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.

Early and subtle abnormalities of left ventricular function in clinically stable coronary artery disease patients with normal ejection fraction.

BACKGROUND: It has been reported that, in the initial phase of ischemic cardiomyopathy, the earliest alterations of left ventricular function are detected during the relaxation phase. The aim of this study was to look for precocious abnormalities in the early stage of ischemic cardiomyopathy in both left ventricular systolic and diastolic phases. METHODS AND RESULTS: Using simultaneous left ventricular catheterization and echo-Doppler techniques, we studied both systolic and diastolic function in 44 (37 males and 7 females, mean age 55.7+/-8) normotensive, clinically stable, coronary artery disease patients with normal left ventricular ejection fraction in comparison to 9 age- and sex-matched normal control subjects (7 males and 2 females, mean age 54.7+/-9). Mean values of E deceleration time, tau, left ventricular end-diastolic volume and pressure, and end-systolic volume and lowest diastolic pressure were significantly higher (from P<.05 to P<.01), whereas mean dP/dt/P values significantly lower (P<.05) in coronary artery disease patients than in controls. A strict relationship (P<.001) between dP/dt/P and tau, left ventricular lowest and end-diastolic pressure was found in all subjects studied. CONCLUSION: Early and subtle abnormalities in parameters of both systolic and diastolic function can be found in the majority of coronary artery disease patients with normal ejection fraction.

[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.

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.

Microalbuminuria during acute myocardial infarction; a strong predictor for 1-year mortality.

AIMS: Urinary albumin excretion increases during acute myocardial infarction but little is known on the prognostic significance and the pathophysiological mechanisms of microalbuminuria in this clinical setting. The primary aim of the study was to examine whether urinary albumin excretion has predictive power for 1-year mortality after acute myocardial infarction. A secondary objective was to gain insight into the pathophysiological mechanisms of increased urinary albumin in myocardial infarction. METHODS AND RESULTS: This is a prospective cohort study conducted in three coronary care units (Northeast Italy). Four hundred and thirty-two unselected, consecutively enrolled patients with acute myocardial infarction (66.3+/- 12.3 years of age) were studied. The incidence of mortality was related to the baseline urinary albumin:creatinine ratio. The best cut-off for total mortality approximated to 50 mg x g(-1)on the first day after myocardial infarction, 30 mg x g(-1)on the third day, and to 20 mg x g(-1)on the seventh day. At multivariable Cox analysis, the albumin:creatinine ratio was the strongest among several independent predictors of mortality (adjusted relative risks: 3.6 (95% CI, 2.1--6.2) on the first day, 4.9 (95% CI, 2.9--8.2) on the third day and 4.0 (95% CI, 2.3--6.8) on the seventh day). Independent determinants of urinary albumin were plasma aldosterone on the first day, and inflammatory markers on the third and seventh days. CONCLUSION: Urinary albumin assessed in the first week after acute myocardial infarction is a strong prognostic marker for 1-year mortality.

C-reactive protein on admission as a predictor of in-hospital death in the elderly with acute myocardial infarction.

BACKGROUND: The mean age of patients with acute myocardial infarction is increasing and the associated in-hospital mortality is exponentially age-related. Inflammation markers have been related to cardiovascular short and long-term prognosis. The aim of this study was to evaluate the short-term prognostic value of C-reactive protein (CRP) levels on admission in the oldest segment of the patients with acute myocardial infarction. METHODS: CRP was prospectively measured on admission by immunonephelometry in 205 consecutive old women (mean age 82 +/- 5 years) with definite acute myocardial infarction; values were then related to in-hospital mortality and the causes of death. RESULTS: CRP levels ranged from 0.1 to 31.9 mg/dl and were raised in 71% of the patients. It showed no significant correlation with baseline clinical variables such as age, history of diabetes or hypertension or prior myocardial infarction, infarct location, and time from symptom onset to admission. The overall in-hospital mortality rate was 25% and rose from 15% among patients in the lower three quartiles of CRP levels (cut point 6.4 mg/dl) to 55% among those in the upper quartile (p < 0.001). By univariate logistic-regression, the odds ratio for early death was 0.84 (95% confidence interval 0.78-0.89) for every increase by 1 mg/dl of CRP, and 5.7 (95% confidence interval 2.7-11.9) for a CRP level in the upper quartile. Multivariate analysis demonstrated the independence of the relation between CRP levels and in-hospital mortality (p = 0.0001). No significant differences in CRP level were found among deceased patients classified by cause of death (heart rupture 44%, pump failure 41%, comorbidity 5%). CONCLUSIONS: CRP concentration is raised in many old patients with acute myocardial infarction and seems to independently stratify patients for in-hospital mortality risk. This prognostic information may assist in providing the appropriate level and duration of close monitoring and be an additional support to evaluate the risk-benefit ratio of thrombolytic therapy in some cases.

Aortic intramural hematoma: an increasingly recognized aortic disease.

