Functional assessment and quality of life before and after pulmonary endoarterectomy.

PURPOSE: The study investigates Quality of Life (QOL) and correlation with functional status of patients affected by Chronic Thromboembolic Pulmonary Hypertension who undergo Pulmonary Endoarterectomy. METHODS: We investigated with an observational design (before surgery, three and twelve months afterwards) the hemodynamic data (NYHA class, mean pulmonary arterial pressure, cardiac output and pulmonary vascular resistance), the functional status (using the 6-Minute Walk Test) and the QOL, using three questionnaires: Medical Outcome Study Short Form-36 (SF-36), Minnesota Living with Heart Failure Questionnaire (MLHFQ), Saint George Respiratory Questionnaire (SGRQ). We report the results of forty-nine patients. RESULTS: After surgery there was an improvement on functional and hemodynamic parameters and on QOL. The physical domain (PCS) of SF-36 was weakly but significantly associated with all functional parameters. There was no association between functional parameters and mental domain (MCS) of SF-36 or SGRQ. The improvement in 6-Minute Walk Distance was associated with an increase in MLHFQ. CONCLUSIONS: Both QOL and submaximal exercise tolerance improve after surgery. However only the physical domains of SF-36 appear to be significantly associated to the functional data.

Type 2 diabetes mellitus is associated with faster degeneration of bioprosthetic valve: results from a propensity score-matched Italian multicenter study.

BACKGROUND: The present study was aimed at determining the impact of type 2 diabetes mellitus (DM) on postoperative bioprosthetic structural valve degeneration. METHODS AND RESULTS: Twelve Italian centers participated in the study. Patient data refer to bioprosthetic implantations performed from November 1988 to December 2009, which resulted in 6184 patients (mean age 71.3±5.4 years, 60.1% male) being enrolled. Of these patients, 1731 (27.9%) had type 2 DM. The propensity score-matching algorithm successfully matched 1113 patients with type 2 DM with the same number of no-DM patients. The postmatching standard differences were less than 0.1 for each of the covariates, and 64.2% of DM patients were matched. The early (30 days) mortality rate was 7.8% (n=87) versus 2.9% (n=33) in patients with or without type 2 DM (P<0.001), respectively. Seven-year freedom from valve deterioration was significantly lower in patients with DM (73.2% [95% confidence interval, 61.6-85.5] versus 95.4% [95% confidence interval, 83.9-100], P<0.001). In Cox regression models with robust SEs that accounted for the clustering of matched pairs, DM was the strongest predictor of structural valve degeneration (hazard ratio 2.39 [95% confidence interval 2.28-3.52]). When we allowed for interaction between type 2 DM and other key risk factors, DM remained a significant predictor beyond any potentially associated variable. CONCLUSIONS: Patients with type 2 DM undergoing bioprosthetic valve implantation are at high risk of early and long-term mortality, as well as of structural valve degeneration.

Results of the European clinical trial of Arrow CorAide left ventricular assist system.

The aim of this study was to evaluate the safety and performance of the Arrow CorAide left ventricular assist system (LVAS) (Arrow International, Reading, PA, USA), a continuous-flow left ventricular assist device, as bridge to transplantation or recovery as well as destination therapy in patients with New York Heart Association (NYHA) class IV heart failure. Twenty-one patients were implanted with the CorAide LVAS between February 2005 and February 2006 in a prospective, multicenter, nonrandomized trial. Seventeen patients (81%) survived to >180 days or to transplantation. The cumulative time on device was 16.58 patient years (range 23-796 days, median 192 days). No intraoperative technical issues were observed at the time of implantation. Of the 21 implants, nine patients died on device, two were converted to other devices, and 10 were transplanted. Three patient deaths were attributed to pump polymer coating delamination. Postmortem device inspection determined delamination of the polymer coating on the pump's internal surface to be the cause of the late hemolysis and sudden fatal pump stops. No embolic or driveline infection event was recorded. The automatic flow control algorithm functioned reliably throughout the trial. Primary performance trial endpoint was achieved with 81% survival to 180 days or transplantation. Delamination of the polymer coating on the internal surface of the pump with resultant hemolysis and pump stops was the sole major device event in this trial. Elimination of the polymer coating and replacement with an amorphous carbon coating has resolved this in preclinical testing, prior to initiation of further clinical testing of this device.

