Variations In Cardiac Function Research Articles

Correlation Analysis of Activity Levels and Risk Factors in Patients with Stroke: Variations in Cardiac Function According to the Longshi Scale.

This study examined the link between physical activity levels, as measured by the Longshi Scale, and cardiac function and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in stroke patients, aiming to find correlations with stroke risk factors. The study involved 123 apoplexy patients divided into four groups based on the Longshi Scale: bedridden (31), domestic (32), community (30), and health (30). Clinical data was collected, and hemodynamic assessments were performed using impedance cardiography. Cardiac output time index (CTI) and estimated ejection fraction (EF est) were significantly reduced in both the domestic and community groups compared to the health group (P < 0.05), while diastolic arterial blood pressure (DABP) and systemic vascular resistance index (SVRi) were increased. In the bedridden group, stroke volume (SV), cardiac output (CO), CTI, left cardiac work index (LCWi), and EF est were all lower compared to the health group (P < 0.05), with SVRI and NT-proBNP levels being higher. Additionally, the bedridden group exhibited lower SV, CO, DABP, LCWi, CTI, and EF est when compared to the domestic and community groups (P < 0.05), but higher end-diastolic filling rate (EDFR) and NT-proBNP levels. The Longshi Scale grading positively correlated with SV (r = 0.536, P < 0.01), and NT-proBNP, EF, and cognitive dysfunction were found to be associated with activity levels in stroke patients. The Longshi Scale correlates with cardiac function indicators like NT-proBNP and EF, and can help identify stroke patients at risk of cardiac dysfunction. Moreover, cognitive dysfunction was identified as a significant factor influencing the range of activity in patients with stroke.

Intrinsic cardiac neurons as the consulate general of the brain in the heart: A review

Contrary to the prevailing understanding about one-way communication from brain to heart, recent research has unveiled a two-way communication pathway between these two organs, featuring the delivery of signals from the cardiac afferents to the brain. While the medulla oblongata is known to send autonomic signals for cardiac function regulation, 80% of the vagal afferents send signals to the brain for cardiac regulation. The vagus nerve receives these signals from the intrinsic cardiac neurons, often referred to as &amp;ldquo;the little brain of the heart.&amp;rdquo; Intrinsic cardiac neurons are neuronal structures with the same biochemical profile as neurons, communicating with the vagus nerve through acetylcholine and expresses markers of neuronal function such as tyrosine hydroxylase and others. Intrinsic cardiac neurons also influence the autonomic system, which can be studied through heart-rate variability measures. Heart rate variability (HRV) is altered in many types of cardiac disorders and is a well-known measure for studying short- and long-term disease-related variations in cardiac function. Some psychiatric disorders such as post-traumatic stress disorder, schizophrenia, and major depression also exhibited alterations in HRV. HRV is related to heartbeat-evoked potentials (HEPs) and electrical potentials in the brain that are influenced by the heart. HEPs are altered in disease states and can be impacted by environmental factors. This paper reviews the existing literature concerning intrinsic cardiac neurons and their possible role in heart-brain communication.

Genetic architecture of natural variation of cardiac performance from flies to humans.

Deciphering the genetic architecture of human cardiac disorders is of fundamental importance but their underlying complexity is a major hurdle. We investigated the natural variation of cardiac performance in the sequenced inbred lines of the Drosophila Genetic Reference Panel (DGRP). Genome-wide associations studies (GWAS) identified genetic networks associated with natural variation of cardiac traits which were used to gain insights as to the molecular and cellular processes affected. Non-coding variants that we identified were used to map potential regulatory non-coding regions, which in turn were employed to predict transcription factors (TFs) binding sites. Cognate TFs, many of which themselves bear polymorphisms associated with variations of cardiac performance, were also validated by heart-specific knockdown. Additionally, we showed that the natural variations associated with variability in cardiac performance affect a set of genes overlapping those associated with average traits but through different variants in the same genes. Furthermore, we showed that phenotypic variability was also associated with natural variation of gene regulatory networks. More importantly, we documented correlations between genes associated with cardiac phenotypes in both flies and humans, which supports a conserved genetic architecture regulating adult cardiac function from arthropods to mammals. Specifically, roles for PAX9 and EGR2 in the regulation of the cardiac rhythm were established in both models, illustrating that the characteristics of natural variations in cardiac function identified in Drosophila can accelerate discovery in humans.

Proposal of a novel protocol using estimated cardiac index fractional dose to improve aortic contrast enhancement for early-phase dynamic CT.

