First description and validation of a new method for estimating aortic stenosis burden and predicting the functional response to TAVI.

Background: Up to one-fifth of patients continue to have poor quality of life after transcatheter aortic valve implantation (TAVI), with an additional similar proportion not surviving 1 year after the procedure. We aimed to assess the value of a new method based on an integrated analysis of left ventricular outflow tract flow velocity and aortic pressure to predict objective functional improvement and prognosis after TAVI. Methods: In a cohort of consecutive patients undergoing TAVI, flow velocity-pressure integrated analysis was obtained from simultaneous pressure recordings in the ascending aorta and flow velocity recordings in the left ventricular outflow tract by echocardiography. Objective functional improvement 6 months after TAVI was assessed through changes in a 6-min walk test and NT-proBNP levels. A clinical follow-up was conducted at 2 years. Results: Of the 102 patients studied, 82 (80.4%) showed objective functional improvement. The 2-year mortality of these patients was significantly lower (9% vs. 44%, p = 0.001). In multivariate analysis, parameter "(Pressure at Vmax - Pressure at Vo)/Vmax" was found to be an independent predictor for objective improvement. The C-statistic was 0.70 in the overall population and 0.78 in the low-gradient subgroup. All echocardiographic parameters and the valvuloarterial impedance showed a C-statistic of <0.6 for the overall and low-gradient patients. In a validation cohort of 119 patients, the C-statistic was 0.67 for the total cohort and 0.76 for the low-gradient subgroup. Conclusion: This new method allows predicting objective functional improvement after TAVI more precisely than the conventional parameters used to assess the severity of aortic stenosis, particularly in low-gradient patients.

A new integrative approach to assess aortic stenosis burden and predict objective functional improvement after TAVR.

Background: A non-negligible rate of patients undergoing transcatheter aortic valve replacement (TAVR) do not report symptomatic improvement or even die in the short-midterm. We sought to assess the degree of objective functional recovery after TAVR and its prognostic implications and to develop a predictive model. Methods: In a cohort of patients undergoing TAVR, a prospective evaluation of clinical, anatomical, and physiological parameters was conducted before and after the procedure. These parameters were derived from echocardiography, non-invasive analysis of arterial pulse waves, and cardiac tomography. Objective functional improvement 6 months after TAVR was assessed using a 6-min walk test and nitro-terminal pro-brain natriuretic peptide (NT-proBNP) levels. The derived predictive model was prospectively validated in a different cohort. A clinical follow-up was conducted at 2 years. Results: Among the 212 patients included, objective functional improvement was observed in 169 patients (80%) and subjective improvement in 187 (88%). Patients with objective functional improvement showed a much lower death rate at 2 years (9% vs. 31% p = 0.0002). Independent predictors of improvement were as follows: mean aortic gradient of ≥40 mmHg, augmentation index75 of ≥45%, the posterior wall thickness of ≤12 mm, and absence of atrial fibrillation. A simple integer-based point score was developed (GAPA score), which showed an area under the curve of 0.81 for the overall cohort and 0.78 for the low-gradient subgroup. In a validation cohort of 216 patients, these values were 0.75 and 0.76, respectively. Conclusion: A total of 80% of patients experienced objective functional improvement after TAVR, showing a significantly lower 2-year mortality rate. A predictive score was built that showed a good discriminative performance in overall and low-gradient populations.

Validation study to determine the accuracy of central blood pressure measurement using the SphygmoCor XCEL cuff device in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

Central aortic blood pressure could be helpful in the evaluation of patients with aortic stenosis (AS). The SphygmoCor XCEL device estimates central blood pressure (BP) measurement with its easy-to-use, operator-independent procedure. However, this device has not been properly validated against invasive measurement in patients with severe AS. We evaluated the relationship between cuff-brachial BP, transfer function-estimated and invasively measured central aortic pressure in patients with severe AS before and after transcatheter aortic valve replacement (TAVR). Agreement between techniques was analyzed and, according to the ARTERY Society recommendations, the minimum acceptable error was a mean difference ± SD ≤5 ± ≤8 mm Hg. A total of 94 patients with AS undergoing TAVR had simultaneous non-invasive and invasive measurements of central BP before and after the procedure. Before TAVR central systolic BP was in average slightly underestimated, though with wide variability, when using the default calibration of brachial-cuff SBP (mean difference ± SD, -3 ± 15 mm Hg), and after TAVR the degree of underestimation increased (mean difference ± SD, -9 ± 13 mm Hg). The agreement tended to improve for those patients with low aortic gradient stenosis compared to those with high gradient at baseline (mean difference ± SD, -2 ± 11 mm Hg vs. -4 ± 17, respectively, p = .3). The cuff-brachial systolic BP yielded numerically lower degree of agreement and weaker correlation with invasive measurements than SphygmoCor XCEL. In patients with severe AS the SphygmoCor XCEL cuff device, despite showing strong correlation, does not meet the ARTERY Society accuracy criteria for non-invasive measurement of central SBP.

