Metabolic syndrome in heart transplantation: impact on survival and renal function.

The aim of our study was to analyze the early presence of metabolic syndrome (MS) in heart transplant (HTx) patients, and to assess its long-term impact on survival and renal function. From January 2000 to October 2011, 253 consecutive HTx patients who survived more than 90 days were included. MS was diagnosed if patients met revised NCEP-ATP III criteria at HTx or within 3 months post-HTx. The prevalence of MS was 41.9%. Patients with MS had greater overall mortality after a mean follow-up of 1700 ± 979 days (log-rank test, P = 0.020). In the multivariate analysis, and subject to a minimum survival of 90 days, the only independent predictor variables of long-term mortality were the presence of MS (OR, odds ratio 2.087, P = 0.032), and rejection episodes (OR 1.833, P = 0.001). Patients with MS had worse renal function at baseline both in plasma creatinine (1.19 ± 0.44 vs. 1.03 ± 0.29 mg/dl, P = 0.002) and glomerular filtration rate estimated by modified diet in renal disease (73.60 ± 26.76 vs. 87.30 ± 43.55 ml/min/1.73 m(2) , P = 0.005), whereas progressive impairment of renal function was of equal magnitude in both groups. The presence of MS prior to transplant or its development within the first 3 months identified a subgroup at greater risk of mortality and long-term renal dysfunction.

Impact of basal heart rate on long-term prognosis of heart transplant patients.

Previous studies in patients with heart failure have shown that an elevated basal heart rate (HR) is associated with a poor outcome. Our aim with this study was to investigate if this relationship is also present in heart transplantation (HTx) recipients. From 2003 until 2010, 256 HTx performed in our center were recruited. Patients who required pacemaker, heart-lung transplants, pediatrics, retransplants, and those patients with a survival of less than 1 year were excluded. The final number included in the analysis was 191. Using the HR obtained by EKG during elective admission at 1 year post-HTx and the survival rate, an ROC-curve was performed. The best point under the curve was achieved with 101 beats per minute (bpm), so patients were divided in two groups according to their HR. A comparison between survival curves of both groups was performed (Kaplan-Meier). Subsequently, a multivariate analysis considering HR and other variables with influence on survival according to the literature was carried out. A total of 136 patients were included in the group with HR ≤100 bpm, and 55 in the one with HR >100 bpm. There were no basal differences in both groups except for primary graft failure, which was more frequent in the >100 bpm group (30.9 vs. 17%, P = 0.033). Patients with ≤100 bpm had a better long prognosis (P < 0.001). The multivariate analysis proved that high HR was an independent predictor of mortality. Our study shows that HR should be considered as a prognosis factor in HTx patients.

Serum markers of apoptosis in the early period of heart transplantation.

CONTEXT AND OBJECTIVE: To assess the relationship between levels of serum markers of apoptosis and rejection grades in heart transplant (HTx). MATERIALS AND METHODS: A prospective study was conducted in 91 HTx. We correlated apoptosis markers and biopsy samples. The apoptosis markers were: TRAIL, TRAIL-R1, TRAIL-R2, TRAIL-R3, TRAIL-R4, sFas, sTNF-R1 and sTNF-R2. RESULTS: The only significant correlation with rejection grade was sFas (r=0.329; p=0.005). Cyclosporine showed a proapoptotic effect (sTNF-R1 0.02 and sTNF-R2 0.02) and everolimus an antiapoptotic effect (sTNF-R1 r= -0.523; p=0.0001 and sTNF-R2 r= -0.405; p=0.0001). CONCLUSIONS: The utility of specific apoptosis markers in peripheral blood for diagnosis of acute cellular rejection is low. Everolimus may have an anti-apoptotic effect.

A prospective randomized study comparing cyclosporine versus tacrolimus combined with daclizumab, mycophenolate mofetil, and steroids in heart transplantation.

