Biomedical subjects

E Marangoni

Publications and source records attributed to E Marangoni.

At least 19 recordsLinked to original sources

PubMed2005

The effect of volatile anesthetics on respiratory system resistance in patients with chronic obstructive pulmonary disease.

We examined the effect of isoflurane and sevoflurane on respiratory system resistance (Rmin,rs) in patients with chronic obstructive pulmonary disease (COPD). The diagnosis of COPD rests on the presence of airway obstruction, which is only partially reversible after bronchodilator treatment. Ninety-six consecutive patients undergoing thoracic surgery for peripheral lung cancer were enrolled. They were divided into two groups: preoperative forced expiratory volume in 1 s/forced vital capacity ratio <70% or >70%. Rmin,rs was measured after 5 and 10 min of maintenance anesthesia by using the constant flow/rapid occlusion method. Maintenance of anesthesia was randomized to thiopental 0.30 mg . kg(-1) . min(-1) or 1.1 minimum alveolar anesthetic concentration end-tidal isoflurane or sevoflurane. Eleven patients were excluded: two because anesthesia was erroneously induced with propofol and nine because of an incorrect tube position. Maintenance with thiopental failed to decrease Rmin,rs, whereas both volatile anesthetics were able to decrease Rmin,rs in patients with COPD. The percentage of patients who did not respond to volatile anesthetics was larger in those with COPD as well. In conclusion, we have demonstrated that isoflurane and sevoflurane produce bronchodilation in patients with COPD.

Aged↗

PubMed2002

Early experiences with a porcine hepatocyte-based bioartificial liver in acute hepatic failure patients.

Orthotopic liver transplantation (OLT) is the only effective therapeutic modality in severe acute hepatic failure (AHF). The scarcity of organs for transplantation leads to an urgent necessity for temporary liver support treatments in AHF patients. A hepatocyte-based bioartificial liver (BAL) is under investigation with the main purpose to serve as bridging treatment until a liver becomes available for OLT, or to promote spontaneous liver regeneration. We developed a novel radial-flow bioreactor (RFB) for three-dimensional, high-density hepatocyte culture and an integrated pumping apparatus in which, after plasmapheresis, the patient's plasma is recirculated through the hepatocyte-filled RFB. Two hundred thirty grams of freshly isolated porcine hepatocytes were loaded into the RFB for clinical liver support treatment. The BAL system was used 8 times in supporting 7 AHF patients in grade III-IV coma, all waiting for an urgent OLT Three patients with no history of previous liver diseases were affected by fulminant hepatic failure (FHF) due to hepatitis B virus, 3 by primary non-function (PNF) of the transplanted liver, and one by AHF due to previous abdominal trauma and liver surgery. Six out of 7 patients underwent OLT following BAL treatment(s), which lasted 6-24 hours. All patients tolerated the procedures well, as shown by an improvement in the level of encephalopathy, a decrease in serum ammonia, transaminases and an amelioration of the prothrombin time, with full neurological recovery after OLT Our initial clinical experience confirms the safety of this BAL configuration and suggests its clinical efficacy as a temporary liver support system in AHF patients.

Adolescent↗

PubMed2001

Tyrphostin AG 1024 modulates radiosensitivity in human breast cancer cells.

Insulin-like growth factor-1 (IGF-1) plays an important growth-promoting effect by activating the PI3K/Akt signalling pathway, inhibiting apoptotic pathways and mediating mitogenic actions. Tyrphostin AG 1024, one selective inhibitor of IGF-1R, was used to evaluate effects on proliferation, radiosensitivity, and radiation-induced cell apoptosis in a human breast cancer cell line MCF-7. Exposure to Tyrphostin AG 1024 inhibited proliferation and induced apoptosis in a time-dependent manner, and the degree of growth inhibition for IC20 plus irradiation (4 Gy) was up to 50% compared to the control. Examination of Tyrphostin AG 1024 effects on radiation response demonstrated a marked enhancement in radiosensitivity and amplification of radiation-induced apoptosis. Western blot analysis indicated that Tyrphostin AG 1024-induced apoptosis was associated with a downregulation of expression of phospho-Akt1, increased expression of Bax, p53 and p21, and a decreased expression of bcl-2 expression, especially when combined with irradiation. To our knowledge, this is the first report showing that an IGF-1 inhibitor was able to markedly increase the response of tumour cells to ionizing radiation. These results suggest that Tyrphostin AG 1024 could be used as a potential therapeutic agent in combination with irradiation.

