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Biomedical subjects

Laura Scelsi

Publications and source records attributed to Laura Scelsi.

13 recordsLinked to original sources

Reverse right ventricular remodeling after pulmonary endarterectomy.

OBJECTIVES: We sought to evaluate the capability of the right ventricle to regain normal morphology and function after pulmonary endarterectomy, to correlate right ventricular reverse remodeling with functional status, and to identify independent predictors of clinical failure after surgical intervention. METHODS: From December 2000 through August 2003, 45 patients underwent isolated pulmonary endarterectomy. Morphology and function of the right ventricle were studied by using a combination of right heart catheterization, cardiac magnetic resonance, and transthoracic echocardiography. Functional status was evaluated by using New York Heart Association class. Full preoperative data were available for 37 candidates. All patients were evaluated before discharge, at 3 months, and at 1, 2, and 3 years postoperatively using the same modalities. RESULTS: Immediately after surgical intervention, right ventricular cavitary dimensions decreased significantly, and tricuspid regurgitation radically improved. Right ventricular ejection fraction and functional status improved and right ventricular hypertrophy reversed over a longer time period. Higher ventricular dimensions and lower ejection fraction of the right ventricle were associated with poorer functional status at any time postoperatively. At discharge, pulmonary vascular resistance of greater than 509 dyne x sec x cm(-5) and right ventricular ejection fraction of 24% or less predicted clinical failure at 12 months' follow-up. CONCLUSIONS: After pulmonary endarterectomy, the right ventricle recovers and maintains normal architecture and function over time, regardless of the severity of preoperative disease. Accurate preoperative evaluation of the hemodynamics and anatomy of the thromboembolic lesions are mandatory. If pulmonary endarterectomy is not expected to decrease pulmonary vascular resistance to less than 509 dyne x sec x cm(-5), indication for surgical intervention needs to be carefully evaluated.

Adult↗

Baseline echocardiographic characteristics of heart failure patients enrolled in a large European multicentre trial (CArdiac REsynchronisation Heart Failure study).

AIMS: Information on the prevalence and clinical, electrocardiographic and echocardiographic inter-relationships of mechanical dyssynchrony among patients with heart failure (HF) and left ventricular systolic dysfunction derives mainly from relatively small studies. The CARE-HF trial provides the opportunity to address these issues in a large population of patients with advanced HF. METHODS AND RESULTS: The CARE-HF trial enrolled patients with New York Heart Association (NYHA) class III or IV HF, with a QRS duration > or =120 ms, left ventricular (LV) ejection fraction (EF) < or =35% and LV end diastolic diameter > or =30 mm/m (height in m). Patients underwent a thorough echocardiographic evaluation, which included assessment of LV structure, systolic function, mitral inflow pattern, right ventricular (RV) dimensions and function, and interventricular mechanical delay (IVMD) as an index of interventricular dyssynchrony. Echocardiographic measurements were made in a Core Laboratory to ensure consistent quantitative analysis. Of the 813 patients enrolled, 735 had a baseline echocardiographic examination suitable for measurement. Overall patients had advanced LV dysfunction (mean EF 25.5%) but few had a restrictive mitral filling pattern (18%) and both the mean RV diameter and RV function were within normal limits. Interventricular dyssynchrony defined as IVMD >40 ms was present in 455 patients (62%). Clinical, electrocardiographic and standard echocardiographic variables were only loosely associated with IVMD. CONCLUSIONS: Interventricular dyssynchrony appears to be an independent characteristic of patients with advanced HF, and is poorly related to clinical, electrocardiographic or standard echocardiographic variable.

Aged↗

Blunted erythropoietin production and defective iron supply for erythropoiesis as major causes of anaemia in patients with chronic heart failure.

AIMS: Anaemia is often observed in patients with chronic heart failure (CHF), and it may be associated with a worse prognosis. Aim of this study was to identify the individual mechanisms of anaemia in CHF patients. METHODS AND RESULTS: One hundred and forty-eight consecutive patients with haemoglobin concentration <13 g/dL (if males) or <12 g/dL (if females) were enrolled. Factors responsible for anaemia were investigated by evaluating endogenous erythropoietin (Epo) production, serum cytokines levels, body iron status, and iron supply for erythropoiesis. Most patients (57%) presented anaemia of chronic disease and among them, 92% showed evidence of a defective endogenous Epo production. This was indicated by an observed/predicted log(serum Epo) ratio less than 0.8 and/or a defective iron supply for erythropoiesis diagnosed by low transferrin saturation and/or increased value of soluble transferrin receptor. According to regression analysis sex, renal failure, and serum Epo were correlated with anaemia. CONCLUSION: According to our study, about half of anaemic CHF patients showed anaemia of chronic disease with blunted endogenous Epo production and/or a defective iron supply for erythropoiesis. Determination of the individual mechanisms of anaemia in CHF could justify a rational therapeutic approach to anaemia.