BACKGROUND: Cyclosporine (CsA) and tacrolimus (Tac) in heart transplantation (HTx) have been compared but with certain drawbacks. We compared both drugs in a prospective analysis with medium-term follow-up. METHODS: Hundred and six patients were randomized to receive CsA or Tac (53 per group). Target levels of CsA were 200-300 ng/mL in the first six months and 100-200 ng/mL thereafter. Tac levels were 10-15 and 5-10 ng/mL, respectively. We also used daclizumab as induction and mycophenolate mofetil (MMF) and steroids as maintenance therapy. RESULTS: Baseline characteristics were similar. Survival (CsA 88.7% vs. Tac 81.1%; p = 0.493) was similar. There was a tendency for longer time to first rejection with CsA (93 ± 110 vs. 55 ± 81 d; p = 0.122). There were more rejection-free patients with Tac (39 vs. 28%; p = 0.233). CsA patients suffered more viral infections (0.41 ± 0.58 vs. 0.11 ± 0.31; p = 0.003). CsA patients developed hypertension often (64 vs. 43%; p = 0.032). Tac patients suffered more gastrointestinal complications (16 vs. 6%; p = 0.042). Renal function and the development of diabetes, dyslipidemia, or neurological complications was similar. CONCLUSIONS: Tac patients showed a tendency for longer time to first rejection, and there were more rejection-free patients with Tac and suffered fewer viral infections. Tac patients developed less hypertension and needed less drugs for its control. Renal function was similar in both groups.

Predictor factors for the development of arterial hypertension following heart transplantation.

INTRODUCTION: Up to 95% of the patients with heart transplantation (HT) suffer from arterial hypertension (AHT). The development of de novo AHT after HT has not been greatly studied. AIM: To identify the predictor variables for the development of de novo AHT after HT. MATERIALS AND METHODS: We retrospectively studied 253 patients with HT and who did not previously have AHT. We excluded cases of early mortality, re-transplants and combined transplants. We considered AHT as the constant need to take anti-hypertensive drugs to maintain blood pressure < 140/90 mmHg. We studied all the variables relating to recipient, donor, surgical procedure, immunosuppression and follow-up. The statistics used were the Student's t-test, chi-square statistic and a logistic regression analysis. RESULTS: Of the 253 patients, 109 (43%) developed AHT. The variables associated with more prevalent AHT were male recipient/donor, idiopathic dilated cardiomyopathy (IDCM) as cause of HT, having been a smoker as well as renal deterioration (RD) and hypercholesterolemia after HT. The multivariate analysis found smoking prior to the HT and hypercholesterolemia during follow-up as independent risk factors and urgent HT as a protective variable. CONCLUSIONS: AHT after HT is frequent. The variables associated in our population were smoking before HT, male recipient/donor, IDCM prior to HT and hypercholesterolemia and RD after HT.

Novel Imaging Techniques for Heart Failure.

Imaging techniques play a main role in heart failure (HF) diagnosis, assessment of aetiology and treatment guidance. Echocardiography is the method of choice for its availability, cost and it provides most of the information required for the management and follow up of HF patients. Other non-invasive cardiac imaging modalities, such as cardiovascular magnetic resonance (CMR), nuclear imaging-positron emission tomography (PET) and single-photon emission computed tomography (SPECT) and computed tomography (CT) could provide additional aetiological, prognostic and therapeutic information, especially in selected populations. This article reviews current indications and possible future applications of imaging modalities to improve the management of HF patients.

Repeated CMV infection in a heart transplantation patient.

Infections are one of the leading causes of morbidity and mortality in heart transplantation (HTx). Cytomegalovirus (CMV) is the most common viral infection during the first year after HTx, but it is more unusual after this time. We present the case of a patient who underwent an HTx due to a severe ischemic heart disease. Although the patient did not have a high risk for CMV, infection, he suffered a reactivation during the first year and then up to six more episodes, especially in his eyes. The patient received different treatments against CMV and the immunosuppression was changed several times. Finally, everolimus was introduced instead of cyclosporine, and mycophenolate mofetil was withdrawn. The presented case provides an example of how the immunosupresion plays a key role in some infections in spite of being a suitable antiviral treatment.

