Tumour biomarkers: association with heart failure outcomes.

BACKGROUND: There is increasing recognition that heart failure (HF) and cancer are conditions with a number of shared characteristics. OBJECTIVES: To explore the association between tumour biomarkers and HF outcomes. METHODS: In 2,079 patients of BIOSTAT-CHF cohort, we measured six established tumour biomarkers: CA125, CA15-3, CA19-9, CEA, CYFRA 21-1 and AFP. RESULTS: During a median follow-up of 21 months, 555 (27%) patients reached the primary end-point of all-cause mortality. CA125, CYFRA 21-1, CEA and CA19-9 levels were positively correlated with NT-proBNP quartiles (all P < 0.001, P for trend < 0.001) and were, respectively, associated with a hazard ratio of 1.17 (95% CI 1.12-1.23; P < 0.0001), 1.45 (95% CI 1.30-1.61; P < 0.0001), 1.19 (95% CI 1.09-1.30; P = 0.006) and 1.10 (95% CI 1.05-1.16; P < 0.001) for all-cause mortality after correction for BIOSTAT risk model (age, BUN, NT-proBNP, haemoglobin and beta blocker). All tumour biomarkers (except AFP) had significant associations with secondary end-points (composite of all-cause mortality and HF hospitalization, HF hospitalization, cardiovascular (CV) mortality and non-CV mortality). ROC curves showed the AUC of CYFRA 21-1 (0.64) had a noninferior AUC compared with NT-proBNP (0.68) for all-cause mortality (P = 0.08). A combination of CYFRA 21-1 and NT-proBNP (AUC = 0.71) improved the predictive value of the model for all-cause mortality (P = 0.0002 compared with NT-proBNP). CONCLUSIONS: Several established tumour biomarkers showed independent associations with indices of severity of HF and independent prognostic value for HF outcomes. This demonstrates that pathophysiological pathways sensed by these tumour biomarkers are also dysregulated in HF.

Relationship between endothelial dysfunction, videocapillaroscopy and circulating CD3+CD31+CXCR4+ lymphocytes in systemic lupus erythematosus without cardiovascular risk factors.

OBJECTIVE: The objective of this paper is to analyse whether digital capillary morphology, analysed by nailfold videocapillaroscopy (NVC), and the number of circulating CD3 + CD31 + CXCR4 + lymphocytes (angiogenic T cells) could be markers of endothelial dysfunction (ED) in systemic lupus erythematosus (SLE) without cardiovascular disease (CVD) and CV risk factors. METHODS: Nineteen consecutive SLE patients, according to Systemic Lupus International Collaborating Clinics Classification Criteria, with a disease duration less than five years, low disease activity, without CVD and CV risk factors (diabetes, chronic renal disease, uncontrolled systemic arterial hypertension, smoking, hypercholesterolemia, obesity), statin or beta-blocker use were enrolled. Each patient and sex- and age-matched healthy control (HC) underwent Doppler echocardiogram, an endothelial function study by peripheral arterial tonometry technique, NVC and peripheral blood immunophenotyping. RESULTS: SLE ED+ more frequently showed NVC abnormalities compared with HCs ( p < 0.0001) in terms of minor alterations ( p = 0.017), lower capillary numbers ( p = 0.0035) and major alterations. SLE ED + showed a higher rate of CD3 + CD31 + CXCR4 + lymphocytes compared with SLE ED- and with HCs. NVC + SLE showed a significantly reduced rate of total CD3 + cells, but a higher rate and absolute number of CD3 + CD31 + CXCR4 + , compared with NVC- SLE. CONCLUSION: NVC alterations are frequent in SLE without any CV risk factors and CVD. They are associated with ED and increased circulating CD3 + CD31 + CXCR4 + lymphocytes. These findings demonstrate a clear microvascular perturbation in patients with short disease duration, low disease activity and no CV risk factors.

[Role of inflammation mediators in the pathogenesis of heart failure]. / Ruolo dei mediatori dell'infiammazione nella patogenesi dello scompenso cardiaco.