Maximum aortic computed tomography value (CTV) is difficult to control because of variations in cardiac function and patient physique. Therefore, to improve early-phase aortic enhancement on dynamic computed tomography (CT), we developed an estimated cardiac index fractional dose (eciFD). The eciFD protocol is a novel and original protocol for administering fractional dose (FD), representing the amount of iodine per unit body weight per injection duration, based on cardiac index (cardiac output divided by body surface area) as estimated by age in early-phase dynamic CT. At the time of administration, by selecting FD based on the patient's age and selecting a parameter that can achieve this FD, an aortic CTV ≥300 HU (ACTV≥300) can be obtained. This study aimed to investigate aortic enhancement on CT angiography using the eciFD protocol.This retrospective study investigated 291 consecutive patients who underwent dynamic CT from neck to abdomen after recommendation of the eciFD protocol at our institution. We compared early-phase aortic CTV distributions by scan delay between an eciFD group (eciFD applied, n = 135) and a non-eciFD group (eciFD not applied, n = 80). The effect of eciFD on early-phase ACTV≥300 was evaluated using logistic regression analysis adjusted for several potentially meaningful clinical confounders related to aortic CTV, namely male sex, heart rate ≤80 beats/min, estimated glomerular filtration rate ≤40 mL/min, use of eciFD, bolus tracking (BT), history of myocardial infarction, and order from the emergency center.The eciFD protocol was a significant factor for early-phase ACTV≥300 after adjusting for several confounders (odds ratio 3.03; 95% confidence intervals 1.59–5.77; P = .001). No interaction was seen between BT and eciFD protocol (p for interaction = 0.76). In terms of CTV distribution, with both a fixed scan delay time and BT, the eciFD group showed a high aortic CTV. The combination of eciFD protocol with BT provided a particularly high percentage of patients with ACTV≥300 (86.4%).The eciFD protocol was useful for improving aortic contrast enhancement. These findings need to be validated in a randomized controlled study.

Characterization of the Insular Role in Cardiac Function through Intracranial Electrical Stimulation of the Human Insula

The link between brain function and cardiovascular dynamics is an important issue yet to be elucidated completely. The insula is a neocortical brain area that is thought to have a cardiac chronotropic regulatory function, but its role in cardiac contractility is unknown. We aimed to analyze the variability in heart rate and cardiac contractility after functional activation of different insular regions through direct electrical stimulation (E-stim) in humans. This was an observational, prospective study, including patients admitted for stereo-electroencephalographic recording because of refractory epilepsy, in whom the insular cortex was implanted. Patients with anatomical or electrophysiological insular abnormalities and those in whom E-stim produced subjective symptoms were excluded. Variations in heart rate (HR), stroke volume (SV), and cardiac output (CO) were analyzed during insular E-stim and compared with control E-stim of non-eloquent brain regions and sham stimulations. Ten patients were included, 5 implanted in the right insula (52 E-stim) and 5 in the left (37 E-stim). Demographic and clinical characteristics of both groups were similar. E-stim of both right and left insulas induced a significant decrease of the CO and HR, and an increase of the SV. E-stim of control electrodes and sham stimulations were not associated with variations in cardiac function. Blood pressure and respiratory rate remained unaltered. Our results suggest a direct chronotropic and inotropic cardiac depressor function of the right and left insulas. The evidence of an insular direct cardiac regulatory function might open a path in the prevention or treatment of heart failure, arrhythmias, and sudden unexpected death in epilepsy. ANN NEUROL 2021;89:1172-1180.

Hydrogen Sulfide Restored the Diurnal Variation in Cardiac Function of Aging Mice.

The present study was performed to investigate whether H2S could restore the diurnal variation in cardiac function of aging mice and explore the potential mechanisms. We found that ejection fraction (EF) and fractional shortening (FS) in 3-month-old mice exhibited diurnal variations over a 24-hour period. However, the diurnal variations were disrupted in 18-month-old mice, and there was a decline in EF and FS. In addition, the plasma malondialdehyde (MDA) levels were increased, and H2S concentrations and superoxide dismutase (SOD) activities were decreased in 18-month-old mice. Then, CSE KO mice were used to determine if there was a relationship between endogenous H2S and diurnal variations in EF and FS. There was no difference in 12-hour averaged EF and FS between dark and light periods in CSE KO mice accompanying increased MDA levels and decreased SOD activities in plasma, indicating that deficiency of endogenous H2S blunted diurnal variations of cardiac function. To determine whether oxidative stress disrupted the diurnal variations in cardiac function, D-galactose-induced subacute aging mice were employed. After 3-month D-gal treatment, both 12-hour averaged EF and FS in dark or light periods were decreased; meanwhile, there was no difference in 12-hour averaged EF and FS between dark and light periods. After 3-month NaHS treatment in the D-gal group, the plasma MDA levels were decreased and SOD activities were increased. The EF and FS were lower during the 12-hour light period than those during the 12-hour dark period which was fit to sine curves in the D-gal+NaHS group. Identical findings were also observed in 18-month-old mice. In conclusion, our studies revealed that the disrupted diurnal variation in cardiac function was associated with increased oxidative stress and decreased H2S levels in aging mice. H2S could restore the diurnal variation in cardiac function of aging mice by reducing oxidative stress.