Long-term survival following surgery for endomyocardial fibrosis.

We report a successful follow-up after 28 years of a woman with obliterative restrictive endomyocardial fibrosis (EMF) that underwent complete surgical decortication with simultaneous mitral and tricuspid bioprosthetic valve replacement in 1982 and underwent successful reoperation for the structural failure of biological prostheses after 25 years.

Computational finite element analyses to optimize graft sizing during aortic valve-sparing procedure.

BACKGROUND AND AIM OF THE STUDY: Aortic valve-sparing (AVS) procedures have been introduced to treat ascending aorta dilatation and aortic valve insufficiency in the presence of preserved native aortic valve leaflets. Although the surgical technique has been standardized, the choice of best type and size of Dacron graft to be used remains a matter of debate. Herein are presented preliminary results based on a patient-specific finite element model aimed at optimizing the Dacron prosthesis size and shape. Previously, finite element analysis (FEA) has been applied to investigate medical problems and, in particular, to better evaluate the pathophysiology of the aortic root. To date, however, such methodology has not been applied to the patient-specific evaluation of AVS postoperative results. METHODS: The framework of the FEA study included four steps: (i) the creation of a mathematic model of the patient's aortic root; (ii) the creation of a model for two different Dacron grafts (the standard straight graft and a Valsalva graft), with sizes of each type ranging from 24 to 30 mm; (iii) a virtual computer-based simulation of the AVS procedure, using each graft; and (iv) a virtual computer-based simulation of the diastolic closure of the repaired valve and an evaluation of post-implant physiology, based on three parameters: the height of coaptation ratio (H(C)R); the length of coaptation ratio (L(C)R); and the distance between the central point of coaptation and the ideal geometrical centre (D(C)). RESULTS: The simulation results of post-implant performance of the aortic valve revealed that both H(C)R and L(C)R were decreased as the graft size was increased, but no significant differences were identified between two types of graft. In contrast, the Valsalva graft, when compared to the standard straight graft, led to a significant reduction in D(C). The results in terms of H(C)R, L(C)R and D(C) recommended unequivocally, for the specific case under investigation, that a 30 mm straight graft and a 28 mm Valsalva graft would ensure the most physiological valve behavior for the patient under investigation. CONCLUSION: In evaluating the potential of a preoperative prediction of the optimal graft size, using FEA, the virtual simulation of the AVS procedure proved to be feasible and useful in predicting the postoperative physiology of the aortic root. In particular, this finite element model might have a clinical impact as may be used to optimize the surgeon's choice of prosthesis size.

Should we perform heart retransplantation in early graft failure?

Cardiac retransplantation represents the gold standard treatment for a failing cardiac graft but the decision to offer the patient a second chance is often made difficult by both lack of donors and the ethical issues involved. The aim of this study was to evaluate whether retransplantation is a reasonable option in case of early graft failure. Between November 1985 and June 2008, 922 patients underwent cardiac transplantation at our Institution. Of these, 37 patients (4%) underwent cardiac retransplantation for cardiac failure resulting from early graft failure (n = 11) or late graft failure (acute rejection: n = 2, transplant-related coronary artery disease: n = 24). Survival at 1, 5 and 10 years of patients with retransplantation was 59%, 50% and 40% respectively. An interval between the first and the second transplantation of less than (n = 11, all in early graft failure) or more than (n = 26) 1 month was associated with a 1-year survival of 27% and 73%, and a 5-year survival of 27% and 65% respectively (P = 0.01). The long-term outcome of cardiac retransplantation is comparable with that of primary transplantation only in patients with transplant-related coronary artery disease. Early graft failure is a significant risk factor for survival after cardiac retransplantation and should be considered as an exclusion criteria.

Long-term outcome after pulmonary endarterectomy.

