Fluorescence and computational studies of thymidine phosphorylase affinity toward lipidated 5-FU derivatives.

Thymidine phosphorylase (TP) is an enzyme that is up-regulated in a wide variety of solid tumors, including breast and colorectal cancers. It is involved in tumor growth and metastasis, for this reason it is one of the key enzyme to be inhibited, in an attempt to prevent tumor proliferation. However, it also plays an active role in cancer treatment, through its contribution in the conversion of the anti-cancer drug 5-fluorouracil (5-FU) to an irreversible inhibitor of thymidylate synthase (TS), responsible of the inhibition of the DNA synthesis. In this work, the intrinsic TP fluorescence has been investigated for the first time and exploited to study TP binding affinity for the unsubstituted 5-FU and for two 5-FU derivatives, designed to expose this molecule on liposomal membranes. These molecules were obtained by functionalizing the nitrogen atom with a chain consisting of six (1) or seven (2) units of glycol, linked to an alkyl moiety of 12 carbon atoms. Derivatives (1) and (2) exhibited an affinity for TP in the micromolar range, 10 times higher than the parent compound, irrespective of the length of the polyoxyethylenic spacer. This high affinity was maintained also when the compounds were anchored in liposomal membranes. Experimental results were supported by molecular dynamics simulations and docking calculations, supporting a feasible application of the designed supramolecular lipid structure in selective targeting of TP, to be potentially used as a drug delivery system or sensor device.

Prospective randomized comparison of antiarrhythmic therapy versus first-line radiofrequency ablation in patients with atrial flutter.

BACKGROUND: Despite the high success rate of radiofrequency (RF) ablation, pharmacologic therapy is still considered the standard initial therapeutic approach for atrial flutter. OBJECTIVE: We prospectively compared the outcome at follow-up of patients with atrial flutter randomly assigned to drug therapy or RF ablation. METHODS: Patients with at least two episodes of symptomatic atrial flutter in the last four months were randomized to regimens of either antiarrhythmic drug therapy or first-line RF ablation. After institution of therapy, end points included recurrence of atrial flutter, rehospitalization and quality of life. RESULTS: A total of 61 patients entered the study, 30 of whom were randomized to drug therapy and 31 to RF ablation. After a mean follow-up of 21 +/- 11 months, 11 of 30 (36%) patients receiving drugs were in sinus rhythm, versus 25 of 31 (80%) patients who underwent RF ablation (p < 0.01). Of the patients receiving drugs, 63% required one or more rehospitalizations, whereas post-RF ablation, only 22% of patients were rehospitalized (p < 0.01). Following RF ablation, 29% of patients developed atrial fibrillation which was seen in 53% of patients receiving medications (p < 0.05). Sense of well being (pre-RF 2.0 +/- 0.3 vs. post-RF 3.8 +/- 0.5, p < 0.01) and function in daily life (pre-RF 2.3 +/- 0.4 vs. post-RF 3.6 +/- 0.6, p < 0.01) improved after ablation, but did not change significantly in patients treated with drugs. CONCLUSION: In a selected group of patients with atrial flutter, RF ablation could be considered a first-line therapy due to the better success rate and impact on quality of life, the lower occurrence of atrial fibrillation and the lower need for rehospitalization at follow-up.

False positive head-up tilt: hemodynamic and neurohumoral profile.

