RESUMO
Acquired aplastic anemia (AA) is a rare heterogeneous disorder characterized by pancytopenia and hypoplastic bone marrow. The incidence is 2-3 per million population per year in the Western world, but 3 times higher in East Asia. Survival in severe aplastic anemia (SAA) has improved significantly due to advances in hematopoietic stem cell transplantation (HSCT), immunosuppressive therapy, biologic agents, and supportive care. In SAA, HSCT from a matched sibling donor (MSD) is the first-line treatment. If a MSD is not available, options include immunosuppressive therapy (IST), matched unrelated donor, or haploidentical HSCT. The purpose of this guideline is to provide health care professionals with clear guidance on the diagnosis and management of pediatric patients with AA. A preliminary evidence-based document prepared by a group of pediatric hematologists of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Hemato-Oncology (AIEOP) was discussed, modified and approved during a series of consensus conferences that started online during COVID 19 and continued in the following years, according to procedures previously validated by the AIEOP Board of Directors.
Assuntos
Anemia Aplástica , Transplante de Células-Tronco Hematopoéticas , Anemia Aplástica/terapia , Anemia Aplástica/diagnóstico , Anemia Aplástica/etiologia , Humanos , Criança , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Itália , COVID-19/diagnóstico , Imunossupressores/uso terapêutico , SARS-CoV-2RESUMO
This study identifies a new chronic form of immune neutropenia in the young with or without detectable indirect anti-neutrophil antibodies, characterized by mild/moderate neutropenia low risk of severe infection (14%), tendency to develop autoimmune phenomena over the course of the disease (cumulative incidence of 58.6% after 20 years of disease duration), leukopenia, progressive reduction of absolute lymphocyte count and a T- and B-cell profile similar to autoimmune disorders like Sjogren syndrome, rheumatoid arthritis, and systemic lupus erythematosus (increased HLADR+ and CD3 + TCRγδ cells, reduced T regulatory cells, increased double-negative B and a tendency to reduced B memory cells). In a minority of patients, P/LP variants related to primary immuno-regulatory disorders were found. This new form may fit the group of "Likely acquired neutropenia," a provisional category included in the recent International Guidelines on Diagnosis and Management of Neutropenia of EHA and EUNET INNOCHRON ACTION 18233. The early recognition of this form of neutropenia would help clinicians to delineate better specific monitoring plans, genetic counseling, and potentially targeted therapies.
Assuntos
Artrite Reumatoide , Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Neutropenia , Trombocitopenia , Humanos , Neutropenia/etiologia , Neutropenia/terapia , Doenças Autoimunes/complicações , Lúpus Eritematoso Sistêmico/complicações , Trombocitopenia/complicaçõesRESUMO
Ovarian cancer (OC) displays the highest mortality among gynecological tumors, mainly due to early peritoneal dissemination, the high frequency of tumor relapse following primary debulking, and the development of chemoresistance. All these events are thought to be initiated and sustained by a subpopulation of neoplastic cells, termed ovarian cancer stem cells (OCSC), that are endowed with self-renewing and tumor-initiating properties. This implies that interfering with OCSC function should offer novel therapeutic perspectives to defeat OC progression. To this aim, a better understanding of the molecular and functional makeup of OCSC in clinically relevant model systems is essential. We have profiled the transcriptome of OCSC vs. their bulk cell counterpart from a panel of patient-derived OC cell cultures. This revealed that Matrix Gla Protein (MGP), classically known as a calcification-preventing factor in cartilage and blood vessels, is markedly enriched in OCSC. Functional assays showed that MGP confers several stemness-associated traits to OC cells, including a transcriptional reprogramming. Patient-derived organotypic cultures pointed to the peritoneal microenvironment as a major inducer of MGP expression in OC cells. Furthermore, MGP was found to be necessary and sufficient for tumor initiation in OC mouse models, by shortening tumor latency and increasing dramatically the frequency of tumor-initiating cells. Mechanistically, MGP-driven OC stemness was mediated by the stimulation of Hedgehog signaling, in particular through the induction of the Hedgehog effector GLI1, thus highlighting a novel MGP/Hedgehog pathway axis in OCSC. Finally, MGP expression was found to correlate with poor prognosis in OC patients, and was increased in tumor tissue after chemotherapy, supporting the clinical relevance of our findings. Thus, MGP is a novel driver in OCSC pathophysiology, with a major role in stemness and in tumor initiation.