Autonomic nervous system dysfunction in advanced systolic heart failure.

BACKGROUND: An alteration of the autonomic nervous system has been described in heart failure (HF). The aim of this study was to assess, compare and relate the impairment of both arms of the autonomic nervous systems, the sympathetic and parasympathetic (SNS and PNS) in a same group of patients. METHODS: We analyzed 23 patients with advanced HF (NYHA III-IV/IV and IV/IV) and EF<35% who were on the waiting list for heart transplantation. We assessed the SNS by determining cardiac uptake of (123)I metaiodobenzylguanidine, and analyzed the heart mediastinum rate (HMR) and the myocardial washout rate (WR). The PNS was assessed by 24-hour Holter ECG recording and subsequent analyses of heart rate turbulence (HRT) in which turbulence onset (TO) and turbulence slope (TS) were determined. RESULTS: In the study of the SNS, HMR values were 1.32 ± 0.12, and WR 0.36 ± 0.1. Higher creatinine levels were associated with a lower WR (r=-0.604; p=0.02). In the study of the SNP, TO was higher the lower the LVEF (r=-0.410; p=0.052), and age was associated with a lower TS (r=-0.4; p=0.059). In the study of the relationships between the SNS and PNS, HMR was correlated in a nearly significant manner with TO (r=-0.399; p=0.059) and WR with TS (r=-0.447; p=0.033). CONCLUSIONS: In stable patients with advanced HF (NYHA III-IV and IV/IV), a significant and parallel impairment occurs in both arms of the autonomic nervous system. This could have prognostic implications and would help to prioritize patients on the waiting list for heart transplantation.

Are there differences in acute phase inflammation markers regarding the type of heart failure?

This study aimed to determine if there are differences in inflammatory markers in the acute phase between systolic heart failure and heart failure with preserved systolic function. One hundred and thirty-one patients with acute heart failure were recruited consecutively. At admission, plasma fibrinogen, C-reactive protein, sialic acid, von Willebrand factor, vascular endothelial growth factor, interleukin-6 and NTproBNP were all evaluated. If the ejection fraction was 45% or over patients were included in the HF-PSF group; the remaining patients were included in the SHF group. The HF-PSF patients were older (72±10 vs 63±12 years, P<0.001), presented a higher rate of atrial fibrillation (56.1 vs 21.3%, P<0.001), and had a lower rate of hemoglobin (12.2±2 vs 13.3±2.1 g/dL, P<0.01). No significant differences were observed in the inflammation markers analyzed among SHF and HF-PSF groups. In the acute phase of heart failure there is a marked elevation of inflammatory markers but there are no differences in the inflammatory markers analyzed between the two different types of heart failure.

Repeated daclizumab administration to delay the introduction of calcineurin inhibitors in heart transplant patients with postoperative renal dysfunction.

Daclizumab is an interleukin-2 receptor antagonist which is used for induction therapy in heart transplant patients. It has few side effects and is associated with a low infection rate. Postoperative renal failure after heart transplantation is common and potentially fatal. The administration of calcineurin inhibitors in the postoperative period can aggravate the situation. We report the cases of six patients who underwent heart transplantation and developed acute renal failure in the immediate postoperative period. All were administered daclizumab weekly to avoid the introduction of calcineurin inhibitors and to facilitate recovery of renal function. Calcineurin inhibitors were introduced only once renal function had improved. Renal function recovered in all cases and there was a low complication rate. The administration of repeated doses of daclizumab to patients who experience acute postoperative renal failure after heart transplantation may provide an alternative therapeutic approach that enables calcineurin inhibitors to be avoided and, consequently, renal function to recover.

Inflammatory markers in stable heart failure and their relationship with functional class.