OBJECTIVES: This study examined differences in mechanisms of head-up tilt (HUT)-induced syncope between normal controls and patients with neurocardiogenic syncope. BACKGROUND: A variable proportion of normal individuals experience syncope during HUT. Differences in the mechanisms of HUT-mediated syncope between this group and patients with neurocardiogenic syncope have not been elucidated. METHODS: A 30-min 80 degrees HUT was performed in eight HUT-negative volunteers (Group I), eight HUT-positive volunteers (Group II) and 15 patients with neurocardiogenic syncope. Heart rate and blood pressure (BP) were monitored continuously. Epinephrine and norepinephrine plasma levels, as well as left ventricular dimensions and contractility determined by echocardiography, were measured at baseline and at regular intervals during the test. RESULTS: The main findings of this study were the following: 1) All parameters were similar at baseline in the three groups; and 2) During tilt: a) the time to syncope was shorter in Group III than in group II (9.5 +/- 3 vs. 17 +/- 3 min p < 0.05); b) there was an immediate, persisting drop in mean BP in Group III; c) the decrease rate of left ventricular end-diastolic dimensions was greater in Group III than in Group II or Group I (-1.76 +/- 0.42 vs. -0.87 +/- 0.35 and -0.67 +/- 0.29 mm/min, respectively, p < 0.05); d) the leftventricular shortening fraction was greater in Group III than in the other two groups (39 +/- 1 vs. 34 +/- 1 and 32 +/- 1%, respectively, p < 0.05); and e) although the norepinephrine level remained comparable among the groups, there was a significantly higher peak epinephrine level in Group III than in Group II and Group I (112.3 +/- 34 vs. 77.6 +/- 10 and 65 +/- 12 pg/ml, p < 0.05). CONCLUSIONS: Mechanisms of syncope during HUT appeared to be different in normal volunteers and patients with neurocardiogenic syncope. In the latter, there was evidence of an impaired vascular resistance response from the beginning of the orthostatic challenge. Furthermore, in the patients there was more rapid peripheral blood pooling, as indicated by the echocardiographic measurements of left ventricular end-diastolic changes, leading to more precocious symptoms. In syncopal patients, the higher level of plasma epinephrine probably mediated the increased cardiac contractility and possibly contributed to the impaired vasoconstrictive response.

Frequency and significance of conduction defects early after orthotopic heart transplantation.

To define the clinical significance of conduction defects after orthotopic heart transplantation sequential electrocardiograms (ECG) of 124 patients were analyzed during their postoperative hospital stay. The first ECG was abnormal in 90 patients (73%), with a predominance of right bundle branch block, and normal in 34 (27%). Sex, age, mean donor ischemic time, duration of aortic cross clamping and use of previous antiarrhythmic therapy were not significantly different in the 2 groups. During hospital follow-up, patients were grouped according to evolution of the initial electrocardiographic abnormalities. In group 1, 25 patients continued to have an initially normal ECG. In groups 2 and 3, 30 and 48 patients, respectively, had evidence of transient and permanent conduction defects. The 21 patients in group 4 showed progressive deterioration of conduction with either a new (9 patients) or worsening preexisting conduction defect (12 patients). The evolution of the initial ECG was strongly dependent on the duration of the donor heart ischemic time and the severity of the in-hospital cardiac rejection. Patients with persistent conduction abnormalities had a statistically longer ischemic time than either patients with normal or transient conduction defects (182 +/- 84 vs 144 +/- 68 and 130 +/- 66 minutes, p = 0.04). Although the overall percentage of patients with histologic evidence of moderate to severe rejection was similar across the groups, 66.6 and 46.1% of patients in groups 3 and 4, respectively, had multiple episodes of rejection compared with 16.6 and 0% in the remaining 2 groups (p = 0.044).(ABSTRACT TRUNCATED AT 250 WORDS)

Systolic and diastolic effects of variable atrioventricular delay in patients with complete heart block and normal ventricular function.

This study was designed to demonstrate the effects of varying the atrioventricular delay (AVD) on ventricular diastolic filling dynamics and the resultant stroke volume in patients with complete heart block and normal cardiac function. We studied 7 patients with normal cardiac function in whom a dual chamber pacemaker had been implanted because of complete heart block. Doppler and M-mode echocardiography was performed at 70, 100, 140, 180, and 220 ms, AVD with the device in DDD mode at a rate of 80 beats/min. The effects of these variable intervals on the contribution of the E and A waveform to the diastolic filling, on the stroke volume, and on the systolic intervals were evaluated. Optimization of this interval, with a 19% increase in stroke volume was achieved in the group of patients at an AVD of 140 ms. When considered individually, the AVD associated with the largest stroke volume, was 100 ms in 2 patients and 140 ms in the remaining 5. At this individual optimal AVD the ventricular septal contraction occurred 31 +/- 14 ms, before the end of the transmitral flow. The optimal AVD is, therefore, the one which synchronizes the ventricular and atrial systole so that the first ventricular septal contraction occurs after the peak of the A wave, just before the end of the transmitral flow. Because of the different functional cardiovascular status of the single patient, this parameter should be individualized; this can be clinically important as it may lead, in this patient population, to an improvement of the stroke volume up to 42%.

Natural history, determinants, and clinical relevance of conduction abnormalities following orthotopic heart transplantation.

