Atrial fibrillation during acute myocardial infarction: association with all-cause mortality and sudden death after 7-year of follow-up.

AIMS: Atrial fibrillation/flutter (AF/FL) is a common complication of acute myocardial infarction (AMI). Indeed, the determinants of AF/FL in AMI-patients and the association of AF/FL with mortality are not well-known. The purpose of the present study was to investigate the relationship between presence of AF/FL and mortality in patients with AMI and to report on predictors of AF/FL. METHODS: We studied 505 patients enrolled in three intensive care units with definite AMI and followed up for 7 years. No patient was lost to follow-up. Patients with AF/FL during the 1st week of hospitalisation were compared with those with steady sinus rhythm. End-points were all-cause mortality and modes of death. RESULTS: At multivariable logistic regression analysis, elderly, body mass index, congestive heart failure (CHF), history of hypertension and plasma cholesterol (in a negative fashion) were independently associated with the presence of AF/FL. At survival analysis, after full adjustment, AF/FL was not associated with in-hospital mortality. After 7 years of follow-up, AF/FL was found to be associated with all-cause mortality [adjusted odds ratio (OR) = 1.6; 95% confidence interval (CI) = 1.2-2.3], together with age, diabetes mellitus, creatine kinase-MB isoenzyme (CK-MB) peak, CHF, estimated glomerular filtration rate and thrombolysis. At adjusted logistic polynomial regression analysis, AF/FL was found to be associated with an excess of mortality for reasons of sudden death (SD) (adjusted OR = 2.7; 95% CI = 1.2-6.4). No interaction was observed between AF/FL and medications on in-hospital mortality. For 7-year mortality, angiotensin-converting enzyme (ACE)-inhibitors and digitalis showed an independent negative (protective) interaction chiefly on SD (adjusted OR = 0.06; 95% CI = 0.01-0.74, and RR = 0.10; 95% CI = 0.02-0.58, respectively). CONCLUSIONS: Patients with AMI and AF/FL portend a poor prognosis in the long-term chiefly because of an excess of SD. Treatment with ACE-inhibitors and digitalis may have long-term beneficial effects on SD.

Pharmacokinetics and electrophysiological effects of intravenous ajmaline.

The pharmacokinetics of ajmaline were studied in 10 patients with suspected paroxysmal atrioventricular block who received a 1 mg/kg intravenous dose over 2 minutes for diagnostic purposes (ajmaline test). Plasma concentration decay followed a triexponential time course with a final half-life much longer (7.3 +/- 3.6 hours) than that previously found by other investigators (about 15 minutes). Mean total plasma clearance and renal clearance were 9.76 ml/min/kg and 0.028 ml/min/kg, respectively. Although most of the dose was eliminated through the extrarenal route (only 3.5% of the intravenous dose was recovered in urine), no fluorescent metabolites could be detected either in plasma or urine. The steady-state volume of distribution averaged 6.17 L/kg, and plasma protein binding ranged between 29 and 46%. Three patients developed a transient atrioventricular block after ajmaline administration. In the remainder, the drug prolonged atrio-His bundle (AH interval), His bundle-ventricular (HV interval) and intraventricular (QRS interval) conduction times. Corrected ventricular repolarisation time (QTc interval) showed less marked changes, which were biphasic at times. The mean maximum ajmaline-induced increase in HV interval was 98%, in QRS was 58%, in AH was 30%, and in QTc was 17%. In most cases the time course of electrocardiographic changes lagged behind that of plasma concentrations, suggesting a delayed equilibrium of plasma concentrations with the site of action (hysteresis). Despite that, the pharmacokinetic-pharmacodynamic model, which accounted for hysteresis, failed to fit the experimental data adequately.(ABSTRACT TRUNCATED AT 250 WORDS)

Ajmaline test in a patient with chronic renal failure. A pharmacokinetic and pharmacodynamic study.

Pharmacokinetic and pharmacodynamic properties were studied after intravenous administration of ajmaline 1 mg/kg in an anuric patient, who underwent the electrophysiological ajmaline test. The magnitude and rate of onset of the typical electrophysiological effects of ajmaline (prolongation in atrio-Hisian and His-ventriculum conduction times) were within the range of normal values. The plasma concentration curve showed a triexponential decay with half-lives as follows: initial phase (t1/2 alpha) 1.34 min, fast elimination phase (t1/2 beta) 10.13 min and terminal (slow) phase (t1/2 gamma) 258.6 min. Other relevant pharmacokinetic parameters calculated were: total plasma clearance 45.91 L/h; volume of distribution 285.6L; protein binding 47%. Five hours after administration the patient underwent a 3.5h haemodialysis without any substantial increase in the slope of the final elimination phase of the curve. A major problem in interpreting the pharmacokinetic results is the lack of reliable reference data in healthy subjects. It is likely that the ajmaline t1/2 reported in the literature (13.4 min) does not reflect the true terminal t1/2 of the drug, because it was determined during an unduly short sampling period (30 min). Nevertheless, if we compare just the first 30 min of the concentration-time curves, our results are nearly superimposable on those found in healthy subjects.