Adenocarcinoma↗

PubMed2001

Responsiveness to intravenous administration of salbutamol in chronic obstructive pulmonary disease patients with acute respiratory failure.

OBJECTIVE: In chronic obstructive pulmonary disease (COPD) patients with acute respiratory failure (ARF), bronchodilating agents administered by inhalation have, in general, little effect on dynamic hyperinflation and concurrent static intrinsic positive end-expiratory pressure (PEEPi,st). Since in COPD the severely obstructed segments of the lung may not be reached by inhaled medication, we reasoned that drug efficiency may be enhanced by intravenous administration of the agent. DESIGN: Physiological study. SETTING: Two four-bed surgical-medical ICUs of a university hospital. PATIENTS: Fourteen COPD patients were studied within 36 h from the onset of ARF. MEASUREMENTS AND RESULTS: Static compliance (Cst,rs), minimal (Rmin,rs) and additional (DeltaRrs) resistance of the respiratory system, and PEEPi,st were measured before and after intravenous administration of salbutamol. All patients had limitation of air flow before and after salbutamol administration. On average, after salbutamol there was a small, though significant, decrease in Rmin,rs (-9%), DeltaRrs (-12%) and PEEPi,st (-8%). CONCLUSION: The changes in resistance and PEEPi,st after intravenous administration of salbutamol were too small to be of clinical significance.

Acute Disease↗

PubMed2001

BCR-ABL down-regulates the DNA repair protein DNA-PKcs.

This study demonstrates in both stable and inducible BCR-ABL-expressing hematopoietic cells a down-regulation of the major mammalian DNA repair protein DNA-PKcs by BCR-ABL. Similar results were found in BCR-ABL CD34(+) cells from patients with chronic myelogenous leukemia (CML). DNA-PKcs down-regulation is a proteasome-dependent degradation that requires tyrosine kinase activity and is associated with a marked DNA repair deficiency along with increased sensitivity to ionizing radiation. The conjunction of a major DNA repair deficiency and a resistance to apoptosis, both induced by BCR-ABL, provides a new mechanism to explain how secondary genetic alterations can accumulate in CML, eventually leading to blast crisis. The down-regulation of DNA-PKcs was reversible in CD34(+) CML cells suggesting that this approach might offer a novel and powerful therapeutic strategy in this disease, especially to delay the blast crisis. (Blood. 2001;97:2084-2090)

Acetylcysteine↗

PubMed2000

A Ku80 fragment with dominant negative activity imparts a radiosensitive phenotype to CHO-K1 cells.

DNA non-homologous end joining, the major mechanism for the repair of DNA double-strands breaks (DSB) in mammalian cells requires the DNA-dependent protein kinase (DNA-PK), a complex composed of a large catalytic subunit of 460 kDa (DNA-PKcs) and the heterodimer Ku70-Ku80 that binds to double-stranded DNA ends. Mutations in any of the three subunits of DNA-PK lead to extreme radiosensitivity and DSB repair deficiency. Here we show that the 283 C-terminal amino acids of Ku80 introduced into the Chinese hamster ovary cell line CHO-K1 have a dominant negative effect. Expression of Ku(449-732) in CHO cells was verified by northern blot analysis and resulted in decreased Ku-dependent DNA end-binding activity, a diminished capacity to repair DSBs as determined by pulsed field gel electrophoresis and decreased radioresistance determined by clonogenic survival. The stable modifications observed at the molecular and cellular level suggest that this fragment of Ku80 confers a dominant negative effect providing an important mechanism to sensitise radioresistant cells.

Animals↗

PubMed2000

Comparison of diagnostic accuracy of sublingual nitroglycerin test and low-dose isoproterenol test in patients with unexplained syncope.