A number of factors are involved in congestive heart failure pathogenesis. Among these, inflammatory mediators could have a crucial role. Patients with congestive heart failure show increased plasma levels of "proinflammatory cytokines", in particular tumor necrosis factor-alpha and interleukin-6. Clinical and experimental models have demonstrated that these cytokines induce left ventricular dysfunction, pulmonary edema, ventricular remodeling, skeletal muscle abnormalities, myocyte apoptosis and endothelial dysfunction, suggesting the possibility that increased plasma concentration of cytokines could not be just an epiphenomenon, but an effective pathogenetic mechanism of disease progression. Additional inflammatory proteins involved in the acute phase response could play a part in the pathogenesis of heart failure. Pentraxin 3 is a prototypical long pentraxin, structurally related, although with different functions, to C-reactive protein, is produced by immune system cells, fibroblasts and particularly by cardiac endothelial cells and myocytes, as demonstrated in murine and human models. Its synthesis is rapidly induced after exposition to bacterial lipopolysaccharide and proinflammatory cytokines, as interleukin-1beta and tumor necrosis factor-alpha. In heart diseases, pentraxin 3 could be involved in the acute local inflammatory response to myocardial injury (e.g. necrosis) and in heart failure pathogenetic mechanisms, but its exact role is not yet settled. Defining the specific part played by these molecules in the pathogenesis of heart failure could lead to new therapeutic approaches in the treatment of cardiac insufficiency.

Long-term changes in left ventricular mass, chamber size and function after valve replacement in patients with severe aortic stenosis and depressed ejection fraction.

We studied 21 patients undergoing valve replacement for severe aortic stenosis and marked left ventricular dysfunction (mean ejection fraction 27 +/- 7.9%) without significant coronary disease or other valve diseases. At 5-60 months (average 26 +/- 18) after surgery, the patients underwent a clinical history, physical examination and a complete M-mode, two-dimensional and Doppler transthoracic echocardiographic study. Thirteen patients were examined with cardiopulmonary exercise testing. Two patients with a low preoperative transvalvular pressure gradient (<50 mm Hg) died postoperatively. Nineteen patients were tested at follow-up. All patients showed an improvement in functional class, an increase in ejection fraction (EF), a normalization in left ventricular diameters, volumes and stress indices and a reduction in left ventricular mass which correlated with EF increase. Cardiopulmonary exercise testing showed a good exercise capacity. In conclusion, in patients affected by severe aortic stenosis and marked preoperative left ventricular dysfunction valve replacement induces a favorable remodeling of the left ventricle, as shown by a late postoperative examination. The regression of hypertrophy is a positive event which correlates with the improvement in EF.

[Prognosis in patients with myocardial infarction and angiographically normal coronaries]. / La prognosi nei pazienti con infarto miocardico e coronarie angiograficamente normali.

From a survey on 8,000 coronary angiographic studies performed in our Institute between January 1980 and June 1990, 105 patients were identified as having angiographically normal coronary arteries and myocardial infarction (MI). Coronary arteries considered as normal were subdivided in completely normal (Group I), or slightly abnormal, with minimal lesions resulting in less than 30% narrowing of a major artery, defined as mild coronarosclerosis (Group II). Thirty-five patients were excluded from the study, because of the lack of complete follow-up data; the remaining 70 patients represent the study group we examined. The following parameters were examined: sex, age at the time of acute MI, family of ischemic heart disease, hypertension, dyslipidemia, diabetes, smoking, stable or unstable angina before MI, location of the MI, ejection fraction (EF), presence of completely normal coronary arteries or mild coronarosclerosis. Follow-up was obtained by contacting the patients or their families; post infarction angina, reinfarction, sudden death or cardiac death were noted. The subjects were divided in 2 groups, according to the coronary anatomy; Group I consisted of 41 patients with completely normal coronary arteries and Group II consisted of 29 patients with mild coronarosclerosis. No significant statistical difference was noted between the 2 groups regarding age, sex and coronary risk factors (except for dyslipidemia which was significantly more prevalent in the subjects with mild coronarosclerosis). Prevalence of left ventricular impairment (EF < 45%) and coronary events (angina, reinfarction and death) were significantly higher in Group II. There was no significant difference in age or clinical risk factor prevalence between patients with complicated and non complicated clinical course.(ABSTRACT TRUNCATED AT 250 WORDS)

Dynamic cardiomyoplasty as an effective therapy for dilated cardiomyopathy.

