A new echo-Doppler method to measure interatrial conduction time. Validation and clinical usefulness.

AIM: The aim of this study was to assess if knowing the interatrial conduction time is useful to better program atrioventricular delay in sequential pacing. The study proposes a new echo-Doppler method to measure interatrial conduction time, correlating it with electrophysiological measures. METHODS: The new method was tested in 30 subjects who underwent electrophysiological study. Interatrial conduction time by new method was taken during atrial pacing as the interval between the artefact of electrocardiogram pacing, shown on screen echo, and the onset of the A wave of the echo-Doppler mitral inflow. The electrophysiological measures were obtained, in the same subjects and at the same time, by a decapolar catheter in coronary sinus as intervals between the artefact of atrial pacing and the first positive left atrial deflection at proximal (C7C8) and distal (C1C2) electrodes. RESULTS: Echo-Doppler mean time was 114±12 ms, electrophysiological time was 107±14 ms at C7C8 and 124±11 ms at C1C2. Statistical analysis showed a good correlation (r=0.92, P<0.001) and accord (mean difference=6.6 ms) between the two methods. CONCLUSION: The new method to measure interatrial conduction time is consistent with the electrophysiological method; it could be particularly useful in programming the best AV delay in sequential and biventricular pacing, to avoid atrial contraction against a closed mitral valve.

Plasma and skin concentration of 5-methoxypsoralen in psoriatic patients after oral administration.

The aim of this work was to investigate the distribution of 5-methoxypsoralen in the skin after oral administration of the drug and to examine the correlation between skin and plasma concentrations. 5-Methoxypsoralen skin concentration was measured in both healthy and psoriatic sites of 10 psoriatic patients after single and multiple oral doses. The results obtained show that 5-methoxypsoralen accumulates at higher levels in the more external layers of the skin after oral administration. The high affinity of drug for the stratum corneum was confirmed by in vitro skin affinity measurements. The concentration of 5-methoxypsoralen in the skin was similar in both psoriatic and healthy sites, indicating that the pathology does not influence drug distribution in the skin. After single dose administration, a linear correlation was found between skin and plasma drug concentration. After multiple dose administration, drug concentration in the skin was fairly constant despite the variable plasma concentrations in different subjects.

Electrotherapeutic management of patients with heart failure.

Heart failure is associated with poor long term survival due to progressive refractory heart dysfunction and sudden cardiac death. Cardiac resynchronization through atrio-biventricular pacing has been introduced to treat patients affected by drug-refractory heart failure with desynchronized ventricular activation, as for complete left bundle branch block. The technique is aimed to overcome interventricular and intraventricular conduction delays leading to ventricular dysynchrony, paradoxical septal wall motion, presystolic mitral regurgitation and reduced diastolic filling times. Short term studies demonstrated that biventricular pacing (and perhaps left ventricular pacing alone) may improve both systolic and diastolic function. Initial studies in patients receiving long term pacing consistently showed significant QRS shortening associated with improvement in symptoms, left ventricular ejection fraction, exercise tolerance, quality of life and New York Heart Association functional class. As far as sudden cardiac death prevention in heart failure is concerned, implantable cardioverter defibrillator (ICD) implantation has been demonstrated to be the most effective therapy in patients with prior cardiac arrest due to ventricular fibrillation or poorly tolerated ventricular tachycardia. Low left ventricular ejection fraction, unsustained ventricular tachycardia and inducibility at electrophysiological study also may identify high risk patients requiring ICD implantation. Further studies are needed to evaluate the effect of cardiac resynchronization on hard end-points, such as survival and long term clinical outcome, and to upgrade risk stratification criteria to be used in selection of candidates for ICD implantation.

Postcardioversion atrial electrophysiologic changes induced by oral verapamil in patients with persistent atrial fibrillation.

OBJECTIVES: The aim of our study was to verify the effect of oral administration of verapamil on atrial electrophysiologic characteristics after cardioversion of persistent atrial fibrillation (AF) in humans. BACKGROUND: Discordant findings have been reported regarding the efficacy of verapamil in preventing the electrical remodeling induced by AF. METHODS: We determined the effective refractory periods (ERPs) at five pacing cycle lengths (300 to 700 ms) and in five right atrial sites after internal cardioversion of persistent AF (mean duration 238.1+/-305.9 days) in 19 patients. Nine patients received oral verapamil (240 mg/day) starting four weeks before the electrophysiologic study, whereas the other 10 patients were in pharmacologic washout. RESULTS: The mean ERPs were 202.0+/-22.7 ms in the washout group and 189.3+/-18.5 ms in the verapamil group (p < 0.0001). The degree of adaptation of refractoriness to rate was similar in the two groups (mean slope value in the washout group and verapamil group: 0.07+/-0.03 and 0.08+/-0.05, respectively), showing a normal or nearly normal adaptation to rate in the majority of the paced sites in both groups. The mean ERP was slightly longer in the septum than in the lateral wall and in the roof, both in the washout and verapamil groups. CONCLUSIONS: In patients with persistent AF, long-term administration of verapamil before internal cardioversion resulted in 1) shortening of atrial ERPs; 2) no change in refractoriness dispersion within the right atrium; and 3) no change in atrial ERP adaptation to rate.

