Kan Nawata

Aortic Insufficiency in Patients With Sustained Left Ventricular Systolic Dysfunction After Axial Flow Assist Device Implantation

BACKGROUND Predicting the occurrence of aortic insufficiency (AI) during left ventricular assist device (LVAD) support has remained unsolved. METHODS AND RESULTS We enrolled 52 patients who had received continuous flow LVAD (14 axial and 38 centrifugal pumps) and who been followed for ≥6 months between Jun 2006 and Dec 2013. Native aortic valve (AV) opening was observed in 18 patients (35%) with improved LV systolic function, and none of them had AI. On multivariate logistic regression analysis preoperative shorter heart failure duration was the only independent predictor of postoperative native AV opening (P=0.042; odds ratio [OR], 0.999). Of the remaining 34 patients (65%) with closed AV, 11 had AI with enlargement of the aortic root and narrow pulse pressure. Among those with closed AV, axial pump use (n=13) was the only significant predictor of the development of AI (P=0.042; OR, 4.950). Patients with AI had lower exercise capacity and a higher readmission rate than those without AI during 2-year LVAD support (55% vs. 8%; P<0.001). CONCLUSIONS Native AV opening during LVAD support is profoundly associated with reversal of LV systolic function, especially in patients with preoperative shorter heart failure duration. Among those in whom the native AV remains closed, low pulsatility of axial flow pump may facilitate aortic root remodeling and post-LVAD AI development that results in worse clinical outcome.

Prophylactic Intra-Aortic Balloon Pump Before Ventricular Assist Device Implantation Reduces Perioperative Medical Expenses and Improves Postoperative Clinical Course in INTERMACS Profile 2 Patients

BACKGROUND Although intra-aortic balloon pump (IABP) is sometimes used before cardiac surgery to achieve better outcome in high-risk patients, the clinical impact of prophylactic IABP support before left ventricular assist device (LVAD) implantation in patients with worsening hemodynamics was unknown. METHODSANDRESULTS We enrolled 22 patients with worsening hemodynamics who had received IABP support before LVAD (IABP group), and also enrolled 22 patients receiving neither IABP nor extracorporeal membrane oxygenation before LVAD, who were selected on propensity score matching (non-IABP group). Although both groups had similar preoperative background, the IABP group had shorter postoperative intensive care unit (ICU) stay, and more improved hemodynamics (P<0.05 for all). Serum total bilirubin and creatinine decreased significantly in the IABP group compared with the non-IABP group during 1 month after LVAD implantation (P<0.05 for both). Medical expenses during perioperative ICU stay were significantly lower in the IABP group compared with the non-IABP group, even including the cost of preoperative IABP support (P<0.05). CONCLUSIONS Prophylactic IABP support in heart failure patients with worsening hemodynamics improves post-LVAD clinical course and reduces perioperative medical expenses.

Advantage of Pulsatility in Left Ventricular Reverse Remodeling and Aortic Insufficiency Prevention During Left Ventricular Assist Device Treatment

BACKGROUND A continuous flow (CF) left ventricular assist device (LVAD) has various advantages over a pulsatile flow (PF) LVAD, but the extent of preventing aortic insufficiency (AI) by each type of LVAD remains controversial. METHODSANDRESULTS Of 86 patients with non-ischemic cardiomyopathy who underwent LVAD implantation between 2006 and 2015, 20 propensity score-matched patients with PF LVADs and 20 with CF LVADs were enrolled in this study. There were no significant differences in the baseline variables of both groups. During the 6-month LVAD treatment, the LV ejection fraction of the PF group was significantly higher than that of the CF group; the PF group also had a wider pulse pressure and less enlargement of the aortic root (P<0.05 for all). Patients in the PF group experienced more frequent opening of the native aortic valve and less AI than those in the CF group (P<0.05 for both). The PF LVAD was explanted in 5 patients (25%), and a CF LVAD was explanted in 1 patient (5%). CONCLUSIONS Compared with CF LVADs, PF LVADs seem to have an advantage in improving LV reverse remodeling and preventing AI. It may be best to incorporate pulsatility into current CF LVADs while retaining their existing benefits.

