Secretome profile of Cellulomonas sp. B6 growing on lignocellulosic substrates.

AIMS: Lignocellulosic biomass deconstruction is a bottleneck for obtaining biofuels and value-added products. Our main goal was to characterize the secretome of a novel isolate, Cellulomonas sp. B6, when grown on residual biomass for the formulation of cost-efficient enzymatic cocktails. METHODS AND RESULTS: We identified 205 potential CAZymes in the genome of Cellulomonas sp. B6, 91 of which were glycoside hydrolases (GH). By secretome analysis of supernatants from cultures in either extruded wheat straw (EWS), grinded sugar cane straw (SCR) or carboxymethylcellulose (CMC), we identified which proteins played a role in lignocellulose deconstruction. Growth on CMC resulted in the secretion of two exoglucanases (GH6 and GH48) and two GH10 xylanases, while growth on SCR or EWS resulted in the identification of a diversity of CAZymes. From the 32 GHs predicted to be secreted, 22 were identified in supernatants from EWS and/or SCR cultures, including endo- and exoglucanases, xylanases, a xyloglucanase, an arabinofuranosidase/ß-xylosidase, a ß-glucosidase and an AA10. Surprisingly, among the xylanases, seven were GH10. CONCLUSIONS: Growth of Cellulomonas sp. B6 on lignocellulosic biomass induced the secretion of a diverse repertoire of CAZymes. SIGNIFICANCE AND IMPACT OF THE STUDY: Cellulomonas sp. B6 could serve as a source of lignocellulose-degrading enzymes applicable to bioprocessing and biotechnological industries.

Translating the combination of gene therapy and tissue engineering for treating recessive dystrophic epidermolysis bullosa.

The combination of gene therapy and tissue engineering is one of the most promising strategies for the treatment of recessive dystrophic epidermolysis bullosa (RDEB). RDEB is a rare genetic disease characterised by mutations in the COL7A1 gene, encoding type VII collagen (COLVII), which forms anchoring fibrils at the dermal-epidermal junction of the skin. This disease causes severe blistering and only palliative treatments are offered. In this study, the base of a strategy combining gene therapy and a tissue-engineered skin substitute (TES), which would be suitable for the permanent closure of skin wounds, was set-up. As a high transduction efficiency into fibroblasts and/or keratinocytes seems to be a prerequisite for a robust and sustained correction of RDEB, different envelope pseudotyped retroviral vectors and the transduction enhancer EF-C were tested. When green fluorescent protein (GFP) was used as a reporter gene to evaluate the retroviral-mediated gene transfer, the fibroblast infection efficiency was 30 % higher with the Ampho pseudotyped vector as compared with the other pseudotypes. At least a 3.1-fold and a 1.3-fold increased transduction were obtained in fibroblasts and keratinocytes, respectively, with EF-C as compared with polybrene. A continuous and intense deposit of haemagglutinin (HA)-COLVII was observed at the dermal-epidermal junction of self-assembled TESs made of cells transduced with a HA-tagged COL7A1 vector. Furthermore, HA-tagged basal epidermal cells expressing keratin 19 were observed in TESs, suggesting stem cell transduction. This approach could be a valuable therapeutic option to further develop, in order to improve the long-term life quality of RDEB patients.

Tricuspid annular plane systolic excursion and pulmonary arterial systolic pressure relationship in heart failure: an index of right ventricular contractile function and prognosis.