Despite the widespread use of head-up tilt testing as a means for diagnosing vasovagal syncope, standardization of test methodology remains a controversial issue. The aim of this study was to compare the diagnostic value of head-up tilt testing potentiated with sublingual nitroglycerin with that of head-up tilt testing potentiated with low-dose isoproterenol. For this purpose, 71 patients with unexplained syncope (mean age 43 years) and 30 asymptomatic controls were studied. All underwent the sublingual nitroglycerin and low-dose isoproterenol tests on separate days in a randomized fashion. The protocol of the 2 tests was similar and consisted of 2 phases. Initially, subjects were tilted at 60 degrees for 20 minutes without medication; then, if syncope did not occur, patients and controls received sublingual nitroglycerin (300 microg) or low-dose intravenous isoproterenol (mean infusion rate 1.3 +/- 0.5 microg/min) and continued to be tilted at 60 degrees for a further 20 minutes. During the sublingual nitroglycerin test, a positive response (syncope associated with sudden hypotension and bradycardia) occurred in 35 patients (49%), a negative response in 36 (51%), and drug intolerance in none (0%). During the low-dose isoproterenol test, these percentages were 41%, 59%, and 6%, respectively. A concordant response was observed in 53 cases (75%). Among controls, 3 subjects (10%) had a positive response to the sublingual nitroglycerin test and 4 (13%) to the low-dose isoproterenol test. It is concluded that sublingual nitroglycerin and low-dose isoproterenol are equivalent tests for evaluating patients with unexplained syncope. The sublingual nitroglycerin test, however, is simpler, better tolerated, and safer than the low-dose isoproterenol test and, thus, more suitable for routine clinical use.

Administration, Sublingual↗

PubMed2000

Radiation-induced expression of functional Fas ligand in EBV-positive human nasopharyngeal carcinoma cells.

Ionizing radiation remains a major therapeutic tool against human cancers, especially epithelial tumors, which account for the majority of human malignancies. Although Fas and Fas-L are essential determinants of apoptosis, few data support their role in the cytotoxic effect of ionizing radiation. Epstein-Barr-virus (EBV)-positive nasopharyngeal carcinoma (NPC) were chosen to address this question owing to their known sensitivity to ionizing radiation and their constitutive expression of the Fas-receptor. We here report that, in xenografted NPC cells, Fas-L expression, which was very low in basal conditions, was dramatically increased by tumor irradiation. Both the Fas receptor and the Fas ligand were found to be functional in this model, and a high proportion of irradiated NPC cells underwent apoptosis following tumor irradiation. Induction of Fas-L expression and apoptosis were observed for doses as low as 2 Gy. These data show an increase in Fas-L expression upon irradiation exposure, and strongly suggest that, in some epithelial malignancies, Fas-mediated apoptosis can play a major role in the anti-tumor effect of ionizing radiation, in the range of doses used for therapeutic applications.

Animals↗

PubMed2000

Transfer of Ku86 RNA antisense decreases the radioresistance of human fibroblasts.

Ku86 has been shown to be involved in DNA double-strand break (DSB) repair and radiosensitivity in rodents, but its role in human cells is still under investigation. The purpose of this study was to evaluate the radiosensitivity and DSB repair after transfection of a Ku86-antisense in a human fibroblast cell line. Simian virus 40-transformed MRC5V1 human fibroblasts were transfected with a vector (pcDNA3) containing a Ku86-antisense cDNA. The main endpoints were Ku86 protein level, Ku DNA end-binding and DNA protein kinase activity, clonogenic survival, and DSB repair kinetics. After transfection of the Ku86-antisense, decreased Ku86 protein expression, Ku DNA end-binding activity, and DNA protein kinase activity were observed in the uncloned cellular population. The fibroblasts transfected with the Ku86-antisense showed also a radiosensitive phenotype, with a surviving fraction at 2 Gy of 0.29 compared with 0.75 for the control and 20% of unrepaired DSB observed at 24 hours after irradiation compared with 0% for the control. Several clones were also isolated with a decreased level of Ku86 protein, a surviving fraction at 2 Gy between 0.05 and 0.40, and 10-20% of unrepaired DSB at 24 hours. This study is the first to show the implication of Ku86 in DSB repair and in the radiosensitivity of human cells. This investigation strongly suggests that Ku86 could constitute an appealing target for combining gene therapy and radiation therapy.

Amino Acid Sequence↗

PubMed2000

Decreased DNA-PK activity in human cancer cells exhibiting hypersensitivity to low-dose irradiation.

Low-dose hyper-radiosensitivity (HRS) (below 0.5 Gy) has been extensively documented in the past few years. The molecular basis of this phenomenon remains largely unknown and the purpose of this study was to investigate the possible implication of the DNA repair DNA-PK complex. The activity of the DNA-PK complex, i.e. Ku DNA-end binding activity and kinase activity of the whole complex, was studied in 10 human cancer cell lines, 2 h after 0.2, 0.5 and 1 Gy irradiation. After low-dose irradiation (0.2 Gy), a marked decrease in DNA-PK activity was found in all six cell lines exhibiting HRS, whereas the DNA-PK activity was increased in the four cell lines which did not exhibit HRS. This modulation of DNA-PK activity was a rapid phenomenon occurring within the 2 h following low-dose radiation exposure. These data strongly suggest the implication of the DNA-PK repair complex in the HRS phenomenon.

