BMP7-based peptide agonists of BMPR1A protect the left ventricle against pathological remodeling induced by pressure overload.

Aortic stenosis (AS) exposes the left ventricle (LV) to pressure overload leading to detrimental LV remodeling and heart failure. In animal models of cardiac injury or hemodynamic stress, bone morphogenetic protein-7 (BMP7) protects LV against remodeling by counteracting TGF-ß effects. BMP receptor 1A (BMPR1A) might mediate BMP7 antifibrotic effects. Herein we evaluated BMP7-based peptides, THR123 and THR184, agonists of BMPR1A, as cardioprotective drugs in a pressure overload model. We studied patients with AS, mice subjected to four-week transverse aortic constriction (TAC) and TAC release (de-TAC). The LV of AS patients and TAC mice featured Bmpr1a downregulation. Also, pSMAD1/5/(8)9 was reduced in TAC mice. Pre-emptive treatment of mice with THR123 and THR184, during the four-week TAC period, normalized pSMAD1/5/(8)9 levels in the LV, attenuated overexpression of remodeling-related genes (Col 1α1, ß-MHC, BNP), palliated structural damage (hypertrophy and fibrosis) and alleviated LV dysfunction (systolic and diastolic). THR184 administration, starting fifteen days after TAC, halted the ongoing remodeling and partially reversed LV dysfunction. The reverse remodeling after pressure overload release was facilitated by THR184. Both peptides diminished the TGF-ß1-induced hypertrophic gene program in cardiomyocytes, collagen transcriptional activation in fibroblasts, and differentiation of cardiac fibroblasts to myofibroblasts. Molecular docking suggests that both peptides bind with similar binding energies to the BMP7 binding domain at the BMPR1A. The present study results provide a preclinical proof-of-concept of potential therapeutic benefits of BMP7-based small peptides, which function as agonists of BMPR1A, against the pathological LV remodeling in the context of aortic stenosis.

Validation of multiparametric approaches for the prediction of sudden cardiac death in patients with Brugada syndrome and electrophysiological study.

INTRODUCTION AND OBJECTIVES: Multiparametric scores have been designed for better risk stratification in Brugada syndrome (BrS). We aimed to validate 3 multiparametric approaches (the Delise score, Sieira score and the Shanghai BrS Score) in a cohort with Brugada syndrome and electrophysiological study (EPS). METHODS: We included patients diagnosed with BrS and previous EPS between 1998 and 2019 in 23 hospitals. C-statistic analysis and Cox proportional hazard regression models were used. RESULTS: A total of 831 patients were included (mean age, 42.8±13.1; 623 [75%] men; 386 [46.5%] had a type 1 electrocardiogram (ECG) pattern, 677 [81.5%] were asymptomatic, and 319 [38.4%] had an implantable cardioverter-defibrillator). During a follow-up of 10.2±4.7 years, 47 (5.7%) experienced a cardiovascular event. In the global cohort, a type 1 ECG and syncope were predictive of arrhythmic events. All risk scores were significantly associated with events. The discriminatory abilities of the 3 scores were modest (particularly when these scores were evaluated in asymptomatic patients). Evaluation of the Delise and Sieira scores with different numbers of extra stimuli (1 or 2 vs 3) did not substantially improve the event prediction c-index. CONCLUSIONS: In BrS, classic risk factors such as ECG pattern and previous syncope predict arrhythmic events. The predictive capabilities of the EPS are affected by the number of extra stimuli required to induce ventricular arrhythmias. Scores combining clinical risk factors with EPS help to identify the populations at highest risk, although their predictive abilities remain modest in the general BrS population and in asymptomatic patients.

Long-term prognosis of women with Brugada syndrome and electrophysiological study.

