedly. Additionally, systolic pulmonary artery pressure (sPAP), left atrial diameter (LAD), RV end-diastolic diameter (RVEDD) and estimated RV systolic pressure (esRVP) changed with PAWP changes. In this patient, LV failure and hyperdynamic RV caused the CPEs, which we treated by adjusting the LVAD output to the RV output. Determining LVAD output, RV function and LV end-diastolic diameter are typically referred, and PAWP, LAD, RVEDD, and sPAP could be also referred.

[Preoperative Use of Tolvaptan in a Patient with Constrictive Pericarditis].

Tolvaptan is a new selective vasopression V2-receptor antagonist. We report our experience with a use of tolvaptan for preoperative fluid management in a patient with severe constrictive pericarditis. A 66-year-old man presented with heart failure symptoms derived from constrictive pericarditis. Chest X-ray showed right pleural effusion and chest computed tomography demonstrated severe pericardial calcification. Despite that he received optimal conventional medical treatments, his hemodynamic condition further exacerbated during hospitalization. We administered tolvaptan in an attempt to optimize preoperative fluid management. Tolvaptan was found to be remarkably effective in that regard. The body weight decreased and the heart failure symptoms improved. Pericardiectomy was performed successfully, and he recovered uneventfully.