Amino Acid Sequence↗

PubMed1999

Cross-resistance to ionizing radiation in a murine leukemic cell line resistant to cis-dichlorodiammineplatinum(II): role of Ku autoantigen.

cis-Dichlorodiammineplatinum(II) (CDDP; cisplatin) is commonly used in combination with ionizing radiation (IR) in the treatment of various malignancies. In vitro, many observations suggest that acquisition of CDDP resistance in cell lines confers cross-resistance to IR, but the molecular mechanisms involved have not been well documented yet. We report here the selection and characterization of a murine CDDP-resistant L1210 cell line (L1210/3R) that exhibits cross-resistance to IR because of an increased capacity to repair double-strand breaks compared with parental cells (L1210/P). In resistant cells, electrophoretic mobility shift assays revealed an increased DNA-end binding activity that could be ascribed, by supershifting the retardation complexes with antibodies, to the autoantigen Ku. The heterodimeric Ku protein, composed of 86-kDa (Ku80) and 70-kDa (Ku70) subunits, is the DNA-targeting component of DNA-dependent protein kinase (DNA-PK), which plays a critical role in mammalian DNA double-strand breaks repair. The increased Ku-binding activity in resistant cells was associated with an overexpression affecting specifically the Ku80 subunit. These data strongly suggest that the increase in Ku activity is responsible for the phenotype of cross-resistance to IR. In addition, these observations, along with previous results from DNA-PK- mutant cells, provide evidence in favor of a role of Ku/DNA-PK in resistance to CDDP. These results suggest that Ku activity may be an important molecular target in cancer therapy at the crossroad between cellular responses to CDDP and IR.

Animals↗

PubMed1998

Coexistence of mitochondrial DNA and beta myosin heavy chain mutations in hypertrophic cardiomyopathy with late congestive heart failure.

OBJECTIVE: To investigate the possible coexistence of mitochondrial DNA (mtDNA) mutations in patients with beta myosin heavy chain (beta MHC) linked hypertrophic cardiomyopathy (HCM) who develop congestive heart failure. DESIGN: Molecular analysis of beta MHC and mtDNA gene defects in patients with HCM. SETTING: Cardiovascular molecular diagnostic and heart transplantation reference centre in north Italy. PATIENTS: Four patients with HCM who underwent heart transplantation for end stage heart failure, and after pedigree analysis of 60 relatives, eight additional affected patients and 27 unaffected relatives. A total of 111 unrelated healthy adult volunteers served as controls. Disease controls included an additional 27 patients with HCM and 102 with dilated cardiomyopathy. INTERVENTION: Molecular analysis of DNA from myocardial and skeletal muscle tissue and from peripheral blood specimens. MAIN OUTCOME MEASURES: Screening for mutations in beta MHC (exons 3-23) and mtDNA tRNA (n = 22) genes with denaturing gradient gel electrophoresis or single strand conformational polymorphism followed by automated DNA sequencing. RESULTS: One proband (kindred A) (plus seven affected relatives) had arginine 249 glutamine (Arg249Gln) beta MHC and heteroplasmic mtDNA tRNAIle A4300G mutations. Another unrelated patient (kindred B) with sporadic HCM had identical mutations. The remaining two patients (kindred C), a mother and son, had a novel beta MHC mutation (lysine 450 glutamic acid) (Lys450Glu) and a heteroplasmic missense (T9957C, phenylalanine (Phe)-->leucine (Leu)) mtDNA mutation in subunit III of the cytochrome C oxidase gene. The amount of mutant mtDNA was higher in the myocardium than in skeletal muscle or peripheral blood and in affected patients than in asymptomatic relatives. Mutations were absent in the controls. Pathological and biochemical characteristics of patients with mutations Arg249Gln plus A4300G (kindreds A and B) were identical, but different from those of the two patients with Lys450Glu plus T9957C(Phe-->Leu) mutations (kindred C). Cytochrome C oxidase activity and histoenzymatic staining were severely decreased in the two patients in kindreds A and B, but were unaffected in the two in kindred C. CONCLUSIONS: beta MHC gene and mtDNA mutations may coexist in patients with HCM and end stage congestive heart failure. Although beta MHC gene mutations seem to be the true determinants of HCM, both mtDNA mutations in these patients have known prerequisites for pathogenicity. Coexistence of other genetic abnormalities in beta MHC linked HCM, such as mtDNA mutations, may contribute to variable phenotypic expression and explain the heterogeneous behaviour of HCM.