Echo-derived pulmonary arterial systolic pressure (PASP) and right ventricular (RV) tricuspid annular plane systolic excursion (TAPSE; from the end of diastole to end-systole) are of basic relevance in the clinical follow-up of heart failure (HF) patients, carrying two- to threefold increase in cardiac risk when increased and reduced, respectively. We hypothesized that the relationship between TAPSE (longitudinal RV fiber shortening) and PASP (force generated by the RV) provides an index of in vivo RV length-force relationship, with their ratio better disclosing prognosis. Two hundred ninety-three HF patients with reduced (HFrEF, n = 247) or with preserved left ventricular (LV) ejection fraction (HFpEF, n = 46) underwent echo-Doppler studies and N-terminal pro-brain-type natriuretic peptide assessment and were tracked for adverse events. The median follow-up duration was 20.8 mo. TAPSE vs. PASP relationship showed a downward regression line shift in nonsurvivors who were more frequently presenting with higher PASP and lower TAPSE. HFrEF and HFpEF patients exhibited a similar distribution along the regression line. Given the TAPSE, PASP, and TAPSE-to-PASP ratio (TAPSE/PASP) collinearity, separate Cox regression and Kaplan-Meier analyses were performed: one with TAPSE and PASP as individual measures, and the other combining them in ratio form. Hazard ratios for variables retained in the multivariate regression were as follows: TAPSE/PASP

Effects on survival of loop diuretic dosing in ambulatory patients with chronic heart failure using a propensity score analysis.

OBJECTIVE: To ascertain whether increasing doses of orally administered furosemide are associated with impaired survival in outpatients with chronic heart failure (CHF) and left ventricular (LV) systolic dysfunction. METHODS: Transthoracic echo-Doppler examination was carried out at baseline in 813 consecutive CHF outpatients with LV ejection fraction ≤ 45%. The total daily dose of furosemide was assessed for each patient. Chronic kidney disease (CKD) was defined by a glomerular filtration rate < 60 ml/min/1.73 m(2). The end-point was all-cause mortality. To control the prognostic effect of furosemide for the propensity of using high doses of the drug, the Cox model was stratified by the propensity score, itself computed from a multivariable logistic model. Mean follow up was 44 months. RESULTS: After stratification for the propensity score, the risk of death increased linearly across quartiles of furosemide dose (HR 1.38, 95% CI 1.14-1.68, p < 0.001). A daily dose of 50 mg was identified as the best threshold value to predict a high risk of death within 3 years with an area under the ROC curve of 0.68 (95% CI 0.64-0.72). Increasing doses of furosemide were associated with an increased risk of death regardless of LV filling pattern, CKD and background therapy with ACE-inhibitors or beta-blockers. CONCLUSIONS: In outpatients with CHF, after stratification for the propensity score, the risk of death increased linearly across quartiles of furosemide daily dose. A threshold furosemide dose of 50 mg was related with the worse outcome.

Paediatric nurses' perception of the child-family dyad's autonomy in managing a chronic disease situation: the experience of an Italian paediatric department.

INTRODUCTION: Chronically ill patients have to take several medications and non-adherence to treatment can lead to severe and negative outcomes. Therefore, several interventions are suggested in literature to improve adherence rates in clinical practice. Adherence to treatment can be particularly troublesome in adolescents, who strive for autonomy and self-care independence. Literature suggests that improving adherence is useful to guarantee positive outcomes and reduce costs. AIM: To explore how nurses perceived autonomy in parents, adolescents, and children related to the management of chronic disease. MATERIALS AND METHODS: A qualitative study including 1 focus group and 7 semi-structured interviews conducted between September 2011 and October 2011. The qualitative date were analysed with the thematic analysis method. The sample included 12 paediatric nurses working in a Children's Cystic Fibrosis Unit and Neuromuscular Disease Unit. RESULTS: The 5 main categories that emerged from this qualitative study after he process of categorization were: 'Changes in daily lifestyle', 'Nurses' attitude towards educating the dyad', 'Adolescence and transition', 'Parents' attitudes towards chronic disease', and 'Availability of information'. DISCUSSION: Correct information and education is crucial for families who have a chronically ill child. Internet can be a misleading source of information and provide wrong information also in relation to prevention.

Sodium nitroprusside for advanced heart failure. A metanalysis of literature data.