RATIONALE: There are few follow-up studies on long-term cardiopulmonary function after pulmonary endarterectomy (PEA), the operation of choice for chronic thromboembolic pulmonary hypertension (CTEPH). OBJECTIVES: To prospectively evaluate long-term outcome of patients with CTEPH treated with PEA. METHODS: Between 1994 and 2006, 157 patients (mean age 55 yr) were treated with PEA at Pavia University Hospital. The patients were evaluated before PEA and at 3 months (n = 132), 1 year (n = 110), 2 years (n = 86), 3 years (n = 69), and 4 years (n = 49) afterward by NYHA class, right heart hemodynamic, spirometry, carbon monoxide transfer factor (Tl(CO)), arterial blood gas, and treadmill incremental exercise test. MEASUREMENTS AND MAIN RESULTS: Cumulative survival was 84%. Within 3 months, 18 patients died in-hospital and 2 had lung transplantation; during long-term follow-up, 6 died, 1 had lung transplantation, and 3 had a second PEA (2.5 events per 100 person-years). NYHA class III-IV was the most important predictor of late death, lung transplant, or PEA redo (hazard ratio, 3.94). Extraordinary improvement in NYHA class, hemodynamic, and Pa(O(2)) were achieved in the first 3 months (P < 0.001) and persisted during follow-up; exercise tolerance progressively increased over time (P < 0.001). At 4 years, although 74% of the patients were in NYHA class I and none was in class IV, 24% had pulmonary vascular resistance greater than 500 dyne.s/cm(5) or Pa(O(2)) less than 60 mm Hg; they were significantly older and were more frequently in NYHA class III-IV 3 months after surgery than the others. CONCLUSIONS: After PEA, long-term survival and cardiopulmonary function recovery is excellent in most patients.

Initial results of clinical trial with a new left ventricular assist device (LVAD) providing synchronous pulsatile flow.

OBJECTIVES: A multicentric European Clinical Study is ongoing to evaluate safety and efficacy of a new pulsatile implantable LVAD (BestBeat), smaller and lighter than similar devices, capable of providing synchronous and counterpulsating flow with respect to the LV of end-stage heart failure patients. Preliminary clinical results are reported. METHODS: The new BestBeat LVAD was used, consisting of an implantable pulsatile blood pump, electromechanically driven by a ball screw mechanism, and a wearable electronic controller and power sources. The clinical trial was conducted at 5 european centers. Adult patients affected by CHF in NYHA Class IV despite optimized medical treatment were enrolled. The primary study endpoint was survival at 90 days. Further study endpoints were maintenance of adequate LVAD pump flow and a minimum rate of adverse events during support. RESULTS: As of June 2008, 6 patients received the implant. Cumulative support time was 3.7 years, median support time 176 days. All patients who completed the study survived except for one, who died after 48 days, due to combined infection and cerebrovascular accident. Another two patients died: one from intracranial bleeding 113 days after implant, and one from septic shock after 123 days. Hemodynamic improvement with CI>2.0 l/min/m2 and recovery of end-organ function expressed by consistent improvement of BUN, creatinine and bilirubin were reached in all patients. No device failure was observed. There was no bleeding requiring re-exploration, no hemolysis and only two device-related infections (both in one patient). Neurologic events were reported, the most serious ones occurring in patients with pre-implant respiratory and kidney failure. Three patients were discharged home. Two patients were successfully transplanted, one after 6 months and one after 13 months on device. CONCLUSIONS: Good performance and efficacy of the device were observed; the endpoints of the study were achieved, and its safety was consistent with expectations. The ongoing study will allow further conclusions to be drawn.

The axillary artery as an alternative site of cannulation for redo port access-assisted minimally invasive mitral valve surgery: early report of 2 cases.

The minimally invasive Heartport (HP)-assisted technique has become first choice option for mitral valve surgery in many centres.The pool of patients potentially treated using HP techniques, however, is still limited by the presence of peripheral vessel disease, expecially in the elderly population. Alternative approaches to using the HP technique safely in such a subset of patients, therefore, should be evaluated. Here, we present our preliminary experience using the axillary artery as an alternative site of cannulation for HP-assisted redo mitral valve surgery in patients with concomitant peripheral vessel disease.

Impact of dose reductions on efficacy outcome in heart transplant patients receiving enteric-coated mycophenolate sodium or mycophenolate mofetil at 12 months post-transplantation.