To study the long-term evolution, determinants, and clinical relevance of the conduction abnormalities after orthotopic heart transplantation, 87 patients, followed for a mean of 105 +/- 72 weeks, were divided into 3 groups according to the characteristics of their electrocardiograms compared with their initial electrocardiogram recorded at study entry. The first group consisted of 24 patients whose initial electrocardiogram was normal, and subsequent electrocardiograms remained normal throughout the study. The second group included 27 patients who developed electrocardiographic evidence of progressive conduction system damage. The third group comprised 36 patients whose initial electrocardiogram was abnormal and subsequent electrocardiograms remained unchanged during follow-up. Although the hemodynamic and echocardiographic evaluation of right and left ventricular function were initially similar among the 3 groups, groups 2 and 3 demonstrated a significant deterioration of left ventricular ejection fraction (62 +/- 12% to 55 +/- 16% and 62 +/- 8% to 57 +/- 14%, respectively; p < 0.05) and cardiac index (2.7 +/- 0.6 to 2.3 +/- 0.5 and 3.0 +/- 0.9 to 2.5 +/- 0.9 L/min/m2, respectively; p < 0.05) while patients in group 1 maintained their normal baseline indices. Incidence and progression of coronary artery disease, as well as frequency of rejection episodes, were comparable among the groups. Mortality was higher in the 2 groups with evidence of conduction defects. Sudden death associated with complete heart block (2 patients) or ventricular arrhythmias (3 patients) was exclusively confined to patients with evidence of progressive electrocardiogram abnormalities. We conclude that, following orthotopic heart transplantation, stable or progressive conduction system damage on the electrocardiogram is associated with left ventricular dysfunction and increased mortality. Sudden death is not uncommon among patients demonstrating worsening cardiac conduction and, in some cases, is related to the development of potentially preventable complete heart block.

Frequency of superior vena cava syndrome following radiofrequency modification of the sinus node and its management.

In a series of 35 consecutive patients, the presence of a permanent pacemaker appears to be a strong risk factor for developing superior vena cava syndrome after radiofrequency modification of the sinus node. Treatment of this complication with balloon venoplasty is as effective as surgical repair.

Usefulness of ibutilide in facilitating successful external cardioversion of refractory atrial fibrillation.

We repeated direct-current cardioversion of atrial fibrillation after ibutilide injection in patients who failed conventional cardioversion. Eleven of 12 patients (92%) had successful cardioversion and avoided the need for internal cardioversion.

Ablation of right and left ectopic atrial tachycardias using a three-dimensional nonfluoroscopic mapping system.

We report our experience with mapping and ablation of right and left atrial tachycardia using a 3-dimensional nonfluoroscopic mapping system. Twenty-nine ectopic atrial tachycardias were successfully ablated. This novel mapping system has the potential to increase a successful cure of this arrhythmia by catheter ablation.

Use of sublingual nitroglycerin during head-up tilt-table testing in patients >60 years of age.

Previous work had demonstrated a reduced specificity associated with head-up tilt protocols using high-dose isoproterenol in patients between 20 and 50 years of age. We evaluated the specificity of head-up tilt testing using different isoproterenol infusion doses and administration of nitroglycerin in patients aged >60 years. In addition, whether the same protocols have impact on the sensitivity of the test was also assessed. One hundred sixty subjects were included in this study. Seventy-six were volunteers randomized to either head-up tilt test with low-dose, 3- and 5-microg/min of isoproterenol (group I) or to a protocol including 0.4 mg of sublingual nitroglycerin (group II). In addition, after an upright tilt drug-free state, 58 patients with a history of syncope underwent repeat head-up tilt with increasing doses of isoproterenol infusion, followed by sublingual nitroglycerin if the test result remained negative. The remaining 33 patients were subjected to the nitroglycerin protocol after the drug-free state phase. In the control groups, the incidence of false-positive responses was 88% and 95%, respectively. In patients with syncope after a negative test result during 5 microg of isoproterenol infusion, nitroglycerin administration increased the number of positive responses from 45% to 79%. The percentage of positive tilt in patients undergoing nitroglycerin administration after the drug-free state part of the protocol was 78%. Administration of nitroglycerin was the most significant predictor of a positive upright tilt in patients with syncope. In subjects aged >60 years, head-up tilt protocols with high-dose isoproterenol infusion and nitroglycerin maintained an adequate specificity. In this subset of patients, nitroglycerin seemed to provide a better sensitivity than isoproterenol.