Advanced heart failure (HF) is associated with a very poor prognosis and places a big burden on health-care services. The gold standard treatment, i.e. long-term mechanical circulatory support or heart transplantation, is precluded in many patients but observational studies suggest that the use of SNP might be associated with favourable long-term clinical outcomes. We performed a metanalysis of published studies that compared sodium nitroprusside (SNP) with optimal medical therapy to examine the safety and efficacy of SNP as part of the treatment regimen of patients hospitalized for advanced heart failure (HF). We searched PUBMED, EMBASE and WEB OF SCIENCE for studies that compared SNP with optimal medical therapy in advanced HF on July 2022. After screening 700 full-text articles, data from two original articles were included in a combined analysis. The analysis demonstrated a 66% reduction in the odds of death in advanced HF patients treated with SNP. The results show the potential importance of the inclusion of SNP in the treatment regimen of patients hospitalized because of advanced HF and underlines that controlled, randomized studies are still required in this condition.

Iatrogenic atrial septal defect does not affect acute hemodynamic modifications after transcatheter edge-to-edge repair in patients with functional mitral regurgitation.

OBJECTIVE: The correction of functional mitral regurgitation (FMR) with transcatheter edge-to-edge repair (TEER) can favorably affect patients' hemodynamic profile. However, the procedure requires inter-atrial trans-septal access and the hemodynamic relevance of the residual iatrogenic atrium septal defect (iASD) is still debated. This study aimed at investigating the hemodynamic modifications during TEER with MitraClip, before and after the iASD creation, in patients with heart failure with reduced ejection fraction (HFrEF) and severe FMR. METHODS: Thirty-nine HFrEF patients with 3+ or 4+/4+ FMR were included. Right heart catheterization was performed at baseline after general anesthesia induction and at the end of TEER, both before and after removing the device guiding catheter. RESULTS: Compared with baseline, MitraClip positioning was followed by a significant immediate improvement in cardiac output (respectively: 3.36 vs 5.05 ml/min), pulmonary artery wedge pressure (23.7 vs 18.2 mmHg), mean pulmonary artery pressure (34.4 vs 27.7 mmHg) and pulmonary vascular resistance (3.6 vs 2.2 Wood Units) (all p < 0.001). No further significant modifications occurred after removing the device guiding catheter. CONCLUSIONS: Our data suggest that the acute hemodynamic modifications after TEER are not influenced by the induction of iASD in patients with FMR.

The tailored medical therapy in patients with advanced heart failure referred for cardiac transplantation.

INTRODUCTION: Optimal pharmacologic management of heart transplant (HT) candidates is required prior to evaluation so as to obtain a reliable prognostic stratification and to address the donor shortage. The aim of this study was to determine whether a tailored medical approach was effectively achieved before HT waiting list enrollment. MATERIALS AND METHODS: This study concerned 40 consecutive patients referred for HT evaluation who underwent a clinical assessment, including hemodynamic, echocardiographic, and brain natriuretic peptide determinations. Medical therapy was optimized according to the clinical assessment to improve neurohormonal and hemodynamic profiles. We analyzed the distribution of the different drugs between the first and the following evaluation to demonstrate whether a significant improvement of medical therapy could be achieved in advanced chronic heart failure (ACHF). RESULTS: The mean age was 53 years, including 93% males. The etiology of disease was ischemic in 40% and idiopathic in 45%. The mean left ventricular ejection fraction was 23%, mean values of hemodynamic data were cardiac index (CI) 2+/-0.6 L/min/m(2), mean pulmonary arterial pressure (mPAP) 30+/-10 mm Hg, wedge pressure (PWP) 23+/-8 mm Hg; mean BNP was 618 pg/mL. Median follow-up was 397 days; 82% of candidates underwent HT waiting-list enrollment. The medical treatment was modified as follows: beta-blockers were introduced or uptitrated in 32%, angiotensin receptor blockers (ARB) were introduced in 7.5%, spironolactone was started in 42%, nitrates were introduced in 20%, and diuretics were uptitrated in 35% of patients. CONCLUSION: In patients with ACHF referred for HT, a further effort in the assessment of the medical treatment is strongly recommended.

Left atrial dilatation in systolic heart failure: a marker of poor prognosis, not just a buffer between the left ventricle and pulmonary circulation.