Mycophenolic acid (MPA) dose reduction is associated with increased risk of rejection and graft loss in renal transplantation. This analysis investigated the impact of MPA dose changes with enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) in de novo heart transplant recipients. In a 12-month, single-blind trial, 154 patients (EC-MPS, 78; MMF, 76) were randomized to either EC-MPS (1080 mg bid) or MMF (1500 mg bid) in combination with cyclosporine and steroids. The primary efficacy variable was the incidence of treatment failure, comprising a composite of biopsy-proven (BPAR) and treated acute rejection, graft loss or death. Significantly fewer patients receiving EC-MPS required > or =2 dose reductions than patients on MMF (26.9% vs. 42.1% of patients, p = 0.048). Accordingly, the average daily dose of EC-MPS as a percentage of the recommended dose was significantly higher than for MMF (88.4% vs. 79.0%, p = 0.016). Among patients requiring > or =1 dose reduction, the incidence of treated BPAR grade > or =3A was significantly lower with EC-MPS compared with MMF (23.4% vs. 44.0%, p = 0.032). These data suggest that EC-MPS-treated heart transplant patients are less likely to require multiple dose reductions than those on MMF which may be associated with a significantly lower risk of treated BPAR > or =3A.

Iatrogenic circumflex coronary lesion in mitral valve surgery: case report and review of the literature.

Ischemic iatrogenic lesions can complicate surgical procedures on the mitral valve. One of the causative mechanisms is direct injury to or distortion of the circumflex coronary artery. The risk of damaging the circumflex coronary artery depends mainly upon the proximity of that vessel to the posterior segment of the mitral annulus, and this varies from patient to patient. Herein, we report a case of iatrogenic circumflex coronary artery lesion after mitral annuloplasty, and we review the literature on the subject, in order to highlight a possible relationship between iatrogenic circumflex lesions and coronary dominance. In a 60-year-old man who had severe mitral regurgitation due to prolapse of both leaflets, preoperative coronary angiography showed irregularities only along the left anterior descending coronary artery and a coronary network of right dominance. The patient underwent mitral annuloplasty (32-mm Carpentier-Edwards ring) by means of minimally invasive right thoracotomy through the right 4th intercostal space (HeartPort). When the procedure was over, and before the patient was taken to intensive care, ventricular fibrillation developed; the administration of direct-current shock (200 joules) resulted in a resumption of sinus rhythm. Repeat transesophageal echocardiography showed posterolateral dyskinesis of the left ventricle and ST-segment elevation suggestive of acute lateral myocardial infarction. Emergency cardiac catheterization revealed a subocclusion of the distal circumflex coronary artery. Dual percutaneous angioplasty and stenting (Taxus, 2.5 x 24 mm) was performed with optimal result. At the 1-year follow-up, the patient showed good results of the mitral annuloplasty.

Evaluation of cytomegalovirus DNAaemia versus pp65-antigenaemia cutoff for guiding preemptive therapy in transplant recipients: a randomized study.

METHODS: A bicentre, randomized, prospective open-label study aimed at defining a DNAaemia versus antigenaemia cutoff for guiding preemptive therapy of human cytomegalovirus (HCMV) infections in solid organ transplant recipients (SOTR) was completed. Overall, 99 patients were enrolled in the DNAaemia arm and 101 patients in the antigenaemia arm. Patients were randomized to be monitored for HCMV infection in the blood by either assay. Antiviral treatment was started in both seropositive and seronegative patients when levels greater than 300,000 DNA copies/ml blood or 100 pp65-positive leukocytes in the relevant arm were reached. RESULTS: HCMV infection was detected in 81/99 (81.8%) patients in the DNAaemia arm and in 87/101 (86.1%) patients in the antigenaemia arm (P=ns). Antiviral treatment was given to 23/99 (23.0%) patients in the DNAaemia arm and 42/101 (41.0%) patients in the antigenaemia arm (P = 0.01). In the DNAaemia arm, antiviral therapy was significantly delayed and duration of the first course of treatment was significantly greater than in the antigenaemia arm. However, total duration of treatment was comparable in the two arms. No case of HCMV disease occurred in patients treated after reaching the relevant cutoff. However, four patients (three in the antigenaemia arm, and one in the DNAaemia arm) suffered from HCMV disease prior to reaching the relevant cutoff. CONCLUSIONS: Compared with antigenaemia, a single DNAaemia cutoff: (i) significantly reduces the number of patients requiring treatment; (ii) may be safely adopted to guide preemptive therapy of both primary and reactivated HCMV infections in SOTR; and (iii) does not significantly modify the overall duration of treatment.