Gender differences in autonomic cardiovascular regulation: spectral, hormonal, and hemodynamic indexes.

The autonomic nervous system drives variability in heart rate, vascular tone, cardiac ejection, and arterial pressure, but gender differences in autonomic regulation of the latter three parameters are not well documented. In addition to mean values, we used spectral analysis to calculate variability in arterial pressure, heart rate (R-R interval, RRI), stroke volume, and total peripheral resistance (TPR) and measured circulating levels of catecholamines and pancreatic polypeptide in two groups of 25 +/- 1.2-yr-old, healthy men and healthy follicular-phase women (40 total subjects, 10 men and 10 women per group). Group 1 subjects were studied supine, before and after beta- and muscarinic autonomic blockades, administered singly and together on separate days of study. Group 2 subjects were studied supine and drug free with the additional measurement of skin perfusion. In the unblocked state, we found that circulating levels of epinephrine and total spectral power of stroke volume, TPR, and skin perfusion ranged from two to six times greater in men than in women. The difference (men > women) in spectral power of TPR was maintained after beta- and muscarinic blockades, suggesting that the greater oscillations of vascular resistance in men may be alpha-adrenergically mediated. Men exhibited muscarinic buffering of mean TPR whereas women exhibited beta-adrenergic buffering of mean TPR as well as TPR and heart rate oscillations. Women had a greater distribution of RRI power in the breathing frequency range and a less negative slope of ln RRI power vs. ln frequency, both indicators that parasympathetic stimuli were the dominant influence on women's heart rate variability. The results of our study suggest a predominance of sympathetic vascular regulation in men compared with a dominant parasympathetic influence on heart rate regulation in women.

Epinephrine, vasodilation and hemoconcentration in syncopal, healthy men and women.

Healthy young people may become syncopal during standing, head up tilt (HUT) or lower body negative pressure (LBNP). To evaluate why this happens we measured hormonal indices of autonomic activity along with arterial pressure (AP), heart rate (HR), stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and measures of plasma volume. Three groups of normal volunteers (n = 56) were studied supine, before and during increasing levels of orthostatic stress: slow onset, low level, lower body negative pressure (LBNP) (Group 1), 70 degrees head up tilt (HUT) (Group 2) or rapid onset, high level, LBNP (Group 3). In all groups, syncopal subjects demonstrated a decline in TPR that paralleled the decline in AP over the last 40 s of orthostatic stress. Ten to twenty seconds after the decline in TPR. HR also started to decline but SV increased, resulting in a net increase of CO during the same period. Plasma volume (PV, calculated from change in hematocrit) declined in both syncopal and nonsyncopal subjects to a level commensurate with the stress, i.e. Group 3 > Group 2 > Group 1. The rate of decline of PV, calculated from the change in PV divided by the time of stress, was greater (p < 0.01) in syncopal than in nonsyncopal subjects. When changes in vasoactive hormones were normalized by time of stress, increases in norepinephrine (p < 0.012, Groups 2 and 3) and epinephrine (p < 0.025, Group 2) were greater and increases in plasma renin activity were smaller (p < 0.05, Group 2) in syncopal than in nonsyncopal subjects. We conclude that the presyncopal decline in blood pressure in otherwise healthy young people resulted from declining peripheral resistance associated with plateauing norepinephrine and plasma renin activity, rising epinephrine and rising blood viscosity. The increased hemoconcentration probably reflects increased rate of venous pooling rather than rate of plasma filtration and, together with cardiovascular effects of imbalances in norepinephrine, epinephrine and plasma renin activity may provide afferent information leading to syncope.

Selective interference with pacemaker activity by electrical dental devices.

OBJECTIVE: We sought to determine whether electromagnetic interference with cardiac pacemakers occurs during the operation of contemporary electrical dental equipment. STUDY DESIGN: Fourteen electrical dental devices were tested in vitro for their ability to interfere with the function of two Medtronics cardiac pacemakers (one a dual-chamber, bipolar Thera 7942 pacemaker, the other a single-chamber, unipolar Minix 8340 pacemaker). Atrial and ventricular pacemaker output and electrocardiographic activity were monitored by means of telemetry with the use of a Medtronics 9760/90 programmer. RESULTS: Atrial and ventricular pacing were inhibited by electromagnetic interference produced by the electrosurgical unit up to a distance of 10 cm, by the ultrasonic bath cleaner up to 30 cm, and by the magnetorestrictive ultrasonic scalers up to 37.5 cm. In contrast, operation of the amalgamator, electric pulp tester, composite curing light, dental handpieces, electric toothbrush, microwave oven, dental chair and light, ENAC ultrasonic instrument, radiography unit, and sonic scaler did not alter pacing rate or rhythm. CONCLUSIONS: These results suggest that certain electrosurgical and ultrasonic instruments may produce deleterious effects in medically fragile patients with cardiac pacemakers.