Assuntos
Proteínas Hedgehog , Neoplasias Ovarianas , Animais , Feminino , Humanos , Camundongos , Proteínas de Ligação ao Cálcio/metabolismo , Transformação Celular Neoplásica , Proteínas da Matriz Extracelular/metabolismo , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Recidiva Local de Neoplasia , Neoplasias Ovarianas/metabolismo , Microambiente Tumoral , Proteína de Matriz GlaRESUMO
BACKGROUND: The search for biomarkers to evaluate ovarian cancer (OC) homologous recombination (HR) function and predict the response to therapy is an urgent clinical need to improve the selection of patients who could benefit from platinum- and olaparib (poly-ADP ribose polymerase inhibitors, PARPi)-based therapies. METHODS: We used a large collection of OC patient-derived xenografts (PDXs) (n = 47) and evaluated their HR status based on BRCA1/2 mutations, BRCA1 promoter methylation and the HRDetect score. RAD51 foci were quantified in formalin-fixed, paraffin-embedded untreated tumour specimens by immunofluorescence and the messenger RNA expression of 21 DNA repair genes by real-time PCR. RESULTS: Tumour HR deficiency predicted both platinum and olaparib responses. The basal level of RAD51 foci evaluated in geminin-positive/replicating cells strongly inversely correlated with olaparib response (p = 0.011); in particular, the lower the foci score, the greater the sensitivity to olaparib, while low RAD51 foci score seems to associate with platinum activity. CONCLUSIONS: The basal RAD51 foci score is a candidate predictive biomarker of olaparib response in OC patients as it can be easily translatable in a clinical setting. Moreover, the findings corroborate the importance of OC-PDXs as a reliable tool to identify and validate biomarkers of response to therapy.
Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Cisplatino/farmacologia , Recombinação Homóloga , Neoplasias Ovarianas/patologia , Ftalazinas/farmacologia , Piperazinas/farmacologia , Rad51 Recombinase/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoAssuntos
Ecocardiografia/métodos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Diálise Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND AIM: Low serum 25-hydroxyvitamin D [25(OH)D] levels may have an important role in predisposing to hypertension and myocardial disease. We investigated the relationship between 25(OH)D and left ventricular (LV) structure and function, assessed by echocardiography, in a series of patients with essential hypertension (EH). METHODS AND RESULTS: Sixty-two newly diagnosed never-treated patients (32 male/30 female), aged 18-65 years, with grade 1-2 hypertension, no diabetes, no obesity, no hyperlipidemia, and no cardiopulmonary, renal, or hepatic disease, were studied. Twenty-four healthy normotensive sex-, age-, BMI-matched subjects served as controls. Hypertensive patients with 25(OH)D deficiency, defined as serum 25(OH)D levels <50 nmol/L, had higher prevalence of LV hypertrophy (LVH) than their 25(OH)D-sufficient counterparts (57.1 vs 17.6%, P = 0.02); no differences between the two groups were found in blood pressure levels as well as in other biochemical and hormone parameters. There was an inverse correlation between LV mass index and 25(OH)D levels (r = -0.366, P < 0.003) and a direct correlation between LV mass index and BMI (r = 0.333, P < 0.006) in the entire hypertensive population. The two variables remained independently associated with LVH at multivariable logistic regression analysis (OR 1.05, P < 0.005 and OR 1.25, P = 0.03, respectively). Prevalence of 25(OH)D deficiency was similar in EH patients and controls (45.1 vs 41.6%, P = 0.89), whereas no correlation between echocardiographic parameters and hormone levels was found. CONCLUSIONS: In the absence of major cardiovascular risk factors, 25(OH)D deficiency is a frequent finding in EH patients and is independently associated with LVH.