Incorporation of the Living Heart Model into the 4D XCAT Phantom for Cardiac Imaging Research.

The 4D extended cardiac-torso (XCAT) phantom has provided a valuable tool to study the effects of anatomy and motion on medical images, especially cardiac motion. One limitation of the XCAT was that it did not have a physiological basis which to realistically simulate variations in cardiac function. In this work, we incorporate into the XCAT anatomy the four-chamber FE Living Heart Model (LHM) developed by the Living Heart Project (LHP). The LHM represents the state of the art in cardiac FE simulation because of its ability to accurately replicate the biomechanical motion of the entire heart and its variations. We create a new series of 4D phantoms capable of simulating patients with varying body sizes and shapes; cardiac positions, orientations, and dynamics. While extendable to other imaging modalities and technologies, our goal is to use the FE-enhanced XCAT models to investigate the optimal use of computed tomography (CT) for the evaluation of coronary artery disease (CAD). With the ability to simulate realistic, predictive, patient quality 4D imaging data, the enhanced XCAT models will enable optimization studies to identify the most promising systems or system parameters for further clinical validation.

The day/night proteome in the murine heart.

Circadian rhythms are essential to cardiovascular health and disease. Temporal coordination of cardiac structure and function has focused primarily at the physiological and gene expression levels, but these analyses are invariably incomplete, not the least because proteins underlie many biological processes. The purpose of this study was to reveal the diurnal cardiac proteome and important contributions to cardiac function. The 24-h day-night murine cardiac proteome was assessed by two-dimensional difference in gel electrophoresis (2D-DIGE) and liquid chromatography-mass spectrometry. Daily variation was considerable, as ∼7.8% (90/1,147) of spots exhibited statistical changes at paired times across the 24-h light- (L) dark (D) cycle. JTK_CYCLE was used to investigate underlying diurnal rhythms in corresponding mRNA. We next revealed that disruption of the L:D cycle altered protein profiles and diurnal variation in cardiac function in Langendorff-perfused hearts, relative to the L:D cycle. To investigate the role of the circadian clock mechanism, we used cardiomyocyte clock mutant (CCM) mice. CCM myofilaments exhibited a loss of time-of-day-dependent maximal calcium-dependent ATP consumption, and altered phosphorylation rhythms. Moreover, the cardiac proteome was significantly altered in CCM hearts, especially enzymes regulating vital metabolic pathways. Lastly, we used a model of pressure overload cardiac hypertrophy to demonstrate the temporal proteome during heart disease. Our studies demonstrate that time of day plays a direct role in cardiac protein abundance and indicate a novel mechanistic contribution of circadian biology to cardiovascular structure and function.

Impact of growth hormone (GH) treatment on circulating Nt-proBNP concentrations and on cardiac function in adult GH-deficient patients

Severe adult growth hormone deficiency (AGHD) is associated with increased cardiovascular risk. We have therefore investigated levels of amino terminal pro-brain natriuretic peptide (Nt-proBNP), a well established biomarker for cardiac failure, in adult GHD patients before and after GH replacement therapy, and potential parallel variations in cardiac function. Nt-proBNP concentrations were determined at baseline and after GH treatment in two studies including 28 and 12 patients with severe AGHD, respectively. In the second study, a maximal exercise test and a doppler echocardiography were performed to assess cardiac functional parameters. At baseline, Nt-proBNP levels were higher in AGHD patients than in controls (median: 7.8 vs. 3.7 pmol/L; p < 0.01 in study 1; 8.4 vs. 4.1 pmol/L; p < 0.01 in study 2). Following GH treatment, Nt-proBNP levels decreased significantly in both studies. None of the AGHD patients had signs of cardiac dysfunction at baseline and no significant effect of GH replacement therapy was observed on cardiac functional parameters, independent of changes in Nt-proBNP. In conclusion, GH treatment markedly reduces Nt-proBNP concentrations in adult GHD patients without obvious parallel changes in cardiac functional parameters. These results suggest that Nt-proBNP may appear as a biomarker of GH status and GH treatment efficiency.

