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.

Ventricular septal rupture after myocardial infarction: diagnosis by two-dimensional and pulsed Doppler echocardiography.

Rupture of the ventricular septum in the acute phase of myocardial infarction (MI) requires prompt recognition for correct management. The 2-dimensional and pulsed Doppler echocardiographic findings are reported from 11 patients with ventricular septal (VS) rupture. VS rupture was confirmed by cardiac catheterization in 9 patients, surgery in 4 patients and necropsy examination in 3 patients. Two-dimensional echocardiography (echo) directly visualized the rupture in 7 patients and assessed the size and location of an associated aneurysm in 10. In all patients, M-mode pulsed Doppler echo allowed detection of the left-to-right shunting due to VS rupture, but failed to indicate the rupture site. M-mode pulsed Doppler echo was reliable for detecting VS rupture after MI. Conversely, 2-dimensional echo was less effective in the direct visualization of the rupture, but provided anatomic and functional information that was useful in medical and surgical management. Thus, the techniques are complementary and should be used in combination for the assessment of VS rupture in acute MI.

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.

Color flow Doppler mapping studies of "physiologic" pulmonary and tricuspid regurgitation: evidence for true regurgitation as opposed to a valve closing volume.

Color flow Doppler mapping using either an Aloka 880 or a Toshiba SSH65A system was performed in 39 normal subjects (aged 13 to 45 years) and 43 patients (aged 13 to 82 years) with pathologic tricuspid or pulmonary regurgitation to evaluate the incidence of "physiologic" regurgitation of right heart valves and to determine the differentiating characteristics in the spatial distribution and velocity encoding of "normal" and "pathologic" regurgitant jets. In the normal subjects, tricuspid and pulmonary regurgitation were documented in 32 (83%) and 36 (93%), respectively, and were unrelated to the system being used. Flow acceleration and aliasing were imaged on the right ventricular side of the tricuspid regurgitant orifice and on the pulmonary artery side of the pulmonary valve (in both normal subjects and patients), and indicated flow convergence for true regurgitation through an orifice as opposed to blood being driven retrogradely by the closing valve. Such proximal acceleration was documented in all patients with pathologic tricuspid regurgitation, in 31/32 of the normal subjects with tricuspid regurgitation, and was also observed in 12/15 (80%) of the patients and 4/12 (33%) of normal subjects with pulmonary regurgitation who were examined with the Toshiba system. The dimensions (mean +/- SD) of tricuspid regurgitant jets (length [JL] and area [JA]) were consistently larger in the patients than in the normal subjects [JL: 3.4 +/- 0.9 vs 1.2 +/- 0.5 cm, p less than 0.001; and JA: 5.7 +/- 2.0 vs 1.4 +/- 0.7 cm2, p less than 0.001) as were the pulmonary regurgitation jet dimensions (JL: 1.8 +/- 0.4 vs 0.9 +/- 0.08 cm, p less than 0.001; JA: 1.8 +/- 0.7 vs 0.3 +/- 0.08 cm2, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Synthesis and biological properties of alkyl esters of polyene antibiotics.

Several new alkyl esters of polyene antibiotics were prepared by an improved general procedure, and their toxicity and microbiological activity were tested. Some of these alkyl esters were more active than the nonesterified polyenes against Candida albicans but were less effective than the known methyl esters. Their toxicity was much less than that of the parent compounds.

Relationship between acute toxicity in mice and polymorphic forms of polyene antibiotics.

Marked differences in LD50 values were found between various batches of polyene antibiotics (mepartricin and nystatin) after intraperitoneal administration in suspension to mice. Such differences do not seem attributable to the particle size but to different molecular spatial arrangements of the products, which modify their solubility and biological availability. In the samples obtained by chemical treatments of some batches of the polyene substances, it has been possible to change the toxicity drastically and then to bring it back to its original value.

[The role of echocardiography and pulsed Doppler in the congenital absence of the pericardium. Description of 2 cases]. / Il ruolo dell'ecocardiografia e del Doppler pulsato nell'assenza congenita del pericardio. Descrizione di due casi.

Congenital absence of the left pericardium, partial or complete, is an uncommon cardiac defect. Most patients affected by this abnormality are asymptomatic. Usually it is suspected on the basis of a chest X-ray showing a normal sized cardiac shadow projecting entirely to the left of the spine. Computed axial tomography confirmed the absence of the left pericardium detecting the interposition of the left lung between the ascending aorta and main pulmonary artery. The M-mode, two-dimensional, and Doppler-cardiographic findings of complete congenital absence of the left pericardium are described in two cases. Imaging seems to be not specific for this abnormality; however in both cases pulsed Doppler detected mild tricuspid and pulmonic valve regurgitation.

[Myocardial infarction in the young: evolution and clinico-coronarographic correlation (author's transl)]. / L'infarto miocardico in età giovanile. Evoluzione e correlazioni clinico-coronarografiche.