BACKGROUND: A male predominance in Brugada syndrome (BrS) has been widely reported, but scarce information on female patients with BrS is available. OBJECTIVE: The purpose of this study was to investigate the clinical characteristics and long-term prognosis of women with BrS. METHODS: A multicenter retrospective study of patients diagnosed with BrS and previous electrophysiological study (EPS) was performed. RESULTS: Among 770 patients, 177 (23%) were female. At presentation, 150 (84.7%) were asymptomatic. Females presented less frequently with a type 1 electrocardiographic pattern (30.5% vs 55.0%; P <.001), had a higher rate of family history of sudden cardiac death (49.7% vs 29.8%; P <.001), and had less sustained ventricular arrhythmias (VAs) on EPS (8.5% vs 15.1%; P = .009). Genetic testing was performed in 79 females (45% of the sample) and was positive in 34 (19%). An implantable cardioverter-defibrillator was inserted in 48 females (27.1%). During mean (± SD) follow-up of 122.17 ± 57.28 months, 5 females (2.8%) experienced a cardiovascular event compared to 42 males (7.1%; P = .04). On multivariable analysis, a positive genetic test (18.71; 95% confidence interval [CI] 1.82-192.53; P = .01) and atrial fibrillation (odds ratio 21.12; 95% CI 1.27-350.85; P = .03) were predictive of arrhythmic events, whereas VAs on EPS (neither with 1 or 2 extrastimuli nor 3 extrastimuli) were not. CONCLUSION: Women with BrS represent a minor fraction among patients with BrS, and although their rate of events is low, they do not constitute a risk-free group. Neither clinical risk factors nor EPS predicts future arrhythmic events. Only atrial fibrillation and positive genetic test were identified as risk factors for future arrhythmic events.

Initial experience and treatment of atrial fibrillation using a novel irrigated multielectrode catheter: Results from a prospective two-center study.

BACKGROUND: PV electrical isolation has become the cornerstone of catheter ablation for the treatment of atrial fibrillation (AF). Several strategies have been proposed to achieve this goal. The aim of this study was to assess the efficacy and safety of AF ablation using a new circular irrigated multielectrode ablation catheter designed to achieve single-delivery pulmonary vein (PV) isolation. METHODS: Thirty-five patients with drug refractory paroxysmal AF and normal ejection fraction from two centers were prospectively enrolled in this study. All patients underwent PV isolation with an nMARQ circular irrigated multielectrode ablation catheter guided by an electroanatomic mapping system. Magnetic resonance imaging was performed to exclude PV stenosis. RESULTS: PV isolation was achieved in 138 of 140 (98.57%) targeted veins. The mean procedure time was 79.5 min (SD 39.3 min). During a mean follow up of 16.8±2.8 months, 27 of 35 (77.2%) patients were free of AF. No PV narrowing was observed. One case of pericardial effusion due to perforation of the left atrial free wall during catheter manipulation did occur. CONCLUSIONS: PV isolation with a circular irrigated multielectrode ablation catheter is a feasible technique with a high acute success rate. The majority of patients remained asymptomatic during the midterm follow-up period. PV stenosis was not detected. While only a single serious adverse event occurred, this technique׳s safety profile should be tested in larger studies.

Prevención primaria con cardiodesfibrilador implantable y terapia de resincronización cardíaca en pacientes ancianos: resultados de un estudio multicéntrico español

Propósito: a la fecha sigue sin haber pruebas en cuanto a los resultados del uso de dispositivos para arritmias ventriculares en pacientes añosos, y menos aun para indicaciones de prevención primaria. La finalidad del estudio fue describir la evolución en términos de la eficacia y seguridad de la terapia con cardiodesfibriladores implantables (CDI) en una gran cohorte de pacientes añosos. Métodos y resultados: estudio multicéntrico retrospectivo realizado en 15 hospitales españoles. Se incluyeron pacientes consecutivos referidos para implante de CDI antes de 2011. Se consideró que 162 de los 1.174 pacientes (13,8%) con 75 años o más eran “añosos”. Comparado con aquellos pacientes <75 años, este subgrupo presentaba más comorbilidades como hipertensión, enfermedad pulmonar obstructiva crónica y falla renal, y más internaciones previas debido a insuficiencia cardíaca (IC). A lo largo de una media de seguimiento de 104,4 ± 3,3 meses, fallecieron 162 pacientes (14%), 120 de los más jóvenes (12,4%) y 42 (24,4%) de los añosos. El análisis de Kaplan-Meier mostró un aumento de la probabilidad de morir con el aumento de la edad (17, 24, 28, y 69% a los 12, 24, 48, y 60 meses de seguimiento en el grupo de pacientes añosos). No hubo diferencias entre la tasa de intervenciones con CDI apropiadas o inapropiadas. Conclusión: en el mundo real, los pacientes añosos constituyen ~15% de los implantes de CDI para prevención primaria de la muerte súbita cardíaca (MSC). Si bien la tasa de terapias apropiadas es similar en los diferentes grupos, el beneficio de CDI se ve atenuado por un mayor aumento del riesgo de mortalidad entre los pacientes que son mayores de 75 años al momento del implante.

