Impact of Baseline Mitral Regurgitation on Postoperative Outcomes After Left Ventricular Assist Device Implantation as Destination Therapy.

BACKGROUND: Currently, there are no guidelines for management of moderate to severe mitral regurgitation (MR) in patients undergoing left ventricular assist device (LVAD) implantation. The present study aimed to investigate the impact of baseline MR on short and midterm survival in patients who had LVAD as destination therapy (DT). METHODS: The DT-LVAD patients were classified into 2 groups based on baseline MR status: ≥ moderate MR and < moderate MR. Baseline clinical characteristics and post-LVAD implant adverse events were compared. Unadjusted mortality rates at 30 days, 1 year, and 2 years were analyzed. RESULTS: Of 91 patients studied, 62 (68%) had ≥ moderate MR before LVAD implantation; ≥ moderate MR patients had a higher incidence of concomitant pulmonary disease (11% vs 0%; P = .001) and ≥ moderate tricuspid regurgitation (55% vs 23%, P = .004) than < moderate MR patients. Other baseline clinical characteristics were similar in both groups. Post-LVAD adverse events did not differ between the 2 groups. Survival rates at 30 days, 1 year, and 2 years for both groups (≥ moderate MR vs < moderate MR) were 90% vs 100% (P = .03), 63% vs 90% (P = .001), and 52% vs 83% (P = .002), respectively. On multivariable analysis, age, female sex, ≥ moderate tricuspid regurgitation, and ≥ moderate MR at baseline were found to be independent predictors of overall all-cause mortality. Overall survival was significantly lower in the ≥ moderate MR group than the < moderate MR group (log-rank test, P = .03). CONCLUSION: In DT LVAD patients, ≥ moderate MR is common and is associated with worse survival at both short and midterm follow-up.

Left ventricular assist device in patients with body mass index greater than 30 as bridge to weight loss and heart transplant candidacy.

INTRODUCTION: In obese patients with heart failure, weight reduction may be difficult due to physical restrictions, but may be necessary to achieve heart transplant candidacy. We report the outcomes of obese patients who underwent implantation of a left ventricular assist device (LVAD) using a pulsatile (HeartMate XVE [XVE]) or continuous flow (HeartMate II [HMII]) design and the effect on body mass index (BMI). METHODS: Of 37 patients with BMI >30 kg/m(2) who underwent LVAD implantation, 29 survived at least 30 days and were followed for weight change. In the 30-day survivors, end points of the study were continued LVAD support, heart transplant, or death. One patient underwent gastric bypass surgery and was excluded. RESULTS: In the 28 patients who met inclusion criteria, BMI was 35.6 ± 4.4 kg/m(2) at baseline, and at follow-up was 33.1 ± 5.5 kg/m(2) (mean BMI change -2.5 kg/m(2); P = .063), with a mean follow-up time of 301.6 ± 255.5 days. The XVE group showed a significant BMI reduction of 3.9 kg/m(2) (P = .016 vs baseline); however, the HMII group showed 0.1 kg/m(2) increase in BMI. BMI <30 kg/m(2) at follow-up was achieved in 6 patients (21%), 5 of 19 (26%) in XVE group, and 1 of 9 (11%) in HMII group. In the 14 patients (12 XVE, 2 HMII) or 50% who received a heart transplant, the mean decrease in BMI was 4.6 kg/m(2) (P = .003). CONCLUSIONS: LVAD placement in patients with BMI >30 kg/m(2) provided significant weight loss in the pulsatile XVE group, but not in recipients of the continuous flow HMII. In patients successfully bridged to a heart transplant after LVAD insertion, mean reduction in BMI was 4.6 kg/m(2) (P = .003). LVAD implantation provides a period of hemodynamic support for obese patients with advanced heart failure, during which time opportunity may be available for weight loss. Pulsatile devices appear to be associated with greater weight loss than nonpulsatile continuous flow devices. Additional therapies may be necessary to achieve significant weight loss in recipients of the continuous flow LVAD.

Use of ventricular assist device as bridge to simultaneous heart and kidney transplantation in patients with cardiac and renal failure.

