Switching to abacavir versus use of a nucleoside-sparing dual regimen for HIV-infected patients with tenofovir-associated renal toxicity.

OBJECTIVES: We investigated the reversibility of tenofovir disoproxil fumarate (TDF)-associated renal decline and tubular dysfunction using different antiretroviral strategies. METHODS: A successive evaluation of renal [estimated glomerular filtration rate (eGFR)] and tubular (phosphataemia, proteinuria, albuminuria, phosphaturia, uricosuria, glycosuria and tubular proteinuria) parameters was performed in 231 patients, before and after switching from TDF to abacavir (n = 60), using dual therapy (n = 49), or continuing the same regimen including TDF (n = 122). RESULTS: In a successive evaluation after a median of 8.86 months, or less time if treatment was switched (4.8 months vs. 13.3 months to second evaluation; P < 0.01), a significant improvement in eGFR (median change +0.3 vs. -2.91 mL/min/1.73 m2 in patients who did not discontinue TDF; P = 0.04) and tubular dysfunction (median change -40% vs. +30%, respectively; P < 0.01) was observed. Lineal regression showed that age (ß = -0.14; P = 0.04), previous eGFR decline (ß = -0.42; P < 0.01), and time on TDF (ß = -0.19; P = 0.04) were associated with impaired eGFR recovery. There were no differences in eGFR slopes between patients using abacavir instead of TDF and those using a dual therapy, who showed similar improvement in proteinuria (-22% vs. -19%, respectively), phosphaturia (+10.1% vs. +9.4%, respectively), and urinary beta-2-microglobulin (-9% vs. -15%, respectively; P > 0.1 for all), although patients receiving the dual regimen were more heavily pretreated. A eGFR decrease (-6.17 mL/min/1.73 m2 ) was observed in patients taking dolutegravir or rilpivirine, but with similar improvement to that observed in the rest of switching patients in tubular abnormalities. CONCLUSIONS: Tenofovir disoproxil fumarate discontinuation was associated with a rapid and significant improvement in eGFR and tubular abnormalities, regardless of whether abacavir or dual therapy was chosen. Switching to a regimen that included dolutegravir and/or rilpivirine was associated with a eGFR decrease without differences in the rate of tubular dysfunction improvement in comparison with the rest of patients who discontinued tenofovir.

The calculation of baseline serum creatinine overestimates the diagnosis of acute kidney injury in patients undergoing cardiac surgery.

INTRODUCTION AND OBJECTIVES: The current definition and classification of acute kidney injury is based on consensus criteria (RIFLE and AKIN systems). Creatinine is the most commonly used of the recommended parameters (creatinine, glomerular filtration rate and diuresis). If the baseline value is not known, it can be calculated based on the simplified MDRD equation, assuming a filtration rate of 75 ml/min/1.73 m2 for the calculation. The aim of this study was to evaluate the diagnostic impact of using estimated baseline creatinine compared to the actual value measured in patients undergoing cardiac surgery. METHODS: Analysis of patients undergoing major cardiac surgery, who were prospectively included in a database. The maximum RIFLE stage reached was calculated for each patient using the measured and estimated baseline creatinine levels. The impact on the diagnosis was analysed using intraclass correlation coefficients, concordance analysis and Bland-Altman plots. RESULTS: The incidence of postoperative acute kidney injury in 2103 cases between 2002 and 2007 was 29.1%, according to estimated creatinine (14.3% with the measure). This represents an overestimation of 104%, with an intraclass correlation of 0.12. By excluding patients with known chronic kidney disease (glomerular filtration rate [<60 ml/min/1.73 m2), both the overestimation (2.4%) and the correlation (0.57) improved. CONCLUSIONS: The calculation of baseline creatinine using the MDRD equation overestimates the incidence of acute kidney injury after cardiac surgery, and is an inadequate method for detection when the baseline value is unknown.

Randomized comparison of efficacy of cooled tip catheter ablation of atrial flutter: anatomic versus electrophysiological complete isthmus block.

