Predictors of left atrium appendage clot detection despite on-target warfarin prevention for atrial fibrillation.

BACKGROUND AND PURPOSE: The antithrombotic management of atrial fibrillation (AF) is currently based on clinical scores (CHADS(2) or CHA(2)DS(2)VASc). The prevalence of left atrium (LA) thrombi in effectively anticoagulated AF patients has been reported as being up to 7.7 %. We tried to correlate LA/LA appendage (LAA) thrombus detection with possible clinical predictors in warfarin-treated patients. METHODS: We performed trans-esophageal echocardiography on 430 patients (mean age, 60.3 ± 9.8 years) receiving oral anticoagulant (OAC) therapy and undergoing pulmonary vein isolation. In 10/430 (2.3 %), an LA thrombus was found despite therapeutic OAC (mean INR 2.6 ± 0.6; range, 2.0-3.8) over the previous 4 weeks. RESULTS: Two study groups were identified: 1. T-positive group = with LAA thrombus (10 patients) 2. T-negative group = without LAA thrombus (420 patients) The T-positive patients had a higher CHADS(2) score (1.5 ± 0.7 versus 0.7 ± 0.8; p = 0.004), a lower LVEF (54.7 ± 9.5 % versus 60.2 ± 7.4; p = 0.02), and a larger LA size (LA diameter, 56 ± 12.2 mm versus 46 ± 6.5 mm; p < 0.001and normalized LA volume: 140.2 ± 66 ml/m² vs. 67 ± 39 ml/m²; p < 0.05). On multivariate analysis, a larger LA diameter and normalized LA volume (OR, 1.14; 95 % C.I., 1.04-1.26; p = 0.006 and OR, 1.02; 95 % C.I., 1.01-1.03; p = 0.001, respectively) and a higher CHA(2)DS(2)VASc score (OR, 2.4; 95 % C.I., 1.4-4.2; p = 0.001) predicted left atrium appendage (LAA) thrombus. In another 42/430 (9.8 %) patients, an LA spontaneous echo-contrast (SEC) was detected. Thus, cumulatively, 52/430 (12.1 %) patients had either LAA thrombi (10 patients) or SEC (42 patients). LA diameter continued to predict the presence of either thrombi or SEC (OR, 1.14; 95 % C.I., 1.07-1.2; p < 0.05). CONCLUSIONS: We found a 2.3 % prevalence of LA thrombus (12.1 % when SEC was also considered). The thrombus was present despite on-target warfarin prevention. In addition to a higher CHA(2)DS(2)VASc score, a larger LA size was a strong predictor of clot detection.

Solubilization of lipid bilayers by myristyl sucrose ester: effect of cholesterol and phospholipid head group size.

The solubilization of biological membranes by detergents has been used as a major method for the isolation and purification of membrane proteins and other constituents. Considerable interest in this field has resulted from the finding that different components can be solubilized selectively. Certain membrane constituents are incorporated into small micelles, whereas others remain in the so-called detergent-resistant membrane domains that are large enough to be separated by centrifugation. The detergent-resistant fractions contain an elevated percentage of cholesterol, and thus its interaction with specific lipids and proteins may be key for membrane organization and regulation of cellular signaling events. This report focuses on the solubilization process induced by the sucrose monoester of myristic acid, beta-D-fructofuranosyl-6-O-myristyl-alpha-D-glucopyranoside (MMS), a nonionic detergent. We studied the effect of the head group and the cholesterol content on the process. 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and dioctadecyl-dimethyl-ammonium chloride (DODAC) vesicles were used, and the solubilization process was followed using Laurdan (6-dodecanoyl-2-dimethylaminonaphthalene) generalized polarization (GP) measurements, carried out in the cuvette and in the 2-photon microscope. Our results indicate that: (i) localization of the MMS moieties in the lipid bilayer depends on the characteristics of the lipid polar head group and influences the solubilization process. (ii) Insertion of cholesterol molecules into the lipid bilayer protects it from solubilizaton and (iii) the microscopic mechanism of solubilization by MMS implies the decrease in size of the individual liposomes.

