Search

Cardiac amyloidosis is a disease of complex diagnosis and treatment. Some subtypes of cardiac amyloidosis are inherited. Among these, the most common variant is caused by mutations in the transthyretin gene. Correct identification of amyloidosis produced by a genetic defect is of great importance because it modifies the diagnostic and therapeutic approach in patients and their families. We describe our experience in the evaluation of two families with hereditary transthyretin cardiac amyloidosis. We discuss a number of considerations related to the evaluation of these patients and the diagnostic and therapeutic approach to perform in relatives.

Cardiac amyloidosis is a disease of complex diagnosis and treatment. Some subtypes of cardiac amyloidosis are inherited. Among these, the most common variant is caused by mutations in the transthyretin gene. Correct identification of amyloidosis produced by a genetic defect is of great importance because it modifies the diagnostic and therapeutic approach in patients and their families. We describe our experience in the evaluation of two families with hereditary transthyretin cardiac amyloidosis. We discuss a number of considerations related to the evaluation of these patients and the diagnostic and therapeutic approach to perform in relatives.

Introduction and objectives: The Kansas City Cardiomyopathy Questionnaire (KCCQ) is specifically designed to evaluate quality of life in patients with chronic heart failure (CHF). The purpose of this study was to assess the reliability, validity, and responsiveness to change of the Spanish version of the KCCQ.

Introduction and objectives: The Kansas City Cardiomyopathy Questionnaire (KCCQ) is specifically designed to evaluate quality of life in patients with chronic heart failure (CHF). The purpose of this study was to assess the reliability, validity, and responsiveness to change of the Spanish version of the KCCQ. Methods: The multicenter study involved 315 patients with CHF. Patients were evaluated at baseline and at weeks 24 and 26. The KCCQ, the Minnesota Living with Heart Failure Questionnaire (MLHFQ), and the Short Form-36 (SF-36) were administered. Reliability was assessed in stable patients (n = 163) by examining test–retest and internal consistency measures between weeks 24 and 26. Validity was evaluated at baseline (n = 315) by determining how KCCQ scores varied with New York Heart Association functional class and by comparing scores with those on similar domains of the MLHFQ and SF-36. Responsiveness to change was assessed in patients who experienced significant clinical improvement between baseline and week 24 (n = 31) by determining the effect size. Results: Reliability coefficients ranged between 0.70 and 0.96 for the different domains. Mean KCCQ scores varied significantly with New York Heart Association functional class (P < .001). Correlations with

La amiloidosis cardiaca causa una miocardiopatia restrictiva de mal pronostico debida al deposito intersticial de proteina anomala en el miocardio. Esta proteina puede tener diversos origenes y dar lugar a subtipos de amiloidosis con diferente pronostico y manejo terapeutico. Los farmacos utilizados habitualmente en la insuficiencia cardiaca son poco eficaces en la amiloidosis, y la indicacion de trasplante cardiaco es controvertida porque la enfermedad afecta a multiples organos y por la probabilidad de recidiva en el organo trasplantado. La utilizacion de nuevas tecnicas para la identificacion del tipo de amiloidosis, la aparicion de procedimientos capaces de impedir o disminuir la produccion de amiloide, la posibilidad de monitorizar la respuesta al tratamiento y, sobre todo, la formacion de equipos multidisciplinarios capaces de realizar tratamientos combinados, que incluyen el trasplante multiorganico, han contribuido a mejorar sustancialmente el pronostico de la enfermedad.

Cardiac amyloidosis is associated with the interstitial deposition of abnormal protein in the myocardium, which can lead to a form of restrictive cardiomyopathy with a poor prognosis. This protein can have a number of different origins, which give rise to various subtypes of amyloidosis that have different prognoses and that require different therapeutic approaches. Drugs commonly used in heart failure have little effect in amyloidosis and the use of heart transplantation is controversial because amyloidosis is a multi-organ disease and because there is a possibility of disease recurrence in the graft. The use of new techniques to identify the specific amyloidosis subtype, the emergence of novel ways of preventing or decreasing amyloid production, the ability to monitor responses to therapy and, above all, the introduction of multidisciplinary teams that can implement a combination of therapies, including multiple organ transplantation, have contributed to a substantial improvement in the prognosis of this disease.

Background Prognosis of advanced cardiac light-chain amyloidosis (ACAL) is ominous. Diagnosis of ACAL is frequently preceded by several biopsies of non-clinically affected tissues, which can result in dangerous treatment delays. Combinations of alkylators and steroids have a limited role in its therapy. Definitive efficacy of bortezomib in ACAL is not widely described. In this study we analyze the diagnostic yield of biopsies and compare the effect of bortezomib with other therapeutic strategies in ACAL patients. Methods This study is a retrospective analysis of 40 consecutive ACAL patients treated at our hospital (2005 to 2015). For comparison purposes, the cohort was divided into 2 groups: patients treated with bortezomib ( n = 23) and those treated with other therapeutic approaches (non-bortezomib, n = 8). Results Sensitivity of biopsies of non-clinically affected organs was 23%, as compared with 97% for affected organ biopsies ( p 2 biopsies resulted in an average delay in diagnosis of 4.1 months ( p = 0.007). Hematologic response was observed in 96% of patients in the bortezomib group compared with 25% in the non-bortezomib group (relative risk=3.8; 95% confidence interval 1.14 to 12.75; p = 0.0002). Cardiac response criteria were met by 60% of patients in the bortezomib group as compared with none in the non-bortezomib group ( p = 0.005). Survival at 6 months and 1 and 2 years for bortezomib patients was 91%, 91% and 73%, as compared with 58%, 15% and 0% for non-bortezomib patients (log rank, p Conclusion In our experience, the sensitivity of biopsies from non-affected organs in ACAL is poor and could result in diagnostic delay. Bortezomib was associated with higher hematologic and cardiac response rates as well as survival when compared with other therapies.