Return to work after thoracic organ transplantation in a clinically-stable population.

PURPOSE: To evaluate the rate of return to work after transplantation and its determinants in a clinically-stable population of patients transplanted and followed-up at a single institution in Italy. METHODS: 151 thoracic organ transplant recipients (72 lung, 79 heart) were examined. Patients were asked about daily activities, level of education, employment and clinical condition. A six-minute walking test was performed with measurement of dyspnoea using the Borg scale. Quality of Life was evaluated with the SF-36 and GHQ questionnaires. RESULTS: Before transplantation 131 patients (87%), (70 heart and 61 lung) worked. After transplantation, 51 patients (39%) went back to work and 3 more started working. We found that younger age, a better quality of life (mainly in the mental domain), having had an occupation previously (particularly as an entrepreneur/freelancer), and having been off work for less than 24 months, were independent predictors of return to work. CONCLUSIONS: Considering their good, objective and subjective, functional status, some patients who could have returned to work, chose not to. Identifying factors which affect return to work might help health professionals to adopt the best course of treatment and psychological support in order to fulfil this goal; however, return to work should not be considered as the only expression of a patient's real psychophysical condition.

Valve-sparing removal of aortic fibroelastoma through ministernotomy.

Cardiac papillary fibroelastoma is a rare benign tumor which involves the heart valves and may cause thromboembolism or mechanical interference with valvular function. The case is presented of an asymptomatic, 22-year-old man in whom a fibroelastoma was localized on the ventricular aspect of the right coronary leaflet of the aortic valve. The tumor was identified during transthoracic echocardiography performed to monitor a mitral valve prolapse that had occurred at the age of 16 years. The patient underwent surgical intervention by means of a minimally invasive thoracotomy. The postoperative course was uneventful, and the patient was discharged on postoperative day 5. Due to the high incidence of embolism, the tumor must be surgically removed immediately a diagnosis is confirmed. A minimal surgical approach appears to be safe and allows good exposure of the lesion.

B-cell posttransplant lymphoproliferative disorders in heart and/or lungs recipients: clinical and molecular-histogenetic study of 17 cases from a single institution.

BACKGROUND: Posttransplantation lymphoproliferative disorders (PTLDs) are heterogeneous lymphoid proliferations representing a major complication of solid organ transplant. This study details the clinicopathological and molecular features of 17 B-cell PTLDs observed in a single center series of 988 heart and/or lung transplant recipients. METHODS: Cases were classified according to World Health Organization lymphoma classification and tested for Epstein-Barr Virus (EBV), clonality, histogenetic phenotypic (CD10, Bcl-6, MUM1, CD138), and genotypic (immunoglobulin and BCL-6 genes somatic hypermutation) markers. RESULTS: This series of 17 PTLDs included: two B-cell monoclonal polymorphic PTLDs and 15 B-cell monomorphic PTLDs (13 diffuse large B-cell lymphomas [DLBCL] and 2 Burkitt lymphomas [BL]). EBV was detected in 9/17 cases. A monoclonal immunoglobulin variable (IGV) genes rearrangement was documented in 17/17 cases; IGV somatic hypermutation was found in 88% of cases, indicating a prevalent origin from germinal center (GC)-experienced B cells. Using immunophenotypic markers, three histogenetic profiles were identified: a) CD10/bcl-6/MUM1/CD138, mimicking GC B-cells; b) CD10-/bcl-6+/MUM1+/CD138-, reminiscent of B-cells at the latest phases of GC reaction; and c) CD10-/bcl-6-/MUM1+/CD138+/-, consistent with preterminally differentiated B-cells. CONCLUSIONS: Correlation between morphology, histogenesis, and EBV status demonstrated a high degree of homogeneity in the two GC-related groups, mostly including EBV-negative cases with BL and DLBCL-centroblastic features; the third group, consisting of post GC EBV-positive cases, was histologically less homogeneous, as it included polymorphic PTLDs and DLBCL with immunoblastic and anaplastic features. The EBV-negative cases with GC histogenetic phenotype showed a slightly better outcome; however, such less aggressive prognostic trend was not confirmed by statistical analysis.