There is a subset of patients with failed ablation of the cavotricuspid isthmus (CTI) using standard catheters and with 10% of the patients having recurrences. The purpose of this study was to compare the cooled and standard ablation with regard to acute successful electrophysiological achievement of bidirectional isthmus block and the subacute anatomic characteristics of the lesions. This randomized, experimental study compares the effects of ablation on the isthmus using a cooled catheter with those of a standard ablation catheter in 16 pigs. In 12 animals, CTI block was achieved after ablation (8/8 cooled and 4/8 standard). In two animals, it was not possible to achieve complete isthmus block and two had persistent slow conduction (all four using the standard catheter). After 1 week, the animals were slaughtered. The size of the lesion was greater with the irrigated tip catheters. Transmural lesions were found in 14 animals. A complete line of anatomic isthmus block was not documented after thefirst line in six animals, four with the standard and two with the cooled catheter. A conduction block was never present across gaps > or = 5 mm. In conclusion cooled catheters achieved a complete line of electrophysiological and anatomical block in a significantly higher percentage than the standard catheters.

[Macroscopic and microscopic study of the right coronary artery after radiofrequency catheter ablation of cavotricuspid isthmus in an experimental model]. / Estudio macro y microscópico de la arteria coronaria derecha tras ablación con catéter y radiofrecuencia del istmo cavotricuspídeo en un modelo experimental.

INTRODUCTION AND OBJECTIVES: The right coronary artery (RCA) is found in the AV groove, just below the ablation target of atrial flutter, the cavotricuspid isthmus (ICT). After radiofrequency (RF) ablation with standard catheters, there have been no reports of complications, but it may not be successful in 10% of the cases. However, the use of irrigated tip catheters, which create deeper lesions, might potentially damage the coronary tree. METHODS: We analyzed the effects of ICT RF ablation on the coronary tree, with macroscopic and microscopic anatomopathological study. Ablation on ICT was performed using an irrigated tip catheter in 16 pigs and was randomly compared with a standard ablation catheter. There were no clinical problems, modifications of ST or new arrhythmias during the ablation. The heart was extracted at 1 week. RESULTS: The macroscopic study demonstrated that the right coronary artery was preserved, along the ICT, surrounded by the epicardial fat. The microscopic study showed an inflammatory reaction in the epicardial fat that reached the adventitia of the coronary artery, but never produced necrosis in 14 cases. The muscular wall of the artery had signs of focal inflammation without endothelium involvement in 2 cases. However, we found a subepicardial vein completely damaged by the radiofrequency. CONCLUSIONS: Although the right coronary artery is located just below the isthmus, no necrosis was observed in any case. However, there was an inflammatory reaction that focally reached the muscular wall. The veins may be damaged in RF ablation, perhaps due to the different blood flow of each vessel.

Biochemical markers and cardiac troponin I release after radiofrequency catheter ablation: approach to size of necrosis.

BACKGROUND: We designed this study to determine the value of serum levels of several cardiac markers in patients who underwent radiofrequency ablation and to establish the utility of cardiac troponin I (cTnI). After radiofrequency ablation there is always a small localized endomyocardial necrosis. The volume of the necrosis may be estimated by the rise of several biochemical marker levels, classically creatinine kinase (CK) and CK-MB. cTnI is a newly available biochemical marker with a high cardiac specificity. METHODS AND RESULTS: We analyzed the data from 51 patients who underwent radiofrequency ablation and from 16 control patients who underwent an electrophysiologic study without ablation. The levels of CK, CK-MB mass, cTnI, and myoglobin were compared with clinical findings, ST-T wave abnormalities, and the presence of arrhythmias. The study shows that there is a higher release of cTnI compared with the standard markers CK, CK-MB, and myoglobin. A pathologic value of cTnI was found in 92% of the patients of the ablation group. CK-MB had a lower sensitivity (63%). The area under the receiver operating characteristic curve for cTnI was 0.9375, significantly superior to the other biochemical markers (P <.05). We found a moderate level of correlation between the number of radiofrequency pulses and cardiac cTnI release (r = 0.69, P <.0001). CONCLUSIONS: The serum level of cTnI detects the minor myocardial damage produced by radiofrequency ablation. This would be useful information to have in patients who might have the potential for other ischemic events. The other biochemical or ablation parameters usually reported, including the radiofrequency ablation parameters, have no good correlation with the size of the myocardial necrosis. Therefore we suggest that monitoring of cTnI is the best way to detect and quantify the size of myocardial necrosis created by radiofrequency ablation.