BACKGROUND: The relation between systolic pulmonary pressure (sPAP) and left atrium in patients with heart failure (HF) is unclear. Diastolic dysfunction, expressed as restrictive mitral filling pattern (RMP), and functional mitral regurgitation (FMR) are associated with both LA enlargement and increased sPAP. We aimed to evaluate whether atrial dilation might modulate the consequences of RMP and FMR on the pulmonary circulation of patients with HF with reduced ejection fraction (HFrEF). METHODS: 1256 HFrEF patients were retrospectively recruited in four Italian centers. Left ventricular (LVD) and atrial (LAD) diameters were measure by m-mode, and EF were measured. RMP was defined as E-wave deceleration time lower than 140 ms. FMR was quantitatively measured. sPAP was evaluated based on maximal tricuspid regurgitant velocity and estimated right atrial pressure. RESULTS: Final study population was formed by 1005 patients because of unavailability of sPAP in 252 patients. Mean EF was 33 ± 3, 35% had RMP, 67% had mild, and 26% moderate-to-severe FMR. 69% of patients had increased sPAP. A significant association was observed between sPAP and EF, RMP, FMR, and LAD (p < 0.0001 for all). At multivariate analysis, LAD was positively associated with sPAP (p < 0.0001) independently of EF, RMP, and FMR. Analogously, LAD (p < 0.05) was associated with more severe symptoms and worse prognosis after adjustment for LV function and FMR. CONCLUSION: LA dilation was positively associated with sPAP independently of EF, RMP, and FMR. This highlights that LA size should be considered a marker of the severity of the disease.

Cloning and sequence analysis of the TcP2 beta cDNA variants of Trypanosoma cruzi.

P2 beta acidic ribosomal protein is a relevant antigen in Chagas' disease. cDNA cloning demonstrated that Trypanosoma cruzi expresses at least six types of TcP2 beta transcripts that differed by point nucleotides substitutions. The distribution and type of mutations seemed to follow the typical structural organization of eukaryotic acidic ribosomal proteins. Most of the synonymous changes clustered in the amino-terminus, suggesting that conservation of this domain was crucial for an equivalent functional ability of each TcP2 beta variant to bind to the ribosome. Interestingly, most amino acid changes in the central-globular and hinge domains caused polymorphism in putative phosphorylatable sites.

Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure.

OBJECTIVES: We sought a better understanding of the coupling between right ventricular ejection fraction (RVEF) and pulmonary artery pressure (PAP), as it might improve the accuracy of the prognostic stratification of patients with heart failure. BACKGROUND: Despite the long-standing view that systolic function of the right ventricle (RV) is almost exclusively dependent on the afterload that this cardiac chamber must confront, recent studies claim that RV function is an independent prognostic factor in patients with chronic heart failure. METHODS: Right heart catheterization was performed in 377 consecutive patients with heart failure. RESULTS: During a median follow-up period of 17 +/- 9 months, 105 patients died and 35 underwent urgent heart transplantation. Pulmonary artery pressure and thermodilution-derived RVEF were inversely related (r = 0.66, p < 0.001). However, on Cox multivariate survival analysis, no interaction between such variables was found, and both turned out to be independent prognostic predictors (p < 0.001). It was found that RVEF was preserved in some patients with pulmonary hypertension, and that the prognosis of these patients was similar to that of the patients with normal PAP. In contrast, when PAP was normal, reduced RV function did not carry an additional risk. CONCLUSIONS: These observations emphasize the necessity of combining the right heart hemodynamic variables with a functional evaluation of the RV when trying to define the individual risk of patients with heart failure.

Effect of transdermal nitroglycerin or N-acetylcysteine, or both, in the long-term treatment of unstable angina pectoris.