INTRODUCTION AND OBJECTIVES: While it appears to be clear that an inflammatory process occurs in heart failure (HF), it is still to be defined whether inflammation depends to a greater extent on HF etiology, functional class (FC), or the extent of depression of ejection fraction (EF). Our objectives were to analyze differences in inflammatory marker levels as compared to a healthy population, to assess differences depending on HF etiology, and to relate values with FC and EF. PATIENTS AND METHODS: Fifty-nine consecutive outpatients with stable HF (57 + or - 9 years, 89% males) and 59 controls (55 + or - 8 years, 85% males) were enrolled into the study. Causes of HF included ischemic heart disease (n=24), idiopathic dilated cardiomyopathy (n=24), and miscellaneous conditions (n=11). Patients with decompensation in the past 6 months were excluded from the study. Protein fibrinogen, sialic acid, C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-alpha) were measured. Echocardiography was performed in all study patients. FC was assessed using the NYHA classification. RESULTS: A comparison of inflammatory marker levels between the HF and control groups showed significant differences in all markers, except for TNF-alpha. Protein fibrinogen in controls: 253 + or - 54 mg/dl, protein fibrinogen in HF: 294 + or - 67 mg/dl; p<0.05. Sialic acid in controls: 53 + or - 1 mg/dl, sialic acid in HF: 61 + or - 12 mg/dl; p<0.05. CRP in controls: 1.3 + or - 0.7 mg/dl, CRP in HF: 7.8 + or - 1.2 mg/dl; p<0.05. TNF-alpha in controls: 183 + or - 51 ng/ml, TNF-alpha in HF: 203 + or - 13 ng/ml; p=0.2. No differences were found between the different etiologies of HF. A positive association was seen between FC and protein fibrinogen and TNF-alpha (p<0.05), but not with EF. CONCLUSIONS: Increased inflammatory marker levels related to FC of the patient, but not to EF, are found in chronic HF.

Inflamación y disfunción endotelial en la insuficiencia cardíaca aguda y crónica / Endothelial dysfunction and inflammation in chronic and acute heart failure / Inflamação e disfunção endotelial na insuficiência cardíaca aguda e crônica

Introducción. En la insuficiencia cardíaca (IC) existe una importante activación neurohormonal e inflamatoria. También parece existir una disfunción endotelial. Nuestro objetivo ha sido comparar ambos procesos (inflamación y disfunción endotelial) en pacientes con IC. Material y métodos. Comparamos marcadores de disfunción endotelial (células endoteliales circulantes, macropartículas circulantes y factor von Willebrand) y de inflamación (proteína C reactiva, interleuquina 6 y fibrinógeno funcional) en 16 pacientes con insuficiencia cardíaca aguda (ICA), 16 con insuficiencia cardíaca crónica (ICC) estable y 32 controles sanos. Resultados. El número de células endoteliales circulantes fue mayor en los pacientes con ICA que en el grupo ICC y que en el grupo control (115,10 ± 63,44 vs 19,67 ± 3,17 vs 11,71 ± 2,92 cel/mL). La cantidad de macropartículas circulantes fue mayor en el grupo ICA que en el ICC y en ambos grupos frente al grupo control (9.627 ± 4.986 vs 3.970 ± 3.452 vs 1.371 ± 739 p/µL). El factor von Willebrand fue mayor en ambos grupos IC que en el control (234,3 ± 45,31 vs 245,92 ± 117,89 vs 100,14 ± 20,7%). Los valores de proteína C reactiva fueron mayores en el grupo ICA que en el ICC y que en el control (20,29 ± 17,56 vs 7,65 ± 4,27 vs 1,44 ± 1,10 mg/dL). La interleuquina 6 se encontró más elevada en los pacientes con ICA respecto al resto de grupos y en los pacientes con ICC respecto a los sanos (9,73 ± 9,37 vs 1,69 ± 1,36 vs 1,01 ± 1,09 pg/mL). Referente al fibrinógeno funcional, sólo encontramos diferencias significativas entre el grupo ICA y el resto de grupos (350 ± 60,48 vs 264,08 ± 67,02 vs 254,29 ± 23,69 mg/dL). Conclusiones. De forma paralela a la inflamación ya conocida en la IC, se produce una disfunción endotelial que a su vez parece ser proporcional a la gravedad de la IC.

