ABSTRACT
INTRODUCTION: While the growing knowledge on HIV among solid organ transplant recipients (SOT) is limited to either pretransplant infection or allograft transmission, there are only sparse reports describing HIV-infection after transplantation through sexual route, the primary mode of transmission in the general population. METHODS: From two different centers, we report nine new cases of HIV infection in SOT recipients attributed to sexual acquisition: eight cases of kidney-transplant recipients and one heart-transplant recipient. FINDINGS: There were nine cases of post-transplant HIV-infection detected among 14 526 transplants performed 1998 to 2015. In 6/9 cases, infection was contracted 5 years after SOT. All but one patient had stable allograft function under immunosuppressive therapy. The main trigger to diagnosis was late CMV disease and sexually transmitted diseases; five patients had CDC-stage 3 HIV infection. In 7/9 patients, virologic response and CD4 recovery were achieved within 3 months after starting antiretroviral therapy (ART). After an average of 3.6 years post diagnosis, 5/9 patients remained alive with well-controlled infection and functioning allograft. CONCLUSION: Sexual acquisition of HIV infection after SOT represents a difficult challenge, as it may occur in any kind of transplant and at any time. The course of infection resembles that of the general population, with life-threatening infectious complications, but good response to ART. Assessment of lifestyle and risk behavior is paramount, as indications may be not disclosed without direct questioning.
Subject(s)
Antiviral Agents/therapeutic use , HIV Infections/epidemiology , Heart Transplantation/adverse effects , Kidney Transplantation/adverse effects , Postoperative Complications/epidemiology , Adult , Female , Follow-Up Studies , Graft Rejection/prevention & control , HIV/drug effects , HIV/isolation & purification , HIV Infections/drug therapy , HIV Infections/virology , Health Risk Behaviors , Humans , Immunosuppressive Agents/therapeutic use , Life Style , Male , Middle Aged , Postoperative Complications/drug therapy , Postoperative Complications/virology , Sustained Virologic ResponseABSTRACT
Cardiovascular diseases have become a significant cause of morbidity in patients with human immunodeficiency virus (HIV) infection. Heart transplantation (HT) is a well-established treatment of end-stage heart failure (ESHF) and is performed in selected HIV-infected patients in developed countries. Few data are available on the prognosis of HIV-infected patients undergoing HT in the era of combined antiretroviral therapy (cART) because current evidence is limited to small retrospective cohorts, case series, and case reports. Many HT centers consider HIV infection to be a contraindication for HT; however, in the era of cART, HT recipients with HIV infection seem to achieve satisfactory outcomes without developing HIV-related events. Consequently, selected HIV-infected patients with ESHF who are taking effective cART should be considered candidates for HT. The present review provides epidemiological data on ESHF in HIV-infected patients from all published experience on HT in HIV-infected patients since the beginning of the epidemic. The practical management of these patients is discussed, with emphasis on the challenging issues that must be addressed in the pretransplant (including HIV criteria) and posttransplant periods. Finally, proposals are made for future management and research priorities.
Subject(s)
Antiretroviral Therapy, Highly Active/adverse effects , HIV Infections/complications , Heart Failure/surgery , Heart Transplantation , HIV Infections/drug therapy , Heart Failure/chemically induced , Humans , PrognosisABSTRACT
AIMS: Patients with heart failure (HF) as well as atrial fibrillation (AF) have suboptimal response to cardiac resynchronization therapy (CRT). Identification of mechanical abnormalities, amenable to correction with CRT, might improve the selection of candidates and CRT efficiency. We evaluated whether abnormal septal motion, assessed by the presence of septal flash (SF) is related to CRT response in patients with AF. METHODS AND RESULTS: Ninety-four CRT patients with AF were included. Echocardiography was performed in all subjects at baseline and at 12-month follow-up. Abnormal septal motion was defined by the presence of SF (early septal inward/outward motion within the isovolumic contraction period/QRS duration). Response to CRT was defined as a reduction (>15%) of the end-systolic volume of the left ventricle (LV). Univariate and multivariate analyses were performed to identify the predictors of CRT response. The mean age was 69 ± 8 years, 79% were males, and 59% of patients responded to CRT. Cardiovascular death was 14.4% and all-cause mortality was 16.5% during follow-up. Patients with SF at baseline that was acutely corrected by CRT were significantly more likely to respond than patients without SF. Baseline SF was an independent predictor of CRT response (OR 5.24; 95% CI 1.95-14.11). CONCLUSION: Abnormal septal motion, assessed by the presence of SF, is a mechanism amenable to CRT correction. Its correction is associated with a higher likelihood of CRT response in HF patients with long-standing AF. This could improve the selection of candidates to CRT in a subgroup with particularly poor response and long-term prognosis.
