Management of multidrug-resistant CMV infection in immunocompromised patients: case report of a heart-transplant recipient and review of the literature.

Cytomegalovirus (CMV) remains a leading cause of morbidity after solid organ transplantation. The efficiency of antivirals for the treatment of CMV infections may be hampered because of the emergence of CMV resistance to antivirals. The development of CMV multidrug resistance, which remains uncommon but does occur, constitutes a clinically challenging complication and may contribute to difficult therapeutic management and adverse clinical outcome. We report here the observation of the emergence of a multidrug-resistant CMV infection in a heart-transplant recipient and review the literature on similar cases to identify the potential strategies for the successful management of CMV multidrug resistance among immunocompromised patients.

Multislice computed tomography to rule out coronary allograft vasculopathy in heart transplant patients.

BACKGROUND: This study assessed if invasive coronary angiogram (CA) could be replaced by multislice (64- or 256-row) computed tomography (MSCT) to systematically rule out coronary allograft vasculopathy in heart transplant patients. METHODS: Electrocardiogram-gated contrast-enhanced MSCT (64-row for the first 25 patients and 256-row for the others) was compared with CA. MSCT parameters, adapted to the patient's weight, included 120 kV, 800 mAs, 0.625-mm slice thickness, and 0.42/0.27-second rotation time. The primary end point was the negative predictive value (NPV) of MSCT for the detection of significant (>50%) coronary stenosis. Secondary end points were the comparison of X-ray (mSv) and iodine contrast agent (ml) exposures. RESULTS: The study prospectively included 102 patients (mean age, 53±14 years). Transplantation occurred 6±5 years before inclusion. At CA, 41.8% had stenosis ≤50% and 8% had stenosis>50%. Among the 1,308 angiographic coronary segments ≥1.5 mm, 1,250 (95.6%) were evaluable by MSCT. The NPV of MSCT was 96.6% by patient analysis and 99.7% by segment analysis. The positive predictive value (PPV) was 45.5%. The total volume of contrast agent was 139±43 vs 91±12 vs 56±19 ml (p<0.05) with 64-row MSCT, 256-row MSCT, and CA, respectively. The effective radiation dose was higher using retrospective gating (17.8±5.5 mSv, p<0.05), but similar with prospective gating (6.2±1.9 mSv, p = 0.571) compared with CA (6.0±3.5 mSv). CONCLUSION: Newer generations of MSCT (64- or 256-row) have a good NPV and may represent an alternative to invasive CA to rule out significant (>50%) coronary vasculopathy in heart transplant patients, despite a low PPV.

First experimental use of magnets in cardiac valve repair.

BACKGROUND AND AIM OF THE STUDY: Valve repair is currently performed to treat mitral regurgitation, but aortic valve repair remains a surgical challenge. In contrast, aortic valve replacement leads to complications and constraints on the patients' quality of life and valve durability. The mechanisms that produce malcoaptation of the aortic leaflets, with resultant insufficiency, are mainly due to prolapse or retraction of the leaflets. Thus, a new strategy has been proposed to correct valvular insufficiency, using magnetic force. METHODS: Low-profile permanent magnets were implanted in seven sheep, under cardiopulmonary bypass (CPB), through a transverse aortotomy, and maintained in place for three months. No aortic insufficiency was created in these first experiments. Two-dimensional color Doppler echocardiography was used to assess the function and safeguarding of the aortic valve. Blood samples were withdrawn to assess hemolysis, and histopathologic examinations performed at necropsy. RESULTS: Direct implantation of the three permanent magnets was possible in all seven animals, but the surgical procedure resulted in major complications in three cases. Only five animals could be weaned from CPB, and only four survived the procedure at three months. One magnet was also shown to have migrated postoperatively. Echocardiography confirmed the stability of the aortic leaflet contours. The biocompatibility of the implanted magnets (i.e., absence of hemolytic reaction) was found to be satisfactory, without a need for postoperative anticoagulation. CONCLUSION: The use of magnetic force to correct valvular insufficiency has not previously been reported, and is an interesting field of investigation. Whilst these experiments are at an early stage of development, future changes in magnet design and surgical approach are indicated.

[Virtual endoscopic navigation and body transparency based on computed tomography. A step towards in vivo imaging]. / Navigation endoscopique et transparences corporelles par scanner à RX, une étape en imagerie in vivo.

