Tricuspid valve replacement with mechanical prostheses: Short and long-term outcomes.

BACKGROUND AND AIM: Tricuspid valve replacement has been associated with high mortality and poor long-term outcomes. We report the preoperative risk factors associated with short and long-term outcomes following tricuspid valve replacement with mechanical prostheses. METHODS: In 62 patients who underwent mechanical tricuspid valve replacement, clinical, laboratory, and echocardiographic findings were analyzed using both univariate and multivariate analyses to describe operative and long-term mortality. RESULTS: In our population (mean age 59 ± 9.7 years, 82.3% female), most common causes of tricuspid valve disease were rheumatic fever (69.4%) and functional regurgitation (19.4%). Operative and long-term mortality were 17.7 and 33.9%, respectively. Age, diabetes mellitus, and coronary artery disease were independently associated with increased long-term mortality. New York Heart Association (NYHA) class and right heart failure symptoms significantly improved during follow-up. CONCLUSIONS: In this series of mechanical tricuspid valve replacements in patients with predominately rheumatic heart disease, operative and long-term mortality were increased; however, survivors had significant improvement in their NYHA class and freedom from right heart failure symptoms. Three preoperative factors (age, diabetes mellitus, and coronary artery disease) were independently associated with long-term mortality.

The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies.

Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue - GLA p.(Arg118Cys) -, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands' close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease. The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for "rare" condition.

Myocarditis with concomitant tuberculosis infection presenting with solitary ventricular tachycardia: a case report.

Background: Myocarditis is an infrequent extrapulmonary manifestation of tuberculosis that confers an unfavourable prognosis. Case summary: A 36-year-old man presented to the hospital with palpitations and dyspnoea. Tests revealed the presence of non-sustained ventricular tachycardia, with mild elevation of troponin and C-reactive protein levels. Coronary angiography showed normal results. A cardiac magnetic resonance (CMR) showed moderate hypertrophy, preserved ejection fraction, and an extensive multi-segmental pattern of fibrosis and oedema. An 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET-CT) scan revealed multiple hypermetabolic adenopathies and patchy cardiac uptake. A tuberculin skin test and interferon-gamma release assay were both positive. An endomyocardial biopsy (EMB) showed inflammation without granulomas; and microbiological stains were negative. Biopsy of an adenopathy revealed the presence of multiple necrotizing granulomas with Langhans cells. Based on the test results and clinical presentation, the suspected diagnosis was tuberculous myocarditis. Treatment with anti-tuberculosis drugs was started. One month later, the presence of mycobacterium tuberculosis (MT) was detected in the lymph node culture. At 7 months of follow-up, the patient remains asymptomatic, ventricular arrhythmias have ceased, and radiological signs of inflammation have resolved. Discussion: Ventricular arrhythmia is one of the clinical manifestations of tuberculous myocarditis. Cardiac magnetic resonance and 18F-FDG-PET-CT imaging are an essential component of the non-invasive evaluation of inflammatory cardiomyopathy. However, a confirmatory biopsy may be required to identify potentially treatable aetiologies. Although the diagnosis of tuberculous myocarditis requires an isolation of MT by staining or culture in EMB, the diagnostic yield is very low. For this reason, extra-cardiac findings may provide the definitive diagnostic clue.

Host cell-derived cardiomyocytes in sex-mismatch cardiac allografts.

BACKGROUND: Mesenchymal precursor cells are able to respond to tissue signals and differentiate into a phenotype characteristic of mature cells of that tissue. We sought to investigate whether adult human cardiomyocytes can be derived from recipient precursor cells in sex-mismatched cardiac allografts. METHODS: We studied four male patients who received hearts from female donors, and four female patients who received an allograft from a male donor. Four sex-matched transplant patients, two of each sex served as controls. Combined fluorescence in situ hybridization with probes specific for X- and Y-chromosomes and immunohistochemistry with alpha-actin was used to identify cardiac muscle cells 4 and 12 months after transplantation. Slides were examined with a fluorescence microscope to detect the presence of male cells with one X and one Y signal in the nucleus, and female cells containing two X signals. RESULTS: Mature cardiomyocytes from the host (1-2%) were found in five endomyocardial biopsy specimens at 4 months, and in three specimens at 12 months. In addition, recipient cells negative for cytoplasmic alpha-actin were also identified (1-21% per slide). The number of infiltrating recipient cells was not associated with the degree of rejection of the sample or with the number of prior rejection episodes. Echocardiographic evaluation showed no improvement in cardiac performance in hearts from patients with more than 10% chimeric recipient cells. CONCLUSIONS: Our data confirm the existence of mature cardiomyocytes derived from host cells, likely mesenchymal precursors, in the adult cardiac allograft in vivo.

Distinct left bundle branch block pattern in ischemic and non-ischemic dilated cardiomyopathy.