Subject(s)
Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/therapy , Cardiac Resynchronization Therapy/methods , Heart Septum/diagnostic imaging , Aged , Chronic Disease , Female , Follow-Up Studies , Humans , Male , Prognosis , Reproducibility of Results , Sensitivity and Specificity , Treatment Outcome , UltrasonographyABSTRACT
Toxoplasma gondii is an opportunistic pathogen that causes neurologic and extraneurologic manifestations in immunosuppressed patients. Encephalitis and intracranial mass lesions are easily recognized as typical manifestations of toxoplasmosis. However, meningitis caused by T. gondii is a rare condition with very few cases described in the literature. We present the case of a heart transplant recipient who developed toxoplasmic encephalitis associated with meningitis. After an extensive review of the medical literature, we found only 1 case of meningitis in solid organ transplant recipients and <25 cases in immunosuppressed patients, such as patients infected with human immunodeficiency virus or those with Hodgkin's disease. In this report, we consider toxoplasmosis in the differential diagnosis of meningitis in immunocompromised individuals.
Subject(s)
Encephalitis/parasitology , Heart Transplantation/adverse effects , Meningitis/parasitology , Toxoplasmosis, Cerebral/etiology , Antiprotozoal Agents/administration & dosage , Antiprotozoal Agents/therapeutic use , Clindamycin/administration & dosage , Clindamycin/therapeutic use , Drug Therapy, Combination , Humans , Male , Meningitis/complications , Middle Aged , Protein Synthesis Inhibitors/administration & dosage , Protein Synthesis Inhibitors/therapeutic use , Pyrimethamine/administration & dosage , Pyrimethamine/therapeutic use , Toxoplasmosis, Cerebral/parasitologyABSTRACT
BACKGROUND: Pulmonary function tests (PFTs) are often impaired in patients with advanced heart failure. There is limited data about their impact on survival after heart transplantation (HT). We sought to assess the prevalence and type of PFT abnormalities in patients on HT waiting list and their impact on outcomes. METHODS: We performed a retrospective analysis of a prospective registry of consecutive patients undergoing HT between 2012 and 2018. Patients were classified into 4 groups according to pre-HT PFT results: 1. normal pattern: forced vital capacity (FVC) ≥ 80% and forced expiratory volume in 1 second (FEV1) to FVC ratio (FEV1/FVC) ≥ 0.7; 2. obstructive: FEV1/FVC < 0.7; 3. nonobstructive: FEV1/FVC ≥ 0.7 and FVC < 80% when total lung capacity value was not available; and 4. restrictive: FEV1/FVC ≥ 0.7 and total lung capacity < 80%. The prevalence of impaired carbon monoxide diffusing capacity corrected for hemoglobin < 80% and FEV1 < 70% was also analyzed. High-urgency HT patients and those referred from other centers without quantitative pulmonary evaluation were excluded. RESULTS: Among 123 patients who underwent HT, 83 patients with complete PFT were included. Median follow-up was 2.7 ± 1.9 years. Of these, 29 (34.9%) had an obstructive pattern, 20 (24.1%) a nonobstructive, 18 (21.7%) a restrictive, and 16 (19.3%) a normal pattern. Fifty-one (61.4%) patients had FEV1 < 70% and 58 (69.9%) a carbon monoxide diffusing capacity corrected for hemoglobin < 80%. There was a tendency to lower survival in all altered PFT groups compared with normal (P = .054) but not within the other groups. Patients with an impaired FEV1 had significantly higher mortality than patients with normal values (P = .008). Area under receiver operating characteristic curve for FEV1 was 0.73 (95% confidence interval [0.60-0.86]). A cutoff value of FEV1 (60.5) predicts mortality with 66% sensitivity and 64% specificity. CONCLUSIONS: PFT alterations have a very high prevalence on HT waiting list patients. Patients with impaired FEV1 had worse outcomes after heart transplantation.
