Myocarditis after administration of clozapine.

OBJECTIVE: Clozapine is an atypical antpsychotic medication with established efficacy in patients diagnosed of resistant schizophrenia. However, clozapine has multiple side effects. Cardiac complications such as myocarditis and cardiomyopathy have always been related with treatment with clozapine. METHODS: A 42 year old Caucasian male, with history of schizophrenia developed a acute myocarditis after commencement of clozapine. RESULTS: The patient recovered with intensive medical support. The symptoms occurred approximately 20 days after starting clozapine. CONCLUSIONS: Myocarditis is an ingreasingly recognized complication associated with clozapine. Use of clozapine must be based on a balance of its risks and benefits on an individual basis which for the most part defines its use in treatment refractory schizophrenia. Appropriate monitoring of adverse events is an essential part of the clinical usage of clozapine and should be charted for at least two years.

Heart rate effect on hemodynamics during mechanical assistance by the intra-aortic balloon pump.

UNLABELLED: Heart rate (HR) has been characterized as an important cardiovascular parameter that affects acute hemodynamic performance of intra-aortic balloon counterpulsation (IABC). However, the effect of HR on hemodynamics during mechanical assistance by the IABC has neither been clarified nor quantified. We sought to evaluate the relationship between IABC and HR and also to examine whether there is a range of HR with optimum hemodynamic response to IABC. METHODS: 20 patients (14 males--6 females, mean age 64.4 +/- 11.4 years) with post-infarction cardiogenic shock undergoing IABC treatment were evaluated. Hemodynamics were recorded for each patient once per day during the assistance period; 131 measurements were taken and thus a wide range of heart rates was obtained (64-141 bpm). The following changes in aortic pressures were used to evaluate acute IABC performance on: a) the maximal increase of diastolic aortic pressure induced by IABC and b) the reduction in systolic and end-diastolic aortic pressure. RESULTS: Non-linear regression analysis and analysis of variance revealed that a significant correlation exists between IABC performance indices and heart rate. At HR<80 bpm, IABC performance tended to be reduced, whereas the increase in HR above 110 bpm resulted in a significant reduction of all IABC performance indices. In contrast, IABC operating at 80-110 bpm resulted in optimum hemodynamic performance. In conclusion, the effect of heart rate on IABC performance is non-linear indicating that IABC may be more effective when operating within 80-110 bpm.

Arterial compliance is an independent factor predicting acute hemodynamic performance of intra-aortic balloon counterpulsation.

Data concerning the effect of arterial compliance (AC) on hemodynamics during intraaortic balloon counterpulsation (IABC) are lacking. This study examines the effect of AC on acute hemodynamics induced by IABC in 15 patients with post-infarction cardiogenic shock. AC was estimated by aortic pulse wave analysis using the reflection time index (RTI). Measurements were obtained once per day during IABC. The % reduction in systolic aortic pressure (ASAP), end-diastolic aortic pressure (AEDAP) and the peak aortic diastolic augmentation (PADA) were used as performance indices of IABC; 107 sets of measurements were obtained. Multivariate analysis indicated an independent association of each IABC performance index with AC (p<0.05). A high AC group (RTI< or =20.6%, n=40) and a low AC group (RTI>20.6%, n=67) were obtained. DeltaSAP deltaEDAP and PADA were significantly higher in the low AC group by almost 75%, 54.6% and 11.3% (p<0.03), while arterial blood pressure did not significantly differ. Arterial compliance is an independent factor affecting hemodynamics during IABC. RTI values higher than 20.6% may predict a better acute hemodynamic response to IABC.

Correlation and stability of heart rate and ventricular ectopy variability in patients with congestive heart failure.

The stability of indexes of heart rate variability and their possible association with spontaneous variability of ventricular ectopy was examined in 13 patients with advanced congestive heart failure over 14 consecutive days of 24-hour ambulatory electrocardiographic recording. It was found that time and frequency domain measures of heart rate variability are stable over time and are inversely correlated with spontaneous variability of ventricular ectopy.

Pulse pressure in normotensives: a marker of cardiovascular disease.