Differences in nucleotide-binding site of isoapyrases deduced from tryptophan fluorescence.

Comparative studies of intrinsic and extrinsic fluorescence of apyrases purified from two potato tuber varieties (Pimpernel and Desirée) were performed to determine differences in the microenvironment of the nucleotide binding site. The dissociation constants (K(d)) of Pimpernel apyrase for the binding of different fluorescent substrate analogs: methylanthranoyl (MANT-), trinitrophenyl (TNP-), and epsilon -derivatives of ATP and ADP were determined from the quenching of Trp fluorescence, and compared with K(d) values previously reported for Desirée enzyme. Binding of non-fluorescent substrate analogues decreased the Trp emission of both isoapyrases, indicating conformational changes in the vicinity of these residues. Similar effect was observed with fluorescent derivatives where, in the quenching effect, the transfer of energy from tryptophan residues to the fluorophore moiety could be additionally involved. The existence of energy transfer between Trp residues in the Pimpernel enzyme was demonstrated with epsilon -analogues, similar to our previous observations with the Desirée. From these results we deduced that tryptophan residues are close to or in the nucleotide binding site in both enzymes. Experiments with quenchers like acrylamide, Cs(+) and I(-), both in the presence and absence of nucleotide analogues, suggest the existence of differences in the nucleotide binding site of the two enzymes. From the results obtained in this work, we can conclude that the differences found in the microenvironment of the nucleotide binding site can explain, at least in part, the kinetic behaviour of both isoenzymes.

Electrophysiological properties of the atrioventricular node and ageing: evidence of a lower incidence of dual nodal pathways in the elderly.

AIMS: The purpose of this study was to investigate the relationship between the incidence of dual atrioventricular (AV) nodal pathways and age. Age-related changes in the AV node electrophysiological properties have rarely been investigated. AV nodal re-entrant tachycardia is more frequent in the young than in the elderly. METHODS AND RESULTS: From 1988 to 1998, premature atrial stimulation was performed in 1,435 patients referred to our institution for transoesophageal electrophysiological study. 1,276 patients (89%) with a diagnosis of ventricular pre-excitation, supraventricular arrhythmia or AV block were excluded. The study cohort consisted of the remaining 159 patients (11%) of the whole group) referred for syncope (8.2% of the subgroup), suspected ventricular pre-excitation (10.7%), suspected sinus node dysfunction (52.8%) or undetermined palpitations (28.3%). The 159 study patients were divided into 3 groups according to age: group A (11-30 years, 50 patients), group B (30-60 years, 35 patients) and group C (>60 years, 74 patients). A dual AV nodal pathway was found in 16 patients of group A (32.0%), 6 patients of group B (17.1%) and 8 patients of group C (10.8%), the difference between group A and group C being significant (P<0.05). CONCLUSION: The incidence of dual AV nodal pathways decreases with ageing, suggesting that the AV node undergoes age-related electrophysiological changes. This finding could explain the uncommon onset of AV nodal re-entrant tachycardia in the elderly.

Sensitized photoxygenation of piroxicam in neat solvents and solvent mixtures.

Detection of O(2)(1Delta(g)) phosphorescence emission, lambda(max)=1270 nm, following laser excitation and steady state methods were employed to determine the total rate constant, k(T), for the reaction between the non-steroidal anti-inflammatory drug piroxicam (PRX) and singlet oxygen in several solvents. Values of k(T) ranged from 0.048+/-0.003 x 10(6) M(-1) s(-1) in chloroform to 71.2+/-2.2 x 10(6) M(-1) s(-1) in N,N-dimethylformamide. The chemical reaction rate constant, k(R), was determined by using thermal decomposition of 1,4-dimethylnaphthalene endoperoxide as the singlet oxygen source. In acetonitrile, the k(R) value is equal to 5.0+/-0.4 x 10(6) M(-1) s(-1), very close to the k(T) value. This result indicates that, in this solvent, the chemical reaction corresponds to the main reaction path. Dependence of total rate constant on the solvent parameters pi* and beta can be explained in terms of a reaction mechanism that involves the formation of a perepoxide intermediate. Rearrangement of the perepoxide to dioxetane followed by ring cleavage and transacylation accounts for the formation of N-methylsaccharine and N-(2-pyridyl)oxamic acid, the main reaction products. Data obtained in dioxane-water (pH 4) mixtures with neutral enolic and zwitterionic tautomers of piroxicam in equilibrium show that the zwitterionic tautomer reacts with singlet oxygen faster than the enolic tautomer.

