Biomarkers in heart failure.

The meaning of the term biomarker has been standardized by a working group of the National Institutes of Health as "a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention". The ability of a biomarker to enhance the quality and efficacy of clinical care depends on several factors, including pretest probability, sensitivity and specificity, costs, benefits, risks, and even patient preference and alternatives. With the aim to better diagnose the multifactorial and complex syndrome of heart failure, research has led to discover many categories of potential pathophysiologic biomarkers for this debilitating disease. Such categories have been mainly designed by matching different molecules levels to different pathophysiological stages of chronic heart failure, and comprise biomarkers of inflammation, oxidative stress, extracellular-matrix remodeling, neurohormones, myocte injury and stress, with an additional group of new biomarkers not yet fully characterized. The quest for an ideal biomarker in heart failure is still underway, and several newly discovered, but also old and overlooked markers might prove their relevance. Since at present we cannot apply the application of the perfect marker, maybe combining different molecules will provide information compensating for the shortcoming of individual tests. The accumulated basic and clinical research experience, and the continuing exploration of the genome, coupled with the evolving disciplines of proteomics and metabolomics, ensure that there will be no shortage of newly discovered candidate biomarker molecules for the future.

Independent and incremental prognostic value of (201)Tl lung uptake at rest in patients with severe postischemic left ventricular dysfunction.

BACKGROUND: An elevated (201)Tl lung uptake after stress is related to an adverse prognosis. METHODS AND RESULTS: The functional and prognostic significance of resting (201)Tl lung uptake was assessed in 124 consecutive patients with ischemic heart disease and ejection fraction 0.61 best separated patients with and without events (ROC area under curve 0.82). Event-free survival was significantly lower in patients with L/H >0.61 (P:<0. 001); L/H >0.61 (chi(2)=10.8; P:<0.001) and a restrictive filling pattern (chi(2)=3.6; P:<0.05) were independent predictors of events. The prognostic value of L/H was incremental over that obtained by clinical, echographic and Doppler data (global chi(2)=20.8). CONCLUSIONS: In patients with severe postischemic left ventricular dysfunction undergoing rest-redistribution (201)Tl imaging, an increased lung tracer uptake showed incremental prognostic value over clinical and other imaging findings, providing clinically useful risk assessment.

Accurate noninvasive estimation of pulmonary vascular resistance by Doppler echocardiography in patients with chronic failure heart failure.

OBJECTIVES: This study was undertaken to explore further the relationship between Doppler-derived parameters of pulmonary flow and pulmonary vascular resistance (PVR) and to determine whether PVR could be accurately estimated noninvasively from Doppler flow velocity measurements in patients with chronic heart failure. BACKGROUND: The assessment of PVR is of great importance in the management of patients with heart failure. However, because of the inconclusive and conflicting data available, Doppler estimation of PVR is still considered unreliable. METHODS: Simultaneous Doppler echocardiographic examination and right heart catheterization were performed in 63 consecutive sinus rhythm heart failure patients with severe left ventricular systolic dysfunction. Hemodynamic PVR was calculated with the standard formula. The following Doppler variables on pulmonary flow and tricuspid regurgitation velocity curve were correlated with PVR: maximal systolic flow velocity, pre-ejection period (PEP), acceleration time (AcT), ejection time, total systolic time (TT), velocity time integral, and right atrium-ventricular gradient. RESULTS: At univariate analysis, all variables except maximal systolic flow velocity and velocity time integral showed a significant, although weak, correlation with PVR. The best correlation found was between AcT and PVR (r = -0.68). By regression analysis, only PEP, AcT and TT entered into the final equation, with a cumulative r = 0.87. When the function (PEP/AcT)/TT was correlated with PVR, the correlation coefficient further improved to 0.96. Of note, this function prospectively predicted PVR (r = 0.94) after effective unloading manipulations. CONCLUSIONS: The analysis of Doppler-derived pulmonary systolic flow is a reliable and accurate tool for estimating and monitoring PVR in patients with chronic heart failure due to left ventricular systolic dysfunction.

Estimation of pulmonary wedge pressure by transmitral Doppler in patients with chronic heart failure and atrial fibrillation.