Stroke and Systemic Embolism After Successful Ablation of Typical Atrial Flutter.

BACKGROUND: Following successful cavotricuspid isthmus (CTI) ablation during typical atrial flutter (AFL), anticoagulation therapy is usually withdrawn. However, potential subsequent atrial fibrillation (AF) in these patients may increase embolic risk in the long term. Embolic rates in this setting have not been clearly established. Our aim was to determine the incidence of stroke/systemic embolism following radiofrequency ablation of AFL, particularly in those without a prior history of AF. HYPOTHESIS: After succesful AFL ablation, patients may suffer embolic complications in the long-term follow-up, mainly due to asymptomatic AF episodes. METHODS: We conducted a retrospective analysis of all patients who underwent CTI ablation due to AFL in our center between 2006 and 2009. RESULTS: During the study period, 188 patients (mean age, 62.9 ± 8.6 years) underwent CTI ablation; 120 without prior AF were included in the study. At the end of the follow-up period (mean, 5.0 ± 2.4 years), 56.7% of patients (68/120) remained in sinus rhythm, 7/120 experienced a recurrence of AFL, and 45/120 (38%) developed AF. Ischemic stroke occurred in 11 patients and systemic embolism in 1. Of these patients, 5 had documented AF following AFL ablation. In the remaining 7 cases, previously undiagnosed AF was subsequently diagnosed at the time of stroke/embolism. CONCLUSIONS: Patients with AFL who undergo successful ablation are by no means free from embolic complications during long-term follow-up, mainly due to a high rate of AF development. Given the difficulties in detecting AF and the uncertainty about the temporal relation of AF and stroke, oral anticoagulation may need to be continued in those patients with underlying stroke risk factors.

Primary prevention implantable cardioverter-defibrillator and cardiac resynchronization therapy-defibrillator in elderly patients: results of a Spanish multicentre study.

AIMS: Currently, there continues to be a lack of evidence regarding outcomes associated with device-based therapy for ventricular arrhythmias in elderly patients, even more in primary-prevention indications. We aimed to describe the follow-up in terms of efficacy and safety of implantable cardioverter-defibrillator (ICD) therapy in a large cohort of elderly patients. METHODS AND RESULTS: Retrospective multicentre study performed in 15 Spanish hospitals. Consecutive patients referred for ICD implantation before 2011 were included. One hundred and sixty-two of 1174 patients (13.8%) ≥75 years were considered as 'elderly'. When compared with those patients <75, this subgroup presented more co-morbid conditions, including hypertension, chronic obstructive pulmonary disease , and renal failure, and more previous hospitalizations due to heart failure (HF). During a mean follow-up of 104.4 ± 3.3 months, 162 patients (14%) died, 120 in the younger age (12.4%), and 42 (24.4%) in the elderly. Kaplan-Meier analysis showed an increased probability of death with increasing age (17, 24, 28, and 69% at 12, 24, 48, and 60 months of follow-up in the elderly group). There was neither difference regarding the rate of appropriate nor inappropriate ICD intervention. CONCLUSION: In a real-world scenario, elderly patients comprise ∼15% of ICD implantations for primary prevention of sudden cardiac death (SCD). Although the rate of appropriate therapy is similar between groups, the benefit of ICD is attenuated for a major increase in mortality risk among those patients ≥75 years at the moment of device implantation.

