Continuous invasive hemodynamic monitoring with an implantable device during biventricular mechanical support

COMMENTS AND OPINIONS Continuous invasive hemodynamic monitoring with an implantable device during biventricular mechanical support Riet Dierckx, MD, Marc Goethals, MD, and Marc Vanderheyden, MD From the Cardiovascular Center, OLV Hospital, Aalst, Belgium

‘‘Fixed’’ pulmonary hypertension (PH), defined as a mean pulmonary artery pressure (PAP) 425 mm Hg, a pulmonary vascular resistance (PVR) 42.5 Wood units (WU) and a transpulmonary gradient (TPG) 412 mm Hg after pharmacologic manipulation, is a contraindication for heart transplantation (HTx).1 Long-term mechanical unloading with a left ventricular assist device (LVAD) has been shown to lower PVR and reverse fixed PH,2–4 converting seemingly ineligible patients into potential transplant candidates. In this population, serial invasive assessment of pulmonary hemodynamics is of utmost importance. However, whereas PAP can still be measured accurately by right heart catheterization after LVAD implantation, this is not the case in patients with a biventricular assist device (biVAD) due to cannulation of the right atrium and the pulmonary artery. A 45-year-old woman with end-stage heart failure due to valvular cardiomyopathy was screened and listed for HTx. While waiting for HTx, her clinical situation deteriorated toward INTERMACS Level 3 and she underwent implantation of a biVAD as a bridge to transplantation. A biVAD was preferred over LVAD because of severe biventricular heart failure with renal and hepatic dysfunction. The last right heart catheterization, performed 6 weeks before surgery and under optimal medical therapy, showed a mean PAP of 26 mm Hg and a pulmonary capillary wedge pressure (PCWP) of 20 mm Hg, with TPG of 6 mm Hg and PVR of 2.2 WU. As this patient had an indwelling implantable hemodynamic monitor (IHM; Remon ImPressure, Remon Medical Technologies, now part of Boston Scientific), post-operative evolution of PAP could be followed. The ImPressure monitoring system includes a miniature implant, positioned percutaneously in the right pulmonary artery. Ultrasonic energy is used for wireless communication between an external hand-held unit and the implant. The PAPIRUS II trial has reported on the feasibility, safety and accuracy of the device.5 As demonstrated by the IHM, PAP increased temporarily after biVAD implantation due to a severe pulmonary infection.

Figure 1 Pulmonary artery pressure curves, recorded by the IHM (Remon) device. (A) PAP curves measured on the morning of May 16, 2011 [red circles in (B) and (C)], the day before biVAD implantation. (B) Diastolic PAP curves between March 2011 and February 2012. The black line marks the date of admission due to decompensated advanced heart failure. The patient was treated with intravenous diuretics and inotropics, resulting in a decrease in PAP. On May 17, a biVAD was implanted. After an initial rise—due to severe post-operative pulmonary infection—PAP dropped acutely and further decreased to 15.9/6.6 mm Hg (systolic/diastolic) at Day 1,800, 162 days after biVAD implantation. The blue line shows the date of admission with hypovolemic shock. Diastolic PAP was 9 mm Hg and dropped to 7 mm Hg (green line), followed by a rise after transfusion and surgery. (C) Evolution of the systolic PAP during the same time interval. After biVAD and after resolution of pulmonary infection, systolic PAP dropped from 45.2 to 24.5 mm Hg and further decreased to 15.9 mm Hg at Day 1,800, 162 days after biVAD. At the time of hypovolemic shock systolic PAP dropped from 18.2 (blue line) to 15.5 mm Hg (green line).

However, after recovery we noted a progressive decrease in systolic and diastolic PAP and normalization of renal and hepatic parameters together with clinical improvement (Figure 1). Seven months after biVAD implantation, the patient had severe hypovolemic shock caused by a ruptured ovarian cyst. As would be expected, this resulted in a further decrease in PAP (Figure 1). Right heart catheterization can be performed easily in patients with LVAD. However, due to cannulation of the pulmonary artery, invasive hemodynamic assessment is not feasible in patients with a biVAD or a total artificial heart (TAH). Although LVAD support has been shown to exert

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The Journal of Heart and Lung Transplantation, Vol 32, No 3, March 2013

beneficial effects on pulmonary hemodynamics, little is known about the evolution of PAP in patients with a biVAD or TAH. In the patient described herein, the presence of an IHM before biVAD implantation offered the unique opportunity to monitor invasively and continuously the evolution of PAP after biVAD. Although she did not have fixed PH, as demonstrated by right heart catheterization before biVAD implantation, the case is illustrative and clearly demonstrates that continuous monitoring of pulmonary artery pressures with the ImPressure device appears to be safe, feasible and useful. In addition, clinical events correlated with PAP, as measured by the device, providing valuable therapeutic information. We speculate that patients on hemodynamic support with a biVAD or TAH may benefit from implantation of an IHM to monitor pulmonary pressures and tailor therapy. Although this approach seems attractive, additional clinical research and further experience will be needed before advocating its use on a routine basis.