Assuntos
Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/fisiopatologia , Deficiência de Vitamina D/fisiopatologia , Vitamina D/análogos & derivados , Adolescente , Adulto , Idoso , Pressão Sanguínea , Doenças Cardiovasculares , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Hipertensão/sangue , Hipertensão/complicações , Hipertrofia Ventricular Esquerda/complicações , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Vitamina D/sangue , Deficiência de Vitamina D/complicações , Adulto JovemRESUMO
Cardiac autonomic dysfunction is associated with increased cardiovascular mortality. No data on sympathovagal balance are available in patients with Cushing's syndrome, in whom cardiovascular risk is high. We studied 10 patients with newly diagnosed Cushing's syndrome (1 male/9 females; age mean+/-SD, 47+/-10 yr) and 10 control subjects matched for age, sex, body mass index, and cardiovascular risk factors. In both groups there were 7 patients with arterial hypertension, 3 with diabetes mellitus, and 2 with obesity. Cardiac autonomic function was evaluated by analysis of short time heart rate variability (HRV) measures in frequency domain over 24-h, daytime, and nighttime. The 24-h ambulatory blood pressure monitoring and echocardiography were also performed. In comparison with controls, patients with Cushing's syndrome had lower 24-h (1.3+/-0.6 vs 3.7+/-1.5, mean+/-SD, p<0.01), daytime (2.0+/-1.4 vs 4.5+/-1.6, p<0.01), and night-time (1.0+/-0.4 vs 3.5+/-2.3, p<0.01) low-frequency/ high frequency (LF/HF) power ratio. In the presence of similar LF power, the difference was due to elevation in HF power in Cushing's syndrome compared to controls: 24-h, 12.7+/-6.7 vs 5.8+/-2.8, p<0.01; daytime, 10.2+/-7.3 vs 4.5+/-2.1, p<0.05; nighttime, 14.2+/-7.0 vs 7.8+/-4.7, p<0.05. Eight Cushing patients vs 4 controls had a non-dipping blood pressure profile. At echocardiography, Cushing patients had a greater left ventricular mass index and/or relative wall thickness, and impaired diastolic function, compared with controls. Compared to controls, patients with Cushing's syndrome showed a sympathovagal imbalance, characterized by a relatively increased parasympathetic activity. Whether this autonomic alteration is meant to counterbalance cortisol-induced effects on blood pressure and cardiac structure/function or has a different pathophysiological significance is still unknown.
Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Síndrome de Cushing/fisiopatologia , Frequência Cardíaca/fisiologia , Hormônio Adrenocorticotrópico/sangue , Monitorização Ambulatorial da Pressão Arterial , Síndrome de Cushing/diagnóstico por imagem , Ecocardiografia , Feminino , Humanos , Hidrocortisona/sangue , Hidrocortisona/urina , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND AIM: Insulin resistance is recognized as the pathophysiological hallmark of non-alcoholic fatty liver disease (NAFLD). A relation between insulin sensitivity and left ventricular morphology and function has been reported in essential hypertension, where a high prevalence of NAFLD has been recently found. We investigated the inter-relationship between left ventricular morphology/function, metabolic parameters and NAFLD in 86 never-treated essential hypertensive patients subdivided in two subgroups according to the presence (n = 48) or absence (n = 38) of NAFLD at ultrasonography. METHODS AND RESULTS: The two groups were similar as to sex, age and blood pressure levels. No patient had diabetes mellitus, obesity, hyperlipidemia, or other risk factors for liver disease. Body mass index, waist circumference, triglycerides, glucose, insulin, homeostasis model of assessment index for insulin resistance (HOMA-IR), aspartate aminotransferase and alanine aminotransferase were higher and adiponectin levels were lower in patients with NAFLD than in patients without NAFLD, and were associated with NAFLD at univariate analysis. Patients with NAFLD had similar prevalence of left ventricular hypertrophy compared to patients without NAFLD, but a higher prevalence of diastolic dysfunction (62.5 vs 21.1%, P < 0.001), as defined by E/A ratio <1 and E-wave deceleration time >220 ms. Diastolic dysfunction (P = 0.040) and HOMA-IR (P = 0.012) remained independently associated with NAFLD at backward multivariate analysis. CONCLUSIONS: Non-alcoholic fatty liver disease was associated with insulin resistance and abnormalities of left ventricular diastolic function in a cohort of patients with essential hypertension, suggesting a concomitant increase of metabolic and cardiac risk in this condition.