Background Excessive alcohol consumption is a well-known aetiology of atrial arrhythmias but there is little information concerning the prevalence or incidence of malignant ventricular arrhythmias in alcoholic cardiomyopathy (ACM). This study sought to investigate incidence and predictive factors of ventricular arrhythmias in ACM. Methods Retrospective observational study of the clinical characteristics and long-term arrhythmic events in 282 consecutive patients with ACM (94 individuals) and idiopathic dilated cardiomyopathy (IDCM) (188 individuals) evaluated between 1993 and 2011. Results During a median follow-up of 38months (IQR:12–77), 42 patients died and 79 underwent heart transplantation [31 (33%) with ACM vs 90 (48%) with IDCM; p=0.017]. A total of 37 (13%) patients [18 (19%) ACM vs 20 (11%) IDCM; p=0.048] suffered malignant ventricular arrhythmias. On multivariate analysis, left bundle branch block (LBBB) (OR 2.4; CI95%: 1.2–5; p=0.015) and alcoholic aetiology (OR 2.3; CI95%: 1.1–4.5; p=0.026) were the only independent predictors of malignant ventricular arrhythmic events. A total of 18 (19%) ACM patients experienced 20 malignant ventricular arrhythmic events (4 aborted SCD, 8 SCD and 8 appropriate ICD therapies). At baseline evaluation, the only independent predictor of malignant ventricular arrhythmias in ACM patients was LBBB (OR 11.2; CI95%: 2.6–50; p=0.001). No malignant ventricular arrhythmias were recorded during follow-up in ACM patients if left ventricular ejection fraction (LVEF) had increased or remained ≥40%. Conclusions Malignant ventricular arrhythmias are more frequent in ACM than in IDCM. LBBB identifies ACM patients with increased risk of SCD. No malignant ventricular arrhythmias were found during follow-up in ACM patients when LVEF was ≥40%.

IMPORTANCE: Worsening chronic heart failure (HF) is a major public health problem.OBJECTIVE: To determine the optimal dose and tolerability of vericiguat, a soluble guanylate cyclase stimulator, in patients with worsening chronic HF and reduced left ventricular ejection fraction (LVEF).DESIGN, SETTING, AND PARTICIPANTS: Dose-finding phase 2 study that randomized 456 patients across Europe, North America, and Asia between November 2013 and January 2015, with follow-up ending June 2015. Patients were clinically stable with LVEF less than 45% within 4 weeks of a worsening chronic HF event, defined as worsening signs and symptoms of congestion and elevated natriuretic peptide level requiring hospitalization or outpatient intravenous diuretic.INTERVENTIONS: Placebo (n = 92) or 1 of 4 daily target doses of oral vericiguat (1.25 mg [n = 91], 2.5 mg [n = 91], 5 mg [n = 91], 10 mg [n = 91]) for 12 weeks.MAIN OUTCOMES AND MEASURES: The primary end point was change from baseline to week 12 in log-transformed level of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The primary analysis specified pooled comparison of the 3 highest-dose vericiguat groups with placebo, and secondary analysis evaluated a dose-response relationship with vericiguat and the primary end point.RESULTS: Overall, 351 patients (77.0%) completed treatment with the study drug with valid 12-week NT-proBNP levels and no major protocol deviation and were eligible for primary end point evaluation. In primary analysis, change in log-transformed NT-proBNP levels from baseline to week 12 was not significantly different between the pooled vericiguat group (log-transformed: baseline, 7.969; 12 weeks, 7.567; difference, -0.402; geometric means: baseline, 2890 pg/mL; 12 weeks, 1932 pg/mL) and placebo (log-transformed: baseline, 8.283; 12 weeks, 8.002; difference, -0.280; geometric means: baseline, 3955 pg/mL; 12 weeks, 2988 pg/mL) (difference of means, -0.122; 90% CI, -0.32 to 0.07; ratio of geometric means, 0.885, 90% CI, 0.73-1.08; P = .15). The exploratory secondary analysis suggested a dose-response relationship whereby higher vericiguat doses were associated with greater reductions in NT-proBNP level (P CONCLUSIONS AND RELEVANCE: Among patients with worsening chronic HF and reduced LVEF, compared with placebo, vericiguat did not have a statistically significant effect on change in NT-proBNP level at 12 weeks but was well-tolerated. Further clinical trials of vericiguat based on the dose-response relationship in this study are needed to determine the potential role of this drug for patients with worsening chronic HF.TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01951625.