Anticoagulación oral en la enfermedad renal crónica con fibrilación auricular / Oral anticoagulation in chronic kidney disease with atrial fibrillation

La presencia de fibrilación auricular en pacientes con enfermedad renal crónica (ERC) resulta un hallazgo frecuente que aumenta de forma considerable el riesgo embólico. Las escalas CHADS2 y HAS-BLED, utilizadas en la población general para valorar el riesgo/beneficio de la anticoagulación oral (ACO), infraestiman, respectivamente, los riegos de embolia y hemorragia en la ERC, haciendo complicada la indicación de ACO en estos pacientes. Con la evidencia disponible, parece indicada la ACO en ERC estadio 3, siendo controvertido su uso en estadios más avanzados. Si bien resultan prometedores los nuevos ACO, dabigatrán y rivaroxaban, aprobados para ERC estadio 3, su papel esta aún por esclarecer (AU)

Atrial fibrillation is a common finding in patients with chronic kidney disease (CKD), which increases markedly the embolism risk. The CHADS2 and HAS-BLED scales, used in the general population to assess the risk/benefit of oral anticoagulation (OAC), underestimate respectively the risk of embolism and haemorrhage in CKD, making it difficult to decide whether to use OAC or not. Based on the available evidence, it seems indicated to use OAC in stage 3 CKD, while it is controversial in advanced stages. New OAC such as dabigatran and rivaroxaban have been approved in stage 3 CKD but their role is still somewhat uncertain (AU)

[Oral anticoagulation in chronic kidney disease with atrial fibrillation]. / Anticoagulación oral en la enfermedad renal crónica con fibrilación auricular.

Atrial fibrillation is a common finding in patients with chronic kidney disease (CKD), which increases markedly the embolism risk. The CHADS2 and HAS-BLED scales, used in the general population to assess the risk/benefit of oral anticoagulation (OAC), underestimate respectively the risk of embolism and haemorrhage in CKD, making it difficult to decide whether to use OAC or not. Based on the available evidence, it seems indicated to use OAC in stage 3 CKD, while it is controversial in advanced stages. New OAC such as dabigatran and rivaroxaban have been approved in stage 3 CKD but their role is still somewhat uncertain.

Successful retrieval of an irretrievable jugular tesio catheter using a fogarty arterial embolectomy catheter.

Long life expectancy and wide development of therapies have increased the number of patients under artificial treatment for lost kidney function or dialysis. Different options for vascular access are suitable for receiving this therapy. The use of tunneled catheters has consequently increased complications related to its use. A difficult retrieval of catheters caused by a hard fibrin sheath along its trajectory is a common drawback. Herein, we report a woman with suspicion of hemodialysis catheter infection and an irretrievable Tesio catheter. A novel technique using a Fogarty arterial catheter allowed a successful retrieval and avoided an aggressive management.

Cryoablation versus radiofrequency ablation for the treatment of atrioventricular nodal reentrant tachycardia: results of a prospective randomized study.

PURPOSE: Radiofrequency ablation (RF) of atrioventricular reentrant tachycardia (AVNRT) is an effective method for treating this arrhythmia. However, inadverted AV block requiring implantation of permanent pacemaker is a worrisome side effect. Although permanent AV block seems to be rare nowadays, patients are by no means spared from this severe complication. Catheter cryoablation is emerging as an alternative technology with an excellent safety profile, but limited data exist regarding its efficacy. METHODS: We conducted a randomized study among patients with AVNRT remitted to our center for EP study and ablation between January 2008 and June 2010. After giving a written consent, patients were randomized to conventional RF or cryoablation, unless specific preference of patient was stated. Primary outcomes were acute success, SVT recurrence, and complications, including AV block. RESULTS: One hundred nineteen patients were included (60 cryoablation and 59 conventional RF). There were no differences in demographic and clinical baseline data between groups. Acute procedural success was achieved in 59 patients (98 %) in cryoablation group and 59 (100 %) in RF. One patient in RF group underwent complete AV block and pacemaker implantation. Over a mean follow-up period of 256.6 days, there was a significant difference in AVNRT recurrence between cryoablation and RF patients (15 versus 3.4 %, p = 0.03). CONCLUSION: Catheter cryoablation of AVNRT is a clinically effective alternative to RF ablation, with excellent acute success rate. Despite a slightly higher rate of recurrence during long-term follow-up, these results suggest that cryoablation may be considered as first-line approach, especially in younger people, where the risk of permanent pacing because of inadvertent AV block may be relevant.