OBJECTIVES: This study was designed to evaluate whether the addition of transdermal nitroglycerin or oral N-acetylcysteine, or both, to conventional medical therapy improves the natural history of unstable angina pectoris. BACKGROUND: Transdermal nitroglycerin is widely used to treat angina pectoris, but the development of tolerance is a major problem that may reduce its clinical efficacy. It has been suggested that the addition of N-acetylcysteine to nitroglycerin reverses the development of tolerance, potentiates the hemodynamic response to nitroglycerin and may improve in-hospital prognosis in unstable angina. METHODS: We assessed the efficacy of adding transdermal nitroglycerin or oral N-acetylcysteine, or both, to conventional medical therapy in a randomized, double-blind, placebo-controlled trial involving 200 patients with unstable angina who were followed up for 4 months. RESULTS: Outcome events--death, myocardial infarction or refractory angina requiring revascularization--occurred in 31% of patients receiving nitroglycerin, 42% of those receiving N-acetylcysteine, 13% of those receiving nitroglycerin plus N-acetylcysteine and 39% of those receiving placebo (p = 0.0052). Kaplan-Meier curves showed a higher probability (p < 0.01) of no failure of medical treatment in the group receiving both nitroglycerin and N-acetylcysteine than in those receiving placebo, N-acetylcysteine or nitroglycerin alone. The combination of nitroglycerin and N-acetylcysteine was associated with a high incidence of side effects (35%), mainly intolerable headache, which was almost twice as frequent as in patients receiving nitroglycerin alone. CONCLUSIONS: The combination of nitroglycerin and N-acetylcysteine, associated with conventional medical therapy in the long-term treatment of patients with unstable angina, reduces the occurrence of outcome events. However, the high incidence of side effects limits the clinical applicability of this therapeutic strategy at least at the dosage used in the present study.

Granulocyte function in coronary artery disease.

Granulocytes defend the body against invading microbes by producing a complex armamentarium of toxic substances, such as proteolytic enzymes, oxygen radicals and arachidonic acid metabolites. Under certain circumstances, however, such compounds may be released in the absence of phagocytosable particles, resulting in injury to normal cell and connective tissue degradation. Recent experimental studies have emphasized the potential role of granulocytes in the pathogenesis of myocardial ischemia. Clinical investigations have also shown alterations in neutrophil function in stable and unstable clinical manifestations of ischemic heart disease. "Priming" of granulocytes in stable forms of coronary disease may predispose to the subsequent development of acute coronary events, whereas activation of neutrophils may lead to alterations in vascular permeability and coronary flow regulation, leading to further myocardial and endothelial injury in acute myocardial infarction, unstable angina and coronary angioplasty.

Effects of atrial pacing and dipyridamole administration on coronary hemodynamics of collateralized myocardial regions in stable angina pectoris.

Great cardiac vein blood flow by thermodilution and great cardiac vein oxygen saturation were measured in 14 patients with stable exertional angina and an angiographic pattern of complete occlusion of the proximal left anterior descending artery retrogradely filled by collateral vessels supplying still viable myocardium. Measurements were obtained under control conditions, at peak atrial pacing and after dipyridamole administration (0.56 mg/kg intravenously over 4 minutes). Both stress tests induced ischemic electrocardiographic changes in all patients, but dipyridamole administration resulted in greater ST-segment depression in 11 patients (1.6 +/- 0.5 vs 2.4 +/- 1.6 mm, p less than 0.05) and transient ST-segment elevation in 3 patients. Dipyridamole provoked ischemia at a lower value of rate-pressure product (145.3 +/- 30.6 vs 202.9 +/- 36.6 beats/min . mm Hg . 10(-2), p less than 0.0005) and anterior region myocardial oxygen consumption (9.32 +/- 4.76 vs 11.39 +/- 3.91 ml/min, p less than 0.05), despite a greater increase in great cardiac vein flow (139.4 +/- 45 vs 93 +/- 27.4 ml/min, p less than 0.0025) and a greater decrease in the calculated index of anterior region coronary resistance (0.87 +/- 0.27 vs 1.46 +/- 0.43 mm Hg/ml/min, p less than 0.0005). Moreover, great cardiac vein oxygen saturation increased more significantly during dipyridamole-induced ischemia than at peak pacing (63 +/- 12 vs 35 +/- 8%, p less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Morphologic changes induced by acetylcholine infusion in normal and atherosclerotic coronary arteries.

