Cardiac resynchronisation therapy response predicts occurrence of atrial fibrillation in non-ischaemic dilated cardiomyopathy.

AIM: The aim of this study was to determine whether or not cardiac resynchronization therapy (CRT) has a favourable effect on the incidence of new-onset atrial fibrillation (AF) in a homogeneous population of patients with non-ischaemic idiopathic-dilated cardiomyopathy and severe heart failure. METHODS: We designed a single-centre prospective study and enrolled 58 patients AF naïve when received CRT. After 1 year of follow-up our population was subdivided into responders (72.4%) and non-responders (27.6%), so as to compare the incidence of AF after 1, 2 and 3 years of follow-up in these two groups. RESULTS: Already after 1 year, there was a significant (p < 0.05) difference in new-onset AF in non-responder patients with respect to responders (18.2% vs. 3.3%). These data were confirmed at 2 years (33.3% vs. 12.2%) and 3 years (50.0% vs. 15.0%) follow-up. In particular, 3 years after device implantation non-responders had an increased risk to develop new-onset AF (OR = 5.67). CONCLUSIONS: This is the first study analysing long-term effects of CRT in a homogeneous population of patients with non-ischaemic dilated cardiomyopathy, indicating the favourable role of this non-pharmacological therapy on the prevention of AF.

Indirect pathway of liver glycogen synthesis in humans is predominant and independent of beta-adrenergic mechanisms.

The relative contribution of the direct and indirect pathways to liver glycogen formation was assessed in humans by using a combined tracer-hepatic vein catheterization technique. An oral glucose load (75 g) labelled with 1-14C-glucose was administered to five subjects (control group) and 4.5 h later hepatic glycogen was flushed with glucagon and analysed to determine the randomization of 14C. The specific activity (SA) of the glycogen derived glucose (1-14C-glucose SA+recycled 14C-glucose SA) was 61 +/- 7% of the mean blood glucose SA of the interval 0-180 min after the oral glucose load. The relative values due to 1-14C-glucose and recycled 14C-glucose were 33 +/- 7 and 28 +/- 3%, respectively. The data indicate that the indirect pathway of glycogen formation is not only active in humans but contributes substantially (at least 50%) to liver glycogen formation. In order to investigate whether the basal adrenergic tone plays a role in the maintenance of the indirect pathway, the same protocol was also performed in a second group of subjects (n = 5) who received propranolol before the oral glucose load (propranolol group). The SA of the glycogen-derived glucose was considerably smaller than that of the control group (18 +/- 5 vs. 61 +/- 7%, P < 0.001), suggesting lesser glycogen formation. However, the ratio of 1-14C to recycled-14C in the glucose molecule was similar in the control (1.3 +/- 0.4) and propranolol group (1.9 +/- 1.2). We conclude that the basal adrenergic tone does not play any role in the operation of the indirect pathway of liver glycogen synthesis.

[The reduction of beta-adrenoceptor density and the suppression of ectopic ventricular activity with low doses of amiodarone]. / Riduzione della densità beta-adrenocettoriale e soppressione dell'attività ectopica ventricolare con basse dosi di amiodarone.

In 5 patients with frequent premature ventricular ectopic beats, refractory to other antiarrhythmic treatments, amiodarone, given orally at the dose of 200 mg once a day for 4 weeks, reduced beta-adrenoceptor density from 202.9 +/- 62 to 101.1 +/- 33 fmol/mg protein (p < 0.01). Similarly, kd decreased from 21.0 +/- 6 to 3.9 +/- 1 (p < 0.05). Changes in beta-adrenoceptor population were accompanied by a marked reduction in mean premature ventricular complexes (PVC) frequency from the control value of 428.9 +/- 150.3 to 13.4 +/- 10.7 PVC/h (p < 0.05) and by a decrease in heart rate, from 83.8 +/- 4 to 73.9 +/- 4 b/min (p < 0.01). On the contrary, mean arterial pressure remained unchanged. Patients did not show side effects during treatment. Therefore, low dose oral amiodarone has important pharmacologic and therapeutic effects. It significantly reduces lymphocyte beta-adrenoceptor density and is effective in treatment of ventricular arrhythmias. Additional studies were performed in vitro exposing lymphocytes to increasing concentrations of amiodarone. The analysis of variance for repeated measures showed that amiodarone-induced reduction in lymphocyte beta-adrenoceptor density is a dose-depending phenomenon. Accordingly, treatment with doses of amiodarone higher than that used in the present study may induce a major reduction in lymphocyte beta-receptor density and exert a depressant cardiac effect.

Subclinical cardiotoxicity by doxorubicin: a pulsed Doppler echocardiographic study.