Dronedarone for recurrent ventricular tachycardia: a real alternative?

Sustained ventricular tachycardia (VT) is an important cause of morbidity and sudden death in patients with dilated cardiomyopathy. Although ICD effectively terminate VT episodes and improve survival, shocks reduce quality of life, and episodes of VT predict increased risk of heart failure and death despite effective therapy. Patients suffering recurrent VT episodes remain a challenge. Antiarrhytmic therapy reduces VT episodes, but it is associated with serious adverse events, and disappointing efficacy. Catheter ablation has emerged as an important option to control recurrent VT, but major procedure-related complications, and even death, are still issues to concern. And even with these armamentaria, some patients still have recurrent VT episodes and ICD shocks. We report on a patient with non-ischemic dilated cardiomyopathy and recurrent ventricular tachycardia resistant to multiple antiarrhytmic agents, in whom dronedarone was effective in completely suppressing ventricular tachycardia episodes.

Impact of drug eluting stents on the clinical practice of revascularisation of coronary artery disease.

AIMS: Drug-eluting stents (DES) have shown to reduce restenosis rates in all lesional subsets. This has expanded the application of percutaneous intervention (PCI). In this study we address the impact of the high DES penetration on the management of patients referred for coronary angiography. METHODS AND RESULTS: We have studied the cohorts of patients referred for coronary angiography in 2000-2001 prior to DES availability, and in 2005-2006 with a 73% DES implementation. In 2000-1 of 2,458 coronary angiographic studies, 84% had significant lesions (>50%), 56% had PCI, 8.8% had CABG and in 443 (18%) with significant lesions no revascularisation was attempted. In 2005-6 out of 2,600 angiographies, 84% had significant lesions, 64% had PCI, 6% had CABG and in 312 (12%) with significant lesions no revascularisation was done. The increase in PCI, the reduction in CABG and the decrease in non-revascularised diseased cases were all significant (p<0,001). The PCI and CABG groups in 2005-6 compared to 2000-1 had a more complex lesion profile with, however, less in-stent restenotic lesions treated (10% vs 4.2%; p<0.001). CONCLUSIONS: The wide clinical introduction of DES was associated with a significant increase in patients undergoing any kind of revascularisation, increasing the PCI volume to the detriment of CABG activity. Patients with PCI in 2006 had more complex lesions treated, whereas restenosis was less frequent.

Repeat mitral valve replacement: 30-years' experience.

Prosthetic heart valve dysfunction is an acquired condition that carries a significant risk of emergency surgery. However, the long-term natural history of the condition is not well understood. Between 1974 and 2006, 1535 isolated mitral valve replacements were performed at our hospital (in-hospital mortality 5%). In total, 369 patients needed a second operation (in-hospital mortality 8.1%), while 80 (age 59.8+/-11.4 years) needed a third. The reasons for the third intervention were structural deterioration (67.5%), paravalvular leak (20%) and endocarditis (6.3%). Some 15 patients died in hospital (18.8%). After a mean follow-up period of 17.8 years, 21 patients needed another intervention (i.e., a fourth intervention). The actuarial reoperation-free rate at 20 years was 40.1+/-13.8%. The late mortality rate was 58.5% (18-year survival rate 15.4+/-5.4%). Indications for repeat mitral valve replacement must be judged on an individual basis given the high risk associated with surgery.

Reintervenciones múltiples sobre la válvula mitral: 30 años de experiencia / Repeat mitral valve replacement: 30-years’ experience

La disfunción protésica es una enfermedad adquirida con significativo riesgo quirúrgico inmediato, aunque la historia natural a largo plazo es poco conocida. Entre 1974 y 2006 se realizaron 1.535 recambios mitrales aislados (mortalidad hospitalaria, 5%). Un total de 369 pacientes requirieron una segunda intervención (mortalidad hospitalaria, 8,1%) y 80, una tercera (59,8 ± 11,4 años). Las causas de la tercera intervención fueron deterioro estructural (67,5%), dehiscencia periprotésica (20%) y endocarditis (6,3%). La mortalidad hospitalaria fue 15 (18,8%) pacientes. Tras un seguimiento medio de 17,8 años, 21 pacientes precisaron nueva intervención (cuarta intervención) y la curva actuarial libre de reoperación fue del 40,1% ± 13,8% a 20 años. La mortalidad tardía fue del 58,5% (supervivencia a 18 años, 15,4% ± 5,4%). La indicación de una reintervención reiterativa mitral debe evaluarse de forma individualizada, dado el alto riesgo quirúrgico asociado (AU)