Effects of acute K-strophantidin administration on left ventricular relaxation and filling phase in coronary artery disease.

In 10 patients with coronary artery disease, preserved left ventricular (LV) performance and absence of previous myocardial infarction, the effects of an acute intravenous administration of k-strophantidin (0.005 mg/kg over 10 minutes) on selected parameters of both LV systolic and diastolic function, including relaxation, were evaluated. An increase in positive first derivative of LV pressure (dP/dt) and in the ratio between dP/dt and the pressure developed (dP/dt/P) (1,530 +/- 287) 1,600 +/- 329 mm Hg/s [p less than 0.05], and 30 +/- 6 to 34 +/- 8 s-1 [p less than 0.05], respectively) demonstrated the inotropic effect of k-strophantidin, whereas volumetric parameters of systolic function (end-systolic and stroke volume indexes, and ejection fraction) did not show any significant change. However, LV relaxation was impaired by k-strophantidin injection; in fact, mean values of T constant were significantly increased from 50 +/- 12 to 55 +/- 13 ms (p less than 0.01). Lowest LV and end-diastolic pressures increased from 8 +/- 4 to 11 +/- 4 mm Hg (p less than 0.05) and from 17 +/- 6 to 20 +/- 8 mm Hg (p less than 0.05), respectively. The end-diastolic volume and maximal rate of volumetric increase during the early and late filling phases were not modified by k-strophantidin. Mean aortic pressure increased from 110 +/- 10 to 120 +/- 12 mm Hg (p less than 0.001). Therefore, in patients with coronary artery disease and LV preserved performance, an acute intravenous administration of k-strophantidin appears to stimulate contractility and to worsen relaxation, and minimal LV and end-diastolic pressures.

Cardiovascular effects induced by the injection of a new nonionic contrast medium (Iopamidol): experimental study in dogs.

The hemodynamic effects induced by the injection in the pulmonary artery of the new nonionic water soluble contrast medium Iopamidol were compared with those obtained by the injection of two other currently used contrast media (meglumine diatrizoate and sodium iothalamate). The experiments were carried out in nine mongrel dogs. Hemodynamic variables were continuously measured prior to, during, and for 8 minutes after injection of the contrast media. Injections of iopamidol produced significantly smaller decreases in aortic pressure (p less than 0.01), contractile indices (p less than 0.01), and peripheral resistances (p less than 0.01), and changes in heart rate and in cardiac output were less pronounced. At 3-4 minutes after injection, an increase in Vmaxd was observed with all three contrast media, but it was significantly lower after injecting Iopamidol. The role of hyperosmolality in causing cardiovascular changes is discussed. The less significant changes induced by Iopamidol appear to be the result of its lower osmolality, which is about a third that of meglumine diatrizoate or sodium iothalamate.

Detection of early abnormalities of left ventricular function by hemodynamic, echo-tissue Doppler imaging, and mitral Doppler flow techniques in patients with coronary artery disease and normal ejection fraction.

We have investigated the possibility of detecting early abnormalities of left ventricular function at the initial phase of ischemic cardiomyopathy. Sixteen normotensive patients with coronary artery disease and normal left ventricular ejection fraction and 6 control patients were studied by invasive hemodynamic techniques in combination with transmitral Doppler flow or with echo-tissue Doppler imaging. The extent of the percentage of left ventricular longitudinal shortening and the systolic peak velocity at echo-tissue Doppler were significantly higher in the control patients than in patients with ischemic cardiomyopathy (P <.01). Left ventricular end-diastolic pressure was higher (P <.05), whereas mean values of isovolumic contraction and relaxation indexes (dP/dt/P: P <.05; +dP/dt: P <.05; -dP/dt: P <.01) were lower in patients with ischemic cardiomyopathy. Tau was significantly longer in ischemic patients (42.7 +/- 8.8 versus 34.5 +/- 3.7 ms, P <.05). In the control patients, the aortic valve closure to peak E interval by transmitral Doppler flow was significantly longer than that measured by echo-tissue Doppler (P <.001), whereas in patients with ischemic cardiomyopathy, this interval difference was still present and significantly shorter (P <.05). In patients with coronary artery disease and normal ejection fraction, minor and early abnormalities of left ventricular function related to isovolumic contraction and relaxation as well as to longitudinal shortening could be detected. In addition, a suction-like effect, detected during early filling evaluation with echo-tissue Doppler, is significantly decreased but not abolished during the early stages of coronary artery disease.