Electrophysiology of atrial fibrillation: evolving insights.

In the last few years many studies have been performed to better understand the pathophysiological nature of atrial fibrillation (AF). These recent observations provide new insights into the initiation and perpetuation of AF, underlying the importance of the pulmonary veins as major sources of atrial triggers and introducing new concepts such as atrial electrical remodeling and spatial heterogeneity of the electrophysiologic characteristics of this arrhythmia. The purpose of this review was to provide current knowledge about AF electrophysiology in an effort to unite old models and new concepts.

[Epidural spinal stimulation in the treatment of refractory angina pectoris. Its clinical efficacy, complications and long-term mortality. An Italian multicenter retrospective study]. / La stimolazione spinale epidurale nel trattamento dell'angina pectoris refrattaria. Efficacia clinica, complicanze e mortalità a lungo termine. Studio retrospettivo multicentrico Italiano.

BACKGROUND: Spinal cord stimulation has been used for many years in the treatment of refractory angina pectoris. Its anti-anginal and anti-ischemic effect has been well documented in several studies, but the long-term efficacy, safety and survival rate are not well known. The aim of this study was to carry out a retrospective analysis of a series of patients from the Italian Multicenter Registry, the data of which were collected in five centers, by means of a questionnaire. METHODS: One hundred and thirty patients (83 males, 47 females, mean age 74.8 +/- 9.8 years) were submitted to spinal cord stimulator implantation for refractory angina pectoris in the period 1988-1995 and controlled during a mean follow-up of 31.4 +/- 25.9 months. A previous myocardial infarction had already occurred in 69.3% of patients, whereas in 67.6% multivessel coronary artery disease was documented. A left ventricular dysfunction (ejection fraction < 0.40) was present in 34% of patients; bypass surgery and coronary angioplasty were performed in 49.6% and in 27% of patients respectively. In 96.3% of cases revascularization procedures were not advisable. RESULTS: A complete follow-up of 116 patients (89.2%) was available. The spinal cord stimulator induced a significant reduction in NYHA functional class from 2.5 +/- 1.2 to 1.5 +/- 0.9 (p < 0.01). During the follow-up 41 patients (35.3%) died, and in 14.2% a new acute myocardial infarction developed. The total percentage of minor spinal cord stimulation-related complications was 6.8%. No major complications occurred. The annual total mortality rate was 6.5%, whereas the cardiac mortality rate was 5%. Compared to the survivors, patients who died showed a higher incidence of left ventricular dysfunction, previous myocardial infarction and bypass surgery at implantation. CONCLUSIONS: In our experience, spinal cord stimulation is an effective therapy in patients affected by refractory angina pectoris and who cannot undergo revascularization procedure. The complication rate is low, with the total and cardiac mortality showing a trend as that reported for patients with similar coronary disease.

Spinal cord stimulation for the treatment of refractory angina pectoris: a two-year follow-up.

Twenty-three patients affected by severe, refractory angina were submitted to permanent spinal cord stimulation (SCS) and then followed in our outpatient clinic for 24 months. During the follow-up period, the number of weekly angina episodes drastically dropped from 9.2 (preimplant) to 1.8 in the 3rd, 2.5 in the 6th, 4.5 in the 12th, and 4.2 in the 24th month, with a statistically significant difference (P < 0.01) between the first and last values. A significant increase in the average exercise time from 320 +/- 120 seconds (in baseline condition) to 410 +/- 115 seconds (during SCS) was observed at the treadmill stress test (P < 0.01). SCS was well tolerated by all the patients. However, 7 patients died during follow-up (3 myocardial infarctions, 2 noncardiac deaths, and 2 sudden deaths). Three generators were replaced because of battery depletion after 15, 17, and 21 months. No serious complication was observed. In conclusion, in patients with otherwise intractable angina or already submitted to myocardial revascularization, SCS is very effective in reducing the number of angina episodes. The time of the work during exercise stress test is also significantly prolonged.

Selective hepatic enrichment of polyunsaturated phosphatidylcholines after intravenous administration of dimethylethanolamine in the rat.