Progress in HR-CTdata processing has led to lower X-ray exposure and to better diagnostic performance. We describe 19 adult patients (among 5000) examined by HR CT with 64 detectors, acquisition and exposure protocols in mSv, spiral, 0.6-mm slices, 5To PACS. After the two usual processing steps (60 gray values, 5122 and 10242 matrices, dedicated workstations for coronaroscopy and virtual coloscopy, 2D multiplanar reformation, surfacic, 3D volumes with dissection and navigation), a third original data processing step on additional workstations was added. Variable matrix extrapolated images, flexible colored curves (different from anatomical conventions), lighting (sources) and transparencies (unavailable with traditional endoscopy) were used. The digital film is a 16-minute "journey "consisting of 19 endo-body navigations in 5 regions, from the head to the bronchi, from the heart to the coronary arteries, and from the digestive tract to the abdomen and pelvis. One possible application is post-operative verification of an aortic graft. The movie is illustrated here with ten plates. This new approach is cost-effective and beneficial for the patient, in terms of early diagnosis and therapeutic follow-up. Ethical issues are also examined.

Long-term outcome after bare-metal or drug-eluting stenting for allograft coronary artery disease.

BACKGROUND: Percutaneous coronary intervention (PCI) with bare-metal stenting (BMS) has been reported to be associated with high rates of target-lesion revascularization (TLR) in heart transplant recipients. We aimed to assess the outcome of successful PCI with BMS or drug-eluting stenting (DES) in such patients. METHODS: Ninety-four consecutive heart transplant recipients with successful PCI of de novo lesions with BMS (n = 53) or DES (n = 60) were prospectively followed-up for 3.7 +/- 2.5 years after PCI. An angiographic lesion-based analysis at 12-month follow-up and a long-term, patient-based survival analysis were performed. RESULTS: The lesion-based analysis within 12 months after PCI showed a reduction of TLR rates with the use of DES (6.6% vs 26.4%, p < 0.01). DES were associated with better preservation of left ventricular function at this time-point. The patient-based, long-term analysis showed sustained local benefit of DES (hazard ratio 4.5 [1.4 to 14.5] for BMS vs DES), but no effect on mortality, remote-site PCI and total revascularization rates. Anti-hypertensive (hazard ratio 0.2 [0.1 to 0.5]) and aspirin (hazard ratio 0.3 [0.1 to 0.8]) therapy, and left ventricular ejection fraction (0.96 [0.94 to 0.98] per percent) were the only correlates of long-term mortality. CONCLUSIONS: Compared with BMS, DES are associated with a sustained reduction in rates of TLR and could safely be used in heart transplant recipients with coronary artery disease. Despite excellent local effects, DES use failed to reduce mortality. Anti-hypertensive and anti-platelet therapy, and left ventricular function preservation, may be considered as aims of treatment to improve long-term survival in such patients.

Extra-corporeal membrane oxygenation temporary support for early graft failure after cardiac transplantation.

OBJECTIVE: Early graft failure (EGF) is a major risk for death after heart transplantation. We studied the impact of an extra-corporeal membrane oxygenation (ECMO) temporary support on the operative mortality and the mean-term survival after EGF. MATERIALS AND METHODS: Between January 2000 and December 2006, 394 patients underwent orthotopic heart transplantation at our institution. EGF was observed in 90 (23%) patients. Fifty-four patients (14%) were treated with ECMO support, eight (2%) with other assisting devices, and 28 (7%) received maximal inotropic drug support only. RESULTS: The overall mortality was 21% (83 patients). EGF was a major risk for death: 13% (35 patients) without EGF versus 58% (49 patients) with EGF, p<0001. Among patients supported with ECMO, 36 (67%) were weaned from the assisting device and 27 (50%) were discharged from the hospital. Overall survival was 73% at 1 year and 66% at 5 years. Absence of EGF improved long-term survival: 78% at 1 year and 70% at 5 years without EGF versus 37% at 1 year and 35% at 5 years with EGF. Patients treated with ECMO have the same 1-year conditional survival as patients not having suffered EGF: 94% at 3 years. CONCLUSIONS: ECMO support is a reliable therapeutic option in severe EGF after cardiac transplantation; furthermore, patients treated with ECMO have the same 1-year conditional survival as patients not having suffered EGF.

Incidence and risk factors for seizures after heart transplantation.

Neurological complications can occur after heart transplantation and present with seizures. We examined the incidence of seizures from a population of adult patients who had received heart transplants over a period of 3 years. Brain MRI and clinical data were analysed to identify the risk factors for the seizures. Eight of the 166 post-transplant patients presented seizures (4.8%). The first seizures occurred with a mean of 30 days after the transplantation. For seven patients, the mean delay was 8 days, and for one, it was longer, 172 days. The analysis of brain MRI showed two main epileptogenic factors in the early post-transplant seizures: posterior reversible encephalopathy syndrome (PRES) due to cyclosporine treatment (n = 4) and cortical ischemic stroke (n = 5). In two patients, we identified multiple epileptogenic factors, including notably the association of PRES and cortical stroke. Since treatment of seizures in patients in the intensive care unit (ICU) after heart transplantation depends on identifying and correcting the causes, FLAIR and diffusion MRI sequences are needed, even if the patients have a previous history of epilepsy. Seizures were easy to control. In patients with PRES, imaging and clinical abnormalities improved when cyclosporine was replaced by another immunosuppressive treatment. Death of three patients was not related to seizures, but to infectious or malignant complications of immunosuppressive treatments (n = 2) or to post-stroke neurological deficit (n = 1). Mortality was similar among patients presenting seizures and those who did not.