Disclosure statement The authors have no conflicts of interest to disclose.

References 1. Mehra MR, Kobashigawa J, Starling R, et al. Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates—2006. J Heart Lung Transplant 2006;25:1024-42. 2. Fang JC, DeMarco T, Givertz MM, et al. World Health Organization pulmonary hypertension group 2: Pulmonary hypertension due to left heart disease in the adult—a summary statement from the Pulmonary Hypertension Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2012;31:913-33. 3. Zimpfer D, Zrunek P, Roethy W, et al. Left ventricular assist devices decrease fixed pulmonary hypertension in cardiac transplant candidates. J Thorac Cardiovasc Surg 2007;133:689-95. 4. Alba CA, Rao V, Ross HJ, et al. Impact of fixed pulmonary hypertension on post–heart transplant outcomes in bridge-totransplant patients. J Heart Lung Transplant 2010;29:1253-8. 5. Hoppe UC, Vanderheyden M, Sievert H, et al. Chronic monitoring of pulmonary artery pressure in patients with severe heart failure: multicenter experience of the monitoring Pulmonary Artery Pressure by Implantable device Responding to Ultrasonic Signal (PAPIRUS) II study. Heart 2009;95:1091-7.

Intestinal Kaposi sarcoma in a lung transplant recipient: Therapy with mammalian target of rapamycin inhibitor and immunosuppression reduction May Brit Lund, MD, PhD,a,b Vemund Paulsen, MD,c and P˚al Aukrust, MD, PhDb,d From the aDepartment of Respiratory Medicine, Oslo University Hospital; bFaculty of Medicine, University of Oslo; cDepartment of Gastroenterology; and the dSection of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Norway

We report the case of a 60-year-old woman who developed reduced kidney function (glomerular filtration rate 35 ml/min) and persistent anemia (hemoglobin

levels 8.0 g/dl) within the first weeks after lung transplantation (LTx). Hematologic and gastroenterologic investigations ruled out that her anemia was caused by factors other than kidney failure. Her lung function was excellent. At 18 months after transplant, the patient’s hemoglobin level dropped to 7.5 g/dl, necessitating blood transfusions. This time she presented with abdominal pain and nausea and vomiting, and occult blood was detected in stool samples. Neither upper endoscopy nor colonoscopy revealed a source of bleeding. Areas of abnormal mucosal thickening of the duodenal wall were detected by abdominal computed tomography scan, and video capsule endoscopy revealed multiple 1-2 cm ulcerated lesions in the jejunum and ileum, suggestive of Kaposi sarcoma (KS). Subsequent balloon-assisted enteroscopy with biopsies was performed. Histologic analysis of lesions in the jejunum revealed spindle cell proliferation with positive human herpesvirus-8 (HHV-8) staining, confirming KS. The tumor also tested positive for the vascular markers CD34, CD31, and factor VIII, which are ancillary diagnostic tests for KS. Since LTx, the patient had been maintained on conventional triple-drug immunosuppression with ciclosporin, mycophenolate mofetil, and prednisolone. When KS was diagnosed, conversion to the mammalian target of rapamycin (mTOR) inhibitor everolimus was initiated, with a target range of 5 to 6 ng/ml throughout. Treatment with mycophenolate mofetil was ceased, and the trough level of ciclosporin was reduced to 50 to 60 ng/ml. The patient’s abdominal symptoms were alleviated within 2 weeks, and her hemoglobin level remained stable, without further blood transfusions. Video capsule endoscopy 4 months later showed considerable regress of KS manifestations, and after another 3 months, the small intestine appeared to be nearly normal. Because the patient responded rapidly to mTOR therapy and reduction in net immunosuppression, we saw no need to add cytotoxic drugs that may cause severe side effects in transplant recipients. At 1 year after diagnosis, there was complete resolution of KS lesions. The patient has now been in complete remission for 18 months. Her hemoglobin level is stable at approximately 10.0 g/dl, and she has no abdominal symptoms. However, the patient’s lung function started to decline 6 months after the change in immunosuppression, and bronchiolitis obliterans syndrome was eventually diagnosed. Low-dose azithromycin was introduced, and her forced expiratory volume in 1 second has now stabilized at 25% of predicted. Renal function has remained unchanged after the alteration in immunosuppression. KS of the gastrointestinal tract in HIV-negative patients is rare, and here we report a case in a LTx recipient. KS in immunosuppressed individuals has traditionally been treated with cytotoxic drugs (eg, doxorubicin), and if possible, less immunosuppression. During recent years, new insight into the pathogenesis of KS has showed the importance of host and KS-derived growth factors such as vascular endothelial