Spanish Heart Transplant Registry. 31th Official Report of the Heart Failure Association of the Spanish Society of Cardiology.

INTRODUCTION AND OBJECTIVES: The present report describes the clinical characteristics and outcomes of heart transplants in Spain and updates the data to 2019. METHODS: We describe the clinical characteristics and outcomes of heart transplants performed in Spain in 2019, as well as trends in this procedure from 2010 to 2018. RESULTS: In 2019, 300 transplants were performed (8794 since 1984; 2745 between 2010 and 2019). Compared with previous years, the most notable findings were the decreasing rate of urgent transplants (38%), and the consolidation of the type of circulatory support prior to transplant, with an almost complete disappearance of counterpulsation balloon (0.7%), stabilization in the use of extracorporeal membrane oxygenation (9.6%), and an increase in the use of ventricular assist devices (29.0%). Survival from 2016 to 2018 was similar to that from 2013 to 2015 (P=.34). Survival in both these periods was better than that from 2010 to 2012 (P=.002 and P=.01, respectively). CONCLUSIONS: Heart transplant activity has remained stable during the last few years, as have outcomes (in terms of survival). There has been a trend to a lower rate of urgent transplants and to a higher use of ventricular assist devices prior to transplant.

Eficacia y seguridad del uso de novo y precoz de tacrolimus de liberación prolongada en el trasplante cardiaco / Efficacy and safety of de novo and early use of extended-release tacrolimus in heart transplantation

Introducción y objetivos: El tacrolimus de liberación prolongada (TLP) permite una dosificación única diaria, lo que simplifica el régimen inmunosupresor. El presente estudio describe la eficacia y la seguridad del uso de TLP de novo y precoz para el trasplante cardiaco. Métodos: Se realizó un estudio observacional, retrospectivo y multicéntrico para comparar el uso de novode TLP (grupo de TLP; n = 94), tacrolimus de liberación estándar (grupo de TLE; n = 42) y la conversión precoz (CP) de TLP a TLE (grupo de CP; n = 44). El TLP se usó entre 2007 y 2012. Se analizaron la tasa de incidencia de rechazo agudo, infección e infección por citomegalovirus al primer año tras el trasplante, así como parámetros de seguridad. Resultados: Entre los grupos no hubo diferencias significativas en la dosis diaria y las concentraciones séricas de tacrolimus durante el primer año tras el trasplante. La incidencia de rechazo fue de 1,05 (IC95%, 0,51-1,54), 1,39 (IC95%, 1,00-1,78) y 1,11 (IC95%, 0,58-1,65) eventos/pacientes-años en los grupos de TLE, TLP y CP respectivamente (p = 0,48). La incidencia de infección fue de 0,75 (IC95%, 0,60-0,86), 0,62 (IC95%, 0,52-0,71) y 0,55 (IC95%, 0,40-0,68) en los grupos de TLE, TLP y CP respectivamente (p = 0,46). Se produjo infección por citomegalovirus en el 23,8, el 20,2 y el 18,2% respectivamente (p = 0,86). No hubo diferencias significativas entre los grupos en los parámetros de seguridad o la función del injerto. Falleció 1 paciente del grupo de TLE y 2 del grupo de TLP. Conclusiones: Parece que el uso de novo de TLP o la CP de TLP a TLE tienen similares eficacia y seguridad que el TLE en el trasplante cardiaco (AU)