Subject(s)
Heart Failure/complications , Heart Transplantation , Lung Diseases/complications , Adult , Female , Heart Transplantation/mortality , Humans , Lung/physiopathology , Lung Diseases/epidemiology , Lung Diseases/physiopathology , Male , Middle Aged , Prevalence , ROC Curve , Respiratory Function Tests , Retrospective StudiesABSTRACT
Cardiac resynchronization therapy (CRT) is a new method for the correction of inter- and/or intraventricular conduction delays of patients with heart failure. The long-term impact of CRT on central hemodynamics is not fully characterized. We performed complete right heart catheterization studies in 31 patients receiving a CRT device pre and 6 months after implantation. Most of the patients improved in their NYHA stage, their LVEF, and in parallel showed reduced right atrial (RA) pulmonary artery (PA) and pulmonary capillary wedge (PCW) pressures and pulmonary vascular resistance both at rest and at 25 watts. In addition, we found a reduction in heart rate accompanied by an increased mean arterial pressure both at rest and at 25 watts. Accordingly, brain natriuretic peptide levels (BNP) were lowered. It was concluded that, besides other well-known effects on ventricular coordination, central hemodynamics after 6 months were improved during CRT.
Subject(s)
Cardiac Pacing, Artificial , Heart Failure/physiopathology , Heart Failure/therapy , Adult , Biomarkers/blood , Cardiac Catheterization , Coronary Artery Disease/complications , Electric Stimulation , Female , Follow-Up Studies , Heart Failure/blood , Heart Failure/etiology , Heart Rate , Humans , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Pacemaker, Artificial , Pulmonary Wedge Pressure , Stroke Volume , Treatment Outcome , Vascular Resistance , Ventricular PressureABSTRACT
INTRODUCTION: Cardiac resynchronization therapy (CRT) using coronary sinus (CS) leads is a new method for the therapy of congestive heart failure (CHF). Because the intervention is more complex than regular pacemaker implantations, information on the feasibility and side effects of this method are of interest. METHODS: From 1999 to June 2005, CRT implantations were attempted in 244 patients (pts; mean age 64+/-12 years, range 14-90 years), 82% were male, 44% had coronary artery disease, 29% were in atrial fibrillation, 71 had preexisting pacemakers. RESULTS: In 97% of the pts the intervention was successful (27% of the systems with defibrillation capabilities). In 285 interventions, 255 CS leads were positioned according to CS vein anatomy in 130 posterolateral, 97 anterolateral and 28 anterior side branches (16 patients received 2 CS leads). Over-the-wire leads were used in 88%, 71% were additionally preshaped. We observed no mortality but 37 complications (12.5%): CS dissection in 9, CS perforation in 1, ventricular fibrillation in 4, asystole in 5, pulmonary edema in 1, pneumothorax in 2, need for early CS lead revision in 19 (dislodgement n=7, phrenic nerve stimulation n=12) and infection with explantation in 2 cases. An improvement in NYHA functional class was found in 88% of pts (only 55% if anterior lead position). CONCLUSION: Perioperative complications during CS lead implantation occur in 10-15% of cases. Most patients responded well to CRT. Patients should be informed about the possible need for a reoperation. During implantation, immediate defibrillation and stimulation capabilities must be available. Anterior lead positions should be avoided.
Subject(s)
Atrial Fibrillation/epidemiology , Atrial Fibrillation/prevention & control , Electrodes, Implanted , Pacemaker, Artificial/statistics & numerical data , Postoperative Complications/epidemiology , Prosthesis Implantation/statistics & numerical data , Risk Assessment/methods , Adolescent , Adult , Aged , Aged, 80 and over , Cardiac Pacing, Artificial/statistics & numerical data , Comorbidity , Coronary Vessels/surgery , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Risk Factors , Treatment Outcome , Veins/surgeryABSTRACT
BACKGROUND: Acute studies in cardiac resynchronization therapy (CRT) showed that hemodynamic effects may depend on the coronary sinus (CS) lead position. However, there are no data on the longterm effect of CS lead position. METHODS: In 45 heart failure patients with left bundle branch block and QRS >150 ms (age 59+/-10 years, 17 dilative cardiomyopathy, 23 ischemic, 5 valvular), biventricular pacemakers were implanted. CS leads were positioned in posterior (P, n=15), lateral (L, n=19) or, if no other option available, anterior (A, n=11) side branches. Before and 6 months after implantation, clinical state, echocardiography, brain natriuretic peptide (BNP) and right heart catheterization were evaluated. RESULTS: Baseline parameters were similar between groups. After 6 months, there were 32/34 responders in groups P and L compared to 7/11 responders in group A (94 vs groups P and L: Arterial pressure +8 and +9% vs +2%; PCWP -23 and -15% vs -4%, pulmonary pressure -18 and -12% vs -3% (p<0.01 for A vs P+L); cardiac index +21 and +12% vs +11% (p=0.03 for A vs P). BNP was reduced by 55, 35, and 27% (p=0.05 for A vs P). Ejection fraction increased in P and L by 40 and 41%, respectively, but only by +19% in A (p<0.03 for A vs P+L). CONCLUSION: Chronic CRT improves ejection fraction, BNP and hemodynamic measurements predominantly in patients with lateral and posterior CS lead positions. Anterior lead positions should be avoided.