Formal hydride transfer mechanism for photoreduction of 3-phenylquinoxalin-2-ones by amines. Association Of 3-phenylquinoxalin-2-one with aliphatic amines

The photophysical and photochemical behavior of 1-methyl-3-phenylquinoxalin-2-one (MeNQ) and 3-phenylquinoxalin-2-one (HNQ) in the presence of amines is reported. While HNQ fluorescence shows an auxochromic effect and a bathochromic shift with added amines, explained by association of HNQ with amine in the ground state and emission from both excited species HNQ and [HNQ-amine], both MeNQ and HNQ are photoreduced efficiently on irradiation in the presence of amines, leading to the semireduced quinoxalin-2-ones, MeNQH(-) and HNQH(-), respectively, via an electron-proton-electron transfer, with unit quantum yields at high amine concentrations. The semireduced quinoxalin-2-ones XNQH(-) (X = H, Me) revert almost quantitatively to the parent XNQ in a dark thermal reaction with an activation free energy for MeNQH(-) of 17.4 and 25.9 kcal/mol in acetonitrile and benzene, respectively. Kinetic and spectroscopic (UV and NMR) evidence supports the proposed reaction mechanism for the reversible photoreduction.

Fluorescence studies of ATP-diphosphohydrolase from Solanum tuberosum var. Desirée.

Chemical modification of potato apyrase suggests that tryptophan residues are close to the nucleotide binding site. Kd values (+/- Ca2+) for the complexes of apyrase with the non-hydrolysable phosphonate adenine nucleotide analogues, adenosine 5'-(beta,gamma-methylene) triphosphate and adenosine 5'-(alpha,beta-methylene) diphosphate, were obtained from quenching of the intrinsic enzyme fluorescence. Other fluorescent nucleotide analogues (2'(3')-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate, 2'(3')-O-(2,4,6-trinitrophenyl) adenosine 5'-diphosphate. 1,N6-ethenoadenosine triphosphate and 1,N6-ethenoadenosine diphosphate) were hydrolysed by apyrase in the presence of Ca2+, indicating binding to the active site. The dissociation constants for the binding of these analogues were calculated from both the decrease of the protein (tryptophan) fluorescence and enhancement of the nucleotide fluorescence. Using the sensitised acceptor (nucleotide analogue) fluorescence method, energy transfer was observed between enzyme tryptophans and ethene-derivatives. These results support the view that tryptophan residues are present in the nucleotide-binding region of the protein, appropriately oriented to allow the energy transfer process to occur.

Studies on ATP-diphosphohydrolase nucleotide-binding sites by intrinsic fluorescence.

Potato apyrase, a soluble ATP-diphosphohydrolase, was purified to homogeneity from several clonal varieties of Solanum tuberosum. Depending on the source of the enzyme, differences in kinetic and physicochemical properties have been described, which cannot be explained by the amino acid residues present in the active site. In order to understand the different kinetic behavior of the Pimpernel (ATPase/ADPase = 10) and Desirée (ATPase/ADPase = 1) isoenzymes, the nucleotide-binding site of these apyrases was explored using the intrinsic fluorescence of tryptophan. The intrinsic fluorescence of the two apyrases was slightly different. The maximum emission wavelengths of the Desirée and Pimpernel enzymes were 336 and 340 nm, respectively, suggesting small differences in the microenvironment of Trp residues. The Pimpernel enzyme emitted more fluorescence than the Desirée apyrase at the same concentration although both enzymes have the same number of Trp residues. The binding of the nonhydrolyzable substrate analogs decreased the fluorescence emission of both apyrases, indicating the presence of conformational changes in the neighborhood of Trp residues. Experiments with quenchers of different polarities, such as acrylamide, Cs+ and I- indicated the existence of differences in the nucleotide-binding site, as further shown by quenching experiments in the presence of nonhydrolyzable substrate analogs. Differences in the nucleotide-binding site may explain, at least in part, the kinetic differences of the Pimpernel and Desirée isoapyrases.