Acquisition and visualization of 5D respiratory-resolved cardiac MRI

We image the heart during free breathing and explicitly resolve 3D volumetric information over both the cardiac and respiratory cycles to capture a 5D view of the heart. This 5D dataset can be displayed in a variety of ways to study disease states that exhibit variations in cardiac function with respect to respiration, such as pericardial tamponade/constriction and diastolic dysfunction.

Assessment of systolic and diastolic function in heart failure using ambulatory monitoring with acoustic cardiography

Introduction. The circadian variation of heart function and heart sounds in patients with and without heart failure (HF) is poorly understood. We hypothesized HF patients would exhibit less circadian variation with worsened cardiac function and sleep apnea. Methods. We studied 67 HF patients (age 67.4 ± 8.2 years; 42% acute HF) and 63 asymptomatic control subjects with no history of HF (age 61.6 ± 7.7 years). Subjects wore a heart sound/ECG/respiratory monitor. The data were analyzed for sleep apnea, diastolic heart sounds, and systolic time intervals. Results. The HF group had significantly greater prevalence of the third heart sound and prolongation of electro-mechanical activation time, while the control group had an age-related increase in the prevalence of the fourth heart sound. The control group showed more circadian variation in cardiac function. The HF subjects had more sleep apnea and higher occurrence of heart rate non-dipping. Conclusions. The control subjects demonstrated an increasing incidence of diastolic dysfunction with age, while systolic function was mostly unchanged with aging. Parameters related to systolic function were significantly worse in the HF group with little diurnal variation, indicating a constant stimulation of sympathetic tone in HF and reduction of diurnal regulation.

Identification of Genes and Networks Driving Cardiovascular and Metabolic Phenotypes in a Mouse F2 Intercross

To identify the genes and pathways that underlie cardiovascular and metabolic phenotypes we performed an integrated analysis of a mouse C57BL/6J x A/J F2 (B6AF2) cross by relating genome-wide gene expression data from adipose, kidney, and liver tissues to physiological endpoints measured in the population. We have identified a large number of trait QTLs including loci driving variation in cardiac function on chromosomes 2 and 6 and a hotspot for adiposity, energy metabolism, and glucose traits on chromosome 8. Integration of adipose gene expression data identified a core set of genes that drive the chromosome 8 adiposity QTL. This chromosome 8 trans eQTL signature contains genes associated with mitochondrial function and oxidative phosphorylation and maps to a subnetwork with conserved function in humans that was previously implicated in human obesity. In addition, human eSNPs corresponding to orthologous genes from the signature show enrichment for association to type II diabetes in the DIAGRAM cohort, supporting the idea that the chromosome 8 locus perturbs a molecular network that in humans senses variations in DNA and in turn affects metabolic disease risk. We functionally validate predictions from this approach by demonstrating metabolic phenotypes in knockout mice for three genes from the trans eQTL signature, Akr1b8, Emr1, and Rgs2. In addition we show that the transcriptional signatures for knockout of two of these genes, Akr1b8 and Rgs2, map to the F2 network modules associated with the chromosome 8 trans eQTL signature and that these modules are in turn very significantly correlated with adiposity in the F2 population. Overall this study demonstrates how integrating gene expression data with QTL analysis in a network-based framework can aid in the elucidation of the molecular drivers of disease that can be translated from mice to humans.

Three-year follow-up with cardiac magnetic resonance in a patient with biventricular non-compaction cardiomyopathy

A 25 year-old male patient symptomatic for heart palpitations underwent cardiovascular magnetic resonance (CMR) examination. CMR showed ventricular non-compaction cardiomyopathy involving both left and right ventricle. Patient started therapy with beta-blockers with a marked reduction in symptoms. During a three-year follow-up, the patient remained asymptomatic and in a second CMR examination, in 2006, showed no substantial variations in cardiac function.