Paracorporeal pulsatile biventricular assist device versus extracorporal membrane oxygenation-extracorporal life support in adult fulminant myocarditis.

OBJECTIVE: Biventricular assist device support with a paracorporeal pulsatile device is known to be an efficient bridge to recovery for patients with fulminant myocarditis-related cardiogenic shock. Whether these patients can be as efficiently supported with femorofemoral extracorporeal membrane oxygenation remains unclear. METHODS: From 2001 to 2006, 11 patients were referred to our cardiac surgery department for fulminant myocarditis-related cardiogenic shock. The first 5 patients (mean age, 32 +/- 2 years) were supported with a biventricular assist device (Thoratec, Pleasanton, Calif; group I), whereas the remaining patients (40 +/- 4 years) were supported with femorofemoral extracorporeal membrane oxygenation (group II). Preimplantation probability of death was calculated by using the APACHE II score, which was 11 +/- 9 in group I versus 24 +/- 18 in group II. RESULTS: One patient in each group died while receiving support. In group I the death occurred after 18 days of support in a patient who had 45 minutes of external resuscitation before biventricular assist device implantation. In group II a patient who remained unstable during extracorporeal membrane oxygenation was switched to a biventricular assist device 13 days later and eventually died of tamponade after 45 days. All other patients were weaned from the device after a mean duration of support of 21 +/- 5 days in group I versus 13 +/- 4 days in group II. At hospital discharge, the mean ejection fraction was 45% +/- 5% in both groups, and at 6 months' follow-up, it was 65% and 75%, respectively, in groups I and II. CONCLUSION: In our experience extracorporeal membrane oxygenation is as efficient as use of a biventricular assist device as a bridge to recovery for patients with fulminant myocarditis-related cardiogenic shock and facilitates renal and hepatic recovery on support.

Resistance pattern of cytomegalovirus (CMV) after oral valganciclovir therapy in transplant recipients at high-risk for CMV infection.

In transplant recipients, cytomegalovirus (CMV) resistance to antivirals causes an increasing problem. Here we report the clinical, therapeutic, and virological characteristics of 11 cases of CMV resistance among transplant recipients at high-risk for CMV infection and receiving valganciclovir as a prophylactic, preemptive or maintenance therapy. Active CMV infection was monitored by viral DNA quantification in whole blood, and CMV resistance was assessed by UL97 and UL54 viral gene sequencing. For 10 patients, ganciclovir resistance detected after valganciclovir therapy was associated with one mutation within UL97 phosphotransferase located at codons 460 and 592-603, which constitutes a similar pattern of resistance to what has been reported previously in AIDS patients treated with valganciclovir. For the last patient, two mutations in UL97 and UL54 genes were identified. The start of valganciclovir maintenance treatment after an intravenous curative treatment while CMV DNA is still detectable in peripheral blood might represent a risk factor for the emergence of CMV resistance. The possible emergence of CMV resistance in transplant recipients at high-risk for CMV infection who receive valganciclovir therapy should be taken into account. Among those patients, CMV infection has to be closely monitored in order to detect promptly the emergence of drug-resistance.

Heart transplantation in systemic (AL) amyloidosis: a retrospective study of eight French patients.

BACKGROUND: Immunoglobulinic (AL) amyloidosis is a complication of plasma cell dyscrasia, characterized by widespread deposition of amyloid fibrils derived from monoclonal light chains. Cardiac amyloid is the main prognostic factor, with a median survival of six months. Cardiac transplantation in AL amyloidosis is associated with high mortality, due to disease recurrence in the allograft and systemic progression. Suppression of light chain (LC) production with chemotherapy by melphalan plus dexamethasone (MD) or high dose melphalan followed by autologous stem cell transplantation (HDM/ASCT) improves survival. However, both the indications and results of chemotherapy in patients transplanted for cardiac AL amyloidosis remain unclear. AIMS: To assess the outcome of cardiac transplantation and haematological therapy in patients with cardiac AL amyloidosis. METHODS: Eight French patients, who underwent heart transplantation for cardiac AL amyloidosis between 2001 and 2006 were studied retrospectively. RESULTS: Before transplantation, six patients received MD (n=5) or HDM/ASCT (n=1). Haematological remission was obtained in three patients treated with MD. In the three remaining patients, postoperative HDM/ASCT (n=2) or allogeneic bone marrow transplantation (n=1) resulted in haematological remission in one patient. In 2 patients not treated before transplantation, post-operative treatment with MD resulted in complete hematological remission in one. After a median follow-up of 26 months from cardiac transplantation, six patients were alive and four had sustained haematological remission, as indicated by normal serum free LC levels. CONCLUSION: Appropriate haematological therapy, including MD, may result in a survival benefit in AL amyloidosis patients with advanced heart failure requiring transplantation.