Fifty patients who suffered from an acute myocardial infarction at age 40 or below and underwent coronary arteriography, were studied from 8 to 184 months after the infarction (mean follow-up 56 months). Hyperlipidaemia (60%) and cigarette-smoking (82%) were the most common risk factors, while hypertension and diabetes mellitus were found in 10% of all patients. Thirty-seven patients had two or more risk factors. Preinfarction angina was present in 7 subjects. Death rate was 14% within five years and was related to the severity of symptoms. Out of the patients with normal coronary arteriogram (6 patients) or with a single vessel disease 21 were free of angina and 30 did not suffer a reinfarction. Out of 17 patients with two or more coronary vessel disease, angina was present in 14 and reinfarction was seen in 5.

Pulsed Doppler diagnosis of tricuspid insufficiency.

To verify the ability of Pulsed Doppler Echocardiography (PDE) to detect flow abnormalities in tricuspid insufficiency (TI), 27 normal controls and 83 heart patients (pts) were studied. The latter group underwent an invasive diagnostic evaluation. The PDE examination did not reveal any significant systolic flow alteration in the normal controls. However, in the heart patients, a systolic turbulence was recorded within the right atrium both on audio and on graphic system (Time Interval Histogram-TIH) in 28 cases. Angiography showed tricuspid regurgitation in 24 pts. The sensitivity of PDE was 92%, the specificity was 93% and the predictive value was 96%. There were two false negative and four false positive cases. In conclusion, Pulsed Doppler Echocardiography is a highly reliable technique for the qualitative diagnosis of tricuspid insufficiency in patients with acquired heart disease. Left-to-Right shunts, namely left-to-right atrium and left ventricle-to-right atrium, can create flow disturbances that mimic tricuspid insufficiency. No criteria were identified, which correlated well with the angiographic severity of the tricuspid regurgitation.

[Echocardiographic diagnosis of left atrial thrombosis (author's transl)]. / Diagnosi ecocardiografica della trombosi dell'atrio sinistro.

70 consecutive patients undergoing heart surgery for mitral valve disease were studied: at operation 6 of them exhibited left atrial thrombi (LAT). Dimension of the thrombi varied from a hazel-nut to an orange, 4 of them adhered to the posterior atrial wall, 2 of these obliterated the left atrial appendage, one partially and the other totally, invading also the left atrial cavity as far as mitral orifice. In 5 cases LAT appeared of old onset, possibly with recent apposition; in one case the thrombus was mainly recent. All the cases had been assessed preoperatively using M-mode and two-dimensional echocardiography: the diagnosis of LAT was made in 5 pts, the only thrombus missed was the one located in the left atrial appendage. Angiocardiography was performed in 4 pts, showing left atrial thrombi in one case. Two-dimensional echocardiography (2D E) demonstrated a high sensitivity by revealing LAT in 5 cases out of 6, with good definition of shape and location. The LAT appeared as echoproducing masse with well defined borders and "muscle" density in 4 cases; in 3 they were seen protruding into the atrial cavity and in one case they were seen located above the posterior mitral leaflet. M-mode revealed multiple echoes parallel to the posterior atrial wall in the first 3 cases, whereas in the fourth it provided no particular finding for the diagnosis. In the only case of recent onset LAT, 2DE showed a single strong echo, parallel to the posterior atrial wall both in long and short-axis views, separated from the atrial wall by an echo-free space of 1.5 cm. Similar features resulted at the M-mode echocardiography. In conclusion, 2DE with gray-scale has an high sensitivity for detecting LAT, in particular when thrombi are old and located in the left atrial cavity. Recent onset thrombi are more difficult to demonstrate and it is possible that the "fresh" component of an old thrombus is missed.

[Human cytomegalovirus and congestive cardiomyopathy (author's transl)]. / Citomegalovirus umano e cardiomiopatia congestizia.

Congestive cardiomyopathy in 3 cases, in which occurrence of human Cytomegalovirus (CMV) infection was demonstrated, is described. In all cases significant rise in total CMV antibodies and in early antigen-antibodies was found: CMV was also isolated from urine and saliva in one, a 13 years old boy, and only from urine in the others two patients, 20 and 26 old men. Immunoglobulin M was raised only in the first case, in which CMV infection was likely in act: instead in the others two CMV infection was late primary or recurrent. The possibility of CMV infection as etiological agent of dilatative cardiomyopathy with congestive heart failure in this 3 cases is, in our opinion, strongly suggestive.

[Peripartum cardiomyopathy (author's transl)]. / La cardiomiopatia peripartum

Three cases of peripartum cardiomyopathy (CMP PP) are presented. In our opinion this term is more correct than post-partum cardiomyopathy. The study was performed both clinically and hemodynamically; patients were followed up for a long period (in one case up to 14 years). Although there were consistent differences in the rise and development of the disease, the clinical and laboratory results could be put together clearly. In the light of this clinical experience, a wide revision of the literature on the topic was carried out, using the hypotrophic-hypokinetic forms of cardiomyopathy (congestive) as a comparison with peripartum cardiomyopathy, which seem to be clinically correlated.

A soluble mepartricin complex (SPA-S-222) of potential oral and parenteral utility in fungal and protozoal infections.

Acute toxicity and absorption data of a soluble complex of mepartricin with sodium laurylsulphate (SPA-S-222) active against C. albicans and T. vaginalis are reported. The results demonstrate an improved bioavailability with respect to the insoluble substance. Preliminary clinical trials proved the good tolerance of the substance and its effectiveness in oral treatment of vaginal trichomoniasis.