Cardiac troponin I and minor cardiac damage: biochemical markers in a clinical model of myocardial lesions.

Radiofrequency (RF) catheter ablation is the curative treatment of choice for many cardiac arrhythmias. After RF ablation there is always a small localized endomyocardial necrosis, necessary to abolish the arrhythmia. We designed this study to determine the serum concentrations of several cardiac markers in patients who underwent RF catheter ablation. The study shows a higher frequency of increase of serum cardiac troponin I (cTnI) than of creatine kinase (CK), the CK MB isoenzyme (CK-MB), or myoglobin. A pathological value of cTnI was found in 47 of 51 patients (92%) in the ablation group. The area under the ROC curve for cTnI was 0.9375, significantly higher than for the other biochemical markers (0.86, 0.76, and 0.75 for CK-MB, myoglobin, and CK, respectively), with P <0.05. We conclude that the serum concentration of cTnI is the best biochemical marker for detecting the minor myocardial damage produced by RF ablation.

[Evaluation of biochemical markers of myocardial lesion after radiofrequency ablation. Value of troponin I]. / Evaluación de marcadores de lesión miocárdica tras la ablación con radiofrecuencia. Utilidad de la troponina I.

INTRODUCTION AND OBJECTIVES: Radiofrequency catheter ablation is the curative treatment of choice for many cardiac arrhythmias. After radiofrequency ablation there is always a localized endomyocardial necrosis, which is necessary to eliminate the arrhythmia. The volume of the necrosis may be evaluated by the rise of several biochemical markers, classically CK and CK-MB. However, the sensitivity and specificity of these markers are not optimal and are probably less than ideal for this purpose. Cardiac Troponin I (cTnI) is a newly available biochemical marker available, with a high cardiac specificity. We designed this study in order to determine the value of serum levels of several cardiac markers in patients who underwent radiofrequency catheter ablation and to establish the utility of cTnI. METHODS: We analyzed the data from 51 patients who underwent radiofrequency ablation and from 16 control patients. In respect to the ablation target, we included in the study 14 left accessory pathways, 7 right accessory pathways, 12 atrioventricular nodal reentry tachycardia, 5 ventricular tachycardia and 13 atrial flutter or fibrillation. The levels of CK, CK-MB, cTnI, and myoglobin were compared with clinical findings, ST-T wave abnormalities and the presence of arrhythmias after ablation. To evaluate the diagnostic capability for each biochemical marker we used the ROC curves. RESULTS: A pathological value of cTnI was found in 47 out of 51 (92%) patients in the ablation group. CK-MB had a lower sensitivity (63%). The sensitivity for the other biochemical markers ranged from 30% for CK to 67% for Myoglobin. The area under the ROC curve for cTnI was 0.9375, significantly superior to the other biochemical markers (0.86, 0.76, 0.75 for MB, Myoglobin, CK respectively) (p < 0.05). The lowest cTnI released was found in patients after nodal reentry tachycardia ablation and the highest after atrial flutter ablation. cTnI increased above normal values in 4 patients in the control group (patients who underwent an electrophysiological study without catheter ablation). We found a moderate level of correlation between the number of radiofrequency pulses and cardiac cTnI release (r = 0.69; p < 0.0001). The correlation was different in each target, ranging between r = 0.25 (p = NS, 0.43) for atrial flutter and fibrillation to r = 0.99 (p < 0.0001) for ventricular tachycardia. CONCLUSIONS: cTnI had the greatest sensitivity (92%) for detecting minor myocardial damage. Thus, we can conclude that the serum level of cTnI detects the minor myocardial damage produced by radiofrequency ablation.