Prosthetic heart valve dysfunction is an acquired condition that carries a significant risk of emergency surgery. However, the long-term natural history of the condition is not well understood. Between 1974 and 2006, 1535 isolated mitral valve replacements were performed at our hospital (in-hospital mortality 5%). In total, 369 patients needed a second operation (in-hospital mortality 8.1%), while 80 (age 59.8[11.4] years) needed a third. The reasons for the third intervention were structural deterioration (67.5%), paravalvular leak (20%), and endocarditis (6.3%). Some 15 patients died in hospital (18.8%). After a mean follow-up period of 17.8 years, 21 patients needed another intervention (ie, a fourth intervention). The actuarial reoperation-free rate at 20 years was 40.1% [13.8%]. The late mortality rate was 58.5% (18-year survival rate 15.4% [5.4%]). Indications for repeat mitral valve replacement must be judged on an individual basis given the high risk associated with surgery (AU)

Gender differences of echocardiographic and gene expression patterns in human pressure overload left ventricular hypertrophy.

Gender influence on left ventricular (LV) remodeling associated to aortic valve stenosis (AS) has been long recognized, but underlying myocardial gene expression patterns have not been explored. We studied whether sex differences in echocardiographic LV anatomy and function in AS patients are associated with specific changes in myocardial mRNA expression of remodeling proteins. AS (n=39) and control (n=23)patients were assessed echocardiographically, and LV myocardial mRNA levels were quantified by PCR. AS patients exhibit increased wall thicknesses and LV mass index (LVMI), but only men show chamber dilation.Collagens and fibronectin mRNA levels increased correlatively to transforming growth factor-beta1 (TGF-beta1). In AS women, collagen I upregulation was proportionally higher than other extracellular matrix (ECM)components. No changes in matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 were detected. Gene expressions of sarcomeric proteins (beta-myosin heavy chain and myosin light chain-2) and TGF-beta1 were directly correlated with each other. Myosin light chain-2 mRNA levels increased proportionally to the transvalvular gradient, but women did so in a greater extent than men for a given gradient. In women, the hypertrophic growth response, reflected by LVMI, was proportional to the expression of genes encoding sarcomeric proteins and TGF-beta1. In men, chamber dilation and deterioration of LVEF was proportional to collagens, fibronectin, and TGF-beta1 gene expression levels. We evidenced gender biased gene expression patterns of the intracellular TGF-beta pathways involving the Smad branch, but not the TAK-1 branch, that could contribute to the remodeling differences observed in AS men and women. Based on these findings, a gender specific therapeutic approach of pressure overload LV hypertrophy could be justified.

Utility of implantable loop recorders for diagnosing unexplained syncope in clinical practice.

BACKGROUND: Establishing a symptom-rhythm correlation in patients with unexplained syncope is complicated because of its sporadic, infrequent, and unpredictable nature. Prolonged monitoring with an implantable loop recorder (ILR) allows the recording of electrocardiogram (ECG) data from a spontaneous syncopal event. HYPOTHESIS: The aim of this study was to evaluate the usefulness of the ILR for the diagnosis of syncope of unknown origin after conventional management in clinical practice. METHODS: We reviewed the results with ILR implantation in patients with syncope of unknown origin after conventional management in the cardiology department at HU Marques de Valdecilla (Santander, Cantabria, Spain). RESULTS: One hundred and forty patients (age 64 +/- 16 y; 86 male [62%]) with syncope of unknown etiology after conventional work-up underwent prolonged monitoring with an ILR from September 1998 to February 2006; 46 patients (33%) had structural heart disease. During a mean follow-up of 346 +/- 160 d, 51 patients (36.5%) had recurrent syncope with diagnostic ECG recording. An arrhythmic cause for syncope was found in 33 of them (64.5%), with bradycardia present in 27 (53%) and tachycardia in 6 (11%). There were no sudden deaths, and 1 patient suffered a complication related to a recurrence of syncope. CONCLUSION: Long-time experience with the ILR confirmed the utility of this device in the diagnosis of unexplained syncope in clinical practice. Most of these patients had syncope of arrhythmogenic etiology that could be successfully treated. This strategy of prolonged monitoring is safe even in patients with structural heart disease.