Assuntos
Fígado Gorduroso/epidemiologia , Hipertensão/epidemiologia , Disfunção Ventricular Esquerda/epidemiologia , Adulto , Estudos Transversais , Diástole , Ecocardiografia , Fígado Gorduroso/diagnóstico por imagem , Feminino , Humanos , Hipertensão/diagnóstico por imagem , Resistência à Insulina , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Fatores de Risco , Disfunção Ventricular Esquerda/diagnóstico por imagemRESUMO
OBJECTIVE: To evaluate by echocardiography the cardiac structure and function in patients with primary adrenocortical insufficiency. DESIGN AND METHODS: Two-dimensionally guided M-mode echocardiograms and spectral Doppler studies were performed in seven consecutive patients with newly diagnosed autoimmune primary adrenal failure before and 4-8 months after an adequate regimen of steroid substitution. Echocardiographic parameters were also studied in ten healthy controls. RESULTS: In the cases with untreated Addison's disease, both left ventricular end-systolic and end-diastolic dimensions were significantly reduced in comparison with those in controls (P<0.01). Four patients had echocardiographic signs of mitral valve prolapse (MVP) at the anterior leaflet, with no evidence of mitral regurgitation by Doppler echocardiography. Systolic clicks characteristic of MVP were present on auscultation in two of these cases. Left ventricular chamber size normalized, i.e. significantly increased (P<0.01), and both echocardiographic and physical signs of MVP resolved after steroid substitution in all patients. All other echocardiographic indices were normal before and after treatment. CONCLUSIONS: Patients with untreated Addison's disease have cardiac abnormalities which regress after steroid substitution. A valvular-ventricular disproportion due to the hypovolemic state could explain these findings.
Assuntos
Doença de Addison/tratamento farmacológico , Anormalidades Cardiovasculares/tratamento farmacológico , Terapia de Reposição Hormonal , Doença de Addison/diagnóstico por imagem , Adulto , Anormalidades Cardiovasculares/diagnóstico por imagem , Cosintropina/uso terapêutico , Ecocardiografia , Feminino , Hemodinâmica/fisiologia , Hormônios/sangue , Humanos , Masculino , Prolapso da Valva Mitral/complicações , Prolapso da Valva Mitral/tratamento farmacológico , Volume Sistólico/efeitos dos fármacosRESUMO
Percutaneous balloon valvuloplasty is used successfully for mitral and aortic rheumatic stenosis. Its application is limited in elderly degenerative aortic stenosis because of its poor long-term results. It is thus indicated only in selected groups of patients at high surgical risk. We describe three cases affected with mitral and aortic stenosis who underwent simultaneous mitral and aortic percutaneous balloon valvuloplasty. Etiology was rheumatic in the first two cases, while it was rheumatic and degenerative in the third case. Immediately after the procedure, mitral and aortic gradients decreased, with a simultaneous increment in aortic and mitral areas and cardiac index. There were no major complications. The follow-up after seven years revealed the persistence of relatively good results in the first two cases affected with rheumatic valvulopathies. In the last case, restenosis recurred a few years after the procedure.