Papillary muscle approximation for ischemic mitral valve regurgitation.

In patients with ischemic left ventricular dysfunction and functional mitral regurgitation, the surgical treatment of the mitral insufficiency remains a challenging issue. Several procedures were described to restore a more normal alignment between the mitral annulus and the laterally displaced papillary muscles. We report a new approach to relocate the displaced papillary toward the mitral annulus and to reduce tethering. This procedure is believed to be technically easy and beneficial in terms of mitral repair.

Long-term results of ascending aorta-abdominal aorta extra-anatomic bypass for recoarctation in adults with 27-year follow-up.

OBJECTIVE: The surgical treatment of recurrent coarctation in adults supposes a redo left thoracotomy with adhesions and high risk of bleeding and injury of adjacent nerves. The rate of paraplegia in these cases may reach 2.6%. Extra-anatomic aortic bypass avoids these complications. We present our results with ascending-to-abdominal aorta extra-anatomic bypass for recurrent aortic coarctation in adults. METHODS: Between September 1979 and November 2006 12 patients underwent ascending-to-abdominal aorta bypass. There were 10 males and 2 females. Mean age was 36.2+/-11.3 (range 21-57) years old. Mean age at primary repair was 14.3+/-4.2 years old (range 8-21). Operative technique consisted of performing an ascending-to-abdominal aorta bypass via median sternotomy extended into the epigastrium with a supra-umbilical laparotomy through the mid-line abdominal fascia. Concomitant procedures were performed in six patients: three isolated aortic valve replacements (AVR), two ascending aorta graft replacements and one AVR associated with coronary artery bypass graft (CABG). RESULTS: No postoperative mortality was observed. Mean follow-up time was 10.4+/-9.3 years (range 0.3-27.8). No patients had any graft-related complication or death and all grafts were patent at the end of the follow-up. One patient developed a dilated myocardiopathy, dying at 14 years of follow-up. Four patients had persistence of arterial hypertension controlled with one drug therapy and five patients were asymptomatic. CONCLUSIONS: Ascending-to-abdominal aorta extra-anatomic bypass is a safe, effective and less invasive technique for aortic recoarctation in adults with good results at long-term.

[Cardiac transplantation in 2008]. / La transplantation cardiaque en 2008.

The number of heart transplants in France has begun to increase again in the past few years, albeit slowly. Indications for transplants must be discussed on a case-by-case basis and no contraindication should be considered absolute. Heart transplant results have not been modified by the expansion of the selection criteria for donors. The "super-urgent" list makes it possible to provide transplants for the patients at highest risk of imminent death, with encouraging results. The repercussions of "super-urgent" transplants must be analyzed regularly. Quality of life must be taken into account in the analysis of heart transplant results, just like survival. New circulatory assist devices can be offered to some patients as an alternative to transplantation.

Prevalence of patent foramen ovale and usefulness of percutaneous closure device in carcinoid heart disease.

The aim of this study was to assess (1) the incidence of patent foramen ovale (PFO) in carcinoid syndrome (CS) and (2) the feasibility of percutaneous closure procedure in selected patients with CS. One hundred eight patients were prospectively studied: 54 with CS and an age- and gender-matched control group. All patients underwent conventional and contrast echocardiography. Patients with clinical signs of dyspnea (New York Heart Association class > or =III), cyanosis, carcinoid heart disease (CHD), and severe PFO were referred for the percutaneous closure of PFO. The prevalence of PFO was 41% in patients with CS and 22% in the control group (p = 0.03) and was significantly higher in patients with CHD (59%, p = 0.009). Four patients (14% of those with CHD) were referred for the percutaneous closure of PFO, and 3 patients ultimately underwent PFO closure (using Amplatzer septal occluders). At 6-month follow-up, New York Heart Association class was improved in all patients, as well as arterial blood gas results (p = 0.04) and 6-minute walking distance (p = 0.03), but all patients presented residual right-to-left shunts. In conclusion, this prospective study demonstrates that in patients with CHD, the prevalence of PFO is high and that percutaneous closure of PFO is feasible, with a reduction in symptoms but with residual shunting.

Congenital bilateral coronary artery to pulmonary artery fistulas associated with left main trunk stenosis.

A rare case of a 57-year-old patient who presented with an acute coronary syndrome with incidental discovery of bilateral coronary arteriovenous fistulas originating from both coronary arteries to the pulmonary artery trunk and coronary artery atherosclerosis.