Resumen Han sido muchos los trabajos publicados en el ultimo ano en las 3 areas recogidas en este articulo: cardiologia clinica, cardiologia geriatrica e insuficiencia cardiaca y trasplante. Entre las novedades en cardiologia clinica se han incluido aportaciones de grupos espanoles en valvulopatia tricuspide y aortica, novedades en fibrilacion auricular, sincope y sobre las caracteristicas clinicas de los cardiopatas, asi como varios trabajos sobre cardiopatias familiares y sobre cardiopatia isquemica cronica. Respecto a la cardiologia geriatrica, los estudios mas relevantes durante el ultimo ano estan centrados en insuficiencia cardiaca, estenosis aortica degenerativa y tambien datos de fibrilacion auricular en la poblacion anciana. En insuficiencia cardiaca y trasplante, las novedades mas destacables se centran en la importancia de las unidades multidisciplinares, asi como en los pacientes con funcion sistolica preservada. Tambien se destacan aportaciones en relacion con el deficit de hierro, los nuevos farmacos y los nuevos dispositivos y biomarcadores. Por ultimo se resenan trabajos centrados en insuficiencia cardiaca aguda y trasplante, como los farmacos inotropicos y los dispositivos de asistencia ventricular.

AimsPrevention of hospital readmissions is one of the main objectives in the management of patients with heart failure (HF). Most of the models predicting readmissions are based on data extracted from hospitalized patients rather than from outpatients. Our objective was to develop a validated score predicting 1-month and 1-year risk of readmission for worsening of HF in ambulatory patients. Methods and resultsA cohort of 2507 ambulatory patients with chronic HF was prospectively followed for a median of 3.3years. Clinical, echocardiographic, ECG, and biochemical variables were used in a competing risk regression analysis to construct a risk score for readmissions due to worsening of HF. Thereafter, the score was externally validated using a different cohort of 992 patients with chronic HF (MUSIC registry). Predictors of 1-month readmission were the presence of elevated natriuretic peptides, left ventricular (LV) HF signs, and estimated glomerular filtration rate (eGFR) 26mm/m(2), heart rate >70 b.p.m., LV HF signs, and eGFR 5% event rate) for 1-month HF readmission. Likewise, low-risk (7.8%), intermediate-risk (15.6%) and high-risk groups (26.1%) were identified for 1-year HF readmission risk. The C-statistics remained consistent after the external validation (

Cardiac allograft vasculopathy remains one of the main causes of morbidity and mortality after heart transplantation, although its impact is becoming somewhat smaller as prophylactic measures are implemented. Advances in the understanding of the molecular and cellular mechanisms involved in the genesis and development of cardiac allograft vasculopathy are opening ways for new diagnostic and therapeutic strategies. Successful prophylaxis of the early stages of the disease has been demonstrated with the use of newer immunosuppressive agents, such as sirolimus and everolimus, that will probably be included in future protocols. For most patients with established cardiac allograft vasculopathy, currently available revascularisation methods and retransplantation are not appropriate options. Antiproliferative agents could provide significant improvement in terms of symptom relief and prognosis, but their definite value must be proven in well-designed trials.

A pesar de los avances en todos los campos de la cardiologia, la incidencia de insuficiencia cardiaca aumenta cada ano. El tratamiento farmacologico, los dispositivos de resincronizacion y la cirugia de la insuficiencia cardiaca han conseguido prolongar la supervivencia de estos pacientes y mejorar sus sintomas. Sin embargo, en las fases mas avanzadas de la enfermedad, estas opciones terapeuticas llegan a ser ineficaces, y son el trasplante cardiaco (TXC) y los dispositivos de asistencia circulatoria (DAC) los que pueden permitir prolongar la supervivencia y mejorar la calidad de vida. El TXC es, desde hace 25 anos, la opcion terapeutica mas efectiva para pacientes con insuficiencia cardiaca en fases terminales. La escasez de donantes apropiados y el desarrollo de otras alternativas terapeuticas eficaces en estadios menos avanzados hacen que este tratamiento se reserve para pacientes jovenes que presentan cardiopatias con poca expectativa de vida a corto plazo. Los DAC han demostrado su efectividad como terapia temporal, ya sea como puente al trasplante o como Puente a la recuperacion, y tambien como soporte permanente en pacientes con contraindicaciones para TXC. Actualmente disponemos de asistencias paracorporeas, intracorporeas e incluso sistemas que permiten la completa sustitucion del corazon. La generalizacion de su uso dependera del establecimiento de unas indicaciones apropiadas, de la mejora en su relacion coste-beneficio, y de la disminucion de la aun importante tasa de complicaciones asociadas.