Subject(s)
Blood Pressure/physiology , Bundle-Branch Block/therapy , Cardiac Output/physiology , Electrocardiography , Heart Failure/therapy , Heart Rate/physiology , Myocardial Contraction/physiology , Pacemaker, Artificial , Pulmonary Wedge Pressure/physiology , Stroke Volume/physiology , Aged , Bundle-Branch Block/etiology , Bundle-Branch Block/physiopathology , Carbon Dioxide/blood , Cardiac Catheterization , Echocardiography , Female , Follow-Up Studies , Heart Failure/etiology , Heart Failure/physiopathology , Hemoglobinometry , Humans , Male , Middle Aged , Oxygen/blood , Ventricular Function, Left/physiologyABSTRACT
BACKGROUND: Failure of compliance with medical regimen is one of the major risk factors associated with morbidity and mortality in heart transplant (HT) recipients. Nevertheless, to date, there is no specific, gold-standard, comprehensive set of tools for assessing compliance in these patients. OBJECTIVE: The objective of the present study was to develop a specific instrument for the assessment of noncompliance with medical recommendations in HT recipients. METHODS: This prospective observational study used a nonprobability sampling method, which was performed from January 2006 to December 2012. All of the patients met clinical criteria for being included on the waiting list for a HT. We designed a scale for measuring the compliance degree at 12 months after heart transplantation. This scale included the most important aspects of the medical regimen, using nine discrete quantitative variables. The total score was described as the patient's Noncompliance Factor (NCF). The results were analysed by mean, ranks, and percentages. RESULTS: The sample was constituted of 61 participants who underwent surgical HT intervention and completed the 12-month follow-up assessment. The overall incidence of noncompliance was around 30% and only 43.1% of the recipients had an acceptable degree of compliance. CONCLUSIONS: The overall incidence of noncompliance in HT recipients is high and this can generate worse clinical outcomes. Evaluation by specific screening instruments like the one proposed in the present study can be useful for a systematic detection of this phenomenon.
Subject(s)
Heart Transplantation/psychology , Mass Screening/methods , Patient Compliance/statistics & numerical data , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Postoperative Period , Prospective Studies , Risk Factors , Sampling Studies , Waiting ListsABSTRACT
In this article, the full description of a heart failure with reduced ejection fraction (HF_REF) cohort of 192 patients is provided. Tables with the baseline demographic, prior history, ECG parameters, echocardiographic parameters, laboratory values and pharmacological treatment of these patients are included. Also, the quartile values of the analyzed circulating biomarkers: high sensitivity Troponin T (hs-TnT), galectin-3 (Gal-3), C-terminal propeptide of type I procollagen (CICP), soluble AXL (sAXL) and Brain Natriuretic Peptide (BNP) are given. The main demographic and clinical features of the patients' subgroups that have hs-TnT, Gal-3, CICP or BNP above the third quartile are described. Tables with Pearson correlation analysis of the HF_REF patients' biomarker levels are included. And Pearson correlation analysis of the HF_REF patients' hs-TnT, Gal-3, CICP levels with patients' biochemical parameters, blood count and inflammation parameters are also described. These data are related to the research articles (AXL receptor tyrosine kinase is increased in patients with heart failure (M. Batlle, P. Recarte-Pelz, E. Roig, M.A. Castel, M. Cardona, M. Farrero, et al., 2014) [1] and Use of serum levels of high sensitivity troponin T, galectin-3 and C-terminal propeptide of type I procollagen at long term follow-up in Heart Failure patients with reduced ejection fraction: comparison with soluble AXL and BNP (M. Batlle, B. Campos, M. Farrero, M. Cardona, B. González, M.A. Castel, et al., 2016) [2].