The purpose of the present study was to evaluate the relation of the systemic arterial pulse pressure and other parameters derived from the 24-h arterial blood pressure (BP) monitoring to the severity of coronary artery disease, carotid lesions, and left ventricular (LV) mass index in patients without arterial hypertension. One hundred ten patients with known coronary artery disease underwent coronary arteriography, 24-h arterial BP monitoring, and ultrasound imaging of the carotid arteries and the myocardium. Measurements of 24-h arterial BP monitoring (systolic, diastolic, and average BP, pulse pressure, abnormal values of systolic and diastolic BP, and heart rate), the severity of coronary heart disease (Gensini score), intima-media thickness (IMT) of the common carotid artery and LV mass index were determined in all patients. By univariate analysis, only 24-h pulse pressure was significantly related to the severity of coronary artery disease (P < .01), carotid IMT(P < .01), and LV mass index (P < .01). In a multivariate analysis, 24-h pulse pressure was also the best predictor of the severity of coronary lesions (P = .009), carotid IMT (P = .003), and LV mass index (P = .009). Gensini score was related (P < .01) to LV mass index and not to carotid IMT. In conclusion, systemic arterial pulse pressure derived from 24-h arterial BP monitoring is related to coronary artery disease, carotid IMT, and LV mass index independently of age or any other derivative of 24-h arterial BP monitoring, indicating that this parameter could be a marker of global cardiovascular risk.

Ankle-brachial index as a predictor of the extent of coronary atherosclerosis and cardiovascular events in patients with coronary artery disease.

Resting ankle-brachial pressure index (ABI) is a noninvasive method to assess the patency of the lower extremity arterial system. This study aimed to examine the relation between ABI and the extent of coronary atherosclerosis, the extracoronary atherosclerosis lesions, and the prognosis of patients referred for elective coronary angiography. One hundred sixty-five consecutive patients underwent coronary angiography, ultrasound imaging for intima-media thickness measurement of carotid and femoral arteries and ABI evaluation; subjects were followed up for 14.5 +/- 2.4 months. With regard to vascular risk factors, only smoking (p = 0.025) and diabetes (p = 0.01) were related to ABI in the multiple regression analysis. ABI was independently and inversely related to carotid bifurcation (p = 0.0002) and common femoral artery intima-media thickness (p = 0.018). ABI was related to the extent of coronary artery disease as measured by number of coronary arteries diseased (analysis of variance, p = 0.04) and Gensini angiographic score (p = 0.01). In the follow-up study ABI < 0.90 was a univariate predictor of cardiovascular events (cardiac death, nonfatal myocardial infarction, unstable angina) and revascularization procedures. The estimated cumulative rate free of cardiovascular events was 90% for ABI > 0.90 and 73% for ABI < 0.90 (p = 0.02). In logistic regression analysis, ABI < 0.90 was an independent predictor for cardiovascular events after adjustment for age, low-density lipoprotein cholesterol, carotid and femoral intima-media thickness, and Gensini score. Further adjustment for the confounding effect of insulin weakened the relation between ABI and cardiovascular events (p = 0.1). In conclusion, ABI is a simple index related to the extent of atherosclerosis in coronary and noncoronary arterial beds, reflecting generalized atherosclerosis. ABI could be useful in assessing the risk for cardiovascular events in patients with coronary artery disease.

Atherosclerotic changes of extracoronary arteries are associated with the extent of coronary atherosclerosis.

The aim of the present study was to examine the association between carotid and femoral artery intima media thickness (IMT) and the extent and severity of coronary artery disease (CAD) as well as the effects of traditional vascular risk factors on the atherosclerotic changes in the carotid and femoral arteries. Two hundred twenty-four patients who underwent coronary angiography for suspected CAD were evaluated by B-mode ultrasound imaging of the common carotid, internal carotid, carotid bifurcation, and femoral artery for measurement of IMT; traditional vascular risk factors were also evaluated in these patients. CAD extent was evaluated by the number of diseased vessels and by Gensini score. Age, male gender, and diabetes were common risk factors for higher CAD extent and higher carotid and femoral IMT. Insulin levels were correlated with femoral IMT and CAD extent, whereas blood lipids were correlated predominantly with carotid IMT. IMT from carotid and femoral arteries increased significantly with an increase in CAD extent. Using multiple stepwise regression analysis, the following parameters were found to be independent predictors of CAD extent: male gender (p<0.0001), common femoral artery IMT (p = 0.0028), common carotid artery IMT (p = 0.015), age (p = 0.02), diabetes mellitus (p = 0.035), and carotid artery bulb IMT (p = 0.04). Common femoral IMT was the only independent parameter for predicting Gensini score (p<0.0001). In conclusion, there are territorial differences in the various arterial beds regarding their response to risk factors. Femoral artery and carotid bulb are independent predictors of CAD extent and the inclusion of these measurements would add information to that provided by the common carotid artery.

Respiratory muscles performance is related to oxygen kinetics during maximal exercise and early recovery in patients with congestive heart failure.