Previous studies have demonstrated that left ventricular (LV) filling pressures can be estimated from transmitral Doppler recording in patients in sinus rhythm who have a broad spectrum of cardiac diseases. However, the correlation between pulmonary wedge pressure (PWP) and mitral Doppler profile has not yet been clearly defined in patients with atrial fibrillation, particularly in the presence of severe LV systolic dysfunction. The aim of this study was to evaluate the correlations between PWP and transmitral Doppler variables in patients with atrial fibrillation and chronic heart failure due to dilated cardiomyopathy. PWP and the mitral Doppler profile were simultaneously recorded in 35 consecutive heart failure patients (28 men, 7 women; mean age, 69 +/- 9 years) with severe LV dysfunction (mean ejection fraction 22% +/- 5%). Doppler measurements were averaged over 10 cardiac cycles. In addition, left atrial areas were derived from the apical 4-chamber view. Significant relations were observed between PWP and several parameters derived from the mitral flow: isovolumic relaxation time (r = -70), acceleration rate (r = 0.78), deceleration rate (r = 0.82), and deceleration time (r = -0.95). However, by stepwise multivariate analysis, deceleration time emerged as the sole independent predictor of PWP (r2 = 0.95, F = 590). The analysis led to the following equation: PWP = 51 - 0.26 (deceleration time). Our data suggest that mitral Doppler echocardiography is a useful tool for predicting PWP in heart failure patients with severe LV dysfunction even in the presence of atrial fibrillation.

Doppler-derived acceleration rate of right ventricular early filling as a measurement of right atrial pressure in chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

This study demonstrates that a Doppler-derived tricuspid flow velocity pattern provides an accurate, feasible, and noninvasive method of estimating and monitoring mean right atrial pressure in patients with heart failure due to left ventricular systolic dysfunction, and who are both in sinus rhythm and atrial fibrillation. In particular, the acceleration rate of early right ventricular filling is a powerful and independent predictor of mean right atrial pressure.

Effects of coronary angioplasty on left ventricular function.

It is well known that myocardial revascularization after successful coronary bypass surgery results in improved left ventricular function. Coronary angioplasty also results in successful revascularization, favorably affecting both stunned and hibernating myocardium. We studied 22 patients with chronic stable angina who underwent successful angioplasty for an isolated narrowing of the proximal or midportion of the left anterior descending artery. These patients also performed isometric exercises before and after angioplasty, which can be used to characterize left ventricular function. Revascularization after angioplasty induced an immediate improvement in left ventricular function in those patients with dysfunction secondary to hibernating myocardium. Further studies are needed to assess the possibility of the myocardial stunning phenomenon occurring after angioplasty in those patients without left ventricular improvement.

Assessment of left ventricular function by isometric handgrip exercise after thrombolysis in patients with refractory unstable angina.

The handgrip test has been proposed for the evaluation of the hemodynamic reserve in patients with coronary artery disease and to quantitate the impairment of left ventricular (LV) function. The present study was designed to evaluate the effect of thrombolytic therapy in patients with refractory unstable angina in order to test the hypothesis that a reduction in intracoronary thrombosis could ameliorate their hemodynamic response to the handgrip test. During left heart catheterization, 20 patients with refractory unstable angina of recent onset performed a handgrip test before (HG1) and 24-72 hours after (HG2) being randomized to receive recombinant tissue-type plasminogen activator or placebo, according to a double-blind parallel group design. HG1 induced an increase in heart rate (p < 0.001), in systolic pressure (p < 0.001), and a reduction in ejection fraction (p < 0.05). Changes in LV end-diastolic pressure during baseline handgrip were highly different in individual patients, resulting in a trend toward an increase. Similarly, a different individual response was observed in the behavior of the isovolumetric and relaxation indices. In comparison with HG1, no difference was detected during HG2 in the 2 treatment groups with respect to changes in LV volumes, ejection fraction, LV systolic and diastolic pressures, +dP/dt, (dP/dt)/P, -dP/dt, and tau index. In patients with refractory unstable angina of recent onset, the handgrip test performed before and after thrombolysis did not prove to be useful in assessing directional changes of LV performance, mainly because of the different individual response to the baseline handgrip test.

Influence of elastic recoil on restenosis after successful coronary angioplasty in unstable angina pectoris.