Adult↗

PubMed1998

Respiratory effects of pharingeal gas insufflation in patients with chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate the effects of pharyngeal gas insufflation (PGI) in clinically stable patients with chronic obstructive pulmonary disease (COPD). DESIGN: Prospective study in humans. SETTING: Department of Intensive Care Medicine at a University Hospital. PATIENTS: Seven clinically stable COPD patients. INTERVENTION: Pharyngeal dry fresh air insufflation (PGI) with a continuous flow rate of 4 L/min was given via a nasal catheter placed into the oropharynx. Baseline measurements with zero flow were made at the beginning and end of the test. After an equilibration period of 1 h at each stage, arterial blood samples were analyzed every 5 min until PaCO2 variation less than 5% confirmed the achievement of a steady state. Thereafter expiratory flow signal and expiratory gas were collected over a period of 3 min and arterial blood was sampled after 1'30" and 2'30" from the beginning of the test for the measurement of effective expiratory volume (VE eff), respiratory rate (RR), tidal volume (VT), dead space fraction (VD/VT), dead space (VD), alveolar ventilation (VA), total expiratory time (TE min), and PaCO2, respectively. RESULTS: During PGI VT, VD/VT, VD and VE eff fell significantly from baseline values, RR was slightly reduced and VA, TE min and PaCO2 remained unchanged throughout the study. CONCLUSIONS: Although in our study the effect of PGI on VD could be overestimated since our device for expiratory gas flow measurement and collection significantly enlarged the anatomical dead space receiving the washout effect of the fresh gas insufflation, under the experimental conditions PGI produces a reduction in VD and VD/VT, and, as a consequence, a significative reduction in respiratory requirements in clinically stable COPD patients. If confirmed in clinical settings, potential advantages of PGI could include: a) reduction of the work of breathing in patients with intact neuro-respiratory coupling; b) minimizing hypercapnic side effects of oxygen therapy often seen in COPD patients.

Aged↗

PubMed1997

Additional inspiratory resistance imposed by the laryngeal mask airway: in vitro versus in vivo comparison.

The present study was designed: (a) to compare the additional inspiratory laryngeal mask airway (LMA) resistance measured in vitro during simulated ventilation and in vivo in five anaesthetised and mechanically ventilated patients; and (b) to evaluate the resistive pressure drop along the length of the LMA. After the differential pressure across the mask was measured, the pressure-flow relationship was characterised by Rohrer's equation and in vitro and in vivo resistance was calculated. Thereafter, the distal pressure measuring point was moved along the length of the LMA and differential pressure was measured at each point under in vitro and in vivo conditions. Values for resistance were approximately twice as great in vivo as those obtained in vitro, with most of the resistive pressure drop occurring across the vertical bars, especially when measured in vivo. We conclude that in vivo positioning of the LMA significantly increases resistance because of the configurational changes occurring when the LMA is in situ.

Adult↗

PubMed1996

Tilt test results in young and elderly patients with syncope of unknown origin.

The effects of aging on the results of prolonged drug-free tilt testing were studied in 175 consecutive patients with unexplained syncope divided into 3 groups: 59 patients < 40 years old; 57 patients between 40 and 60 years; and 59 patients > 60 years old. Tilt-induced vaso-vagal syncope occurred respectively in 17 (29%), 20 (35%), and 18 patients (31%) in the 3 age groups. Vasodepressor, mixed, and cardioinhibitory vaso-vagal syncope occurred similarly in the 3 groups; organic heart disease and systemic hypertension were more frequent in elderly patients without affecting the incidence of tilt-induced syncope. Blood pressure and heart rate variations during syncope were similar in the 3 age groups; in the first 20 minutes of tilt testing, before the appearance of the vaso-vagal reflex, elderly patients showed greater reduction in blood pressure and smaller increase in heart rate than younger patients. Our data indicate that increasing age determines a different blood pressure and heart rate behavior during tilt testing, but apparently does not influence the incidence of vaso-vagal syncope in patients with syncope of undetermined etiology. As the proportion of patients with a positive isoproterenol tilt test was reported to decline with age, our results suggest that the reduced incidence of syncope during isoproterenol tilt testing could be the expression of impaired autonomic response among elderly syncope patients.