BACKGROUND: Dyspnea and fatigue are the main causes of exercise limitation in chronic heart failure (CHF) patients, whose peak inspiratory (Pi(max)) and expiratory pressures (Pe(max)) are often reduced. The aim of this study was to examine the relationship between respiratory muscle performance and oxygen kinetics. METHODS AND RESULTS: A total of 55 patients (NYHA class I to III) and 11 healthy subjects underwent cardiopulmonary exercise tests (CPET) on a treadmill. In 45 of the 55 patients (group I) and in healthy subjects (group II), pulmonary function tests, Pi(max), and Pe(max) were measured before and 10 minutes after exercise, and oxygen kinetics were monitored throughout and during early recovery from CPET. The first degree slope of oxygen consumption (VO(2)) decline during early recovery (VO(2)/t-slope) and VO(2) half-time (T(1/2)) were calculated. In 10 of the 55 CHF patients (group III), the measurements of Pi(max) were repeated 2, 5, and 10 minutes after CPET. A >10% reduction in Pi(max) after CPET (subgroup IA) was measured in 11 of 45 patients. In contrast, 34 of 45 CHF patients (subgroup IB) and all control subjects (group II) had Pi(max)>90% of baseline value after CPET. Subgroup IA patients had significantly lower peak VO(2) (13.5+/-2.1 versus 17.8+/-5.6 mL. kg(-1). min(-1); P<0.001), lower anaerobic thresholds (10.1+/-2.4 versus 13.6+/-4.6 mL. kg(-1). min(-1); P=0.003) and lower VO(2)/t-slopes (0.365+/-0.126 versus 0.519+/-0.227 L. min(-1). min(-1); P=0.008) than subgroup IB patients. CONCLUSIONS: The reduction of Pi(max) after exercise is associated with prolonged early recovery of oxygen kinetics, which may explain, in part, the role played by respiratory muscles in exercise intolerance in CHF patients.

Contraction-excitation feedback in human atrial fibrillation.

BACKGROUND: Contraction-excitation feedback, that is, electrophysiologic changes that are caused or preceded by mechanical changes of the myocardium, has been extensively studied in the ventricles. The role of contraction-excitation feedback in the atria, and more particularly in the genesis and maintenance of atrial fibrillation, has been less adequately investigated. HYPOTHESIS: The aim of the present study was to determine whether increased right atrial pressure (RAP) facilitates the induction of atrial fibrillation (AF) in patients with a history of lone AF. METHODS: Sixteen patients with a history of paroxysmal AF but without structural heart disease were included in the study. All patients underwent electrophysiologic study at both a lower (3.1 +/- 2.0 mmHg) and (in 13 cases) a higher (6.4 +/- 2.5 mmHg) RAP. "Higher" was considered the pressure following rapid (in about 30 min) intravenous administration of normal saline or before the administration of a diuretic. RESULTS: Rapid atrial pacing induced AF in 19 of 29 attempts. At a lower pressure, rapid pacing induced brief (3 s to 3 min) AF in 3 of 16 patients, long-lasting (> 3 min) AF in 3 of 16 patients, and no AF in 10 of 16 patients. At a higher pressure, brief AF was induced in 3 of 10 patients in whom no AF could be induced at a lower pressure, and long-lasting AF in 10 patients in whom either brief AF (3 cases) or no AF (7 cases) was induced at a lower pressure. In 11 patients, in whom Wenckebach periodicity was determined at both higher and lower pressure, the critical cycle length at which atrioventricular block appeared was significantly (p < 0.001, paired t-test) longer (349.1 +/- 44.4 ms, i.e., +15.5 +/- 11.3 ms) at higher than at lower atrial pressure (333.6 +/- 41.0 ms). In nine patients, in whom Wenckebach periodicity was determined and two rhythms occurred at different pressures, the critical cycle length was 332.2 +/- 45.8 ms when associated with sinus rhythm, and significantly (p < 0.01) longer (344.4 +/- 48.0 ms, i.e., +12.2 +/- 8.3 ms) when associated with induction of AF. CONCLUSION: In patients with lone atrial fibrillation, modest increases in atrial pressure may facilitate the induction of atrial fibrillation.

Catecholamine infusion versus intraaortic counterpulsation at the initial phase of left intraventricular balloon pumping in the fibrillating animal heart.