In order to detect subclinical levels of Doxorubicin (D) cardiotoxicity, 21 patients aged 42 +/- 8 years with malignancies and treated with D as a part of a multiple regimen, were evaluated. The mean cumulative dose of D was 242 +/- 112 mg.m-2 (150 to 520 mg.m-2). Patients with systemic hypertension, valvular diseases, suspected coronary artery disease, ejection fraction less than 55% as assessed by radionuclide angiography, and aged more than 50 years were excluded from the study. A Doppler echocardiographic examination was performed before and after the course of D therapy with a mean interval of 142 days. The following variables were assessed: fractional shortening (FS), ejection fraction (EF), stroke volume (SV), isovolumic relaxation time (IVRT), maximal early diastolic flow velocity (Emax), maximal late diastolic flow velocity (Amax), and mitral deceleration time (Mdt). Indices derived from 19 aged-matched normal subjects were compared to those of the patients before the course of therapy. Doppler echocardiographic measurements did not differ significantly between the control group and patients before the course of therapy. While there were no significant changes in FS, EF, and SV in the study group before and after therapy, indices of diastolic filling showed striking differences: IVRT changed from 72 +/- 11 to 87 +/- 19 ms (P less than 0.001), Emax from 81 +/- 12 to 65 +/- 17 cm.s-1 (P less than 0.001), Mdt from 174 +/- 25 to 183 +/- 34 ms (P less than 0.05), Amax from 44 +/- 17 to 52 +/- 16 cm.s-1 (P less than 0.01). These data demonstrate impaired diastolic filling after doxorubicin therapy at conventional dosages.

[Different modalities of classification and prognostic significance of ventricular arrhythmias after acute myocardial infarct. Prospective study]. / Differenti modalitá di classificazione e significato prognostico delle aritmie ventricolari dopo infarto acuto del miocardio. Studio prospettivo.

In our study we compared the prognostic significance of clinical variables, laboratory results and different classification models of ventricular ectopic beats recorded by means of a pre-discharge 24 hour ambulatory electrocardiographic monitoring, in 210 survivors of acute myocardial infarction. In addition a full multivariate analysis of the factors affecting survival time was carried out using Cox's proportional hazards (multiple) regression model. Multivariate stepwise discriminant analysis identified hypertension, congestive heart failure assessed by Killip class, and the grading system for ventricular arrhythmias as the most important prognostic variables. When Moss grading system for ventricular arrhythmias was used, the relative risk was a superior as heavy Moss grading system (Moss 2 vs Moss 1 and Moss 3-4 vs Moss 1, relative risk = 1.2 and 3.6 total death, respectively). Furthermore, the hazard ratio of Moss grading system was higher utilizing as comparison patients without ventricular ectopic beats (relative risk = 1.7 for Moss 2 and 5.3 for Moss 3-4) than patients with ventricular ectopic beats less than one/hour (relative risk = 1.2 for Moss 2 and 3.7 for Moss 3-4). Thus, in survivors of acute myocardial infarction, a rational and useful ventricular ectopic beats categorization includes both frequency and the presence or absence of malignant characteristics.

Transvenous catheter ablation of the His bundle in ventricular tachycardia.

The usefulness of transvenous catheter ablation of the His bundle in three patients with recurrent ventricular tachycardia (VT), in which the initiating mechanism was recognized during a rapid atrial rhythm, is reported. Tachycardia was refractory to conventional treatment and required transthoracic direct-current shocks in all patients. In patient No. 1 double tachycardia (atrial flutter and VT) was documented and VT was easily induced by rapid atrial pacing. In patients Nos. 2 and 3 initiation of VT during junctional reciprocating and atrial tachycardia, respectively, was observed. Interruption of the His bundle was performed by means of fulguration. Stable atrioventricular (AV) block was observed in patient No. 1 after the ablative procedure; patient No. 2 showed anterograde conduction over a posterior septal accessory pathway with no evidence of conduction over the normal conduction system in both the anterograde and retrograde directions. In patient No. 3, transient AV block was observed; AV conduction resumed 2 days later and the cardiac rhythm showed persistent ectopic atrial tachycardia with second-degree AV block. Patients Nos. 1 and 2 underwent pacemaker implantation, but patient No. 2 was not pacemaker dependent. After the procedure, VT no longer occurred in any of the patients (follow-up: 2 years, 5 months, and 6 months).

Effects of long-term molsidomine treatment versus isosorbide dinitrate and placebo on exercise tolerance in stable angina.

A single-blind study (n = 59) was performed to assess the effect of long-term (4 week) orally administered molsidomine (2 mg 4 X daily), isosorbide dinitrate (10 mg 4 X daily), and placebo on exercise tolerance performed on the bicycle ergometer by patients with stable angina on effort and with significant coronary artery disease. Isosorbide dinitrate had similar effects to placebo, both failed to modify the pressure-rate product, the sustained work load, and the ST segment depression, but slightly decreased, although not significantly, the incidence of angina. Although not affecting the pressure-rate product and the mean blood pressure, molsidomine decreased significantly the ST segment depression (p less than .05). In conclusion, by markedly reducing preload and because of its long-lasting effect (up to 6 h), the new vasodilator drug molsidomine plays a useful role in the long-term management of stable angina on effort.

Potassium sparing effect of amiloride in patients receiving diuretics: a quantitative study.

This study was undertaken in order to assess the K+ sparing ability of amiloride. Thirty patients with liver cirrhosis and ascites or congestive heart failure were divided into three groups and treated with amiloride (Group A), hydrochlorothiazide (Group B) and amiloride plus hydrochlorothiazide (Group C) for 15 days. In all groups there was an increased diuresis while only in group A and C there was a statistically significant rise of K+ serum levels and a slight increment of K+ urinary loss. Total body K+ evaluated by 42K increased in group A and C while decreased in group B. Our results seem to confirm that amiloride has a mild diuretic action with a powerful K+ sparing capacity; amiloride is also able to counterbalance and reverse hydrochlorthiazide induced K+ urinary loss.