Midterm outcome of implantable left ventricular assist devices as a bridge to transplantation: Single-center experience in Japan

BACKGROUND Two implantable continuous-flow left ventricular assist devices (LVADs), DuraHeart (Terumo Heart, Ann Arbor, MI, USA) and EVAHEART (Sun Medical, Nagano, Japan), were approved in Japan in April 2011. We analyzed the midterm outcome of patients implanted with these implantable LVADs at the University of Tokyo Hospital. METHODS AND RESULTS A total of 31 patients who underwent implantation of LVADs (10 DuraHeart, 21 EVAHEART) as a bridge to transplantation at our institution between April 2011 and August 2013 were retrospectively reviewed. All patients were followed up through December 2013. Seven patients underwent conversions from NIPRO paracorporeal LVAD (Nipro, Osaka, Japan) to an implantable LVAD. The mean observation period was 483±239 days (41.0 patient years). Eight patients were transplanted and one patient showed functional recovery with subsequent LVAD explantation. Four patients died due to cerebrovascular accident, empyema, or device malfunction due to pump thrombosis after cerebral bleeding. Kaplan-Meier analysis revealed 6-, 12-, and 24-month survival rates of 93%, 86%, and 86%, respectively. The rates of freedom from cerebrovascular accidents and device-related infections at 1 year after LVAD implantation were 65% and 36%, respectively. Twenty-nine patients were discharged home after LVAD implantation. During the period of this study, there were 59 readmissions (53 urgent, 6 elective) among 22 patients (76%). The overall and urgent readmission rates were 1.66 and 1.49 per patient year, respectively. The common reason for readmission was device-related infection (31%), followed by cerebrovascular accidents (17%). The total out-of-hospital time after the primary discharge was 90%. CONCLUSIONS Our midterm survival rate after LVAD implantation is satisfactory. However, patients undergoing LVAD support were often readmitted with adverse events.

Evaluating Japanese patients with the Marfan syndrome using high-throughput microarray-based mutational analysis of fibrillin-1 gene.

Marfan syndrome (MS) is an inherited connective tissue disorder, and detailed evaluations of multiple organ systems are required for its diagnosis. Genetic testing of the disease-causing fibrillin-1 gene (FBN1) is also important in this diagnostic scheme. The aim of this study was to define the clinical characteristics of Japanese patients with MS and enable the efficient and accurate diagnosis of MS with mutational analysis using a high-throughput microarray-based resequencing system. Fifty-three Japanese probands were recruited, and their clinical characteristics were evaluated using the Ghent criteria. For mutational analysis, an oligonucleotide microarray was designed to interrogate FBN1, and the entire exon and exon-intron boundaries of FBN1 were sequenced. Clinical evaluation revealed more pulmonary phenotypes and fewer skeletal phenotypes in Japanese patients with MS compared to Caucasians. The microarray-based resequencing system detected 35 kinds of mutations, including 23 new mutations. The mutation detection rate for patients who fulfilled the Ghent criteria reached 71%. Of note, splicing mutations accounted for 19% of all mutations, which is more than previously reported. In conclusion, this comprehensive approach successfully detected clinical phenotypes of Japanese patients with MS and demonstrated the usefulness and feasibility of this microarray-based high-throughput resequencing system for mutational analysis of MS.

Parasympathetic Reinnervation Accompanied by Improved Post-Exercise Heart Rate Recovery and Quality of Life in Heart Transplant Recipients

Although sympathetic reinnervation is accompanied by the improvement of exercise tolerability during the first years after heart transplantation (HTx), little is known about parasympathetic reinnervation and its clinical impact. We enrolled 21 recipients (40 ± 16 years, 71% male) who had received successive cardiopulmonary exercise testing at 6 months, and 1 and 2 years after HTx. Exercise parameters such as peak oxygen consumption or achieved maximum load remained unchanged, whereas recovery parameters including heart rate (HR) recovery during 2 minutes and the delay of peak HR, which are influenced by parasympathetic activity, improved significantly during post-HTx 2 years (P < 0.05 for both). HR variability was analysed at post-HTx 6 months in 18 recipients, and high frequency power, representing parasympathetic activity, was significantly associated with the 2 recovery parameters (P < 0.05 for all). We also assessed quality of life using the Minnesota Living with Heart Failure (HF) Questionnaire at post-HTx 6 months and 2 years in the same 18 recipients, and those with improved recovery parameters enjoyed a better HF-specific quality of life (P < 0.05 for both). In conclusion, parasympathetic reinnervation emerges along with improved post-exercise recovery ability of HR and quality of life during post-HTx 2 years.