Avoidance of calcineurin inhibitors with use of proliferation signal inhibitors in de novo heart transplantation with renal failure.

BACKGROUND: This study describes our experience with proliferation signal inhibitors in de novo heart transplant recipients with significant renal impairment. To circumvent further nephrotoxicity, calcineurin inhibitors were avoided in the peri-operative period. METHODS: Immunosuppression in 20 patients was with a proliferation signal inhibitor (sirolimus, 14; everolimus, 6), an anti-mitotic drug, and corticosteroids from the time of transplantation. Induction was used in 9 patients (45%). All patients had preoperative significant renal dysfunction (mean glomerular filtration rate <30 ml/min/1.73 m(2)), and 4 patients required dialysis. RESULTS: Post-operatively, the glomerular filtration rate significantly increased (>65 ml/min/1.73 m(2) at Month 1, remaining stable thereafter). No patients required dialysis after the first month of transplantation. Mean follow-up was 500 days. Rejection episodes occurred in 11 patients (55%), and 4 patients died (2 of rejection, although 1 death occurred 48 days after conversion to conventional treatment with tacrolimus). Half of the patients were eventually converted to conventional calcineurin-inhibitor therapy because of proliferation signal inhibitor adverse events. CONCLUSION: Although this immunosuppressive approach was associated with a somewhat high rate of rejection and frequent side effects, it represents an attractive alternative in the complicated peri-operative setting of patients with significant renal impairment. This approach could serve as a temporary bridge to a conventional treatment.

Everolimus-related pulmonary toxicity in heart transplant recipients.

Pulmonary toxicity (PT) is emerging as a frequent and serious complication of sirolimus, a proliferation signal inhibitor (PSI) used in solid-organ transplantation. Everolimus is a more recently developed PSI with molecular structure very similar to that of sirolimus. Surprisingly, although experience with everolimus is increasing and becoming substantial, there remains very little information about everolimus-related PT. Herein we report 2 heart transplant recipients who developed a non-infectious pulmonary syndrome after everolimus treatment was started. Transbronchial pulmonary biopsy specimens showed typical interstitial pneumonitis, and everolimus discontinuation resulted in rapid clinical and radiological improvement. Although PT seems to be more common after sirolimus exposure, everolimus is by no means spared from this potentially lethal complication and should always be suspected in the relevant clinical setting.

Cardiac intracavitary metastasis of a malignant solitary fibrous tumor: case report and review of the literature on sarcomas with left intracavitary extension.

BACKGROUND: Solitary fibrous tumor (SFT) of the pleura with malignant progression occurs uncommonly. Cardiac intracavitary extension of tumors is rarely seen, with left side location being exceptional. METHODS AND RESULTS: The authors report the first case of a malignant SFT metastatic to the heart occurring in a 74-year-old woman. The tumor first presented as a slow-growing pleural SFT that in 6 years reached a size of 16 cm. Two months after a complete surgical resection, the tumor was found to spread to the left atrium by intracavitary extension from the left upper pulmonary vein, simulating a cardiac myxoma. The primary tumor showed established features of malignancy including size greater than 10 cm; gross findings of necrosis; high cellularity, cytological atypia, and eight mitoses per 10 high-power fields. Immunohistochemical study revealed positivity of the tumor cells for CD34, bcl-2, and CD99. Aside from the present report, 52 previous cases of sarcoma with intracavitary extension to the left side of the heart have been described. Bone sarcoma is the type most frequently found. Peripheral arterial embolism can be a complication of advanced mesenchymal malignancy in 21% (11/53) of reported cases. CONCLUSION: Accurate histopathologic recognition of this rare type of metastatic disease is important because of the adverse prognosis as compared to cardiac myxoma.