Background — Data from studies of angiotensin-converting enzyme inhibitors provide evidence that the renin-angiotensin-aldosterone system plays a role as a mediator of atrial remodeling in atrial fibrillation. The present study has evaluated the effect of treatment with the angiotensin I type 1 receptor blocker irbesartan on maintaining sinus rhythm after conversion from persistent atrial fibrillation. Methods and Results — To be included in the present study, patients must have had an episode of persistent atrial fibrillation for >7 days. The patients were then randomized and scheduled for electrical cardioversion. Two groups of patients were compared: Group I was treated with amiodarone, and group II was treated with amiodarone plus irbesartan. The primary end point was the length of time to a first recurrence of atrial fibrillation. From a total of 186 patients assessed in the study, 154 were analyzed with the use of intention-to-treat analysis. Seventy-five patients were randomly allocated to group I and 79 to group II. After 2 months of follow-up in the intention-to-treat analysis, the group treated with irbesartan had fewer patients with recurrent atrial fibrillation (Kaplan-Meier analysis, 84.79% versus 63.16%, P =0.008). The Kaplan-Meier analysis of time to first recurrence during the follow-up period (median time, 254 days [range, 60 to 710]) also showed that patients treated with irbesartan had a greater probability of remaining free of atrial fibrillation (79.52% versus 55.91%, P =0.007). Conclusions — Patients treated with amiodarone plus irbesartan had a lower rate of recurrence of atrial fibrillation than did patients treated with amiodarone alone.

Introduccion y objetivos Una limitacion importante de la ablacion con cateter estandar es el volumen y la profundidad limitada de sus lesiones. Los cateteres irrigados, debido al mayor tamano de la lesion, podrian ser utiles en los pacientes con aleteo auricular tipico. El proposito de este estudio fue comparar, de forma prospectiva, la ablacion con cateter estandar frente a irrigado en estos pacientes. Metodos Se aleatorizo a 37 pacientes consecutivos remitidos para ablacion del istmo cavotricuspideo por aleteo auricular tipico. En 20 pacientes se realizo ablacion con cateter convencional (edad media 62 ± 18 anos, 18 varones). En 17 pacientes se realizo ablacion del istmo con cateter irrigado (edad media de 71 ± 4 anos, 13 varones). Resultados Con los cateteres estandar se consiguio ablacion completa del istmo cavotricuspideo en 18 pacientes (90%), con una media de 19 ± 15 aplicaciones. Con los cateteres irrigados se consiguio ablacion completa del istmo en todos ellos, con una media de 8 ± 7 aplicaciones (p Conclusiones Con el empleo de los cateteres irrigados se puede realizar la ablacion del istmo de forma muy efectiva, reduciendo el tiempo total del procedimiento y escopia.

Introduccion y objetivos En este estudio evaluamos las concentraciones de troponina I cardiaca (cTnI) y distintos marcadores de lesion miocardica tras cardioversion externa electiva o interna a traves de cateteres especificos o de desfibrilador automatico. Material y metodos Analizamos prospectiva y consecutivamente los datos de 30 pacientes tras cardioversion electrica. Se determinaron concentraciones de cTnI, mioglobina, creatincinasa (CK), CK-MB-masa e indice MB/CK en muestras precardioversion, y a las 2, 8 y 24 h poscardioversion. La energia de choque estuvo comprendida entre 50 y 360 J (235 ± 106 J) en cardioversiones externas, y entre 3 y 37 J (15 ± 8 J) en cardioversiones internas. Resultados Tras las cardioversiones externas se detectaron valores anormales de CK en el 33% de los pacientes, asi como de mioglobina, CK-MB e index. Las concentraciones de cTnI permanecieron en todo momento dentro de limites normales, sin detectarse elevaciones patologicas en ninguno de los pacientes. A diferencia de las cardioversiones externas, tras las internas, en los pacientes que la precisaron por fibrilacion auricular, no se detectaron valores patologicos de ningun marcador bioquimico. Por el contrario, si encontramos concentraciones patologicas de CK-MB-masa y mioglobina, e incluso de cTnI en dos de los pacientes que recibieron cardioversion interna a traves de un desfibrilador automatico. Conclusiones La concentracion de cTnI se mantuvo en valores indetectables tras la cardioversion externa, aunque el resto de los marcadores mas inespecificos se modificaran. En el grupo de cardioversion interna por fibrilacion auricular no se detecto ningun movimiento enzimatico.

Pathologies associated with alterations in the vascular system of the pulmonary circuit constitute a separate arena within cardiovascular pathology. Disorders affecting the pulmonary circulation are heterogenous in nature, although all involve the presentation of significant alterations in the pulmonary arterial and/or venous systems, which are identified through macroscopic and microscopic examination (Table 2.1).