Nine male patients with dilated cardiomyopathy unresponsive to maximal medical therapy were submitted to dynamic cardiomyoplasty according to the technique described by Carpentier and Chachques, and preliminary postoperative results are reported. Seven patients were in New York Heart Association (NYHA) Class III and two were in intermittent Class IV. The mean age was 56 years (range 51 to 61 years). Preoperative ejection fraction (EF) by multiple gated acquisition ranged from 14% to 28% (mean 20.7%). No additional surgery was performed. Transesophageal echocardiographic monitoring was used during surgery to guide the wrapping procedure. There was no operative mortality. There was one early death (1 month). One late death (sudden death) occurred 7 months after surgery despite significant clinical improvement. Follow-up ranges from 2 to 16 months. Six patients were submitted to hemodynamic evaluation from 4 to 6 months after surgery by transthoracic and transesophageal echo-Doppler assessment. Effective latissimus dorsi support was clearly documented in all patients by comparing postoperative basal hemodynamic values (Cardiomyostimulator [Medtronic, Inc.] switched off) and data obtained during assisted beats (EF increased from 19.4% +/- 8.6% to 32.6% +/- 13.8%, p = 0.043; and stroke volume increased from 51.6 +/- 20.6 mL to 63.0 +/- 22.0 mL, p = 0.014). All patients who completed the latissimus dorsi training protocol were in NYHA Class I or II. A significant reduction in postoperative medical therapy was achieved in all patients. Our preliminary results confirm that the cardiomyoplasty procedure is to be considered a safe and valuable mean for treating selected patients with dilated cardiomyopathy refractory to maximal pharmacological treatment.

Diagnosis of acute myocardial infarction by indium-111 antimyosin antibodies and correlation with the traditional techniques for the evaluation of extent and localization.

This clinical study evaluated the accuracy of planar myocardial scintigraphy with antimyosin monoclonal antibodies radiolabeled with indium-111 (AMA-Fab) in the detection and localization of acute myocardial infarction (AMI). Fifty-seven patients admitted for suspected AMI were studied; 17 patients underwent thrombolytic therapy with intravenous streptokinase and 11 had clinical signs of reperfusion; 9 had had a previous myocardial infarction. Fifty of 57 patients were discharged from the coronary care unit with a confirmed diagnosis of AMI. The AMA-Fab study results were positive for AMI in 49 patients (98%) and negative in 1 (2%). Among the 7 patients without AMI, 5 had unstable angina, 1 had Prinzmetal's variant angina and 1 had acute pancreatitis. AMA-Fab results were negative in 6 of 7 patients (85%) and positive in 1 (15%). Therefore, the sensitivity and specificity of AMA-Fab scintigraphy were 0.98 and 0.85, respectively. To assess accuracy in defining the extent and location of AMI, AMA-Fab results were compared with those of the electrocardiogram, echocardiogram, technetium-99m pyrophosphate myocardial scintigraphy and coronary angiography and left ventriculography. AMA-Fab scintigraphy showed a good concordance with the traditional techniques in the topographic definition of the infarcted regions. No uptake of AMA-Fab was seen in the regions of previous old infarcts. Ten healthy volunteers also underwent AMA-Fab scintigraphy. No evidence of myocardial tracer uptake was noted in them. No adverse reactions or side effects were noted after injection of AMA-Fab in any patient. It is concluded that planar myocardial scintigraphy with AMA-Fab is a reliable method for AMI detection and location.