The elastic behavior of the dilated coronary vessel has been reported to affect the immediate results of coronary angioplasty. To determine whether elastic recoil may also influence the long-term restenosis process, 98 consecutive patients with unstable angina and 1-vessel disease were studied. An automated coronary quantitative program was used for the assessment of balloon and coronary luminal diameters. Elastic recoil was defined as the percent reduction between minimal balloon diameter at the highest inflation pressure and minimal lesion diameter immediately after coronary angioplasty. Follow-up coronary arteriography was performed 8 to 12 months after the procedure in all patients. The mean elastic recoil averaged 17.7 +/- 16% and was correlated to the degree of residual stenosis immediately after coronary angioplasty (r = 0.64; p < 0.001). Restenosis, defined as > 50% diameter stenosis at follow-up, developed in 53 patients (54%). There was no correlation between the degree of elastic recoil and the changes in minimal lesion diameter observed during follow-up, whereas a positive correlation between the amount of elastic recoil and the incidence of restenosis was documented (r = 0.84; p < 0.05). Thus, the elastic properties of the dilated vessel do not influence the active process of restenosis. However, because elastic recoil negatively influences the initial results of angioplasty, it is more likely that further reductions in lumen diameter during follow-up can reach a threshold of obstruction considered critical for a binary definition of restenosis.

Transitional papillary cell carcinoma of the ureter: a histological and ultrastructural study.

We report a case of transitional papillary carcinoma of the distal left ureter. The histological and ultrastructural features were seen and compared by SEM and TEM. Observations confirm the data of literature that the deep cells of neoplasm are a normal morphological finding while the superficial cells do not have the characteristics present in normal transitional cells. In addition, SEM shows small groups or single cells with "pleomorphic microvilli" on the cell surface. These, in ureter, confirm the studies of many authors who have observed these abnormalities in carcinomas of several organs like breast, colon, liver and mesothelium.

Surgery in Italy.

During the past 15 years, surgery in Italy has undergone significant developments in health care services at the teaching and organizational levels. In 1987, the new teaching regulations of medical and surgical schools came into force with the introduction of integrated courses that converge into educational and training areas with precise objectives. For more than a decade, postgraduate schools have had a common guideline throughout the European community--becoming real "residencies." Surgical activity is provided by university hospital facilities and hospitals with a business administration that is completely autonomous as far as organization, income, management, technique, and accounts are concerned. Research guidelines for future developments are mainly addressed toward optimization of organization and use of the most recent technology. The widespread application of day surgery and video-assisted surgery substantiates this evolution of surgery in Italy.

Chronic mitral regurgitation and Doppler estimation of left ventricular filling pressures in patients with heart failure.

Previous studies relating Doppler parameters and pulmonary capillary wedge pressures (PCWP) typically exclude patients with severe mitral regurgitation (MR). We evaluated the effects of varying degrees of chronic MR on the Doppler estimation of PCWP. PCWP and mitral Doppler profiles were obtained in 88 patients (mean age 55 +/- 8 years) with severe left ventricular (LV) dysfunction (mean ejection fraction 23% +/- 5%). Patients were classified by severity of MR. Patients with severe MR had greater left atrial areas, LV end-diastolic volumes, and mean PCWPs and lower ejection fractions (each P <.01). In patients with mild MR, multiple echocardiographic parameters correlated with PCWP; however, with worsening MR, only deceleration time strongly related to PCWP. From stepwise multivariate analysis, deceleration time was the best independent predictor of PCWP overall, and it was the only predictor in patients with moderate or severe MR. Doppler-derived early mitral deceleration time reliably predicts PCWP in patients with severe LV dysfunction irrespective of degree of MR.

[Systolic-diastolic arterial hypertension versus isolated systolic hypertension]. / L'ipertensione arteriosa sisto-diastolica verso l'ipertensione sistolica isolata.