This experimental study compares the effect of catecholamine infusion to the effect of intraaortic counterpulsation (IABP) while initiating intraventricular balloon pumping (IVBP) in the fibrillating heart. In 12 dogs IVBP started immediately after the induction of ventricular fibrillation. Intravenous adrenaline or noradrenaline (at a progressively increasing infusion rate until the systolic aortic blood pressure was 120 mm Hg) was interchanged with IABP. The systolic aortic pressure, the aortic flow and the mean left atrial pressure were, respectively, 120.4 +/- 0.5 mm Hg, 42 +/- 4 ml kg-1 min-1 and 18.7 +/- 1.2 mm Hg (x +/- SEM) ten min after initiating catecholamine infusion and 97 +/- 5 mm Hg (with a 131 +/- 4 mm Hg diastolic wave), 69.6 +/- 4 ml kg-1 min-1 and 16 +/- 1.5 mm Hg ten min after initiating IABP. The difference in aortic flow was significant (p < 0.001). The results indicate that a better aortic flow may be obtained by combining IVBP and IABP than IVBP and vasoconstrictive agents in the fibrillating heart. If IVBP, IABP and catecholamines are combined, both AF and AP may increase.

Effect of acute blood pressure changes on signal averaged electrocardiogram.

An acute blood pressure elevation may cause ventricular ectopic rhythms, while its reduction may alleviate them. It is studied whether the blood pressure exerts some effect on parameters obtained by the signal averaged electrocardiogram. In 25 patients with either hypertension (8 cases) or ventricular ectopic rhythms (10 cases) or both (7 cases) the blood pressure was reduced by sodium nitroprusside (24 cases) and/or elevated with metaraminol (10 cases) and the signal averaging electrocardiogram was recorded under 2 or 3 pressure values on each patient. During the high pressure (193.6 +/- 20.1 mm Hg) the following differences were noted compared to the low pressure (77.4 +/- 15.2 less): longer QRS duration in all 25 patients (+9.92 +/- 10.51 ms, P < 0.001); longer low (< 40 microV) amplitude signals (LAS) in 18 patients (+6.94 +/- 10.93 ms, P < 0.005); lower root mean square voltage of the terminal 40 ms of the QRS in 22 patients (-15.73 +/- 21.60 microV, P < 0.005); and ventricular ectopic beat incidence higher in 8, lower in 1, and equal in 2 cases (with no arrhythmia in the other 14). The generally and focally reduced conduction, as suggested by the QRS and LAS prolongation, might contribute to the proarrhythmic effect of acute blood pressure elevation.

Effect of 24-hour blood pressure and heart rate variations on left ventricular hypertrophy and dilatation in essential hypertension.

This study correlates variables derived from blood pressure (BP) and heart rate (HR) monitoring with the degree of left ventricular structural changes in essential hypertension. Forty patients with mild-to-moderate hypertension according to World Health Organization criteria underwent 24-hour ambulatory monitoring. Echocardiographic (posterior wall and interventricular septum thickness, left ventricular mass) or ECG (SV1 + RV5) indices of hypertrophy were significantly (p less than 0.01) correlated (positive correlations) with derivatives of BP monitoring (mean systolic and diastolic BP values) but not with HR derivatives. Echocardiographic indices of dilatation (left ventricular end-diastolic volume and diameter) were significantly (p less than 0.01 to less than 0.001) correlated (negative correlations) with derivatives of HR monitoring (mean HR values, mainly during the night) but not with BP derivatives. It is concluded that in essential hypertension, left ventricular hypertrophy depends on mean 24-hour systolic and diastolic BP values, whereas left ventricular dilatation appears to be more prominent in patients with bradycardia mainly during the night.

Intraventricular plus intra-aortic balloon pumping during intractable cardiac arrest.

A method is presented for maintaining aortic flow by mechanical means during intractable cardiac arrest. A spherical balloon was inserted into the left ventricle while the usual intra-aortic balloon was introduced into the thoracic aorta. Ventricular fibrillation was induced by direct current. The pumps operating the two balloons were adjusted to inflate the intraventricular balloon during one third of the pumping cycle and the intra-aortic balloon during the next two thirds of the same cycle. The intraventricular balloon capacity varied from 40 to 110 ml (six dogs weighing 16-24 kg) while the intra-aortic balloon capacity was 20 ml. An optimal pumping rate of 75 beats/min maintained an aortic flow of 0.9-1.5 ml/beat/kg and a mean pressure into the brachiocephalic trunk of 110 +/- 12.5 mm Hg (mean +/- SD). These experimental data indicate that an easily applied mechanical device system (needing no extracorporeal circulation) may be used to bridge the time between intractable cardiac arrest and implantation of an artificial heart or transplantation.