Anemia↗

Epoprostenol in chronic thromboembolic pulmonary hypertension with distal lesions.

BACKGROUND: Although patients with primary pulmonary hypertension and patients with chronic thromboembolic pulmonary hypertension with distal lesions may share similar pathophysiological characteristics, scarce information is available on the usefulness of epoprostenol in this form of secondary pulmonary hypertension. The aim of this study was to evaluate the feasibility, safety and efficacy of epoprostenol therapy in surgically untreatable patients with chronic thromboembolic pulmonary hypertension. METHODS: Continuous infusive therapy with epoprostenol was undertaken in 16 patients with primary pulmonary hypertension and in 11 surgically untreatable thromboembolic pulmonary hypertension patients. The median follow-up was 12.4 months (range 6-23 months). Patients underwent clinical, echocardiographic and hemodynamic evaluation at baseline and a 6-min walk test every 3 months after beginning epoprostenol; ultrasound evaluations were repeated in a subgroup of patients. RESULTS: Epoprostenol therapy improved the clinical status, exercise tolerance and NYHA functional class. A greater left ventricular end-diastolic volume was recorded at echocardiography in both groups. CONCLUSIONS: Epoprostenol therapy may be feasible, safe and clinically effective in patients with surgically untreatable chronic thromboembolic pulmonary hypertension.

Antihypertensive Agents↗

Response of the right ventricle to acute pulmonary vasodilation predicts the outcome in patients with advanced heart failure and pulmonary hypertension.

OBJECTIVES: This study was designed to assess whether testing of potential reversibility of pulmonary hypertension (PHT) may be a useful means of defining the short-term prognosis of patients with advanced heart failure and elevated pulmonary artery pressure. In such patients, the reversibility of PHT after acute vasodilator administration is associated with a low early mortality rate after heart transplantation. However, its short-term prognostic value has not yet been determined. METHODS AND RESULTS: Between 1994 and 1998, 76 patients with advanced heart failure and PHT underwent right heart cathetherization. The hemodynamic measurements, including thermodilution-derived right ventricular ejection fraction, were repeated after an intravenous bolus of nitroglycerin (NTG). During a median follow-up period of 8.2 months (25% and 75% centiles, 3.3 and 18.9 months), 47 patients had a cardiac event (death or urgent heart transplantation). With Cox survival analysis, a multivariate model that included the New York Heart Association class and the hemodynamic variables obtained after NTG administration allowed a better assessement of the short-term prognosis of the patients than a model including the baseline variables. The evaluation of right ventricular function during the acute NTG-induced pulmonary vasodilation was of critical importance in obtaining such a refinement in the prognostic stratification. CONCLUSIONS: The prognostic evaluation of patients with advanced heart failure and PHT should include the assessment of the changes of right ventricular ejection fraction after acute afterload reduction.

Aged↗

Dobutamine-induced ST-segment elevation associated with a biphasic response of wall motion in patients with a recent myocardial infarction is caused by myocardial ischaemia and is abolished by revascularization of the infarct-related artery.