Isolated Heart Function after Ischemia and Reperfusion in Sucrose-Fed Rats: Influence of Gender and Treatment

Sucrose-fed rats (HTG) develop hypertension, hypertriglyceridemia, and other features of the metabolic syndrome. This condition, nowadays a world epidemic, is more prevalent in males and increases the risk of cardiovascular diseases. Weanling male and female rats were given either tap water in control (C) or 30% sucrose solution in HTG groups and commercial rat chow for 3, 5, or 8 months. We studied possible variations in cardiac function, due to gender and length of treatment, in isolated heart after ischemia-reperfusion, since an impaired performance may be more easily detected under stress. Together, sucrose treatment and age affected all cardiac variables. Gender had significant effect on coronary vascular resistance and postischemic levels of the enzyme CK-MB; the percentages of retained cardiac enzymes after ischemia were higher in C and HTG females. C and HTG males had a higher incidence of arrhythmias than females, but only HTG males suffered lethal ventricular fibrillation.

Clinical applications of wall-stress analysis in the pediatric intensive care unit.

To determine whether serial, noninvasive assessment of afterload, contractility, and Doppler-derived cardiac output reliably detects variations in cardiac function in unstable pediatric patients. Prospective, blinded clinical trial. The pediatric intensive care unit at Massachusetts General Hospital. Fourteen critically ill pediatric patients. Pediatric patients meeting criteria for hemodynamic instability underwent serial echocardiograms every 6 hrs until they met exit criteria, generating 75 studies. Shortening fraction, cardiac index (CI), end-systolic wall stress (ESWS), and corrected velocity of circumferential shortening (Vcfc) were measured in each patient. Data points were plotted as a stress-velocity relationship, compared with published normal values, then correlated with changes in vital signs and pharmacologic interventions. Fourteen of 16 patients who were enrolled completed the study. A strong negative correlation between ESWS and Vcfc was confirmed (p < .001). As an internal measure of validity, Vcfc had a strong positive correlation with CI measurements (p = .012). An increase in dopamine infusion was associated with a fall in ESWS (p = .02), an increase in Vcfc (p = .03), and an increase in the CI as measured by Doppler (p = .035). The infusion of dopamine above renal perfusion levels moved patients from zones of normal or compensated contractility for afterload on a modified stress-velocity relationship to a zone of high contractility for afterload. Urine output was the only clinical index of cardiac function that had a significant correlation with the echocardiographic indices. Hemodynamically unstable patients followed similar patterns of deterioration and recovery on the modified stress-velocity graph. All surviving patients returned to a normal or compensated zone. Wall-stress analysis of cardiac function is easily and safely performed on mechanically ventilated pediatric patients with the production of consistently high-quality data. For internal validity, Vcfc and CI measurements were correlated and were strongly positive. Wall-stress indices reliably detected patient deterioration, recovery, and response to changes in dopamine infusion. Patients who failed to return to areas of normal or compensated levels of contractility and afterload did poorly in this study. Noninvasive measures of afterload and contractility appear useful for monitoring cardiac function of critically ill children in an intensive care setting.

Quantification of the voltage-response relationship between punctate and field electrical stimulation and the function of isolated rat left atria and papillary muscles

The effects of varying the electrical stimulation voltage on the noradrenergic tone and systolic and diastolic cardiac function of isolated rat cardiac preparations is unknown. If a wide range of voltages substantially alters the basal noradrerengic tone of isolated cardiac preparations, highly variable responses may complicate the interpretation of the cardiac effects of interventions, such as drugs or toxins. This study was designed to determine whether field or punctate electrode stimulation altered systolic and diastolic cardiac function of isolated rat atrial and ventricular muscle preparations through a β-adrenergic receptor-mediated mechanism. Isolated left atria and right ventricular papillary muscles from adult Sprague-Dawley rats were stimulated to contract isometrically in Krebs bicarbonate buffer (30° C, pH 7.4, 0.5 Hz). Cardiac muscle function was assessed by determining cardiac contractility ( dF dt ), relaxation (80% relaxation time), and muscle stiffness (changes in resting force). Muscles were electrically stimulated to contract using either punctate or field electrodes. Basal values of cardiac function were determined at threshold voltages, and voltage was increased in stepwise fashion, over a wide range, to obtain a voltage response-relation to cardiac function. In left atrial preparations, both punctate and field electrical stimulation caused a 200% increase in cardiac contractility. The greatest changes in contractility occurred at near threshold voltages (less than 5 volts for punctate and 19 volts for field stimulation). The voltage-dependent increases in cardiac contractility were attenuated or abolished by pretreatment with atenolol (10 μmol/L; selective β 1-antagonist) or reserpine (5 mg/kg i.p., 24 hr before euthanasia). In contrast to left atrial preparations, neither field or punctate electrical stimulation had any effect on the cardiac contractility of papillary muscle preparations. Neither field or punctate electrical stimulation had any effect on cardiac relaxation (80% relaxation time) or muscle stiffness (changes in resting force) of left atrial or papillary muscle preparations. This study demonstrates that punctate and field electrical stimulation can significantly increase cardiac contractility of rat left atrial preparations at near threshold voltages by increasing noradrenergic tone. Thus, control of the voltage range may be required to reduce variation in cardiac function of isolated rat left atrial preparations.