The presence of elevated values of both diastolic and systolic arterial blood pressure is one of the most important risk factors for coronary heart disease, stroke, and heart failure; in patients with hypertension, the pharmacological reduction of blood pressure decreases the risk of adverse cardiovascular events, though the optimal blood pressure goal is still being debated. During recent years there has been an increasing interest in isolated systolic hypertension, both as an independent risk factor for cardiovascular disease and as a clinical entity requiring treatment in its own right. The definition of what constitutes isolated systolic hypertension still remains controversial and arbitrary; the criteria generally used is a systolic blood pressure > or = 140 mmHg and a diastolic blood pressure < 90 mmHg. Not only the cut-off levels used to define isolated systolic hypertension, but also the number of occasions on which blood pressure is measured can significantly affect the prevalence of isolated systolic hypertension in the total population. The use of 24-hour ambulatory blood pressure monitoring is a relatively new method for overcoming transient elevations in blood pressure that often occur during clinic measurement; it has a good reproducibility, is subject to little "white-coat" or placebo effect, and finally provides blood pressure measurements within a subject's normal environment. Borderline isolated systolic hypertension (defined as a systolic blood pressure between 140 and 159 mmHg and a diastolic blood pressure < 90 mmHg) is probably the most common type of untreated hypertension among adults over the age of 60; in the following 20 years, about 80% of patients with borderline isolated systolic hypertension will show progression to definite hypertension with increased risk of development of cardiovascular disease. The increase in systolic and diastolic blood pressure with age is typical of Western societies, while it is not observed among some "unacculturated" populations, who tend to be lean and physically active, with a lower daily sodium intake. Maybe environmental, rather than genetic factors may contribute more to the determination of blood pressure throughout life. Pharmacological treatment of isolated systolic hypertension can lead to a significant reduction in total stroke, coronary heart disease, and cardiovascular disease. The question of which antihypertensive agents are most effective is still to be fully elucidated with specifically addressed trials.

Restrictive left ventricular filling pattern as a strong predictor of depressed baroreflex sensitivity in heart failure.

BACKGROUND: The aim of this study was to test the hypothesis that a restrictive left ventricular diastolic filling pattern, as an index of elevated pulmonary wedge pressure, would predict a depressed baroreflex sensitivity (BRS) in patients with chronic heart failure. METHODS: A total of 189 consecutive patients with an ejection fraction < or = 40% at echocardiography, in sinus rhythm and clinically stable for at least 1 month in oral therapy, underwent clinical examination, echo-Doppler study and the phenylephrine test. RESULTS: The correlations between the NYHA functional class, echo-Doppler variables and BRS were weak, although significant (r ranging from -0.15 to 0.40). However, patients with a deceleration time < 140 ms as an expression of restrictive filling, compared to those with a deceleration time > or = 140 ms, had a lower BRS (3 +/- 4 vs 6 +/- 4 ms/mmHg, p < 0.00001), a lower ejection fraction (20 +/- 6 vs 28 +/- 7%, p < 0.00001), greater left ventricular (end-diastolic volume index 137 +/- 43 vs 113 +/- 45 ml/m2, p < 0.00001) and left atrial dimensions (25 +/- 6 vs 20 +/- 5 cm2, p < 0.00001), more severe mitral regurgitation (3 +/- 1 vs 2.3 +/- 1, p < 0.00001) and were in a higher NYHA class (2.3 +/- 0.6 vs 1.8 +/- 0.5, p < 0.00001). Medications at the time of the study were similar in the two groups. At stepwise regression analysis, the deceleration time emerged as the most powerful independent predictor of a depressed BRS (< 3 ms/mmHg), followed by mitral regurgitation, age, and NYHA class (all data p = 0.0001). CONCLUSIONS: In patients with chronic heart failure, the presence of a restrictive left ventricular filling pattern is highly predictive of autonomic derangement as expressed by low values of BRS.

Doppler-derived acceleration rate of right ventricular early filling reliably predicts mean right atrial pressure at baseline and after loading manipulations in patients with chronic heart failure.

BACKGROUND: We investigated whether Doppler-derived variables of tricuspid flow could estimate mean right atrial pressure and monitor its changes after loading manipulations in patients with chronic heart failure. METHODS: Simultaneous mean right atrial pressure (Swan-Ganz catheterization) and tricuspid Doppler recordings were initially evaluated in 136 patients (23 with atrial fibrillation) with chronic heart failure and severe left ventricular systolic dysfunction, and then were repeated in 18 patients after unloading (sodium nitroprusside infusion) and in 13 patients after overloading (active leg elevation) manipulations. RESULTS: A significant correlation was observed between mean right atrial pressure and peak E velocity (r = 0.70), early deceleration time (r = -0.72) and acceleration time (r = -0.75). However, the best correlation found was between the acceleration rate of early flow and mean right atrial pressure, and it was identical in patients in sinus rhythm or with atrial fibrillation (r = 0.98). Moreover, after acute effective unloading or overloading manipulations, although all Doppler tricuspid variables changed significantly, the acceleration rate of early flow still emerged as the strongest independent predictor of mean right atrial pressure (r = 0.95 and 0.99, respectively). CONCLUSIONS: Doppler-derived acceleration rate of early diastolic tricuspid flow is a powerful tool to predict mean right atrial pressure and to monitor its changes after loading manipulations.