Aortic intramural hematoma (IMH) is a rarely diagnosed pathological condition that is not well characterized to date. We diagnosed IMH in 4 of 31 patients with suspected aortic dissection admitted to our coronary care unit from 1992 to 1995. In all 4 cases, IMH was located in the ascending aorta. At the time of hospitalization, all patients showed tachycardia, hypotension and pericardial effusion. Diagnosis of IMH was made by transesophageal echocardiography and computed tomography. We performed aortography in 2 patients, but it was non-diagnostic in both of them. One patient died before surgery. Autopsy confirmed the diagnosis of IMH and showed severe pericardial effusion. In another patient, the diagnosis was confirmed during successful surgery, while the remaining 2 patients recovered after medical therapy. The 3 surviving patients are still under follow-up control 12, 16 and 20 months after the initial acute event. We briefly discuss the epidemiological, clinical, diagnostic, therapeutic and prognostic aspects of IMH.

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.

Left ventricular false aneurysm: an unusually prolonged natural history.

A case of left ventricular false aneurysm of postinfarctual etiology with an unusually prolonged natural history (12 years survival) is reported. A first diagnosis of this rare cardiac complication was made in 1982 on the basis of hemodynamic and echocardiographic results. At that time the patient rejected surgical therapy. Eleven years later the patient came back to our attention after resuscitation from a sudden cardiac death. Hemodynamic and echocardiographic (transesophageal) tests showed a remarkable impairment of left ventricular function and an abnormal enlargement (10 x 8 cm) of a pseudoaneurysmatic cavity full of thrombi. The patient died suddenly in April 1994. We emphasize the unusual, prolonged survival of our patient suffering from an unresected left ventricular false aneurysm of postinfarctual etiology.

[Urinary albumin excretion increases during an acute myocardial infarct especially in patients who develop heart failure]. / L'escrezione urinaria di albumina aumenta durante infarto miocardico acuto soprattutto nei pazienti che sviluppano insufficienza cardiaca.

AIM OF THE STUDY: To evaluate the profile of albumin excretion rate (AER) in the first days of acute myocardial infarction (AMI), its relationship with serum enzymes and the presence of heart failure, and the effect of thrombolytic therapy. METHODS: Two hundred and thirty-one consecutive patients admitted to coronary care unit for suspected AMI were examined. Patients with diabetes mellitus, urinary tract infections or proteinuric diseases were excluded. In 135 patients (95 males, 40 females) AMI diagnosis was confirmed. The remaining 96 (56 males, 40 females) were considered as controls. AER was measured by radioimmunoassay in 24-hour urine samples at the first, third and seventh day after admission and expressed as mg/24h. Statistical analysis was performed after AER logarithmic transformation using repeated measure ANOVA: RESULTS: Mean age was 66.9 +/- 12.2 years (range = 35 -91) in the AMI group and 63.2 +/- 12.3 years (range = 33-91) in the controls (p = 0.023) Age-adjusted blood pressure was lower in the AMI group than in the controls (p < 0.0001 for both systolic and diastolic), while no difference was found in heart rate. Plasma cholesterol, triglycerides, creatinine and uric acid were similar in the 2 groups. Mean AER was 43.4 +/- 64.8, 26.9 +/- 51.2 and 23.9 +/- 52.7 mg/24h at 1st, 3rd and 7th day respectively in the AMI group and 24.9 +/- 58.2, 13.7 +/- 25.8 and 17.9 +/- 44.1 mg/24h respectively in the controls (p = 0.014). In the AMI group, first day AER significantly and positively correlated with CPK (r = 0.287, p = 0.001), CPK-MB (r = 0.239, p = 0.007) and GOT (r = 0.300, p = 0.001). Within the patients with AMI, those who developed heart failure (n = 57), had higher AER (48.6 +/- 68.4, 29.7 +/- 54.9 and 28.1 +/- 55.8 mg/24h at 1st, 3rd and 7th day in patients with mild heart failure -2nd Killip Class- and 100.0 +/- 141.7, 50.3 +/- 66.4 and 64.2 +/- 74.4 mg/24h in those with severe heart failure -3rd and 4th Killip Class-) than those who did not (31.0 +/- 41.7, 19.6 +/- 45.6 and 16.5 +/- 45.7 mg/24h respectively) (p = 0.004). In a multiple linear regression model AER was significantly related to peak values of GOT (1st day) and CPK (3rd day) and to presence of heart failure (3rd and 7th day). Thrombolytic therapy (n = 48) did not influence AER. CONCLUSIONS: The results of the present study show that AER increases following AMI, chiefly in the subjects who develop heart failure. AER correlates with serum enzymes peak levels at 1st and 3rd day and with presence of heart failure at 3rd and 7th day after admission, and is not influenced by thrombolytic therapy. These data suggest that in AMI the initial increase in AER is due to the inflammatory process which accompanies cardiac necrosis, while in a later phase its rise is mainly due to the increased intraglomerular capillary pressure consequent to heart failure.

[Recent morphofunctional findings on the left atrium: their relations to thromboembolic risk]. / Recenti acquisizioni morfo-funzionali sull'auricola sinistra: rapporti con il rischio tromboembolico.