The metabolical effects of L-carnitine in angina pectoris.

We determined the effects of L-carnitine on myocardial metabolism in 18 patients with angiographically-proven coronary artery disease, subjected to two rapid coronary sinus pacing evaluations. L-Carnitine converted lactate production to extraction and increased the percentage of free fatty acid extraction. These results suggest that L-carnitine may be of use to improve the metabolism of coronary artery disease patients.

Double orifice in prolapsing mitral valve.

A prolapsing mitral valve with a double orifice ('hole type') was documented by echocardiography in a 35-year-old male. His symptoms were associated to supraventricular ectopic beats and persisted unchanged during a 3-year follow-up. This malformation is usually considered benign but, as fragmentation of the atrioventricular conduction tissue was reported in some cases, a periodic observation is advisable.

Different effects of acute intravenous administration of k-strophanthidin and prenalterol on the diastolic phase of left ventricular function in patients with coronary arterial disease.

In 21 patients with coronary arterial disease, and with maintained (or mildly depressed) systolic function, we studied the effects of two well-known inotropic agents, namely prenalterol and k-strophanthidin, on the diastolic phase. Selected variables of both systolic and diastolic function were assessed at controlled heart rate by cardiac catheterization and left ventriculography before and after acute intravenous administration of the beta 1 agonist prenalterol (35 micrograms/kg for 3 min) and of k-strophanthidin (0.008 mg/kg for 5-10 min). Ten patients received prenalterol, and 11 patients were injected with k-strophanthidin. Administration of prenalterol induced a remarkable diminution of end-systolic volume index (mean values from 41.8 +/- 11.9 to 32.2 +/- 10.4), while k-strophanthidin showed only a tendency towards a decrease (mean values from 43.4 +/- 13.2 to 40.7 +/- 15.1). After k-strophanthidin, we did not observe any significant changes in the peaks of maximal rate in volumetric increase during filling phase whereas, after prenalterol, a noteworthy increase of the first peak was accompanied by a significant decrease of the second peak. The lowest and end filling left ventricular pressures were decreased by prenalterol (mean values from -0.8 +/- 0.1 to -2 +/- 0.5 and from 10.6 +/- 4.6 to 4.1 +/- 1.1 respectively), whereas k-strophanthidin increased left ventricular end diastolic pressure (mean values from 11.6 +/- 4.3 to 17.1 +/- 9.1). Prenalterol induced a relevant increase of ejection fraction (mean values from 0.52 +/- 0.1 to 0.61 +/- 0.008), whereas k-strophanthidin produced only a nearly significant (P less than 0.06) mild increase (mean values from 0.51 +/- 0.06 to 0.54 +/- 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of verapamil and nifedipine on rate of left ventricular relaxation in coronary arterial disease patients.

We have evaluated the effects of nifedipine and verapamil on rate of left ventricular relaxation in 26 patients having coronary arterial disease with normal ejection fraction and normal left ventricular contractility. None of the patients had myocardial infarction. All patients showed normal contractile indices and abnormally high values of T constant, neg, dP/dt and left ventricular protodiastolic pressure, suggesting an impairment of left ventricular relaxation. Nifedipine, injected intravenously (15 micrograms/kg) in 14 patients induced a significant reduction of afterload parameters and an increase of contractility. Nifedipine also improved left ventricular relaxation, as it induced a reduction of the T constant from 42 +/- 2 msec to 33 +/- 2 msec (P less than 0.01). It induced a tendency to a reduction of negative dP/dt and protodiastolic pressure without reaching statistical significance. Verapamil, injected intravenously in the remaining 12 patients (0.1 mg/kg as a bolus followed by chronic infusion of 0.005 mg/kg/min for 3 min) induced a reduction of the T constant from 43 +/- 10 to 37 +/- 6 msec (P less than 0.01). It reduced the negativity of dP/dt from 2302 +/- 273 to 2021 +/- 252 mm Hg/sec (P less than 0.05) and of left ventricular protodiastolic pressure from 3.2 +/- 1.4 to 1.5 +/- 1.1 mm Hg (P less than 0.01). Verapamil, like nifedipine, reduced the afterload parameters although to a lesser extent. It did not substantially affect the left ventricular contractility. These data suggest that abnormalities of left ventricular relaxation may precede changes in systolic function and that nifedipine and verapamil favourably modify the indices of left ventricular diastolic function in patients with coronary arterial disease.