Low doses of acetylcholine induce "endothelium-dependent" dilatation in normal coronary arteries and constriction of diseased vessels. This study investigated morphologic changes induced by perfusion of normal and diseased coronary arteries with low and high doses of acetylcholine. Vessels were excised from a series of beating hearts explanted at transplantation for idiopathic dilated cardiomyopathy and coronary artery disease. Coronary arteries from other explanted hearts, perfused with saline solution under similar conditions were taken as controls. Samples were studied using conventional histopathologic and immunohistochemical methods. Coronary arteries were grouped according to presence or absence of histologically detectable structural modifications of any type and extent. Low doses of acetylcholine induced changes in all but 1 structurally diseased coronary artery, whereas no change was induced in any but 1 histologically normal coronary artery. High doses of acetylcholine induced contraction changes in both normal and diseased vessels. Changes observed in the wall of the contracted vessels were: (1) endothelial cell contraction with protruding nuclei and detachment of their intercellular junctions with exposure of subjacent collagen to flow, (2) contraction of plaque smooth muscle cells, (3) formation of cushions protruding into vessel lumens causing blunt microchannels. Contraction in both intimal and plaque cells occurred even in diseased vessel segments with intimal denudation. These effects seemed to be dose-dependent in structurally normal vessels because low doses of acetylcholine did not produce any morphologically detectable changes in histologically normal coronary arteries, while low doses of acetylcholine induced similar reactions in vessels affected by both atherosclerosis and subintimal fibrocellular thickening.

Prognostic usefulness of the tricuspid annular plane systolic excursion in patients with congestive heart failure secondary to idiopathic or ischemic dilated cardiomyopathy.

The prognostic value of ultrasound evaluation of right ventricular (RV) performance in patients with congestive heart failure (CHF) is still a matter of investigation. We studied 140 consecutive patients with chronic CHF and a left ventricular ejection fraction <35%. All patients underwent a complete echocardiographic evaluation that systematically included the measurement of the tricuspid annular plane systolic excursion (TAPSE). During a follow-up period of 24 +/- 14 months, 45 patients died and 7 underwent emergency heart transplantation. At the multivariate survival analysis (Cox regression model) backward stepwise selection identified a prognostic model with 2 parameters: New York Heart Association (NYHA) class III or IV and TAPSE < or =14 mm (p <000). In a subgroup of 97 patients in sinus rhythm in whom mitral inflow Doppler variables could be measured, survival was further analyzed according to a model in which the significant parameters were included in the same order as usually used in routine clinical practice: clinical variables first, left ventricular function data second, mitral Doppler variables third, and indexes of right ventricular (RV) function last. TAPSE < or =14 mm added significant (p <0.03) prognostic information to NYHA class III or IV, left ventricular ejection fraction of <20%, and mitral deceleration time of < 125 ms. In conclusion, in patients with CHF, TAPSE adds significant prognostic information to the NYHA clinical classification, to the echocardiographic evaluation of left ventricular function, and to mitral Doppler variables. Furthermore, the measurement of TAPSE is easy to obtain in all patients, irrespective of heart rate and rhythm.

Value of right ventricular ejection fraction in predicting short-term prognosis of patients with severe chronic heart failure.