Introduction and objectives: The extended-release formulation of tacrolimus (ERT) allows once-daily dosage, thus simplifying the immunosuppressive regimen. This study aimed to describe the safety and efficacy of the de novo and early use of ERT in heart transplantation. Methods: This was an observational, retrospective, multicenter study comparing the safety and efficacy of the de novo use of ERT (ERT group [n = 94]), standard-release tacrolimus (SRT group [n = 42]) and early conversion (EC) from SRT to ERT (EC group [n = 44]). Extended-release tacrolimus was used between 2007 and 2012. One-year incidence rates of acute rejection, infection, and cytomegalovirus infection were analyzed. Safety parameters were also evaluated. Results: There were no significant between-group differences in the daily dose or trough levels of tacrolimus during the first year after transplantation. The rejection incidence rates were 1.05 (95%CI, 0.51-1.54), 1.39 (95%CI, 1.00-1.78), and 1.11 (95%CI, 0.58-1.65) episodes per patient-years in the SRT group, ERT group, and EC group, respectively (P = .48). The infection incidence rates were 0.75 (95%CI, 0.60-0.86), 0.62 (95%CI, 0.52-0.71), and 0.55 (95%CI, 0.40-0.68) in the SRT group, ERT group, and EC group, respectively (P = .46). Cytomegalovirus infection occurred in 23.8%, 20.2%, and 18.2% of the patients, respectively (P = .86). No significant between-group differences were found in laboratory tests or in allograft function. There was 1 death in the SRT group and 2 in the ERT group. Conclusions: Both de novo and early use of ERT seem to have similar safety and efficacy profiles to conventional SRT-based immunosuppression (AU)

Efficacy and Safety of de Novo and Early Use of Extended-release Tacrolimus in Heart Transplantation.

INTRODUCTION AND OBJECTIVES: The extended-release formulation of tacrolimus (ERT) allows once-daily dosage, thus simplifying the immunosuppressive regimen. This study aimed to describe the safety and efficacy of the de novo and early use of ERT in heart transplantation. METHODS: This was an observational, retrospective, multicenter study comparing the safety and efficacy of the de novo use of ERT (ERT group [n=94]), standard-release tacrolimus (SRT group [n=42]) and early conversion (EC) from SRT to ERT (EC group [n=44]). Extended-release tacrolimus was used between 2007 and 2012. One-year incidence rates of acute rejection, infection, and cytomegalovirus infection were analyzed. Safety parameters were also evaluated. RESULTS: There were no significant between-group differences in the daily dose or trough levels of tacrolimus during the first year after transplantation. The rejection incidence rates were 1.05 (95%CI, 0.51-1.54), 1.39 (95%CI, 1.00-1.78), and 1.11 (95%CI, 0.58-1.65) episodes per patient-years in the SRT group, ERT group, and EC group, respectively (P=.48). The infection incidence rates were 0.75 (95%CI, 0.60-0.86), 0.62 (95%CI, 0.52-0.71), and 0.55 (95%CI, 0.40-0.68) in the SRT group, ERT group, and EC group, respectively (P=.46). Cytomegalovirus infection occurred in 23.8%, 20.2%, and 18.2% of the patients, respectively (P=.86). No significant between-group differences were found in laboratory tests or in allograft function. There was 1 death in the SRT group and 2 in the ERT group. CONCLUSIONS: Both de novo and early use of ERT seem to have similar safety and efficacy profiles to conventional SRT-based immunosuppression.

Registro Español de Trasplante Cardiaco. Una visión histórica / The Spanish heart transplantation registry. a historical perspective

El Registro Español de Trasplante Cardiaco cumple 24 años de actividad. En el presente artículo se hace referencia histórica a su evolución hasta el presente, incluyendo su organización, los resultados de su actividad y sus potencialidades (AU)

The Spanish Heart Transplantation Registry has been in existence for 24 years. This article provides a historical perspective on the development of the Registry up to the present day and discusses its organization, achievements and future potential (AU)

Rejection after conversion to a proliferation signal inhibitor in chronic heart transplantation.

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 (<5 yr) after transplantation and age <50 yr at the time of conversion. Use of mycophenolate mofetil was a protective factor. Post-conversion rejection did not significantly influence the evolution of left ventricular ejection fraction, renal function, or mortality during further follow-up. Conversion to a CNI-free immunosuppression based on a PSI results in an increased risk of AR. Awareness of the clinical determinants of post-conversion rejection could help to refine the current PSI conversion strategies.

Risk factors associated with moderate-to-severe renal dysfunction among heart transplant patients: results from the CAPRI study.