Background and objectives AL amyloidosis is a rare condition whose management is undergoing changes due to recent advances in diagnosis and treatment. We describe a contemporary series of patients with AL amyloidosis to analyze the features that enable early diagnosis and optimal management. Patients and methods We recruited for analysis 32 patients (19 women; mean age, 63 years) treated consecutively at our center. Results Eighty-four percent of the patients presented with asthenia, dyspnea or edema, with a previous duration of symptoms of 8 months (median). Cardiac (21/32) and renal impairment were the most common type (11/32). All of the patients, except one, had a monoclonal component in serum/urine or abnormal values for free light chains (78%, λ). The bone marrow (BM) showed clonal plasmacytosis in 29 cases. All of the cardiac biopsies and 50% of the BM biopsies showed amyloid deposits. The results of the echocardiogram and/or cardiac resonance were abnormal in 27/30 cases. The median NT-proBNP value at diagnosis was 5200 ng/ml. Thirteen patients died due to heart failure, 2 due to rejection after heart transplantation, 2 due to pneumonia and 1 after a stroke. Ten patients did not undergo treatment, 12 were treated with bortezomib and 5 were treated with alkylating agents. Five patients underwent heart transplantation and 4 underwent autologous bone marrow transplantation. Fourteen patients achieved a complete hematologic response and 10 achieved organ response. The median survival was 17 months. Conclusions Cardiac involvement is the major determinant of prognosis. Yield of involved organ biopsy is high (100% heart biopsies). Antineoplastic treatment with bortezomib and/or autologous bone marrow transplantation achieves hematological responses with improvements in organ impairment.

Fundamento y objetivo: La hipertension pulmonar cronica causada por tromboembolia (HTPTEC) sin trombos centrales que permitan la endarterectomia quirurgica tiene un pesimo pronostico. Los vasodilatadores pulmonares podrian ser de utilidad en esta entidad. El bosentan ha sido utilizado en un pequeno numero de pacientes con HTPTEC con efectos iniciales (3-6 meses) favorables, pero los resultados a mas largo plazo son desconocidos. Pacientes y metodo: Descripcion retrospectiva de los efectos del bosentan en 6 pacientes con HTPTEC con un seguimiento medio de 15 (intervalo, 8-26) meses. Resultados: A los 3 meses se observo mejoria clinica en todos los pacientes, con tendencia a reduccion de las resistencias pulmonares (media [desviacion estandar], 1.008 [624] frente a 768 [392] din/s/cm­5; p = 0,07). A largo plazo, persistia la mejoria clinica (clase funcional de la New York Heart Association [NYHA] basal, 3,0 [0,4] frente a 2,0 [0] al final del seguimiento; p < 0,01) y en la prueba de 6 min (230 [124] m la basal frente a 313 [70] m 1 ano despues), y se mantenia la tendencia a la disminucion del peptido escindido del peptido natriuretico tipo B (NT-proBNP, 2.225 [2.079] frente a 1.056 [1.104] pg/ml 1 ano despues). Conclusiones: El bosentan parece una alternativa valida a largo plazo en este subgrupo de pacientes con HTPTEC.

We sought to determine the incidence, risk factors, and consequences of acute rejection (AR) after conversion from a calcineurin inhibitor (CNI) to a proliferation signal inhibitor (PSI) in maintenance heart transplantation. Relevant clinical data were retrospectively obtained for 284 long-term heart transplant recipients from nine centers in whom CNIs were replaced with a PSI (sirolimus or everolimus) between October 2001 and March 2009. The rejection rate at one yr was 8.3%, stabilizing to 2% per year thereafter. The incidence rate after conversion (4.9 per 100 patient-years) was significantly higher than that observed on CNI therapy in the pre-conversion period (2.2 per 100 patient-years). By multivariate analysis, rejection risk was associated with a history of late AR prior to PSI conversion, early conversion (

We report the case of a 47-year-old man with end-stage ischemic heart disease who underwent implantation of a Berlin Heart EXCOR biventricular assist device (VAD) as a bridge to transplantation (Figure 1). He received oral anticoagulation and dual antiplatelet therapy with acetylsalicylic acid and clopidogrel, according to the standard protocol until, 1 month later, he had a hemorrhagic stroke that left no sequelae. Therefore, the decision was made to discontinue the antiplatelet therapy and to treat the patient with acenocoumarol alone. Three months later, he came to the emergency service because of a warning from the VAD that indicated low flow in the system. He had an international normalized ratio (INR) of 2.6. Inspection of the left VAD (Figures 2A and 2B and video clip [supplementary material]) revealed a moving shadow (s) associated with a thrombus that grew rapidly (e) within the blood chamber, in addition to an abnormal expansion of the outer membrane during systole (Figure 2C). As we suspected rupture of 1 of the membranes that separate the 2 chambers (blood and air) and because of the risk of systemic embolization of the thrombus, the left VAD cannulas were rapidly clamped and the flow in the right VAD was reduced to prevent acute pulmonary edema. The malfunctioning VAD was replaced, (Figure 3) and rupture of the inner membrane (*) of the explanted device and the presence of a large associated thrombus (d) were confirmed. The outcome of this replacement was favorable and the patient received a transplant several weeks later. Thrombotic complications associated with VAD are relatively frequent and potentially fatal events. In this case, early identification of the problem and urgent intervention allowed successful replacement of the device and subsequent transplantation.