BACKGROUND: A high percentage of patients with dilated cardiomyopathy have the electrocardiographic (ECG) pattern of advanced left bundle branch block (LBBB). In the present study we sought to investigate whether patients with dilated cardiomyopathy of ischemic or non-ischemic etiology can be differentiated on the basis of LBBB pattern. METHODS AND RESULTS: The study population included 41 patients with dilated cardiomyopathy of non-ischemic (NIC) (n=26) or ischemic origin (IC) (n=15) and LBBB on surface ECG. ECG duration and voltage were digitally measured. The presence of notching of S wave in right precordial leads (V1-V3) was not statistically different between the groups. The voltages of precordial leads V2, V3 and the Sigma(V1+V2+V3 voltages) were significantly more prominent in patients with NIC (P=0.002, P<0.001 and P=0.002, respectively). The discriminative power of receiver operating characteristic analysis was best at voltages of V3 of 2100 microV (area under the curve, 0.805; standard error, 0.001). The sensitivity and specificity of V3 voltage >2100 microV on surface ECG in the presence of LBBB to identify a cardiomyopathy of non-ischemic origin were 85 and 73%, respectively. CONCLUSIONS: A single ECG criteria, voltage of lead V3, appears to be a useful parameter to identify patients with dilated cardiomyopathy of ischemic or non-ischemic origin in the presence of advanced LBBB.

The use of proliferation signal inhibitors in the prevention and treatment of allograft vasculopathy in heart transplantation.

Cardiac allograft vasculopathy (CAV) currently represents one of the most important causes of long-term morbidity and mortality in the heart transplant population. In well-designed studies with de novo patients, the use of proliferation signal inhibitors (PSIs; everolimus and sirolimus) has been shown to significantly prevent the intimal growth of graft coronary arteries in comparison to other immunosuppressive regimens, reducing the incidence of vasculopathy at 12 and 24 months. In addition, conversion to PSIs in maintenance patients with established CAV has also shown promising results in the reduction of the progression of the disease and its clinical consequences. For these reasons the interest shown by various transplantation units in the potential role of PSIs in this field is growing. The aim of the present article is to review the information obtained to date on the use of PSIs in heart transplant recipients, both in the prevention and the treatment of CAV. The principal published recommendations on the introduction and appropriate management of these drugs in clinical practice are also collected, as well as certain recommendations given by the authors based on their experience.

Influence of induction therapy, immunosuppressive regimen and anti-viral prophylaxis on development of lymphomas after heart transplantation: data from the Spanish Post-Heart Transplant Tumour Registry.

BACKGROUND: Lymphoma after heart transplantation (HT) has been associated with induction therapy and herpesvirus infection. It is not known whether anti-viral agents administered immediately after HT can reduce the incidence of lymphoma. METHODS: This study was a retrospective review of 3,393 patients who underwent HT in Spain between 1984 and December 2003. Variables examined included development of lymphoma and, as possible risk factors, recipient gender and age, induction therapies (anti-thymocyte globulin, OKT3 and anti-interleukin-2 receptor antibodies) and anti-viral prophylaxis (acyclovir or ganciclovir). To study the effect of evolving treatment strategy, three HT eras were considered: 1984 to 1995; 1996 to 2000; and 2001 to 2003. RESULTS: Induction therapy was employed in >60% of HTs, and anti-viral prophylaxis in >50%. There were 62 cases of lymphoma (3.1 per 1,000 person-years, 95% confidence interval: 2.4 to 4.0). Univariate analyses showed no influence of gender, age at transplant, HT era, pre-HT smoking or the immunosuppressive maintenance drugs used in the first 3 months post-HT. The induction agent anti-thymocyte globulin (ATG) was associated with increased risk of lymphoma, and prophylaxis with acyclovir with decreased risk of lymphoma. Multivariate analyses (controlling for age group, gender, pre-HT smoking and immunosuppression in the first 3 months with mycophenolate mofetil and/or tacrolimus) showed that induction increased the risk of lymphoma if anti-viral prophylaxis was not used (regardless of induction agent and anti-viral agent), but did not increase the risk if anti-viral prophylaxis was used. CONCLUSIONS: Induction therapies with ATG or OKT3 do or do not increase the risk of lymphoma depending on whether anti-viral prophylaxis with acyclovir or ganciclovir is or is not employed, respectively.

Cerebrovascular disease as a complication of cardiac transplantation.

BACKGROUND AND OBJECTIVES: To characterize the frequency, risk factors, clinical presentation and etiological subtypes of cerebrovascular diseases (CVD) following cardiac transplantation (CTX). METHODS: In a retrospective review of our CTX database (period 1984-2002), we assessed demographic data, vascular risk factors, surgery and donor details. We classified ischemic stroke (IS) using the clinical criteria of the Oxfordshire Community Stroke Project and the etiological criteria of the TOAST study. Logistic regression analysis and survival curves were carried out. RESULTS: CTX was performed in a total of 314 patients (age 46 +/- 14 years, 78% male) and mean follow-up was 54 +/- 57 months. Twenty-two patients (7%) presented CVD: hemorrhagic stroke in 12%, transient ischemic attack in 28% and IS in 60%. CVD were early postoperative (less than 2 weeks) in 20% of patients and late in 80%. The clinical presentation in patients with IS was total anterior circulation (23.1%), partial anterior (38.4%), lacunar (15.4%) and posterior circulation (23.1%), and the etiological classification was large artery atherosclerosis (15.4%), cardioembolism (14.4%), small vessel disease (15.4%), unusual causes (15.4%) and undetermined cause (38.4%). The only independent predictor of CVD was a prior CVD event with an odds ratio of 8.2 (95% CI, 2.2-30.2, p < 0.02). The estimated risk of CVD at 5 years was greater (p < 0.02) in patients with prior CVD (4.1%) than in those without (1.1%). CONCLUSIONS: CVD are a relatively frequent complication after CTX (7%) and usually occur in the late postoperative phase. CVD prior to transplantation increase the risk of CVD after this procedure.