ABSTRACT
BACKGROUND: Prognostic biomarkers are needed to improve the management of the heart failure (HF) epidemic, being the brain natriuretic peptides the most valuable. Here we evaluate 3 biomarkers, high sensitivity troponin T (hs-TnT), galectin-3 (Gal-3) and C-terminal propeptide of type I procollagen (CICP), compare them with a recently described new candidate (sAXL), and analyze their relationship with BNP. METHODS: HF patients with reduced ejection fraction (n=192) were included in this prospective observational study, with measurements of candidate biomarkers, functional, clinical and echocardiographic variables. A Cox regression model was used to determine predictors for clinical events, i.e. all-cause mortality and heart transplantation. RESULTS: Hs-TnT circulating values were correlated to clinical characteristics indicative of more advanced HF. When analyzing the event-free survival at a mean follow-up of 3.6years, patients in the higher quartile of either BNP, hs-TnT, CICP and sAXL had increased risk of suffering a clinical event, but not Gal-3. Combination of high sAXL and BNP values had greater predictive value (HR 6.8) than high BNP alone (HR 4.9). In a multivariate Cox regression analysis, BNP, sAXL and NYHA class were independent risk factors for clinical events. CONCLUSIONS: In this HF cohort, hs-TnT is a good HF marker and has a very significant prognostic value. The prognostic value of CICP and sAXL was of less significance. However, hs-TnT did not add predictive value to BNP, while sAXL did. This suggests that elevated troponin has a common origin with BNP, while sAXL could represent an independent pathological mechanism.
Subject(s)
Galectin 3/blood , Heart Failure/blood , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Procollagen/blood , Proto-Oncogene Proteins/blood , Receptor Protein-Tyrosine Kinases/blood , Troponin T/blood , Biomarkers/blood , Cohort Studies , Female , Follow-Up Studies , Heart Failure/diagnosis , Heart Failure/epidemiology , Humans , Male , Prospective Studies , Stroke Volume/physiology , Axl Receptor Tyrosine KinaseABSTRACT
In order to establish an assay for the detection of autoimmune sera with broad spectrum activity, we have investigated the effect of unselected normal and Graves' disease sera upon steroidogenesis by gonadal cells. Steroidogenesis was enhanced by the addition of normal serum in a 3-h primary Leydig cell bioassay, but was inhibited by the majority of Graves' sera. The inhibition was not related to clinical thyroid parameters, such as the severity of the TSH-binding inhibition index, and was not overcome by other agonists or second messenger supplements. Although pituitary TSH preparations bound to and stimulated Leydig cells, TSH receptor mRNA was not detectable and pure recombinant TSH failed to bind or stimulate, indicating contamination of pituitary TSH with LH. The binding of hCG to the Leydig cell luteinizing hormone receptor was not perturbed by the Graves' autoimmune sera, indicating that cross-reactive anti-TSH receptor antibodies were not responsible for the inhibition. By use of intermediates in the stimulatory pathway, the site of Graves' serum inhibition was identified to be distal to hormone receptor/adenylate cyclase coupled responses and proximal to supply of cholesterol for steroidogenesis.
Subject(s)
Autoantibodies/analysis , Biological Assay , Graves Disease/immunology , Leydig Cells/metabolism , Receptors, Thyrotropin/immunology , Steroids/biosynthesis , Animals , Cholesterol/metabolism , Chorionic Gonadotropin/metabolism , Chorionic Gonadotropin/pharmacology , Humans , Male , Mice , Thyrotropin/metabolismABSTRACT
Graves' disease is attributed to the presence of autoantibodies with agonist activity which interact with the TSH receptor causing thyroid hyperstimulation and hyperthyroidism. The degree of TSH-binding inhibition (TSH-BI) caused by a Graves' serum in a TSH radioligand receptor assay is considered to be an index of the prevalence of anti-TSH receptor autoantibodies in that serum. We have previously shown that the specific inhibition by Graves' serum of hCG-stimulated steroidogenesis by Leydig cells was at a site distal to receptor binding and second messenger activation. In this report, we have investigated whether the effect of Graves' serum upon Leydig cells is a property of the constitutive antibodies. Immunoglobulin-enriched fractions were obtained from Graves' and normal sera using three increasingly rigorous procedures; ammonium sulphate precipitation, caprylic acid treatment and Protein A or G-affinity purification. The TSH-BI was determined for untreated and extracted sera in two radioreceptor assays developed for use with serum, one using human thyroid membranes and the other using HeLa cells transfected with the human TSH receptor, and the results were compared with effects in the Leydig cell steroidogenesis bioassay. The specific inhibition of hCG-stimulated Leydig cell steroidogenesis by Graves' sera was not retained in the antibody fraction causing TSH-BI. Thus, the inhibitory factor appears not to be an antibody and we are now attempting to purify and identify the responsible factor from Graves' serum.