The longer survival of patients with heart transplantation (HT) favors calcineurin inhibitor-related chronic kidney disease (CKD). It behoves to identify risk factors. At 14 Spanish centers, data on 1062 adult patients with HT (age 59.2 ± 12.3 yr, 82.5% men) were collected at routine follow-up examinations. Glomerular filtration rate, GFR, was estimated using the four-variable MDRD equation, and moderate-or-severe renal dysfunction (MSRD) was defined as K/DOQI stage 3 CKD or worse. Time since transplant ranged from one month to 22 yr (mean 6.7 yr). At assessment, 26.6% of patients were diabetic and 63.9% hypertensive; 53.9% were taking cyclosporine and 33.1% tacrolimus; and 61.4% had MSRD. Among patients on cyclosporine or tacrolimus at assessment, multivariate logistic regression identified male sex (OR 0.44), pre- and post-HT creatinine (2.73 and 3.13 per mg/dL), age at transplant (1.06 per yr), time since transplant (1.05 per yr), and tacrolimus (0.65) as independent positive or negative predictors of MSRD. It is concluded that female sex, pre- and one-month post-HT serum creatinine, age at transplant, time since transplant, and immunosuppression with cyclosporine rather than tacrolimus may all be risk factors for development of CKD ≥ stage 3 by patients with HT.

Prevalence and severity of renal dysfunction among 1062 heart transplant patients according to criteria based on serum creatinine and estimated glomerular filtration rate: results from the CAPRI study.

Chronic kidney disease (CKD) is staged on the basis of glomerular filtration rate; generally, the MDRD study estimate, eGFR, is used. Renal dysfunction (RD) in heart transplant (HT) patients is often evaluated solely in terms of serum creatinine (SCr). In a cross-sectional, 14-center study of 1062 stable adult HT patients aged 59.1±12.5 yr (82.3% men), RD was graded as absent-or-mild (AoM), moderate, or severe (this last including dialysis and kidney graft) by two classifications: SCr-RD (SCr cutoffs 1.6 and 2.5 mg/dL) and eGFR-RD (eGFR cutoffs 60 and 30 mL/min/1.73 m2). SCr-RD was AoM in 68.5% of patients, moderate in 24.9%, and severe in 6.7%; eGFR-RD, AoM in 38.6%, moderate in 52.2%, severe in 9.2%. Among patients evaluated <2.7, 2.7-6.2, 6.2-9.5 and >9.5 yr post-HT (the periods defined by time-since-transplant quartiles), AoM/moderate/severe RD prevalences were <2.7, SCr-RD 74/21/5%, eGFR-RD 47/47/6%; 2.7-6.2, SCr-RD 73/22/5%, eGFR-RD 37/56/7%; 6.2-9.5, SCr-RD 69/24/7%, eGFR-RD 37/54/9%; >9.5, SCr-RD 58/32/10%, eGFR-RD 32/52/16%. The prevalence of severe RD increases with time since transplant. If the usual CKD stages are appropriate for HT patients, the need for less nephrotoxic immunosuppressants and other renoprotective measures is greater than is suggested by direct SCr-based grading, which should be abandoned as excessively insensitive.

[Current surgical treatment of calcified aortic stenosis]. / Tratamiento quirúrgico actual de la estenosis aórtica calcificada.

Currently, aortic stenosis is the main indication for cardiac surgery in western countries. With the aim of describing the clinical and surgical characteristics and the short-term outcome of current surgical treatment, we carried out a retrospective study of 238 patients (mean age 71 years, 43% female) who underwent surgery during 2002-2003. Of these, 73% had a EuroSCORE >6. Surgical procedures included isolated aortic valve replacement in 61%, ascending aorta surgery in 14%, coronary artery by-pass grafting in 21%, and mitral surgery in 4%. The in-hospital mortality rate in the 30 days after surgery was 7.1%. Multivariate analysis, adjusted for age, sex and left ventricular ejection fraction, showed that only concomitant coronary artery by-pass grafting was significantly associated with in-hospital mortality (odds ratio=4; P=.019). Factors associated with mortality at 18 months were: previous neurological disease (hazard ratio [HR]=3.25; P=.017), prosthesis diameter <21 mm (HR=2.86; P=.018), and coronary artery by-pass grafting (HR=2.35; P=.05).