Pathophysiology and Management of Cardiovascular Manifestations in Marfan and Loeys–Dietz Syndromes

Marfan syndrome (MFS) is an autosomal dominant heritable disorder of connective tissue that affects the cardiovascular, skeletal, ocular, pulmonary, and nervous systems and is usually caused by mutations in the FBN1 gene, which encodes fibrillin-1. MFS is traditionally considered to result from the structural weakness of connective tissue. However, recent investigations on molecular mechanisms indicate that increased transforming growth factor-β (TGF-β) activity plays a crucial role in the pathogenesis of MFS and related disorders, such as Loeys-Dietz syndrome (LDS), which is caused by mutation in TGF-β signaling-related genes. In addition, recent studies show that angiotensin II type 1 receptor (AT1R) signaling enhances cardiovascular pathologies in MFS, and the angiotensin II receptor blocker losartan has the potential to inhibit aortic aneurysm formation. However, the relationship between TGF-β and AT1R signaling pathways remains poorly characterized. In this review, we discuss the recent studies on the molecular mechanisms underlying cardiovascular manifestations of MFS and LDS and the ensuing strategies for management.

A deleterious MYH11 mutation causing familial thoracic aortic dissection.

The L1264P and R1275L heterozygous mutations of the myosin heavy chain 11 (MYH11) gene, which are on the same allele, have been reported to cause thoracic aortic aneurysms and/or dissections (TAAD) complicated with patent ductus arteriosus (PDA); however, their contributions to the pathogenesis of TAAD/PDA have not been elucidated. Here we report the first familial case of TAAD with only a MYH11 L1264P mutation, in which PDA was not observed, indicating that L1264P, not R1275L, is responsible for TAAD formation.

Novel scoring system using postoperative cardiopulmonary exercise testing predicts future explantation of left ventricular assist device

BACKGROUND Although cardiopulmonary exercise (CPX) testing is an established tool for predicting survival in patients with heart failure (HF), its prognostic impact on explantation of left ventricular assist device (LVAD) was unknown. METHODS AND RESULTS: We enrolled 33 patients who had undergone implantation of extracorporeal pulsatile flow LVAD and symptom-limited CPX testing at 3 months after operation, and who were followed between 2005 and 2014. Patients who received conversion to continuous flow LVAD were excluded. On Cox regression analysis, E1 (maximum load ≥51W; HR, 27.55), E2 (minute ventilation/carbon dioxide output [V̇E/V̇CO2] slope ≤34; HR, 16.86), and E3 (peak oxygen consumption [PV̇O2] ≥12.8 ml·kg(-1)·min(-1); HR, 18.35) significantly predicted explantation expectancy during 2 years after LVAD implantation (P<0.05 for all). Explantation score, the sum of positive E1-3, significantly stratified 2-year cumulative explantation rate into low (0 points), intermediate (1-2 points), and high (3 points) expectancy groups (0%, 29%, and 86%, respectively, P<0.001). When the scoring system was used for 45 patients with continuous flow LVAD, the 2 patients who had explantation were assigned to the high expectancy group. CONCLUSIONS Explantation score, calculated simply from 3 postoperative symptom-limited CPX testing parameters, is a novel tool to predict explantation expectancy of LVAD and to select good candidates for the weaning test.

Peripartum type B aortic dissection in patients with Marfan syndrome who underwent aortic root replacement: a case series study

To investigate pregnancy outcomes, especially the risk of pregnancy‐related aortic dissection (AD), in patients with Marfan syndrome (MFS) after prophylactic aortic root replacement (ARR).