Background: In the last decade, mTOR inhibitors (mTOR-is) have become the cornerstone of the calcineurin inhibitor (CNI)-reduced/free regimens aimed to the preservation of post-transplant renal function. We compared utility and safety of the total replacement of calcineurin inhibitors with a mTOR-i with a strategy based on calcineurin inhibitor minimization and concomitant use of m-TOR-i. Methods: In a retrospective multi-center cohort of 394 maintenance cardiac recipients with renal failure (GFR - 60 mL/min/1.73 m(2)), we compared 235 patients in whom CNI was replaced with a mTOR-i (sirolimus or everolimus) with 159 patients in whom mTOR-is were used to minimize CNIs. A propensity score analysis was carried out to balance between group differences. Results: Overall, after a median time of 2 years from mTOR-i initiation, between group differences for the evolution of renal function were not observed. In a multivariate adjusted model, improvement of renal function was limited to patients with mTOR-i usage within 5 years after transplantation, particularly with the conversion strategy, and in those patients who could maintain mTOR-i therapy. Significant differences between strategies were not found for mortality, infection and mTOR-i withdrawal due to drug-related adverse events. However, conversion group tended to have a higher acute rejection incidence than the minimization group (p = 0.07). Conclusion: In terms of renal benefits, our results support an earlier use of mTOR-is, irrespective of the strategy. The selection of either a conversion or a CNI minimization protocol should be based on the clinical characteristics of the patients, particularly their rejection risk. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

Introduction and objectives: The present article reports the characteristics and results of heart transplantation in Spain since this therapeutic modality was first used in May 1984. Methods: We summarize the main features of recipients, donors, and surgical procedures, as well as the results of all heart transplantations performed in Spain until December 31, 2012. Results: A total of 247 heart transplantations were performed in 2012. The whole series consisted of 6775 procedures. Recent years have seen a progressive worsening in the clinical characteristics of recipients (34% aged over 60 years, 22% with severe kidney failure, 17% with insulin-dependent diabetes, 29% with previous heart surgery, 16% under mechanical ventilation) and donors (38% aged over 45 years, 26% with recipient: donor weight mismatch > 20%), and in surgical conditions (29% of procedures at >4 h ischemia and 36% as emergency transplantations). The probability of survival at 1, 5, 10, and 15 years of follow-up was 78%, 67%, 53%, and 38%, respectively. These results have remained stable since 1995. Conclusions: In recent years, the number of heart transplantations/year in Spain has remained stable at around 250. Despite the worsening of recipient and donor clinical characteristics and of time-to-surgery, the results in terms of mortality have remained stable and compare favorably with those of other countries. (C) 2013 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S. L. All rights reserved.

et al., [Background]: Mitochondrial disorders (MD) are multisystem diseases that arise as a result of dysfunction of the oxidative phosphorylation system. The predominance of neuromuscular manifestations in MD could mask the presence of other clinical phenotypes such as cardiac dysfunction. Reported here is a retrospective study, the main objective of which was to characterize the clinical and molecular features of a cohort of patients with cardiomyopathy and MD. [Methods and Results]: Hospital charts of 2,520 patients, evaluated for presumed MD were reviewed. The clinical criterion for inclusion in this study was the presence of a cardiac disturbance accompanied by a mitochondrial dysfunction. Only 71 patients met this criterion. The mitochondrial genome (mtDNA) could be sequenced only in 45 and the pathogenicity of 2 of the found changes was investigated using transmitochondrial cybrids. Three nucleotide changes in mtDNA that may be relevant and 3 with confirmed pathogenicity were identified but no mutations were found in the 13 nuclear genes analyzed. [Conclusions]: The mtDNA should be sequenced in patients with cardiac dysfunction accompanied by symptoms suggestive of MD; databases should be carefully and periodically screened to discard mitochondrial variants that could be associated with MD; functional assays are necessary to classify mitochondrial variants as pathogenic or polymorphic; and additional efforts must be made in order to identify nuclear genes that can explain some as yet uncharacterized molecular features of mitochondrial cardiomyopathy., This work was supported by the Instituto de Salud Carlos III (grants PI 07/0167 and PI 10/0703 to R.G., PI 09/00941 and PI 06/0205 to B.B. and PI060547 to M.A.M.) and the Comunidad de Madrid (grant number GEN-0269/2006 to R.G). B.B. is supported by the programme “Intensificación de la Actividad Investigadora”, from Instituto de Salud Carlos III-Ministerio de Ciencia e Innovación (CIII-MICIN) and the Agencia Lain Entralgo (Comunidad de Madrid). M.E.G. receives grant support from the Centre for Biomedical Research on Rare Diseases (CIBERER) and P. Villar and B. Breton from Instituto de Investigación Puerta de Hierro Majadahonda (IDIPHIM).

The number of heart-transplant recipients exceeding 20 years of follow-up is steadily increasing. However, little is known about their functional status, comorbidities, and mortality. Identifying the predictors of prolonged survival could guide the selection of candidates for the low number of available donors.Functional status, morbidities, and mortality of heart-transplant patients between 1984 and 1992 were analyzed. To identify predictors of 20-year survival, a logistic regression model was constructed using the covariates associated with survival in the univariate analysis.A total of 39 patients who survived 20 years (26% of patients transplanted before 1992) were compared to 90 recipients from the same period who died between 1 and 20 years post-transplantation. Major complications were hypertension, renal dysfunction, infections, and cancer. After a mean follow-up of 30 months, 6 survivors had died, yielding a mortality rate of 6% per year (vs 2.5%-3% in years 1-19). Causes of mortality were infection (50%), malignancy (33%), and allograft vasculopathy (17%). Long-term survivors were younger and leaner, and had nonischemic cardiomyopathy and lower ischemic time. Logistic regression identified recipient age45 years (odds ratio=3.9; 95% confidence interval, 1.6-9.7; P=.002) and idiopathic cardiomyopathy (odds ratio=3; 95% confidence interval, 1.4-7.8; P=.012) as independent predictors for 20-year survival.One fourth of all heart-transplant patients in our series survived20 years with the same graft, and most enjoy independent lives despite significant comorbidities. Recipient age45 years and idiopathic cardiomyopathy were associated with survival beyond 2 decades. These data may help decide donor allocation.