Assuntos
Valva Aórtica , Cateterismo , Valva Mitral , Adulto , Idoso , Insuficiência da Valva Aórtica/diagnóstico , Insuficiência da Valva Aórtica/terapia , Cateterismo/instrumentação , Cateterismo/métodos , Feminino , Seguimentos , Humanos , Masculino , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/terapia , Recidiva , Cardiopatia Reumática/diagnóstico , Cardiopatia Reumática/terapiaRESUMO
Normal gestation is associated with adaptative cardiovascular changes. Pregnant women with mitral stenosis may be unable to tolerate these changes despite optimal medical therapy, and life-threatening complications can occur. Commissurotomy or valve replacement during gestation are very high-risk procedures both for mother and fetus. Percutaneous valvuloplasty is a valid alternative to cardiac surgery. In this study, we describe four pregnant women with mild or severe mitral stenosis who underwent percutaneous valvuloplasty after the first trimester of gestation. Despite tailored medical therapy with diuretics and beta blockers, all patients were symptomatic: NYHA class II in two cases, and class III in the last two. In order to protect the fetus from radiation, the patient's pelvic-abdominal area was shielded and left ventriculography was not performed. Fluoroscopy time was 7 +/- 3 min. No major immediate complications were observed after the procedure. Mitral valve area (sec. Gorlin) increased from 1.05 +/- 0.08 cm2 to 2.52 +/- 0.26 cm2 and mitral gradient decreased from 26.7 +/- 5.7 mmHg to 8.5 +/- 3 mmHg. The four women delivered healthy full-term babies. At a mean follow-up of 22 +/- 8 months, all patients are free of symptoms, two patients with diuretics and two without therapy. Percutaneous valvuloplasty can be considered the treatment of choice for pregnant women with symptomatic mitral stenosis refractory to medical therapy.
Assuntos
Cateterismo , Estenose da Valva Mitral/terapia , Valva Mitral , Complicações Cardiovasculares na Gravidez/terapia , Adulto , Cateterismo/instrumentação , Cateterismo/métodos , Terapia Combinada , Feminino , Humanos , Estenose da Valva Mitral/diagnóstico , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico , Resultado da Gravidez , Segundo Trimestre da Gravidez , Medição de Risco , Resultado do TratamentoRESUMO
There is general agreement that left-sided elastomas must be removed to avoid systemic complications. Right-sided localization is less risky and surgical treatment is not agreed upon. We report a case of surgical resected fibroelastoma of the tricuspid valve and discuss the indications to surgery by reviewing the literature on the few reported cases. We feel that, if surgery is timely, the tumor can be resected, thus preserving the native valve. This provides an opportunity to prevent possible right-sided complications due to increasing tumor size and embolization.
Assuntos
Fibroma/cirurgia , Neoplasias Cardíacas/cirurgia , Valva Tricúspide , Adulto , Procedimentos Cirúrgicos Cardíacos , Ecocardiografia , Feminino , Fibroma/diagnóstico por imagem , Fibroma/patologia , Seguimentos , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/patologia , Humanos , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/patologia , Valva Tricúspide/cirurgiaRESUMO
Two cases of left ventricular pseudoaneurysm following myocardial infarction are presented. In the first patient a two-dimensional echocardiography study revealed a small posterior echo-free space that appeared to communicate with the left ventricle through a small defect in the left ventricular posterior wall. Conventional Doppler echocardiography and colour flow imaging demonstrated flow between the left ventricle and the paraventricular chamber. In the other patient, the same study detected an enormous false aneurysm. We found a large extramyocardial echo-free space within the pericardial cavity. The site of this space was posterolateral and communicating with the left ventricular cavity. Cardiac catheterization and surgery confirmed the diagnosis. A postoperative echocardiographic study demonstrated a persistent but smaller saccular echo-free space and a residual shunt through one site of repair in the first patient; in the other, after surgical treatment there was no residual flow, but a left ventricular dysfunction was detected. Two dimensional and color Doppler echocardiography is the best technique among the noninvasive methods, for detecting and following up left ventricular pseudoaneurysms.