Subject(s)
Autoantibodies/pharmacology , Graves Disease/blood , Graves Disease/immunology , Leydig Cells/metabolism , Testosterone/antagonists & inhibitors , Testosterone/biosynthesis , Thyrotropin/antagonists & inhibitors , Thyrotropin/immunology , Ammonium Sulfate/pharmacology , Autoantibodies/blood , Caprylates/pharmacology , HeLa Cells , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin G/isolation & purification , Male , Sepharose , Staphylococcal Protein A/pharmacology , Thyroid Gland/cytologyABSTRACT
We describe a 30-year-old man with end-stage heart failure after therapy with mitoxantrone for multiple sclerosis. A successful orthotopic heart transplantation was performed when intensified medical therapy failed to improve the patient's hemodynamics. In spite of the severe underlying disease he did well on dual immunosuppression with methylprednisone and cyclosporine. Neurologic symptoms remained stable throughout the procedure and, after 2 months, he resumed preoperative ambulatory status. Eight years after the operation, the patient is now in New York Heart Association (NYHA) Class I status. Using canes, he is able to walk short distances. Repeated urinary tract infections caused by Escherichia coli became a problem, but have been controlled by long-term oral antibiotic prophylaxis with trimethoprim.
Subject(s)
Cardiomyopathies/chemically induced , Cardiomyopathies/surgery , Heart Transplantation , Mitoxantrone/adverse effects , Multiple Sclerosis/drug therapy , Adult , Benzimidazoles/administration & dosage , Cyclosporine/administration & dosage , Humans , Immunosuppression Therapy/methods , MaleABSTRACT
BACKGROUND: AXL is a membrane receptor tyrosine kinase highly expressed in the heart and has a conspicuous role in cardiovascular physiology. The role of AXL in heart failure (HF) has not been previously addressed. METHODS AND RESULTS: AXL protein was enhanced 6-fold in myocardial biopsies of end-stage HF patients undergoing heart transplantation compared to controls from heart donors (P<0.0001). Next, we performed a transversal study of patients with chronic HF (n=192) and a group of controls with no HF (n=67). sAXL and BNP circulating levels were quantified and clinical and demographic data were collected. sAXL levels in serum were higher in HF (86.3 ± 2.0 ng/mL) than in controls (67.8 ± 2.0 ng/mL; P<0.0001). Also, sAXL correlated with several parameters associated with worse prognosis in HF. Linear regression analysis indicated that serum creatinine, systolic blood pressure and atrial fibrillation, but not BNP levels, were predictive of sAXL levels. Cox regression analysis indicated that high sAXL values at enrollment time were related to the major HF events (all-cause mortality, heart transplantation and HF hospitalizations) at one year follow-up (P<0.001), adding predictive value to high BNP levels. CONCLUSIONS: Myocardial expression and serum concentration of AXL is elevated in HF patients compared to controls. Furthermore, peripheral sAXL correlates with parameters associated with the progression of HF and with HF events at short term follow-up. All together these results suggest that sAXL could belong to a new molecular pathway involved in myocardial damage in HF, independent from BNP.
Subject(s)
Heart Failure/blood , Heart Failure/diagnosis , Myocardium/enzymology , Proto-Oncogene Proteins/blood , Receptor Protein-Tyrosine Kinases/blood , Aged , Biomarkers/blood , Disease-Free Survival , Female , Follow-Up Studies , Heart Failure/mortality , Humans , Male , Middle Aged , Axl Receptor Tyrosine KinaseABSTRACT
BACKGROUND: The use of short-term ventricular assist devices (VAD) in patients awaiting high-urgency (HU) heart transplantation (HTx) in Spain has steadily increased due to longer waiting times and the new heart allocation system. It is unknown whether the use of short-term VAD support in patients with cardiogenic shock affects HTx outcome. We sought to investigate long-term outcomes of HU transplanted patients with VAD compared with HU transplanted patients without device support. METHODS: We retrospectively evaluated all HTx patients transplanted between 1999 and 2011 in our institution. Patients were categorized by urgency: elective HTx, HU-HTx with VAD (status 0), and HU-HTx without VAD (status 1). Actuarial survival rates were compared. RESULTS: Of 237 transplanted patients, 55 (23%) were HU-HTx, including 16 on VAD support and 39 without VAD. Mean time in the HU waiting list was 6.5 ± 6 days and mean VAD support was 8.4 ± 8 days (range, 1 to 31 days). Assist devices used were Levitronix Centrimag (6), Abiomed (9), and extracorporeal membrane oxygenation (ECMO) (1). After a mean follow-up of 4.6 ± 4.1 years (range 0 to 13 years), 22 patients had died: 5 VAD and 17 non-VAD. The 1- and 5-year survival rates were 73% and 61% for the VAD and 74% and 62% for the non-VAD group, respectively (P = ns). Kaplan-Meier and Cox regression analyses did not show survival differences, HR 1.11 (95% CI 0.41-3.02), P = 0.84. The presence of renal failure was associated with increased mortality risk, HR 1.9 (95% CI 1.1-3.2), P = 0.02. The presence of renal failure was associated with increased mortality risk [HR 1.9 (95% CI 1.1-3.2), P = .02.). CONCLUSIONS: In our experience, the long-term outcome of patients receiving HU-HTx under short-term VAD support is comparable to that of patients undergoing HU-HTx without VAD support. Patients with renal failure had an increased risk for overall mortality in this set of patients.