[Aims]: Mitochondrial haplogroups are known to influence individual predisposition to a wide spectrum of metabolic and degenerative diseases, including ischaemic cardiovascular diseases. We have examined the influence of the mitochondrial DNA (mtDNA) background on the development of human end-stage heart failure (HF) in patients undergoing heart transplantation. The influence of mtDNA haplogroups on the incidence of transplant-related complications, mainly cardiac allograft vasculopathy (CAV), and on post-transplant survival was also studied. [Methods and results]: The most common mitochondrial haplogroups in European populations were genotyped in 450 heart transplant recipients, 248 heart transplant donors, and 206 healthy controls. Mitochondrial haplogroups were determined by PCR amplification of short mtDNA fragments, followed by restriction fragment length polymorphism analysis. After adjustment for age and sex the frequency of haplogroup H was significantly higher in heart transplant recipients than in controls [OR: 1.86 (95 confidence intervals, CI: 1.272.74), P=0.014], and in heart donors [OR: 1.47 (95 CI: 0.992.19), P=0.032]. Likewise, haplogroup Uk was found significantly more frequently among CAV patients than in non-CAV heart allograft recipients [OR: 4.1 (95 CI: 1.51-11.42), P=0.042]. Finally, heart donor haplogroups had no influence on the morbidity or mortality after heart transplantation. [Conclusions]: Mitochondrial haplogroups behave like risk factors for the progress to end-stage HF in a Spanish cardiac transplant population. Mitochondrial DNA variants may have some influence on the appearance of cardiac transplant complications. © 2011 The Author., This work was supported by the Instituto de Salud Carlos III (ISCIII) (grant number PI 06/0205 to B.B. and PI 07/0167 to R.G.); Comunidad de Madrid (grant number GEN-0269/2006 to R.G.); Ministerio de Ciencia e Innovación (SAF2010-22153-C03-03 to C.V.); and Sociedad Española de Cardiología (2008 to M.G.B.). M.E.G. is a Senior Fellow and receives grant support from the Center for Biomedical Research on Rares Diseases (CIBERER); M.E.V. is a Junior Fellow and receives grant support from REDINSCOR, a clinical and scientific research network on heart failure supported by ISCIII.

Aspergillus tracheobronchitis (AT) is an uncommon clinical presentation of pulmonary aspergillosis that frequently progresses to invasive pulmonary aspergillosis. Diagnosis of AT may be delayed because of its insidious onset, non-specific signs and symptoms, and scarcity of radiographic abnormalities. We report the case of a patient who received a heart transplant (HT) because of cardiac amyloidosis and who developed pseudomembranous AT. Possible risk factors concurrent in this case were splenectomy, lymphocytopenia, and previous cytomegalovirus infection. Chest computed tomography scan showed thickening of the left bronchi and a 'tree-in-bud' pattern with multiple small nodules. Bronchoscopic examination revealed raised yellowish pseudomembranous plaques on the tracheobronchial tree. Bronchoalveolar lavage and aspirate cultures yielded Aspergillus fumigatus. The patient recovered with voriconazole. Clinicians should be aware of AT as a potential cause of respiratory symptoms with few radiographic abnormalities in HT recipients, as delay in performing bronchoscopy could result in an unfavorable prognosis.

Acromegaly is characterized by chronic growth hormone hypersecretion. Cardiovascular alterations such as hypertension, left ventricular hypertrophy, cardiac rhythm disturbances and valvular disease are common in this disease and are the main cause of death. Control of acromegaly by surgery or pharmacotherapy has been shown to improve cardiovascular morbidity. We report a case of acromegalic myocardiopathy in a 59-year-old woman with dilated myocardiopathy who presented ventricular diameter and contractility normalization following medical treatment.

Chronic thromboembolic pulmonary hypertension (CTEPH) has a dismal prognosis when there are no central pulmonary thrombi amenable to surgical thromboendarterectomy. Pulmonary vasodilators could be useful in this setting. Initial experience with bosentan in a small group of patients with CTEPH has shown favourable results on the short term (3 to 6 months), but long-term effects remain unknown.We retrospectively describe the effects of bosentan in 6 CTEPH patients with a mean follow-up period of 15 months (range, 8-26).At 3-month follow-up, all patients had experienced clinical improvement, with a statistical trend towards reduced pulmonary vascular resistance [1,008 (624) dyn/sec/cm-5 versus 768 (392), p = 0.07]. Clinical improvement persisted on the long-term, [baseline NYHA functional class 3.0 (0.4) versus 2.0 (0) at the last follow-up visit, p0.01]. Six-minute walk-test results [baseline 230 (124) meters versus a 313 (70) at 1 year] and NTproBNP [2,225 (2,079) pg/ml versus a 1,056 (1,104) at 1 year] were also consistent with persistent beneficial effect.Bosentan seemed to provide long-term benefits in this small series of patients with CTEPH.