BACKGROUND: Ventricular assist device (VAD) implantation as a bridge to cardiac transplantation is an effective treatment option for end-stage heart failure. Renal dysfunction is not uncommon but is considered to be a poor prognostic factor. We present our experience with 6 patients who had combined heart and kidney transplantation (HKT) after VAD implantation for advanced cardiac and renal failure. METHODS: Of 74 patients who underwent VAD implantation as a bridge to transplant from May 2001 to September 2009, 28 patients developed renal failure, and of these, 6 (5 male, 1 female, ages 40-64 years) had HKT. All required hemodialysis because of renal failure before HKT. Immunosuppression consisted of anti-thymocyte globulin followed by triple drug therapy consisting of calcineurin inhibitors, mycophenolate, and corticosteroids. RESULTS: Of the 6 HKT patients, 5 (83%) were alive without hemodialysis at 1 and 2 years; of the 22 patients with renal failure after VAD implantation without subsequent transplant, 1- and 2-year survivals were zero. Interval from VAD implantation to HKT ranged from 36 to 366 days (133 ± 127 days). At 6 months after HKT (100% alive), left ventricular ejection fraction was 60.2 ± 5.8% and serum creatinine 1.1 ± 0.2 mg/dL. Three HKT patients required temporary hemodialysis after surgery. Endomyocardial biopsy showed absence of ISHLT grade 2R-3A or greater cellular rejection, and none showed evidence of definite antibody-mediated rejection. CONCLUSIONS: Based on our initial experience, simultaneous HKT is a safe treatment option with excellent outcomes for patients with advanced heart failure and persistent renal dysfunction after VAD implantation.

Cloning, gene structure and dietary regulation of the type-IIc Na/Pi cotransporter in the mouse kidney.

We have demonstrated previously that the type-IIc Na/Pi cotransporter is a growth-related renal Na/Pi cotransporter that is highly expressed in kidney of the weaning rat. In the present study, we investigated type-IIc Na/Pi cotransporter function further by cloning the mouse gene and characterizing the corresponding protein. The mouse type-IIc transporter amino acid sequence shows a high degree of similarity to the human (86%) and rat (95%) type-IIc Na/Pi-cotransporters. The mouse gene contained 14 exons and mapped to chromosome 2. The DNA sequence upstream from exon 1 is GC rich. The upstream region does not contain an apparent TATA box, but does contain two dietary Pi-responsive elements, which are potential binding sites for the transcription factor micro E3 (TFE3). Microinjection of mouse type-IIc cRNA into Xenopus oocytes demonstrated sodium-dependent Pi cotransport activity. The affinity for Pi was about 200 microM in 100 mM Na. Feeding adult mice fed a low-Pi diet increased the expression of type-IIc protein in the apical membrane of renal proximal tubular cells. Hybrid depletion studies suggested that the type-IIc transporter contributes to about 30% of Na/Pi cotransport in the kidney of adult mice fed a low-Pi diet. The present study suggests that the type-IIc Na/Pi cotransporter is a functional of renal Pi transporter in adult mice fed a low-Pi diet.

Regional differences in myocardial work of the left ventricle in patients with idiopathic dilated cardiomyopathy: Implications for the surgical technique used for left ventriculoplasty.

OBJECTIVES: In this study we measured regional myocardial work of the left ventricle in patients with dilated cardiomyopathy and examined the existence of regional differences in myocardial work. BACKGROUND: Left ventriculoplasty aims to improve the ejection fraction by excluding a region with decreased wall motion and decreasing wall tension. If regional differences in myocardial work are present, left ventriculoplasty will be more effective when a region with decreased myocardial work is excluded. METHODS: The study group consisted of 10 patients with idiopathic dilated cardiomyopathy. Regional work of the ventricle normalized to a unit volume of myocardium (RWM) is given as follows: RWM = -integral sigma(d)[ln(1/H)], where sigma is mean wall stress, and H is wall thickness of the region. After right-sided catheterization, left ventricular pressure was measured with a 3F micromanometer catheter. Echocardiography was performed simultaneously, and a short-axis view of the left ventricle at the level of the papillary muscles was obtained. The derived M-mode image was recorded with left ventricular pressure. sigma-ln(1/H) relations for the ventricle were delineated, and regional work of the interventricular septum and posteroinferior wall were determined. Relationships between regional work of the myocardium and wall thickness, interventricular septal regional work of the myocardium and right ventricular systolic pressure, and right ventricular ejection fraction were also studied. RESULTS: Interventricular septal regional work ranged from -0.84 to 3.34 mJ/cm3 (0.74 +/- 1.51 mJ/cm3). Posteroinferior wall regional work ranged from 1.59 to 4.29 mJ/cm3 (2.77 +/- 0.86 mJ/cm3). In the study group, interventricular septal regional work was lower than posteroinferior wall regional work (P <.05). In 8 of these 10 patients, interventricular septal regional work was lower than posteroinferior wall regional work. In the other 2 patients, conversely, interventricular septal regional work was higher than posteroinferior wall regional work. CONCLUSIONS: The existence of differences in regional work between the interventricular septum and the posteroinferior wall suggests the importance of the evaluation of regional work in the selection of an effective treatment for dilated cardiomyopathy.