BACKGROUND: The prognosis of chronic heart failure has been studied extensively, but factors predicting short-term outcome in patients with severe chronic heart failure are still poorly defined, and the current indications for heart transplantation as a treatment for end-stage heart failure need on objective analysis. METHODS: Purpose of the study was to identify the determinants of short-term prognosis in a group of 142 consecutive ambulatory patients (mean age 49.8 +/- 11 years). Referred for heart transplantation because of severe chronic heart failure, the patients were admitted with left ventricular ejection fraction markedly depressed and had had symptoms in spite of an optimal standardized medical therapy for at least 1 month. Baseline clinical and instrumental evaluation included right-sided heart catheterization with a flow-directed multilumen thermodilution catheter, which enables determination of pressures, cardiac output, right ventricular volumes, and ejection fraction. RESULTS: Most patients were in New York Heart Association class III (61%) and IV (24%), and the hemodynamic profile was characterized by mean left ventricular ejection fraction of 20.2% +/- 6%, cardiac index of 2.13 +/- 0.6 l/min/m2, pulmonary capillary wedge pressure of 23.1 +/- 11 mm Hg, right atrial pressure of 7.9 +/- 6 mm Hg, right ventricular ejection fraction of 23.2% +/- 12.4%. During a mean follow-up of 11.1 +/- 9.4 months, 33 patients underwent transplantation (23.4%), 41 died (28.8%), and 68 were still alive (47.8%). There was a substantial overlap in left ventricular ejection fraction between patients divided on the basis of outcome, whereas right ventricular ejection fraction was significantly lower in patients who died or underwent transplantation. Cox multivariate analysis showed three independent prognostic variables: cause (p = 0.03), heart failure score (p = 0.001), and right ventricular ejection fraction (p = 0.000). Short-term survival (10 months) was significantly (p = 0.000) different in patients with > or = 24% or < 24% right ventricular ejection fraction. Statistical analysis identified right ventricular ejection fraction as the single variable to be highly correlated with an increased risk of early death. CONCLUSIONS: This study suggests that right ventricular function is a crucial determinant of short-term prognosis in severe chronic heart failure. Statistical analysis identified right ventricular ejection fraction, determined by thermodilution during right-sided heart catheterization, as the single most important predictor of short-term prognosis in a large cohort of patients who had symptoms in spite of a standardized, optimized, multipharmacologic treatment. The variable allows a useful risk stratification in patients with severe chronic heart failure and uniformly depressed left ventricular ejection fraction and provides guidance in the assessment of indications and timing for transplantation.

Long-term survival and risk stratification in patients with angina at rest undergoing medical treatment.

In order to determine those factors which influence long-term prognosis in patients with angina at rest associated with transient ST-segment changes, 217 patients undergoing medical treatment were followed for a mean of 39 months. All patients underwent coronary arteriography. Univariate analysis identified 12 variables significantly related to prognosis. These were disease of the left main coronary artery; the number of diseased vessels; left ventricular end-diastolic pressure; ejection fraction; baseline electrocardiogram; presence of prior myocardial infarction; ST-segment depression and ventricular arrhythmias during pain; disease of the proximal anterior descending coronary artery; crescendo angina; hypertension; and age. Use of the Cox regression model for survival analysis revealed only 3 variables which were independent predictors of prognosis. They were disease of the left main coronary artery; the number of diseased vessels and left ventricular end-diastolic pressure. The model allowed stratification of patients into 3 groups. Survival at 3 years was 98% in the low risk group; 82% in the intermediate risk group; and 58% in the high risk group. These data indicate that disease of the left main coronary artery, the number of diseased vessels and left ventricular end-diastolic pressure are the independent predictors of prognosis in angina at rest. These variables may allow stratification of patients into groups having different long-term survivals.

Clinical application of monitoring techniques: coronary sinus blood flow monitoring.

Measurement of coronary sinus blood flow by continuous thermodilution is a well established technique for the clinical study of myocardial perfusion. More recently, advances in catheter technology enabled regional left ventricular flow measurements. In particular, measurement of flow from the great cardiac vein appears to accurately reflect the perfusion of the left anterior descending coronary artery. This regional approach allowing the correlation with coronary arterial anatomy, has contributed to an improved understanding of the mechanisms by which functional factors interact with organic narrowing in the genesis of myocardial ischemia at rest, during provocative tests and during exercise. In addition, it has provided useful information in the evaluation of antianginal drugs through the discrimination between the effects on coronary resistance and myocardial oxygen consumption.

Echocardiographic evolution of left ventricular and left atrial thrombi in a patient with left ventricular dysfunction due to alcoholic cardiomyopathy, chronic atrial fibrillation and multiple non-fatal systemic embolisms.

The echocardiographic characteristics and evolution of multiple pedunculated left atrial and left ventricular intracavitary thrombi in a patient with alcoholic cardiomyopathy are reported. The patient had a long history of left ventricular dysfunction and atrial fibrillation but the referring physician had not prescribed anticoagulant prophylaxis. Multiple, non-fatal, systemic embolizations occurred during hospitalization and echocardiography was used to monitor the effect of the anticoagulant therapy on the remodelling and final dissolution of intracavitary thrombi.