In the past, the left atrial appendage has been considered a "useless" structure but associated to thromboembolic complications; its physiologic role is still undefined. Owing to its great distensibility, left atrial appendage positively influences atrial compliance and left ventricular performances. In addition this structure seems to play an important role in circulatory homeostasis by the release of atrial natriuretic factor in response to volume loading and atrial stretch. Transesophageal echocardiography provides a detailed anatomical characterization of this structure and, by means of Doppler flow velocities recordings, supplies relevant functional data. Despite their anatomical contiguity, the left atrium and atrial appendage result from a separate embryonic development; likewise, their function may differentiate. In the left atrial appendage a quadriphasic flow pattern has been described in subjects with sinus rhythm; however, as we reported, in some patients a more complex Doppler pattern can be observed, with an additional systolic forward flow wave which is presumably due to reflection phenomena. In patients with atrial fibrillation, an irregular flow pattern has been detected, which is mostly dependent on the duration of the arrhythmia, the underlying heart disease and the left atrial pressure. By transesophageal echocardiography a clear correlation has been established between the left atrial appendage slow flow and the occurrence of thromboembolic events; however, while waiting data from large studies, stratification of patients according to thromboembolic risk and decisions about anticoagulant prophylaxis should be performed by clinical information and transthoracic echocardiographic findings. No clinical or echocardiographic parameter has been found to be predictive of the thromboembolic events after cardioversion; in this setting the exclusion of atrial or atrial appendage thrombi by transesophageal echocardiography does not rule out the need for anticoagulation in patients with atrial fibrillation undergoing electrical or pharmacological cardioversion.

Do inotropic drugs always induce a positive lusitropic effect? A comparison between k-strophanthidin and dobutamine in patients with coronary artery disease.

The interaction between systolic and diastolic effects of inotropic drugs is an important subject which has not yet been fully clarified in the cardiological literature. The effects of the inotropic drugs k-strophanthidin and dobutamine on left ventricular (LV) relaxation and early filling phase were compared in patients with coronary artery disease (CAD) and preserved systolic function. Twenty-two patients were randomly divided into two groups; group I was infused with 0.0035 mg.kg-1 of k-strophanthidin for 10 min and group II with dobutamine at a rate of 10 micrograms.kg-1.min-1 for 10 min. Both groups underwent simultaneous haemodynamic and echo 2D-Doppler evaluations at controlled heart rate. K-strophanthidin improved contractility indexes (peak of LV systolic pressure P < 0.001, max dP/dt + P < 0.05 and dP/dt P < 0.01) and worsened T constant and LV lowest diastolic pressure, (LVLDP) (P < 0.001 and P < 0.05 respectively) without changing early transmitral filling parameters. Dobutamine induced a significant increase in contractility in group II but at the same time significantly improved LV relaxation variables (max dP/dt - P < 0.01 and T constant P < 0.001). In addition, dobutamine reduced LVLDP (P < 0.05) and significantly increased LV early filling parameters. These results show that an acute administration of either k-strophanthidin or dobutamine enhances contractility, whereas these drugs have the opposite effect on the early diastolic phase.

How do calcium antagonists differ in clinical practice?

The majority of calcium antagonists used clinically belong to three distinct chemical classes: the phenylalkylamines, the dihydropyridines, and the benzothiazepines. In recent years their mode of action has been unravelled, their limitations recognized, and their efficacy and use in the management of patients with a broad spectrum of cardiovascular and other disorders defined. It is clear, however, that these drugs are not all alike, providing an explanation for their differing effects. The final therapeutic effect in humans depends on the mechanisms of action at the molecular level, the tissue selectivity, and the hemodynamic changes of each agent. All these aspects are examined in detail in this article. Concepts that are highlighted are as follows: (a) Molecular biology has allowed recognition of the polypeptide components of the alpha 1 subunit of the L-type Ca2+ channel and the finding of peptide segments covalently labelled by all three classes of drugs. (b) The location of these segments within the peptides is different: Binding sites for dihydropyridines are located externally, whereas those for verapamil and diltiazem are located internally, in the cytosolic part of the membrane. (c) Dihydropyridine binding is voltage dependent. This explains the selectivity of this class of drugs for vascular smooth muscle, which is more depolarized than cardiac muscle. (d) Phenylalkylamines and benzothiazepines reach their receptors at the internal surface of the sarcolemma through the channel lumen. Their binding is facilitated by the repetitive depolarization of atrioventricular and cardiac tissue, a phenomenon described as use dependence. This explains why these drugs are not highly selective, but equipotent for the myocardium, the atrioventricular conducting tissue, and the vasculature. (e) Dihydropyridines act through selective vasodilatation and may increase heart rate and contractility via a reflex mechanism. On the contrary, phenylalkylamines and diltiazem act through a combination of effects, including reduction of afterload, heart rate, and contractility. When taken together, all these differences distinguish the preferential clinical utilization of one of these compounds for a given cardiovascular pathology.

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)

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.