Subject(s)
Heart Failure/surgery , Heart Failure/therapy , Heart Transplantation , Heart-Assist Devices , Ventricular Function, Left , Adult , Female , Heart Failure/diagnosis , Heart Failure/mortality , Heart Failure/physiopathology , Heart Transplantation/adverse effects , Heart Transplantation/mortality , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , Prosthesis Design , Registries , Renal Insufficiency/mortality , Retrospective Studies , Risk Factors , Spain , Survival Rate , Time Factors , Treatment Outcome , Waiting ListsABSTRACT
BACKGROUND: The superiority of tacrolimus (Tac) as primary immunosuppression for heart transplantation (HT) compared with cyclosporine (CsA) is still under debate. Outcomes of comparison studies are not consistent; the duration of these studies has been limited. The aim of this study was to evaluate long-term outcomes of patients undergoing HT based on primary immunosuppression regime. METHODS AND RESULTS: We analyzed a single-center registry of all HT patients between 1998 and 2009, comparing outcomes based on primary immunosuppressions (Tac or CsA). Patients who died before starting immunosuppression were excluded. A total of 197 patients entered the study; 103 received Tac and 94 CsA. There were no differences between groups in baseline characteristics, United Network for Organ Sharing status 1A or ventricular assist device use, except for ischemia time (195 ± 50 min in Tac group vs 182 ± 55 min in CsA; P = .08) and days on waiting list (164 ± 155 vs 100 ± 73; P < .001). After mean follow-ups of 4.5 ± 2.3 years in the Tac group and 6.3 ± 4.3 years in the CsA group, there were 19 and 36 deaths, respectively. Kaplan-Meier analysis showed increased survival for the Tac group (log rank P = .04). Tac also was significantly superior to CsA regarding mortality (relative risk 0.55; 95% confidence interval, 0.31-0.98; P = .04). CONCLUSIONS: In our series the use of tacrolimus resulted in improved long-term survival compared with cyclosporine. At 1-year follow-up, there were no differences in acute rejection episodes or the appearance of vasculopathy.
Subject(s)
Cyclosporine/therapeutic use , Graft Rejection/prevention & control , Graft Survival/drug effects , Heart Transplantation , Immunosuppressive Agents/therapeutic use , Tacrolimus/therapeutic use , Adult , Chi-Square Distribution , Drug Therapy, Combination , Female , Graft Rejection/immunology , Graft Rejection/mortality , Heart Transplantation/adverse effects , Heart Transplantation/immunology , Heart Transplantation/mortality , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , Registries , Retrospective Studies , Risk Assessment , Risk Factors , Spain , Survival Rate , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Thrombospondin-1 (TSP-1) is a potent inhibitor of angiogenesis and an activator of tissue transforming growth factor-beta1 (TGF-beta1). Analyses using genetically modified mice suggested that TSP-1 may play a protective role to prevent infiltration and tissue remodeling responses after myocardial infarction. The expression levels of TSP-1 and their putative role in ventricular remodeling have not been determined in patients with heart failure (HF). MATERIALS AND METHODS: We analyzed the expression of TSP-1 and TGF-beta1 mRNA in myocardial biopsies from 34 subjects with end-stage HF undergoing heart transplantation and 13 healthy controls from heart donors. Among total RNA extracted from the left ventricle, 1 microg was retrotranscribed and mRNA expression levels were quantified by real-time polymerase chain reaction (PCR). RESULTS: The mean age of subjects was 54 +/- 2 years; mean ejection fraction, 21 +/- 5%; end-diastolic diameter and end-systolic diameter, 73 +/- 10 and 61 +/- 11 mm, respectively. TSP-1 mRNA expression in ventricular tissue from HF patients was lower (159.04 +/- 14.55 ng-equivalents [ng-equiv]) than in controls (234 +/- 30.66 ng-equiv; P < .05). Tissue from HF subjects also showed lower levels of TGF-beta1 (68.42 +/- 4.36 vs 80.58 +/- 5.26 ng-equiv; P < .05). TSP-1 mRNA levels correlated positively with TGF-beta1 (P = .001; R(2) = .2), and lower TSP-1 mRNA levels were observed with increasing left ventricular diameters. CONCLUSIONS: Patients with end-stage HF show decreased TSP-1 mRNA levels, which agrees with published results showing lower circulating TSP-1. Ventricular dilatation observed in these patients may be related to lower expression of TSP-1. Surprisingly, TGF-beta1 mRNA levels were lower in failing hearts, which suggested that fibrogenesis takes place in earlier phases of HF.