OBJECTIVE: ST-segment elevation is frequently induced by dobutamine in patients with a recent myocardial infarction and may represent dyskinesia of the infarcted region or myocardial viability and ischaemia. Revascularization of the infarct-related artery may abolish myocardial ischaemia, and thus represents a useful tool to verify the significance of this finding. The aim of this study was to assess the relation between ST-segment elevation and wall motion response during dobutamine echo stress test and to evaluate the effect of coronary revascularization with percutaneous coronary angioplasty of the infarct-related artery on stress test results. METHODS AND RESULTS: Twenty-two patients (17 men; mean age 58+/-12 years) with a first acute myocardial infarction (5 anterior (23%) and 17 (77%) inferior) who showed ST-segment elevation during a dobutamine echo stress test performed early (7+/-5 days) after the acute event where included in the analysis. All patients underwent coronary arteriography followed by percutaneous revascularization with coronary angioplasty or atherectomy with or without stenting of the culprit lesion and a second dobutamine echo stress test at a mean of 40+/-20 days after revascularization. The minimal lumen diameter increased from 0.63+/-0.36 to 3+/-0.44 mm and % diameter stenosis decreased from 80+/-11 to 12+/-7 after revascularization. At baseline evaluation there were 62 normal moving segments (34%), 57 (32%) akinetic and 62 (34%) hypokinetic segments within the area at risk. Maximal ST-segment shift changed from a basal mean value of 0.41+/-0.6 to a peak value of 2.15+/-0.9 mm; angina developed in 6/22 patients (22%). A biphasic response to dobutamine indicative of myocardial ischaemia within the infarcted area was observed in 20/22 patients (91%) and in 54/74 (73%) segments showing wall motion abnormalities. After revascularization of the infarct-related artery 78 (43%) segments were considered to be normal, 46 (25%) akinetic and 57 (32%) hypokinetic. Dobutamine-induced ST-segment elevation in 6/22 cases (27%), but the amount of ST-segment shift at peak stress was significantly reduced (from 2.15+/-0.9 to 0.30+/-0.5 mm) and angina was present in 1 patient only (5%) despite a significant increase of double product compared to the pre-revascularization test (from 17,348+/-3536 to 21,005+/-4105, p < 0.003). At echocardiographic analysis, ischaemia involved only 4 segments (2%), 3 of them showing the persistence of a biphasic response to dobutamine. CONCLUSIONS: In patients with a recent myocardial infarction and no baseline dyskinesia dobutamine-induced ST-segment elevation in the infarct-related leads is usually associated with a biphasic response of wall motion within the infarcted region and may be considered an ancillary sign of myocardial ischaemia because it is abolished in the great majority of cases by successful revascularization of the infarct-related artery.

Adrenergic beta-Agonists↗

Infusion therapy in severe heart failure. A reappraisal.

Decompensated heart failure is associated with high rates of morbidity and mortality and it is responsible for numerous hospitalizations. The current approach to acute exacerbations is based on diuretics, vasodilators and inotropes. Compared with the impressive development of new therapeutic agents designed for other cardiovascular diseases, little progress has been observed in developing new drugs for the treatment of decompensated heart failure. Moreover, a series of controlled clinical trials failed to show a better outcome or a reduction in morbidity during treatment with inotropes, even though promising results were recently observed in controlled clinical trials with new classes of drugs, such as calcium sensitizers and nesiritide; these agents will probably modify the treatment options of decompensated heart failure in the coming years.

Cardiotonic Agents↗

Autosomal dominant dilated cardiomyopathy with atrioventricular block: a lamin A/C defect-related disease.

OBJECTIVES: We investigated the prevalence of lamin A/C (LMNA) gene defects in familial and sporadic dilated cardiomyopathies (DCM) associated with atrioventricular block (AVB) or increased serum creatine-phosphokinase (sCPK), and the corresponding changes in myocardial and protein expression. BACKGROUND: It has been reported that familial DCM, associated with conduction disturbances or variable myopathies, is causally linked to LMNA gene defects. METHODS: The LMNA gene and myocardial ultrastructural and immunochemical changes were analyzed in 73 cases of DCM (49 pure, 15 with AVB [seven familial, eight sporadic], 9 with increased sCPK), four cases of familial AVB and 19 non-DCM heart diseases. The normal controls included eight heart donor biopsies for tissue studies and 107 subjects for LMNA gene studies. RESULTS: Five novel LMNA mutations (K97E, E111X, R190W, E317K, four base pair insertion at 1,713 cDNA) were identified in five cases of familial autosomal dominant DCM with AVB (5/15: 33%). The LMNA expression of the myocyte nuclei was reduced or absent. Western blot protein analyses of three hearts with different mutations showed an additional 30-kDa band, suggesting a degrading effect of mutated on wild-type protein. Focal disruptions, bleb formation and nuclear pore clustering were documented by electron microscopy of the myocyte nuclear membranes. None of these changes and no mutations were found in the nine patients with DCM and increased sCPK or in the disease and normal controls. CONCLUSIONS: The LMNA gene mutations account for 33% of the DCMs with AVB, all familial autosomal dominant. Increased sCPK in patients with DCM without AVB is not a useful predictor of LMNA mutation.