Ablation of incisional atrial tachycardias using a three-dimensional nonfluoroscopic mapping system.

Incisional atrial reentrant tachycardias are macroreentrant arrhythmias in which surgical scars or prosthetic material constitute one of the constraining barriers of the circuit. Accurate reconstruction based on fluoroscopy-guided endocardial mapping of the reentrant circuit is often incomplete and time consuming explaining, at least in part, the modest long-term results of this technique. Mapping and ablation of these arrhythmias using a three-dimensional nonfluoroscopic mapping system that allows electroanatomic reconstruction of the reentrant circuit could help in identifying the ablation targets and improve long-term outcome. The study included 20 patients (12 men, mean age 45+/-18 years) with corrected congenital heart disease (4 patients), coronary artery bypass surgery (7 patients), mitral or aortic valve replacement or reconstruction (6 patients), valve replacement and coronary revascularization (2 patients), and mitral valve replacement with maze procedure for atrial fibrillation (1 patient). Endocardial mapping with this novel system was complemented by standard electrophysiological techniques used to identify a critical isthmus of conduction. Two or more nonconductive areas of atrial tissue or surgical prosthetic material delimiting a critical isthmus of conduction were identified in every patient. Radiofrequency linear applications spanning two to more boundaries successfully eliminated the tachycardia in every patient. At a follow-up of 11.5+/-5.1 months (range 17-5 months), two (10%) patients developed a new clinical arrhythmia. The remaining 18 had no recurrences off medical therapy. Mean fluoroscopy time was 45.7+/-15.2 minutes for patients with a single scar and 89+/-41.2 minutes in patients with two or more scars. In conclusions, this new nonfluoroscopic mapping system offers the opportunity to achieve a high rate of cure of complex macroreentrant atrial tachycardias by facilitating reconstruction of the macroreentrant circuit and its boundaries.

Frequency modulation within electrocardiograms during ventricular fibrillation.

Periods of reentrant activation and effective refractory periods are correlated with dominant frequency or reciprocal of cycle periods during ventricular fibrillation (VF). In the present study, we used an analysis technique based on Wigner transforms to quantify time-varying dominant frequencies in electrocardiograms (ECGs) during VF. We estimated dominant frequencies within orthogonal ECGs recorded in 10 dogs during trials of 10 s of VF and in 9 dogs during trials of 30 s of VF. In four additional dogs, we compared dominant frequencies during 10 s of VF before and after administration of amiodarone. Our results showed the following. 1) There was substantial frequency variation or modulation within the ECGs during 10 and 30 s of VF, the average variation being +/-15% from the mean frequency. Amiodarone decreased mean frequencies (P < 0.05) as expected; however, amiodarone also decreased the variation in frequencies (P < 0.05). 2) During 30 s of VF, the dominant frequencies increased continuously from 7.3 to 8.1 Hz (P < 0.05). The increase in frequency was almost linear with a rate of 0.022 Hz/s (r(2) = 0.93, P < 0.0005). 3) Modulation of frequencies during the first and the last one-half of 30 s of VF was not different. Average (in time) mean frequencies and modulation of frequencies were similar in all three ECGs. 4) Although the averages were similar, during any VF episode, dominant frequencies in ECGs recorded from different locations on the body surface were similar to each other at some times and markedly different from each other at other times. We conclude that during VF, 1) frequencies in ECGs vary considerably and continuously, and amiodarone decreases this variation; 2) mean frequencies increase linearly during first 30 s; 3) the variability in frequency does not change during 30 s; and 4) at any given time, the frequencies within spatially different body surface ECGs can be either similar or markedly different.

Defibrillation thresholds are lower with smaller storage capacitors.