Desmin accumulation restrictive cardiomyopathy and atrioventricular block associated with desmin gene defects.

BACKGROUND: Primary desminopathies are caused by desmin gene [DES (MIM*125660)] mutations. The clinical spectrum includes pure myopathies, cardiomuscular diseases and cardiomyopathies. Patients with restrictive cardiomyopathy (RCM) plus atrioventricular block (AVB) due to DES defects are frequently unrecognized unless desmin accumulation is specifically investigated in endomyocardial biopsy (EMB) by ultrastructural study. AIMS: To describe a cardiological phenotype characterized by RCM plus AVB due to desmin accumulation caused by DES defects. METHODS AND RESULTS: Desmin accumulation was diagnosed by means of ultrastructural and immunocytochemical studies of EMB in four unrelated probands with RCM and AVB. Candidate genes [DES and alphaB-crystallin (CRYAB)] were screened using sequence analysis. Four DES gene mutations were identified: three new (R16C, T453I and a 10 bp deletion at the exon-intron boundary of exon 3 disrupting the donor splice site) and one known (R406W). The disease was autosomal dominant in two families, recessive in one and associated with a de novo mutation in one. The mutations cosegregated with phenotype in all patients. CRYAB gene screening was negative. CONCLUSIONS: A cardiac phenotype characterized by RCM and AVB caused by desmin accumulation is associated with DES mutations. Although the mutations affected different domains, the cardiac phenotype was identical.

Diagnostic imaging of lung cancer after heart transplantation.

AIMS AND BACKGROUND: In heart transplant recipients pulmonary neoplasms are among the most frequent solid tumors; they have a rapid and aggressive course, and therefore require an early diagnosis. We describe the role that diagnostic imaging plays in different diagnostic moments of this disease. METHODS: We evaluated the incidence and diagnosis of lung cancer in patients who underwent heart transplants at our institution. Taking into account the few different diagnostic imaging techniques (chest X-ray, high-resolution computed tomography [CT], staging CT and CT-guided biopsy) used in standard surveillance protocols or indicated by clinical symptoms, we evaluated their diagnostic accuracy, their efficacy in tumor staging, and their impact on the therapeutic choices. RESULTS: Seventeen neoplasms in a total of 712 patients were diagnosed (2.4%). In 16 of these 17 cases chest X-ray (routinely performed as follow-up in 11 cases, indicated by symptoms in 5 cases) was diagnostic. In another 11 cases chest X-ray was false positive. The diagnostic accuracy, sensitivity, specificity, positive and negative predictive value of chest X-ray was 98%, 91%, 98%, 50%, and 99%, respectively. Total-body CT correctly staged the tumors and provided information as to whether surgery was indicated or not (stage II or advanced). CONCLUSIONS: Chest X-ray is still the surveillance radiological technique in heart transplant recipients. Considering its low specificity and sensitivity, we propose high-resolution CT imaging during follow-up to identify pulmonary lesions as soon as possible and enable a differential diagnosis with parenchymal inflammation. The use of CT-guided fine-needle biopsy and culture examinations permits to differentiate neoplastic from inflammatory parenchymal opacities. Use of CT in cancer staging is effective for subsequent treatment choices.

Incidence of cancer after immunosuppressive treatment for heart transplantation.

Prolonged or intensive immunosuppressive therapy used after organ transplantation is complicated by an increased incidence of cancer. Striking differences in incidence are observed in heart and heart-lung transplant recipients when compared with renal transplant patients. The most significant increase was in the incidence of lymphomas in cardiac versus renal patients. Moreover, a two-fold greater increase of all neoplasms was found in cardiac recipients, with nearly a six-fold increase in visceral tumors. Several factors may account for these differences. In cardiac allograft recipients, intensive immunosuppression is frequently used to reverse acute rejection and the highest number of cardiac transplants was performed in the era of polypharmacy, usually consisting of triple therapy.