Adolescent↗

Usefulness and limits of transthoracic echocardiography in the evaluation of patients with primary and chronic thromboembolic pulmonary hypertension.

The aim of the study was to evaluate the potential usefulness of transthoracic echocardiography in differentiating patients with primary or chronic thromboembolic pulmonary hypertension and to define the capability of echocardiography to assess right-heart performance in such patients. Right-heart catheterization and ultrasound examination were performed in 111 patients with chronic thromboembolic pulmonary hypertension and in 31 patients with primary pulmonary hypertension. All echocardiographic and Doppler parameters were similar in primary and chronic thromboembolic pulmonary hypertension. A significant correlation was found between the tricuspid annular plane systolic excursion and the right ventricular fractional area change and thermodilution-derived right ventricular ejection fraction (P <.001 for both). Furthermore, different patterns of the pulsed Doppler flow velocity curve into the superior vena cava were associated with different right-heart hemodynamic profiles. In conclusion, in patients with chronic pulmonary hypertension transthoracic echocardiography portends meaningful information on the capability of the right heart to confront the increased afterload but it does not permit etiologic differentiation.

Adult↗

Clinicopathological correlates can predict acute myocarditis in patients with recent-onset heart failure: preliminary data.

BACKGROUND: The aim of this study was to verify whether or not the clinical profile could be helpful in diagnosing myocarditis in patients with recent-onset (< 6 months) heart failure, suspected myocarditis and a biopsy-proven diagnosis. METHODS: From March 1998 to December 2000, 118 patients underwent a complete clinical, hemodynamic, echocardiographic and laboratory examination and a diagnostic endomyocardial biopsy in our Department; among them, 28 patients were admitted with clinically suspected myocarditis; in 9, the diagnosis was confirmed by the histopathologic findings. RESULTS: At the time of presentation, patients with biopsy-proven myocarditis showed early in-hospital admission (median 6 vs 69 days) with fever, a higher sinus rate and a significantly lower systolic blood pressure. Left ventricular dilation was observed in the non-myocarditis group only (left ventricular end-diastolic diameter 65.0 +/- 8.9 vs 52.6 +/- 5.8 mm); right ventricular function, as assessed by evaluation of the tricuspid annulus plane systolic excursion (TAPSE) and the right ventricular ejection fraction (RVEF) were found to be significantly lower in the myocarditis group (TAPSE 14.2 +/- 3.6 vs 20.3 +/- 7.0 mm; RVEF 21.3 +/- 11.1 vs 30.3 +/- 11.5%). Only patients with biopsy-proven myocarditis had an increase in serum creatine kinase and inflammatory markers (erythrocyte sedimentation rate and white blood cell count). Three cases had a clinical presentation of fulminant myocarditis showing marked increases in the serum levels of creatine kinase and inflammatory markers, and severely compromised right ventricular function and cardiac index. CONCLUSIONS: At univariate analysis, an early onset, fever, tachycardia, hypotension, a reduced right ventricular function, increased creatine kinase, erythrocyte sedimentation rate and white blood cell count were predictive of myocarditis. In patients with recent-onset heart failure, the clinical, laboratory and echocardiographic profiles can suggest, but not prove, a diagnosis of myocarditis.

Acute Disease↗

[Levosimendan in heart failure].

Clinical trials investigating traditional inotropic agents in patients with heart failure demonstrated an increased mortality rate (odds ratio 1.50; IC=0.51-3.92), high incidence of discontinuation of infusion therapy (odds ratio 0.46; IC=0.083-2.29) due to major side effects and, most of all, a limited clinical benefit (odds ratio 0.75; IC=1.42-0.08). On this background a new class of inotropic drugs, the calcium-sensitisers, have been developed. The safety and efficacy of levosimendan (Simdax) has been recently demonstrated in trials (LIDO e RUSSLAN) in patients with heart failure due to ischemic and not ischemic disease. Twenty-six patients with decompensated heart failure of different etiology have been treated with 24 hour infusion of levosimendan. In this experience the levosimendan improved the clinical status and the left ventricular ejection fraction.

Calcium Channel Agonists↗