Studies on ATP-diphosphohydrolase nucleotide-binding sites by intrinsic fluorescence

Potato apyrase, a soluble ATP-diphosphohydrolase, was purified to homogeneity from several clonal varieties of Solanum tuberosum. Depending on the source of the enzyme, differences in kinetic and physicochemical properties have been described, which cannot be explained by the amino acid residues present in the active site. In order to understand the different kinetic behavior of the Pimpernel (ATPase/ADPase = 10) and Desirée (ATPase/ADPase = 1) isoenzymes, the nucleotide-binding site of these apyrases was explored using the intrinsic fluorescence of tryptophan. The intrinsic fluorescence of the two apyrases was slightly different. The maximum emission wavelengths of the Desirée and Pimpernel enzymes were 336 and 340 nm, respectively, suggesting small differences in the microenvironment of Trp residues. The Pimpernel enzyme emitted more fluorescence than the Desirée apyrase at the same concentration although both enzymes have the same number of Trp residues. The binding of the nonhydrolyzable substrate analogs decreased the fluorescence emission of both apyrases, indicating the presence of conformational changes in the neighborhood of Trp residues. Experiments with quenchers of different polarities, such as acrylamide, Cs+ and I- indicated the existence of differences in the nucleotide-binding site, as further shown by quenching experiments in the presence of nonhydrolyzable substrate analogs. Differences in the nucleotide-binding site may explain, at least in part, the kinetic differences of the Pimpernel and Desirée isoapyrases.

Efficacy of intravenous propafenone in termination of atrial flutter by overdrive transesophageal pacing previously ineffective.

Fifty patients with symptomatic type I atrial flutter in whom termination of the arrhythmia with transesophageal stimulation was unsuccessful were randomized to undergo a repeat procedure after intravenous propafenone (n = 25) or placebo (n = 25). Immediate sinus rhythm recovery rate was 36% in the propafenone group and 4% in the placebo group (p = 0.005), indicating that intravenous propafenone increases the rate of successful transesophageal stimulation and can be used when a first attempt at conversion is ineffective.

Evaluation of atrial vulnerability with transoesophageal stimulation in patients with atrioventricular junctional reentrant tachycardia. Comparison with patients with ventricular pre-excitation and with normal subjects.

The aim of our work was to evaluate the inducibility of atrial fibrillation in a group of patients with atrioventricular junctional reentrant tachycardia and to compare it with that of patients with a Kent-type ventricular pre-excitation (Wolff-Parkinson-White syndrome) and a control group. One hundred and twenty-five subjects were separated into groups. Group 1 comprised 49 Wolff-Parkinson-White patients, with a mean age of 26.4, range 10-66 years; group 2, 51 patients with atrioventricular junctional reentrant tachycardia inducible by transoesophageal atrial stimulation and/or clinically documented, with a mean age of 43.4, range 16-78 years; group 3, 25 control subjects with a mean age of 26.4, range 13-76 years. Each subject underwent atrial transoesophageal stimulation with the following protocol: programmed atrial stimulation with 1 and 2 stimuli during atrial pacing of 100.min-1 and 150.min-1; atrial stimulation for 10 s at a rate of 200-300-400-500-600.min-1 with intervals of 10 s between stimulations, five successive 'ramp-up' atrial stimulations for 9 s with the rate increasing from 100 to 800.min-1 with intervals of 10 s between stimulations. The end point was the completion of the protocol or induction of sustained atrial fibrillation (> 1 min). The chi-square test was used for statistical analysis. Our results showed that in group 1 atrial fibrillation was induced in 27/49 patients (55.1%); this was sustained in 13/49 (26.5%) and non-sustained in 14/49 (28.5%); in group 2, atrial fibrillation was induced in 22/51 patients (43.0%); it was sustained in 7/51 (13.7%) and non-sustained in 15/51 (29.4%); in group 3, sustained atrial fibrillation was not induced in any subject and in only one subject was a non-sustained atrial fibrillation (4 s) induced. The chi-square test showed that group 2 vs group 1 were non-significant, while group 2 vs group 3 and group 1 vs group 3 were significant (P < 0.003 and P < 0.0007, respectively). Therefore group 2 patients showed a greater atrial vulnerability in comparison to the control subjects and a similar vulnerability to group 1 patients. It is possible that the greater atrial vulnerability in the patients of group 2 was due to the double nodal pathway.