Despite advances in all areas of cardiology, the incidence of heart failure increases each year. Pharmacologic treatment, cardiac resynchronization therapy, and heart failure surgery have resulted in prolonged survival in these patients and in symptomatic improvement. However, in more advanced phases of the disease, these therapeutic options become less effective. This is when heart transplantation and cardiac assist devices are the only techniques that can lengthen survival and improve quality of life. For the past 25 years, heart transplantation has been the most effective therapeutic option for patients with end-stage heart failure. The scarcity of suitable donors and the development of alternative forms of treatment that are effective in less advanced disease stages have led to heart transplantation being reserved for young heart disease patients whose life-expectancy is short. Cardiac assist devices have been shown to be effective as temporary therapy, providing a bridge to heart transplantation or recovery, or as permanent support in patients with contraindications to heart transplantation. Currently both paracorporeal and intracorporeal assist devices are available, and there are even systems that can replace the heart completely. More widespread use of these devices depends on the establishment of appropriate indications, on an improvement in the devices' cost-benefit ratios, and on a reduction in the still high rate of complications.

Bone marrow mononuclear cells (BMCs) from 20 patients with extensive reperfused myocardial infarction (MI) were used to assess their myocardial regenerative capability “in vitro” and their effect on postinfarction left ventricular (LV) remodeling. Human BMCs were labeled, seeded on top of cryoinjured mice heart slices, and cultured. BMCs showed tropism for and ability to graft into the damaged mouse cardiac tissue and, after 1 week, acquired a cardiomyocyte phenotype and expressed cardiac proteins, including connexin43. In the clinical trial, autologous BMCs (78±41×10 6 per patient) were intracoronarily transplanted 13.5±5.5 days after MI. There were no adverse effects on microvascular function or myocardial injury. No major cardiac events occurred up to 11±5 months. At 6 months, magnetic resonance showed a decrease in the end-systolic volume, improvement of regional and global LV function, and increased thickness of the infarcted wall, whereas coronary restenosis was only 15%. No changes were found in a nonrandomized contemporary control group. Thus, BMCs are capable of nesting into the damaged myocardium and acquire a cardiac cell phenotype in vitro as well as safely benefiting ventricular remodeling in vivo. Large-scale randomized trials are needed now to assess the clinical efficacy of this treatment.

In this study we measured the concentrations of cardiac troponin I (cTnI) and several biochemical markers of myocardial damage after elective external cardioversion or internal cardioversion by specific catheters or automatic defibrillators.Biochemical markers were analyzed prospectively for 30 consecutive patients after electrical cardioversion. Concentrations of cTnI, myoglobin, creatine kinase (CK), CK-MB and the MB/CK ratio were determined in samples before cardioversion and 2, 8 and 24 h later. The shock energy ranged from 50 to 360 joules (235 106 joules) in external cardioversions and from 3 to 37 joules (15 8 joules) in internal cardioversions.We detected abnormal concentrations of CK, myoglobin, CK-MB and MB/CK in 33% of the patients after external cardioversion. The concentrations of cTnI remained within normal limits at all times, with no elevations detected. Whereas no abnormal concentration of any biochemical marker was detected in any patient who required internal cardioversion for atrial fibrillation, two patients who underwent external cardioversion from an automatic defibrillator did have abnormal concentrations of CK-MB, myoglobin, and even of cTnI.The concentration of cTnI remained below the detection limit after external cardioversion, even though the other more non-specific markers changed. No enzyme alteration was detected in patients who underwent internal cardioversion of atrial fibrillation.

An important limitation of the ablation with standard catheter is the volume and limited depth of the lesions created. The irrigated catheters, due to a larger and deeper lesion could be useful in patients with typical atrial flutter. The aim of this study was to prospectively compare the ablation procedure with an irrigated-tip catheter versus the standard catheter in this group of patients.A total of 37 consecutive patients referred to ablation of the cavotricuspid isthmus for typical atrial flutter were randomized either to be performed by an standard catheter (20 patients with mean age of 62 18 years, 18 males) or an irrigated-tip catheter (17 patients with mean age 71 4 years, 13 males).With standard catheters, complete ablation of the cavotricuspid isthmus was achieved in 18 patients (90%). With a mean of 19 15 applications. With the irrigated-tip catheters the complete ablation of the isthmus was achieved with a mean of 8 7 applications (p0.001). Both mean duration of the procedure (164 56 versus 70 35 minutes) and fluoroscopic time (40 16 versus 16 8 minutes) was significantly less with irrigated catheters (p0.001). There were no significant clinical complications during the procedure nor later on. No patient presented ischemic symptoms nor alterations on the ST segment.The employment of irrigated-tip catheters achieved a high success rate with safety shortening the procedure time and radiation exposure.