The content of polyunsaturated phosphatidylcholines (PCs) is one of the parameters which regulate membrane functions. Polyunsaturated PCs are preferentially synthesized in the liver by the microsomal enzyme phosphatidylethanolamine N-methyltransferase. The activity of this enzyme may be stimulated in vitro in isolated rat hepatocytes by supplementation with dimethylethanolamine (DME), the polar head group of the precursor of PC along this pathway. The aim of this study was to evaluate in vivo the effect of an intravenous infusion of DME in the rat on the hepatic phospholipid composition. Bile fistula rats were intravenously infused for 15 h with sodium taurocholate (1 mumol/kg per min), with or without the addition of 0.3 mg/kg per min of [14C]DME. The concentration per gram of wet liver of individual phospholipid classes, PC molecular species and of total triacylglycerols, as well as the distribution of radioactivity in liver phospholipids, in rat tissues and body fluids were analyzed. A significant (P less than 0.01) enrichment in PC was found in the liver of DME-infused rats with respect to controls. No differences in the other phospholipid classes were found. DME-infused rats showed a significant (P less than 0.01) decrease in the hepatic concentration of triacylglycerols. At HPLC analysis, the enrichment in PC in DME-infused rats was found to be selectively due to three molecular species (i.e., sn-1 stearoyl/sn-2 arachidonoyl, sn-1 stearoyl/sn-2 linoleoyl, sn-1 stearoyl/sn-2 docosahexanoyl molecular species). In agreement with quantitative data, more than 70% of hepatic radioactivity was recovered in polyunsaturated PC species, with the highest specific activity in the sn-1 stearoyl PCs. The specific activity of hepatic PC approximates that of phosphatidyldimethylethanolamine. This finding together with the effective incorporation of DME in PC suggests that this amino base is methylated after its incorporation into phosphatidyldimethylethanolamine, throughout the stimulation of hepatic N-methyltransferase activity. The selective hepatic enrichment with polyunsaturated PC species after DME infusion may offer a new experimental tool for studying hepatic membrane metabolism.

[The experience in cardiac pacing at the Cardiology Department of St. Camillo Hospital (Rome) (author's transl)]. / L'esperienza della Divisione di Cardiologia dell'Ospedale San Camillo di Roma in tema di elettrostimolazione.

The experience of the Cardiac Electrostimulation Center of S. Camillo Hospital in Rome on 1503 patients treated with permanent pacemakers for an 11 year period is referred. The Authors analyze the increase of the activity of the Center during these years and some events that caused it. 94.5% of the patients were more than 50 years old; the dominant pathology has been ischemic and idiopathic cardiopathy, which together include 94.7% of the totality. The indication to the implant has been A-V block in 70% of the patients; intraventricular block in 20%; sick sinus syndrome in 10%. In the last years the prophylactic indication has increased (from 0.4% to 4.4%). 2459 pacemakers have been used, of which 79.5% was QRS-inhibit. The mercury prosthesis have been progressively substituted with the lithium ones. 1642 catheters (implant and reimplant) have been used; principally endocardic (95%) and monopolar (85%). The substitution of the catheter has been necessary in 9% of the totality; in 2.6% of the endocardic and in 15.9% of the epimyocardic. Among 50 electrodes, after a period of observation of about 7.7 years, 36 are still in function. The percentage of the complications has been 17.1%; the most important complications have been: dislocation (6%), microdislocation (1.5%), late high threshold (2.1%), failure of catheter (1.2%), generator malfunction (2.3%). The total mortality has been 15.4%; 0.2% caused by deficit of the implant; 2% sudden deaths and 13.2% not depending from the implant; 243 patients (16%) are not to be found. The frequency of out-patients controls has decreased in the last 2 years (from 3.8 controls per years to 1.8).

[Conduction disturbances associated with the sick sinus node syndrome. Study of fifteen cases with His bundle electrogram (author's transl)]. / Disturbi della conduzione associati a malattia del nodo del seno. Studio di 17 casi con elettrogramma del fascio di His

Disturbances in atrioventricular conduction were demonstrated in 17 out of 38 cases of sik sinus node syndrome (MNSA). 14 cases had BAV, in varying degrees, 9 had intraventricular conduction disturbances, 13 had pathological values of A-H, 6 pathological values of H-V, 4 contemporaneous lengthening of A-H and H-V. The ECG and hissian electrogram examinations enabled the identification of the seat and the extension of the conduction disturbance, which was schematized as nodal, nodal and truncular, intraventricular (mono-, bi-, and trifascicular) and diffused. It is possible that the damage to the conduction system associated with MNSA has the same etiology. The frequency of the association of MNSA with conduction disturbances suggests, in the case indicated, the use of a ventricular electrostimulation.