Polarographic study of the photodecomposition of nimodipine.

Nimodipine, a calcium antagonist belonging to the dihydropyridine family, produces a well-defined polarographic peak due to the four-electron reduction of the nitro group. This peak was used to track the photodecomposition of nimodipine induced by UV light and daylight. Nimodipine was modified by UV irradiation with degradation following first-order kinetics. A degradation rate constant of 0.099 min-1, with a half-life of 7.78 min, for UV irradiation without a filter was obtained. Furthermore, a quantum yield of 1.32 x 10(-3) molecules/quantum absorbed was measured with a chemical actinometer. The UV degradation product, which was isolated and identified, showed that irradiation of nimodipine causes oxidation of the dihydropyridine ring and transmutation of the nitro group in the nitrobenzene moiety.

[Treatment of malignant ventricular tachyarrhythmia with amiodarone: comparison of empirical administration and administration guided by Holter or ventricular stimulation. Results of the parallel test]. / Trattamento delle tachiaritmie ventricolari maligne con amiodarone: confronto tra somministrazione empirica e somministrazione guidata da Holter o da stimolazione ventricolare. Risultati del test parallelo.

To assess the most appropriate method of administering amiodarone and predicting its efficacy (empiric vs guided by Holter or by ventricular stimulation), 19 patients with sustained ventricular tachycardia or ventricular fibrillation underwent a "parallel study". Fifteen patients were men and 4 women, with a mean age of 65 years. A coronary artery disease with previous myocardial infarction was present in 15 patients, dilated cardiomyopathy in 3 and arrhythmogenic right ventricular dysplasia in 1 (mean left ventricular ejection fraction = 35%). All 19 patients had, as inclusion criteria, 1) frequent (greater than or equal to 30/hour) and/or repetitive (greater than or equal to 10/24 hours) ventricular premature beats during 24-hour Holter monitoring and 2) inducible sustained (greater than 30/sec) ventricular arrhythmias during programmed ventricular stimulation (1-3 extrastimuli from 2 right ventricular sites). Amiodarone was given at an initial dosage of 15 mg/kg/day for 2 weeks and then at a dosage of 5 mg/kg/day. After 15 days 24-hour Holter monitoring and programmed ventricular stimulation were repeated. The data of these tests, however, were not used to guide the therapy that remained empiric, but served only to assess retrospectively the predictive value of Holter monitoring and ventricular stimulation. The following main results were obtained: The mean duration of follow-up was 25 +/- 13 months. During this period 6 patients (32%) died, 3 from sudden and 3 from non-sudden cardiac death. Two other patients had recurrence of sustained ventricular arrhythmias. After 15 days of therapy amiodarone was effective at Holter monitoring in 15 patients (79%) and not effective in 4 (21%). Two of the 15 patients considered responders died suddenly during the follow-up and 2 had arrhythmic recurrence, vs 1 of the 4 non-responder patients who died suddenly (negative predictive value of Holter monitoring: 73%; positive predictive value: 25%; predictive accuracy: 63%). After 15 days of therapy amiodarone was effective at ventricular stimulation in 10 patients (53%) and not effective in 9 (47%). None of the 10 patients considered responders had arrhythmic events during the follow-up, vs 5 of the 9 non-responders, 3 of whom died suddenly and 2 of whom had arrhythmic recurrences (negative predictive value of ventricular stimulation: 100%; positive predictive value: 56%; predictive accuracy: 79%). Only 1 patient discontinued amiodarone after 25 months of follow-up because of development of an important blue-grey skin discoloration.(ABSTRACT TRUNCATED AT 400 WORDS)

[Empiric treatment with amiodarone in patients with sustained ventricular tachyarrhythmia. Results of a long-term follow-up]. / Trattamento empirico con amiodarone in pazienti con tachiaritmie ventricolari sostenute. Risultati a medio e lungo termine.