Assuntos
Falso Aneurisma/diagnóstico , Aneurisma Cardíaco/diagnóstico , Adulto , Idoso , Falso Aneurisma/etiologia , Angiografia Coronária , Ecocardiografia , Ecocardiografia Doppler , Aneurisma Cardíaco/etiologia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnósticoRESUMO
BACKGROUND: Patients with severe congestive heart failure often have high plasma Atrial Natriuretic Factor (ANF) and neurohormonal activation. Ace inhibitors give clinical and hemodynamic benefits and lower plasma angiotensin and norepinephrine levels. The interactions between ANF and the Ace inhibitors are mainly modulated via the renin angiotensin system. METHODS: Plasma ANF, renin activity, urinary aldosterone and catecholamine levels were evaluated in 10 patients with congestive heart failure (at baseline, after 15 days of adequate treatment with digoxin and diuretics, and after 45 days of enalapril) in order to assess the changes of ANF and vasoconstrictor neurohormones with chronic Ace inhibitor therapy. RESULTS: ANF increased significantly in the congestive heart failure group compared to a normal subject control group (P < 0.001). After digoxin and diuretic therapy NHYA class improved significantly, but no significant hormonal changes were found. On the contrary, the addition of enalapril caused a significant decrease of plasma ANF and urinary aldosterone and catecholamines (P < 0.05). CONCLUSIONS: The relationship between the renin angiotensin system and catecholamines is complex but our findings indicate that: 1) Traditional therapy is effective in improving symptoms, but cannot induce a decrease of vasoconstrictive neurohormones; 2) ACE inhibitor therapy reduces ANF and neurohormonal activation. 3) ANF is a useful marker in evaluating the response to treatment.
Assuntos
Fator Natriurético Atrial/sangue , Fator Natriurético Atrial/efeitos dos fármacos , Enalapril/uso terapêutico , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/tratamento farmacológico , Doença Aguda , Idoso , Biomarcadores/sangue , Digoxina/uso terapêutico , Quimioterapia Combinada , Feminino , Furosemida/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Renina-Angiotensina/efeitos dos fármacosRESUMO
For the purpose of evaluating cause, frequency, type and seriousness of arrhythmias in dialysis patients, 14 chronic uremics, 8 on bicarbonate-dialysis, 6 on acetate-dialysis underwent a basal ECG, echocardiography and a Holter dynamic electrocardiography (ECGD) for a duration of 96 hours. Before and after dialysis PAO, body weight, serum electrolytes and arterial pH were controlled. In 11 patients (78%) supraventricular and ventricular arrhythmias were discovered of equal frequency and seriousness both in the inter and intra dialytic phase, even if more frequent in ventricular hypertrophic patients (IVSn) the complex ventricular arrhythmias (Lown greater than 2). The seriousness and frequency of ventricular and supraventricular arrhythmias in the dialytic phase did not seem to depend either on the type of tampon or on the presence or absence of cardiopathies while in the inter-dialytic phase the seriousness of ventricular arrhythmias seems to depend upon the presence of cardiopathies. The Authors conclude that the pathogenesis of arrhythmias in uremic patients on dialysis is multifactorial and that their elevated incidence makes the use of a Holter in these patients recommendable.
Assuntos
Arritmias Cardíacas/diagnóstico , Eletrocardiografia Ambulatorial , Diálise Renal , Uremia/complicações , Idoso , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Uremia/terapiaRESUMO
We studied, by 48-hour Holter monitoring, 33 patients with chronic stable heart failure (radionuclide ejection fraction less than 35%), complex ventricular arrhythmias and no electrolyte abnormalities, after a period during which they were treated with digoxin and diuretics. Before Holter monitoring blood samples were analyzed for serum concentration of sodium, potassium, magnesium, urea, creatinine, digoxin, aldosterone and for plasmatic renin activity in addition to urinary aldosterone and catecholamines determination. After these investigations in 23 patients, 5-20 mg of enalapril were progressively added to the conventional therapy, while 10 patients continued the previous therapy. After 8 weeks 30 patients were subjected to a second 48-hour Holter monitoring and to the same biochemical and hormonal tests. One patient died and 2 were lost to follow up. Only the enalapril group showed a significant decrease in the number of premature ventricular complexes (PVC) (p less than 0.01), and the frequency of couplets and episodes of ventricular tachycardia (VT) declined significantly (P less than 0.01). In the two groups there were no significant changes in digoxin, sodium, or magnesium, while potassium concentration increased in both groups (p less than 0.01). In the enalapril group heart rate and systolic and diastolic pressure declined significantly (p less than 0.01), and New York Heart Association class (NYHA) improved (p less than 0.001). In the other group there were no significant changes in these parameters. Enalapril caused a significant increase in the plasmatic renin activity (p less than 0.01) and a significant fall of plasma and urinary aldosterone (p less than 0.01; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)