Tratamiento quirúrgico actual de la estenosis aórtica calcificada / Current surgical treatment of calcified aortic

La estenosis aórtica es actualmente la indicación más común de cirugía cardiaca en nuestro medio. Para describir el perfil clinicoquirúrgico y los resultados a corto plazo de su tratamiento quirúrgico actual, estudiamos retrospectivamente a 238 pacientes intervenidos durante 2002-2003 (media de edad, 71 años; el 43% eran mujeres). El 73% tenía EuroSCORE > 6. Se realizó: sustitución valvular aórtica aislada al 61% de los pacientes; intervención sobre aorta ascendente al 14%; derivación coronaria al 21% y cirugía mitral al 4%. La mortalidad hospitalaria (antes de 30 días tras la cirugía) fue del 7,1%. En el análisis multivariable ajustado a edad, sexo y fracción de eyección, sólo la derivación coronaria se asoció a una mayor mortalidad hospitalaria (odds ratio = 4; p = 0,019). Los factores asociados a la mortalidad a los 18 meses fueron: enfermedad neurológica previa (hazard ratio [HR] = 3,25; p = 0,017), diámetro protésico < 21 mm (HR = 2,86; p = 0,018) y derivación coronaria (HR = 2,35; p = 0,05) (AU)

Currently, aortic stenosis is the main indication for cardiac surgery in western countries. With the aim of describing the clinical and surgical characteristics and the short-term outcome of current surgical treatment, we carried out a retrospective study of 238 patients (mean age 71 years, 43% female) who underwent surgery during 2002–2003. Of these, 73% had a EuroSCORE >6. Surgical procedures included isolated aortic valve replacement in 61%, ascending aorta surgery in 14%, coronary artery by-pass grafting in 21%, and mitral surgery in 4%. The in-hospital mortality rate in the 30 days after surgery was 7.1%. Multivariate analysis, adjusted for age, sex and left ventricular ejection fraction, showed that only concomitant coronary artery by-pass grafting was significantly associated with in-hospital mortality (odds ratio=4; P=.019). Factors associated with mortality at 18 months were: previous neurological disease (hazard ratio [HR]=3.25; P=.017), prosthesis diameter <21 mm (HR=2.86; P=.018), and coronary artery by-pass grafting (HR=2.35; P=.05) (AU)

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.

Conferencia de Consenso de los Grupos Españoles de Trasplante Cardiaco / Spanish Heart Transplant Units Consensus Conference

La Sección de Insuficiencia Cardiaca, Trasplante Cardiaco y otras Alternativas Terapéuticas de la Sociedad Española de Cardiología desarrolló en Sevilla, en junio de 2005, una Conferencia de Consenso sobre trasplante cardiaco (TC) a la que fueron invitados a participar todos los grupos españoles de TC. El objetivo fue determinar, discutir y consensuar los aspectos más relevantes y/o controvertidos de diferentes áreas del TC en la actualidad: organización, selección del receptor, donantes, rechazo, inmunosupresión, enfermedad vascular del injerto, complicaciones a largo plazo y TC pediátrico. Este documento reúne las recomendaciones del grupo de trabajo incluyendo el grado de evidencia con que se respalda cada una (AU)

The Spanish Society of Cardiology’s working group on heart failure, heart transplantation and associated therapies organized a consensus conference on heart transplantation that was held in Seville, Spain in June 2005 and to which all Spanish heart transplant teams were invited. The aim was to evaluate, discuss and reach a consensus on the most important and controversial topics in different areas of heart transplantation today: organization, recipient selection, donors, rejection, immunosuppression, allograft vasculopathy, long-term complications, and pediatric heart transplantation. This report summarizes the working group’s recommendations, and reports the level of evidence supporting each recommendation (AU)

Sirolimus in de novo heart transplant recipients with severe renal impairment.

Two patients with end-stage heart failure and advanced renal dysfunction (under chronic dialysis therapy) underwent heart transplantation. In order to avoid further renal impairment, a calcineurine inhibitor-free immunosuppression regimen based on the sirolimus was used. Although temporary perioperative support with hemofiltration and dialysis was needed, both patients eventually regained a reasonable renal function with no episodes of clinical rejection and normal cardiac function at 13 and 11 months, respectively, after transplantation. Sirolimus-based immunosuppression might be an interesting alternative to calcineurine inhibitors in the management of patients with significant renal impairment.

[Transient ST Elevation: a finding that may be frequent in percutaneous atrial septal defect closure in adults]. / Elevación transitoria del segmento ST: una alteración que podría ser frecuente durante el cierre percutáneo de comunicaciones interauriculares en adultos.

Transient ST elevation in inferior leads has been described as a rare complication during percutaneous atrial septal defect closure. We present a series of adult patients who underwent percutaneous atrial septal defect closure with the Amplatzer device and in whom transient ST changes were observed frequently.