The long-term follow-up of 52 pts (36 M, 16 F, mean age: 62 years) with sustained ventricular tachyarrhythmias (SVT) was analyzed to assess the efficacy and feasibility of empiric amiodarone treatment. Forty-five pts had organic heart disease (mean EF: 38.3%) and 7 pts no overt heart disease. Twenty pts suffered from syncope or cardiac arrest secondary to sustained ventricular tachyarrhythmias (mean: 2.35 episodes) and 32 did not. All pts were given amiodarone empirically (mean dose: 390 mg) and followed-up for a mean period of 29.5 months (range 1-137). Two pts (3.8%) died of non cardiac causes, 5 (9.6%) of non sudden cardiac death and 7 (13.4%) of sudden death. Fifteen pts (28.8%) experienced non fatal arrhythmic recurrences. Four out of 7 pts who died suddenly experienced non fatal arrhythmic recurrence before death. The actuarial incidence of cardiac death was 10.8, 22.7, 31.5, 31.5% at 1, 2, 3 and 5 years; the actuarial incidence of sudden death was 8.9, 12, 22.1, 22.1% at 1, 2, 3 and 5 years; the actuarial incidence of non fatal arrhythmic recurrences was 17.4, 26.3, 26.3, 26.3, 44.7% at 1, 2, 3, 4 and 5 years. Univariate analysis identified recent myocardial infarction, NYHA functional class, detection of frequent and/or repetitive premature ventricular contractions on Holter monitoring and non fatal arrhythmic recurrences as predictors of cardiac death (p less than 0.05), while only non fatal arrhythmic recurrences were associated with sudden death (p less than 0.05). Twenty-two pts (42.3%) developed side effects. Nine (17.3%) discontinued amiodarone: 6 pts (11.5%) because of side effects and 3 inadvertently.(ABSTRACT TRUNCATED AT 250 WORDS)

A polarographic study of the photodegradation of nitrendipine.

Nitrendipine produces a well-defined polarographic peak due to the four-electron reduction of the nitro group. This peak is used for tracking the photodecomposition of nitrendipine in both UV light and daylight conditions. The results show that nitrendipine remains unaltered in the short time scale of a normal analytical procedure and no special care with visible light exposure is necessary. However nitrendipine is strongly altered with UV irradiation showing a first-order degradation kinetics. A degradation rate constant of 0.0665 min-1 with a t1/2 of 10.423 min has been obtained. The UV degradation product was isolated and identified as the nitro pyridine analogue of nitrendipine.

Antioxidant capacity of diethyldithiocarbamate in a metal independent lipid peroxidative process.

2,2'-Azobis-[2-amidinopropane] initiated lipid peroxidation of egg yolk phosphatydil choline liposomes was measured by oxygen uptake and the emitted visible luminescence. Lipid peroxidation involved a chain process (kinetic chain length = 49 +/- 11) and its rate was independent of added Fe ions. Diethyldithiocarbamate (DDC) behaved as an efficient inhibitor in the microM range, being able to trap 1.05 +/- 0.25 free radicals per added molecule. The efficiency of DDC was also independent of Fe addition to the system. These results indicate that DDC is able to trap the chain carrying free radicals, showing that this compound, besides being a powerful metal chelator, is also an efficient free radical scavenger. It is proposed that the relevant step in this process involves an electron transfer from DDC to the peroxy radical LOO., LOO. + DDC- ----LOO- + DDC. followed by protonation of LOO- and dimerization of the DDC. radical.