Threshold energy dose for enzyme release after direct-current countershock.

Serial measurement of serum total creatine kinase and creatine kinase MB isoenzyme was prospectively performed by photometric assay in 82 consecutive patients (55 male and 27 female; mean age 62 +/- 11 years) after elective DC countershock for atrial flutter or fibrillation. Enzyme release is commonly observed to follow DC shock; the related energy threshold for enzyme release, however, a parameter with potential clinical usefulness, has not yet been determined. The energy dose was individually titrated but the anterolateral paddle-electrode location was used in all cases. The mean +/- S.D. (range) of shock number, peak energy level and cumulative energy dose normalized to body weight were respectively: 1.7 +/- 0.9 (1-5), 228.6 +/- 87.6 (75-400) J and 5.26 +/- 3.74 (1.0-19.7) J/kg. All these parameters had highly significant positive correlation with enzyme release (P < 0.0001), which peaked 16 h after countershock. Only creatine kinase levels changed significantly vs. baseline (P < 0.0001). As evidenced by dose vs. effect scattergram, the energy threshold value for enzyme release was around 4 J/kg for creatine kinase and 6 J/kg for creatine kinase MB isoenzyme. These energy dose figures may provide clinical usefulness to avoid unnecessary muscle damage; moreover, they may be used as a reference when enzyme elevations interfere with the diagnosis of a concomitant ischemic acute myocardial infarction.

Hemodynamic pattern following K-strophanthin in normal and coronary artery disease patients.

Hemodynamic effects of K-strophanthin (0.005 mg/kg i.v.) were evaluated in 7 normal and in 13 non-failing coronary artery disease patients (CAD). Volumetric parameters were obtained by single plane left ventricular angiography. The indexes of "pump" function, the end-systolic pressure-volume relationship and the ratio of peak pressure to systolic volume were also evaluated. Heart rate was maintained constant by atrial pacing. In normal subjects K-strophanthin exerted small effects without peripheral vasoconstriction. CAD patients showed different response to K-strophanthin in vascular tone: an increase (Group 1) or a decrease (Group 2) in total systemic resistance (TSR). No significant differences were found in basal values between the two CAD groups. In Group 2 the indexes of "pump" function increased after K-strophanthin and the end-systolic pressure-volume points shifted upward and to the left, while in Group 1 no improvement in cardiac function was observed and the end-systolic pressure-volume points shifted upward and to the right. Furthermore, we found a direct significant correlation between the percent changes of TSR and end-systolic volume index, and a negative significant correlation between the percent changes of TSR and stroke volume index. Our results show that K-strophanthin in CAD non-failing patients can have either a positive effect or a lack of improvement in ventricular performance. These effects correlate with changes in total systemic resistance.

[Cardiac injury in acute cerebral vasculopathy]. / Sofferenza cardiaca in corso di vasculopatia cerebrale acuta.

Cardiac complications, including focal myocytolysis, electrocardiographic changes, arrhythmias and left ventricular wall motion abnormalities, frequently occur following stroke and contribute to worsen the prognosis. Their clinical spectrum seems to be related to the type of cerebrovascular disease and its localization. Thus, the incidence of arrhythmias and pulmonary edema is significantly higher in subarachnoid hemorrhage than in ischemic stroke, and the lesions in the right insular cortex are a major risk for complex arrhythmias and sudden death. Elevated plasma norepinephrine levels are frequently associated with these events and strongly suggest an underlying sympathetically mediated mechanism. The autonomic and cardiovascular effects of stroke, however, are modulated by concomitant factors such as pre-existent cardiac diseases, electrolyte disorders and, probably, by genetic alterations in the ionic control of myocyte repolarization. Although beta-blockers have been reported to prevent myocardial damage following stroke, adequate clinical trials are lacking, and the widespread use of these drugs in acute cerebrovascular disease is not supported by evidence.

[Spontaneous (idiopathic) pneumopericardium. A case report and review of the literature]. / Pneumopericardio spontaneo (idiopatico). Descrizione di un caso e revisione della letteratura.

Pneumopericardium is a rare entity, but it can occur in a wide variety of clinical situations. The spontaneous cases are very rare and generally can be associated with some predisposing or precipitating conditions. We report a case in which the pathogenesis of pneumopericardium undefined after conventional diagnostic clinical investigation. A concise review of the recent literature is presented, and some practical clinical remarks are made.