Background. There is a neurohormonal an inflammatory activation in heart failure. There is also an endothelial dysfunction. Our objective war to compare both processes (inflammation and endothelial dysfunction) in patients with heart failure. Material and method. We compared endothelial dysfunction markers (circulating endothelial cells, circulating microparticles and Von Willebrand factor) and inflammatory markers (C reactive protein, interleukin-6 and functional fibrinogen) in 16 patients with acute heart failure (AHF), 16 with stable chronic heart failure (SHF) and 32 healthy controls. Results. The number of circulating endothelial cells was greater in AHF patients than in SHF and controls (115.10± 63.44 vs 19.67 ± 3.17 vs 11.71 ± 2.92 cel/mL). The amount of circulating microparticles was greater in the AHF group than in the SHF and in both than controls (9,627 ± 4,986 vs 3,970 ± 3,452 vs 1,371 ± 739 p/µL). Von Willebrand factor was greater in both heart failure groups than in controls (234.3 ± 45.31 vs 245.92 ± 117.89 vs 100.14± 20.7%). C reactive protein was greater in the AHF group than in the SHF group or controls (20.29 ± 17.56 vs 7.65± 4.27 vs 1.44 ± 1.10 mg/dL). Interleukin-6 was also higher in the AHF group than in the SHF and in this greater than in controls (9.73 ± 9.37 vs 1.69 ± 1.36 vs 1.01 ± 1.09 pg/mL). Functional fibrinogen was only greater in the AHF group (350 ± 60.48 vs 264.08 ± 67.02 vs 254.29 ± 23.69 mg/dL). Conclusions. Inflammation and endothelial dysfunction run together in heart failure patients. The endothelial dysfunction observed seems to be proportional to the inflammatory state.

Introdução. Na insuficiência cardíaca existe uma importante ativação neurohormonal e inflamatória. Também parece existir uma disfunção endotelial. Nosso objetivo foi o de comparar ambos processos (inflamação e disfunção endotelial) em pacientes com insuficiência cardíaca. Materiais e métodos. Comparamos marcadores de disfunção endotelial (células endoteliais circulantes, micropartículas circulantes e fator Von Willebrand) e de inflamação (proteína C reativa, interleuquina 6 e fibrinogênio funcional) em 16 pacientes com insuficiência cardíaca aguda (ICA), 16 com insuficiência cardíaca crônica estável (ICC) e 32 controles sãos. Resultados. O número de células endoteliais circulantes foi maior nos pacientes com ICA que no de ICC e que no controle (115,10 ± 63,44 vs 19,67 ± 3,17 vs 11,71 ± 2,92 cel/mL). A quantidade de micropartículas circulantes foi maior no grupo de ICA que no de ICC e em ambos grupos de pacientes em frente ao grupo controle (9.627 ± 4.986 vs 3.970 ± 3.452 vs 1.371 ± 739 p/µL). O fator Von Willebrand foi maior em ambos grupos de insuficiência cardíaca que no controle (234,3 ± 45,31 vs 245,92 ± 117,89 vs 100,14 ± 20,7%). Os valores de proteína C reativa foram maiores no grupo de ICA que no de ICC e que no de sãos (20,29 ± 17,56 vs 7,65 ± 4,27 vs 1,44 ± 1,10 mg/dL). A interleuquina seis encontrou-se mais elevada nos pacientes com ICA com respeito ao resto de grupos e nos pacientes com ICC com respeito aos sãos (9,73 ± 9,37 vs 1,69 ± 1,36 vs 1,01 ± 1,09 pg/mL). Com respeito ao fibrinogênio funcional só encontramos diferenças significativas entre o grupo de ICA e o resto de grupos (350 ± 60,48 vs 264,08± 67,02 vs 254,29 ± 23,69 mg/dL). Conclusões. De forma paralela à inflamação já conhecida na insuficiência cardíaca, se produz uma disfunção endotelial que a sua vez parece ser proporcional à gravidade da insuficiência cardíaca.