Subject(s)
Heart Failure/genetics , Heart Transplantation/pathology , Thrombospondin 1/genetics , Ventricular Remodeling/genetics , Biopsy , Female , Gene Expression Regulation , Heart Failure/pathology , Humans , Male , Middle Aged , Polymerase Chain Reaction , RNA/genetics , RNA, Messenger/genetics , Reference Values , Spectrophotometry , Tissue Donors , Transcription, Genetic , Transforming Growth Factor beta1/geneticsABSTRACT
BACKGROUND: There is a lack of consensus and insufficient data to assess the impact of late steroid withdrawal after heart transplantation (HTx). The aim of the study was to investigate the security and feasibility of corticosteroid withdrawal at 1 year after transplantation. METHODS AND RESULTS: Steroid withdrawal was attempted after at least 12 months of treatment in 86 HTx patients who fulfilled the criteria. At 1 and 3 months after drug discontinuation, patients underwent 2 endomyocardial biopsies (EMB). After a mean follow-up of 25 +/- 13 months, 63% of the patients remained steroid free. In 30 patients (35%) corticosteroids were reinitiated, in 15 cases because of acute rejection (7%), 5 (6%) because of worsening renal function, 5 (6%) because of malignancy, 3 (4%) because of adverse effects of immunosuppressive drugs, and 2 because of severe allograft coronary artery disease. Four patients (5%) died after drug discontinuation. There was a significant decrease in total cholesterol (198 +/- 35 to 181 +/- 38 mg/dL; P < .001) and low-density lipoprotain (LDL) cholesterol levels (113 +/- 30 to 105 +/- 30 mg/dL; P < .001). There were no differences in mortality between patients with and without corticosteroids. CONCLUSION: Steroid withdrawal is feasible and safe in HTx patients. In our study, it was successfully maintained in 63% of the patients. EMB is helpful to identify patients with acute rejection at 1 and 3 months after withdrawal. Short- to mid-term metabolic benefits are significant reductions in serum total and LDL cholesterol.
Subject(s)
Adrenal Cortex Hormones/therapeutic use , Heart Transplantation/physiology , Adrenal Cortex Hormones/adverse effects , Cholesterol/blood , Cholesterol, LDL/blood , Drug Administration Schedule , Feasibility Studies , Follow-Up Studies , Graft Rejection/drug therapy , Graft Rejection/epidemiology , Graft Rejection/immunology , Graft Rejection/mortality , Heart Transplantation/immunology , Heart Transplantation/mortality , Humans , Kidney Function Tests , Patient Selection , Reoperation/statistics & numerical data , Retrospective Studies , Substance Withdrawal Syndrome/physiopathology , Survival Rate , Time FactorsABSTRACT
AIMS: Coronary sinus (CS) lead implantation is a technically challenging procedure owing to variable vein anatomies and a high dislocation rate. Therefore, CS lead technology has undergone evolutionary changes during the last 10 years. The mode of fixation has been a passive one up to now. We want to describe our first clinical experience with the newly available active fixation lead 4195 in terms of dislocation rate and stability of thresholds compared with conventional models. METHODS AND RESULTS: From 1999 to February 2007, we implanted 403 CS leads in 368 patients. Leads were categorized into three different groups on the basis of their fixation mechanism: straight (Easytrak I and Situs OTW; n = 54), curved (Attain 4193 and 4194, Corox, Aescula, Situs ULD; n = 308), and active (Attain 4195; n = 41). Operative and follow-up data were prospectively noted and checked for significance between groups during the first 3 months after implantation. Kaplan-Meier analysis of long-term lead function was also performed. Straight and curved CS leads suffered from significantly more dislocations compared with active fixation (P < 0.001). The active fixation lead (4195) has a stable threshold over time compared with a significant rise after 24 h and thereafter in straight (62%) and curved leads (20%). However, retraction of an active fixation CS lead may be a difficult issue as outlined in two cases requiring pullback of a 4195 lead owing to phrenic nerve stimulation (one unsuccessful despite vigorous traction). CONCLUSION: The active fixation lead 4195 using retention lobes yielded stable thresholds over time and seems to be superior to conventional leads in terms of dislocation. However, extraction may be a difficult or even impossible task.