Adult↗

PubMed1994

Frequency and significance of drug resistance in vulvovaginal candidiasis.

The rates of non-albicans species and susceptibility to the main antimycotic drugs were evaluated in a series of 472 cultures of vulvar or vaginal specimens positive for Candida species. Torulopsis glabrata was associated more frequently than C. albicans with recurrent vulvovaginal candidiasis (18/40 vs. 72/379; p = 0.003, chi 2 test). As evaluated by the results of susceptibility testing, C. albicans isolates were uniformly sensitive to the antifungals tested, whereas 7.5% (3/40) of T. glabrata strains were resistant to imidazole derivatives. All these patients had a history of repeated antimycotic treatments. Previous antimycotic therapies in susceptible individuals could cause a selection of non-albicans species, especially T. glabrata, which is occasionally resistant to the commonly used antimycotic drugs.

AIDS-Related Opportunistic Infections↗

PubMed1993

Factors that predict spontaneous remission of ectopic atrial tachycardia.

Ectopic atrial tachycardia (EAT) is usually considered as benign and easy to treat. The natural history of the disease, however, has not yet been clarified. The purpose of the study was to analyse its spontaneous evolution in a cohort of EAT patients and to define a predictive model of remission based on several factors. Between 1973 to 1989, 46 patients (25 male, 21 female), aged 38 +/- 18 years, entered the study. Clinically EAT was paroxysmal in 23 patients, permanent in 12 and repetitive in 11; six patients were asymptomatic. Thirty-five complained of palpitations; dyspnoea, dizziness and syncope were also reported less frequently. All patients underwent an electrophysiological study to clarify the mechanism of the arrhythmia and to localize its site of origin. In 15 patients no heart disease was documented. Five patients underwent surgery and were excluded from subsequent analysis. Seven patients were discharged without antiarrhythmic treatment. We defined remission as the absence of recurrence of EAT within 6 months from withdrawal of therapy. Logistic regression was applied to identify potential predictors of remission. Seven clinical and electrophysiological covariates were entered in the model; univariate and multivariate tests were performed, using the GLIM3 statistical package. During a follow-up period of 5.1 +/- 4.5 years, 14 instances of remission (34%) were observed in 5/22 patients with paroxysmal EAT, 4/8 patients with permanent EAT and 5/11 patients with repetitive EAT. Mean age of patients with remission was 25 +/- 14 years vs 45 +/- 15 years in the group without remission. No covariate had an independent predictive value.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1990

Prognostic value of hyponatremia in patients with severe chronic heart failure.

In order to evaluate the incidence and the prognostic value of hyponatremia (hypoNa) in patients (pts) with severe chronic heart failure (SCHF), the authors studied 161 consecutive pts (113M, 48F ages sixty-seven +/- ten) with SCHF in NYHA class III-IV. The cause of SCHF was ischemic in 64 pts, hypertensive in 39, valvular in 14, alcohol-related in 3, and idiopathic in 41. Pretreatment hypoNa (less than 135 mmol/L) was found in 64/161 pts (40%) (Group I); Na+ was less than 125 in 10 pts, 125-130 in 19, and 131-135 mmol/L in 35; 42/64 pts (66%) of Group I were in NYHA class IV at admission. In the pts with pretreatment Na+ less than 125 mmol/L, hypoNa was persistent and refractory to high-dose furosemide (less than 500 mg/day) and water restriction. Cardiovascular mortality of Group I pts was 69% within twenty-four months (34 pts died of low-output syndrom and 10 suddenly). All pts with Na+ less than 130 mmol/L died within six months. The 20 pts who normalized Na+ are alive, and in NYHA class II-III (follow-up: twenty-six +/- fifteen, six to sixty months). Pts without hypoNa were 97/161 (Group II), and 58/97 (60%) are alive (follow-up: thirty +/- eighteen, five to fifty-eight months), whereas 39 pts died (27 suddenly, 9 of low-output syndrome, and 3 of extracardiac disease) within twenty-four months. The mortality rate of Group II was significantly lower (40% vs 69%, p less than 0.001) compared with Group I. The two groups were similar for age, sex, and cause and duration of SCHF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