[Primary hyperaldosteronism caused by monolateral adrenal hyperplasia]. / Iperaldosteronismo primario da iperplasia surrenalica monolaterale.

We have reported two patients with unilateral adrenal hyperplasia as a rare cause of primary aldosteronism, and discussed the literature on this subject. When diagnosed by NMR-CT imaging and selective sampling from adrenal veins, the treatment of this disorder appears to be surgical. Whether its pathogenesis is related to the more common varieties of primary aldosteronism is open to speculation according to metabolic findings.

[Nitrates and nitric oxide]. / Nitroderivati e ossido nitrico.

Nitrovasodilators are pro-drugs able to release nitric oxide. They have been used in clinical practice for about 100 years and they are still widely used in the treatment of several diseases such as angina pectoris, acute pulmonary edema, and hypertensive crises. This article discusses the pharmacological differences of nitrovasodilators, describes the biochemical pathway of nitric oxide formation, and suggests some criteria to achieve the best therapeutic results.

[Remodeling of the left ventricle]. / Il rimodellamento del ventricolo sinistro.

Left ventricular remodeling is a frequent and unfavorable evolution of both ischemic and non-ischemic dilative cardiomyopathy with a significant reduction in left ventricular systolic and diastolic performance. By the term "remodeling" we refer to a variety of alterations in left ventricular morphology and volume; while patients with non-ischemic cardiomyopathy frequently show global and quite homogeneous enlargement of the left ventricle, transmural myocardial infarctions can be followed initially by regional expansion and only in a second stage by a global increase in ventricular size. Cardiologists have a number of therapeutic options from which to choose: ACE-inhibitors and probably angiotensin II antagonists can contrast the unfavorable progression of the phenomenon, while beta-blockers such as metoprolol and carvedilol probably can reverse the process. In addition, moderate exercise training not only produces no detrimental effects on infarct size or left ventricular topography, but can prevent the progression of left ventricular dysfunction and its attendant morbidity and mortality in selected populations.

An unusual association of malignant melanoma and small cell lung cancer: case report. An eleven-year-follow-up.

The authors report the case of a patient affected by malignant melanoma and small cell lung cancer. After having underlined the rareness of this pathological association, reviewing the most recent literature, the description of the clinical case aims at opening a discussion on how the surgical treatment performed, associated to chemotherapy, brought to an unhoped-for success, also helped by an unexpected combination of events that were absolutely out of any protocol. Eleven years later, at the present follow-up, the patient shows a complete remission of both diseases.

[Non visible carcinoma of the gallbladder. A strategic problem after video laparoscopic cholecystectomy]. / Il carcinoma non visibile della cistifellea. Un problema strategico dopo videolaparocolecistectomia.

A formal contraindication to laparoscopic cholecystectomy is gallbladder cancer. Sometimes its first appearance is intraoperative finding or microscopic examination of gallbladder removed for presumed benign disease. These patients with "inapparent carcinoma" may be long-term survivors if definitive and curative therapy is performed. We present the case of 56 y. woman which presented a T2 unsuspected carcinoma that was reoperated and cured by wedge liver resection, extended lymph node dissection and large excision of tissue of trocar wounds.

[Reconstruction after pancreaticoduodenectomy for cancer: Whipple-Child vs Traverso-Longmire technique (a National questionnaire 1990 on data of 1,095 cases of surgery)]. / Ricostruzione dopo cefaloduodenopancreatectomia per cancro: Whipple-Child v.s. Traverso-Longmire (questionario nazionale 1990 per una raccolta di 1.095 esperienze).

The Authors report the results of a National multicentric experience in 1.095 cases of pancreaticoduodenectomy for cancer. In order to evaluate the reliability of pyloric preservation mortality, morbidity, and functional results are discussed.