[Value of serial electropharmacologic tests in the treatment of sustained ventricular arrhythmias]. / Valore dei tests elettrofarmacologici seriati nel trattamento delle tachiaritmie ventricolari sostenute.

The value of electropharmacological testing in patients (pts) with sustained ventricular tachyarrhythmias was studied in 46 consecutive pts (24 with sustained ventricular tachycardia (SVT) and 22 with cardiac arrest due to a ventricular tachyarrhythmia. Forty-two pts underwent a baseline electrophysiological study. The ventricular stimulation protocol included up to 3 extrastimuli during spontaneous rhythm and during paced ventricular rhythm at 100/min, 130/min, 160/min and brief bursts pacing at 2 ventricular sites. Ventricular tachycardia was induced in 37/42 pts (88%) (sustained in 32 pts and non sustained in 5 pts). Twenty nine pts underwent 79 trials of different drug regimens (mean 2.72 per pt, range 1-8). A totally successful drug regimen was found in 15/29 pts (51.7%) and a partially successful drug regimen in 11/29 pts (37.9%). Twenty-three pts were discharged on a drug regimen successful during serial electropharmacological testing (Group I) and 23 pts were discharged on an empiric drug regimen (Group II). Each pt was followed-up for a mean period of 15 months (range 1-74). Group I pts had fewer arrhythmia recurrence (SVT and/or sudden death) than Group II pts (2/23 vs 13/23 p less than 0.01). In conclusion electropharmacological testing is an useful tool in the therapy of pts with sustained ventricular tachyarrhythmias.

[Predictive value of the ajmaline test in dysfunction of the sinus node. Prospective 4-year follow-up relative to 77 patients]. / Valore predittivo del test all'ajmalina nelle disfunzioni del nodo del seno. Follow-up prospettico di 4 anni relativo a 77 pazienti.

To establish the usefulness of Ajmaline test for the evaluation of sinus node function, 77 pts (47 M, 30 F, mean age +/- SD = 61 +/- 15 yrs) first underwent an electrophysiologic study and then were followed-up for a mean period of 46.3 months. The following parameters were determined before and after i.v. administration of Ajmaline (1 mg/kg in 1 minute): sinus cycle length (SCL), corrected sinus node recovery time (CSNRT) and sino-atrial conduction time (SACT). The pts were divided into 3 groups: Group A: 10 pts without clinical or electrocardiographic signs of sinus node dysfunction (SND) and with normal control CSNRT and SACT (less than or equal to 500 and less than or equal to 120 msec, respectively); Group B: 46 pts with clinical-electrocardiographic signs of suspected or apparently not severe SND (sinus bradycardia greater than or equal to 40 beats/min and/or syncopes with positive vagal manoeuvres) and/or slightly abnormal control CSNRT (greater than 500 less than or equal to 600 msec) and/or SACT (greater than 120 less than or equal to 150 msec); Group C: 21 pts with clinical-electrocardiographic signs of apparently severe SND (sinus bradycardia less than or equal to 39 beats/min, sino-atrial block, sinus arrest) and/or definitely prolonged control CSNRT and/or SACT (greater than 600 and greater than 150 msec, respectively). The Ajmaline test was considered negative for the presence of a severe SND if SCL was not prolonged after the administration of the drug more than 20% and CSNRT and SACT were not prolonged more than 50% compared to the control values. Otherwise the Ajmaline test was considered positive. Twenty-seven out of the 77 pts studied underwent permanent pacemaker implantation (23 immediately after the electrophysiologic study and 4 during the follow-up). The following results were obtained: the Ajmaline test was negative in 100% of group A, 87% of group B and 48% of group C pts and positive in 0% of group A, 13% of group B and 52% of group C pts; during the follow-up a negative test resulted predictive in 56 out of 60 pts (92%) and a positive test in 16 out of 17 pts (94%). The predictive accuracy of the test was, therefore, 93.5%. These results indicate that Ajmaline test is an useful provocative test for disclosing, during electrophysiologic studies, pts who have severe SND and for selecting those who need pacemaker implantation.