Teruhiko Imamura

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.

Experience of a Vasopressin Receptor Antagonist, Tolvaptan, Under the Unique Indication in Japanese Heart Failure Patients

Tolvaptan is a vasopressin type 2 receptor antagonist. Currently, tolvaptan is indicated for the treatment of severe hyponatremia in most countries, including the United States, but in Japan the indication is broader; it can be used in congestive heart failure patients in addition to standard or optimal diuretic therapy, regardless of their serum sodium levels or systolic function. Our review of this newly introduced drug is based on our experience in Japan.

Urine Aquaporin-2: A Promising Marker of Response to the Arginine Vasopressin Type-2 Antagonist, Tolvaptan in Patients with Congestive Heart Failure

Aquaporin-2, a member of the aquaporin family, is an arginine vasopressin-regulated water channel expressed in the renal collecting duct, and a promising marker of the concentrating and diluting ability of the kidney. The arginine vasopressin type-2 antagonist, tolvaptan, is a new-generation diuretic; it is especially indicated in patients with decompensated heart failure refractory to conventional diuretics. However, the ideal responders to tolvaptan have not yet been identified, and non-responders experience worse clinical courses despite treatment with tolvaptan. Urine aquaporin-2 has recently been demonstrated as a promising predictor of response to tolvaptan. We here validated aquaporin-2-guided tolvaptan therapy in patients with decompensated heart failure. Long-term efficacy of tolvaptan treatment in the responders defined by aquaporin-2 needs to be validated in the future prospective study.

Waon Therapy for Managing Chronic Heart Failure – Results From a Multicenter Prospective Randomized WAON-CHF Study –

BACKGROUND Waon therapy improves heart failure (HF) symptoms, but further evidence in patients with advanced HF remains uncertain. METHODSANDRESULTS In 19 institutes, we prospectively enrolled hospitalized patients with advanced HF, who had plasma levels of B-type natriuretic peptide (BNP) >500 pg/ml on admission and BNP >300 pg/ml regardless of more than 1 week of medical therapy. Enrolled patients were randomized into Waon therapy or control groups. Waon therapy was performed once daily for 10 days with a far infrared-ray dry sauna maintained at 60℃ for 15 min, followed by bed rest for 30 min covered with a blanket. The primary endpoint was the ratio of BNP before and after treatment. In total, 76 Waon therapy and 73 control patients (mean age 66 years, men 61%, mean plasma BNP 777 pg/ml) were studied. The groups differed only in body mass index and the frequency of diabetes. The plasma BNP, NYHA classification, 6-min walk distance (6MWD), and cardiothoracic ratio significantly improved only in the Waon therapy group. Improvements in NYHA classification, 6MWD, and cardiothoracic ratio were significant in the Waon therapy group, although the change in plasma BNP did not reach statistical significance. No serious adverse events were observed in either group. CONCLUSIONS Waon therapy, a holistic soothing warmth therapy, showed clinical advantages in safety and efficacy among patients with advanced HF.

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.

Bosentan improved persistent pulmonary hypertension in a case after implantation of a left ventricular assist device

No medical treatment has been established to ameliorate pulmonary hypertension (PH) due to left heart disease. Heart transplantation (HTx) is thus far the definitive therapy for stage D heart failure, but concomitant PH is one of the major risk factors for death after HTx. Recently, implantation of a left ventricular assist device (LVAD) has been reported to improve PH and has become a major bridge tool for HTx. We experienced a rare case with persistent PH even after the implantation of a continuous-flow LVAD. The administration of an endothelin receptor antagonist, bosentan, significantly decreased pulmonary vascular resistance. Combination therapy with LVAD implantation and anti-PH medication may be useful for patients with stage D heart failure complicated with severe PH.

Platelet-Derived Growth Factor Receptor-Tyrosine Kinase Inhibitor, Imatinib, Is Effective for Treating Pulmonary Hypertension Induced by Pulmonary Tumor Thrombotic Microangiopathy

Pulmonary hypertension (PH) induced by pulmonary tumor thrombotic microangiopathy (PTTM) can be fatal because its rapid progression confounds diagnosis, and it is difficult to control with therapy. Here we describe a woman with symptomatic PTTM-PH accompanying gastric cancer that was suspected from perfusion scintigraphy. PTTM-PH was diagnosed by gastroesophageal endoscopy and lung biopsy after partial control of PH using the platelet-derived growth factor (PDGF) receptor (PDGFR) tyrosine kinase inhibitor, imatinib. Treatment with sildenafil and ambrisentan further decreased PH, and she underwent total gastrectomy followed by adjuvant TS-1 chemotherapy. PH did not recur before her death from metastasis. Postmortem histopathology showed recanalized pulmonary arteries where the embolized cancer masses disappeared. PDGF-A, -B, and PDGFR-α, β expression was detected in cancer cells and proliferating pulmonary vascular endothelial cells. Thus, PTTM-PH was successfully controlled using a combination of imatinib, drugs to treat pulmonary arterial hypertension, and cancer management.

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.