Diurnal variation in blood pressure in patients with biventricular assist devices and retained, nonpumping native hearts.

Studies indicate that centrally mediated rhythms in sympathetic tone play a prominent role in diurnal cardiovascular variability. Recent evidence from heart transplant recipients, in whom blood pressure does not decline during sleep despite normal variability in plasma norepinephrine, however, suggests that afferent cardiac nervous traffic is necessary for the generation of diurnal variability. This implies that in the presence of an innervated heart excluded from the systemic circulation, blood pressure would still decrease during sleep. To assess this hypothesis, we studied 24-hour blood pressure, heart rate, and neuroendocrine variability in patients with biventricular assist devices in whom the retained native hearts had ceased to pump. Eight patients were free of medication and were studied every 3 hours. Pump rates and output were kept constant throughout the study. Blood pressure showed a significant decline during sleep, as did norepinephrine and epinephrine (all P < .05). Atrial natriuretic factor showed a significant increase around midnight (P < .01). Significantly elevated levels were found for all hormones studied except for aldosterone and endothelin. Our results suggest that diurnal variations in cardiac function or in catecholamine levels (indicative of sympathetic activity) as found in cardiac transplant recipients alone are not responsible or sufficient for producing a nocturnal drop in blood pressure. The presence of an innervated heart appears crucial in this respect. This could be of importance for the understanding of circadian cardiovascular pathophysiology.

Duplex ultrasound in carotid artery disease: some diagnostic considerations.

Loss of pressure across a stenosis depends on the geometry of that obstruction, but flow only depends on geometry when both perfusion pressure and peripheral resistance are constant. As cerebrovascular resistance is generally low then flow over a stenosis will be dominated by stenotic resistance. A relatively modest reduction in systolic perfusion pressure will produce a large increase in stenotic resistance. Evaluation of a 'haemodynamically significant' or 'critical' or 'dynamic' stenosis should include consideration of variations in cardiac function and blood pressure as well as local vascular dynamics. Examination of the ultrasound image characteristics of the arterial lesion gives additional structural information of the contents and surface of the lesion and any movement relative to the vessel wall. This may give guidance in separating clinically stable from unstable lesions, and also in following progression or regression of disease. The physical forces which are applied to some lesions may cause the release of material from the substance of the lesion into the arterial lumen or cause damage resulting in progression of the lesion itself.

Comparison of CHOP-B vs CEOP-B in ‘poor prognosis’ non-Hodgkin’s lymphomas. A randomized trial

Sixty consecutive previously untreated patients with non-Hodgkin's lymphomas (intermediate or high grade and/or bulky disease and/or presence of constitutional symptoms), were randomized to receive either CHOP-B or CEOP-B (31 and 29 patients, respectively) to compare the therapeutic activity and toxicity. Complete response was observed in 65% of the patients treated with CHOP-B and 62% with CEOP-B; relapse of the disease occurred, respectively, in 5/20 (25%) and 6/18 (33%) of CR. Relapse-free survival and overall survival at 5 yr resulted in both groups (RFS 68% and 62% and overall survival 62% and 62%, respectively). In addition, increasing the dosage of epirubicin did not result in an increase in the haematologic toxicity or percent of CR. The haematologic toxicity was slightly lower in CEOP-B. The cardiologic monitoring (Eco 2D and EKG-Holter) at 400 mg mq-1 of EDX and ADM did not demonstrate variations in cardiac function in the CEOP-B group, while in the ADM patients the ejection fraction was statistically lower as regards basal values. In conclusion, in our randomized study, substitution of ADM with EDX in non-Hodgkin's lymphomas in the CHOP-B regimen, did not decrease the therapeutic activity of the combined chemotherapy, while less toxicity (haematologic and cardiac) was observed. For these reasons, in our opinion, epirubicin can substitute adriamycin in second and third generation regimens for non-Hodgkin's lymphomas in which the major drawback for a wider diffusion is the severe toxicity observed.