Present implantable cardioverter defibrillators use a wide range of capacitance values for the storage capacitor. However, the optimal capacitance value is unknown. We hypothesized that a smaller capacitor, by delivering its charge in a time closer to the heart chronaxie, should lower the defibrillation threshold (DFT). We compared the energy required to defibrillate 10 open-chest dogs, after 15 seconds of ventricular fibrillation, with a monophasic, time-truncated waveform delivered from either a 85-microF or a 140-microF capacitor. Shocks were delivered through a pair of 14-cm2 epicardial patch electrodes: The two capacitors were randomly tested twice with each dog using a modified 3-reversal method for each DFT determination. The average stored and delivered DFT energies for the 85-microF capacitor were 6.0 +/- 1.7 joules and 5.2 +/- 1.5 joules, respectively, compared to 6.7 +/- 1.7 joules and 6.0 +/- 1.5 joules for the 140-microF capacitor (P = 0.01 and P = 0.004, respectively). The mean leading edge voltages were higher, the pulse duration shorter, and the mean impedance lower for the 85-microF capacitor. The impedance was inversely related to the pulse duration and the voltage decay suggesting that, at least in part, the mechanism of improved defibrillation could be accounted for by the waveform electrical characteristics. There was an equal number of episodes of postshock bradyarrhythmias and tachyarrhythmias following discharges from each capacitor. Moreover, there was no relationship between the likelihood of these arrhythmias and either the initial voltage or the delivered current nor there was a higher number of episodes of postshock hypotension following the smaller capacitor discharges.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of endocardial defibrillation on left ventricular function: a transoesophageal echocardiographic study.

This study evaluates the immediate effects of the endocardial electrical shocks delivered by a transvenous defibrillation system on left ventricular (LV) function in a pig model. A triple-lead system consisting of two endocardial electrodes, in the right ventricular apex and the junction of superior cava-right atrium, and a custom-made defibrillation can implanted subcutaneously in the thorax was set up in 10 close-chest pigs. Transesophageal echocardiography with two dimensional image, m-Mode, and pulse Doppler was performed at baseline and after several episodes of fibrillation/defibrillation (F/DF). Each animal underwent an average of 8 (range 6 to 11) episodes of ventricle F/DF for a total of 210 (range 165 to 290) joules of biphasic-waveform defibrillation shocks. Heart rate, blood pressure, LV end-systolic area, end-diastolic area and fractional area contraction, isovolumic relaxation time, and both ratios of velocities and time-velocity integrals in transmitral Doppler flow E and A waves were unchanged after the shocks. This animal study suggests that multiple countershocks up to 210 joules delivered by a transvenous defibrillation system do not cause LV global systolic and/or diastolic dysfunction.

Bispectral energies within electrocardiograms during ventricular fibrillation are correlated with defibrillation shock outcome.

We investigated whether the degree of phase coupling among orthogonal electrocardiograms during ventricular fibrillation (VF) was correlated with defibrillation shock outcome. We used cross bispectrum to estimate the degree of phase coupling. In dogs, VF was electrically induced and terminated with a defibrillation shock with a 50% probability of success. The defibrillation shock was delivered between the right ventricular apex and a subcutaneous patch electrode. Bispectra were integrated within 8.7-11.7, 8.7-11.7 Hz bandwidths and compared between those trials for which the defibrillation shocks were successful (206 trials, 49%) and unsuccessful (221 trials, 51%) in terminating VF. Results showed that between 200 and 1000 ms before defibrillation shock, unsuccessful trials had greater bispectral energy than successful trials (p<0.05). Although correlations between degree of phase coupling and shock outcome do not indicate causal relationship or predictability, they provide further evidence of the organization during fibrillation. We discuss the nonstationary wavelet hypothesis, previously proposed in the literature by other investigators, as one of the possible mechanisms to explain the correlation between bispectral energy and shock outcome.

Human histopathologic findings following radiofrequency ablation of the tricuspid-inferior vena cava isthmus.

Radiofrequency (RF) ablation of the tricuspid valve-inferior vena cava isthmus is now the first line of treatment in the management of typical atrial flutter. Successful ablation is associated with conduction block in this region, although the histopathologic changes following this procedure have never been reported. We describe the pathologic changes following RF ablation of this region in an explanted heart of a patient undergoing heart transplantation 4 months after successful atrial flutter ablation. The findings confirm the ability of RF ablation to create in the isthmus a chronic full thickness fibrosis, which represents the histopathologic counterpart of the conduction block demonstrated at the end of procedure.