Pulmonary tumor thrombotic microangiopathy: the challenge of the antemortem diagnosis.

Pulmonary tumor thrombotic microangiopathy (PTTM) is known as a rare and severe cancer-related pulmonary complication. Nowadays, fewer than 80 cases have been reported in the literature and very few cases have been diagnosed antemortem. We describe an autopsy case of PTTM associated with cancer of unknown origin. A 56-year-old male patient came to our attention due to a 2-day history of dyspnea. Analysis of the clinical context in combination with laboratory and imaging tests led us to suspect acute pulmonary thromboembolism. However, the computed tomography pulmonary angiogram was negative for thromboembolism; on the contrary it revealed multiple lymphadenopathy. Microscopic pulmonary tumor embolism was suspected and a lymph node biopsy was planned. However, the patient's condition progressively worsened; death occurred 3 days after admission. After autopsy, histologically extensive neoplastic emboli involved the small pulmonary arteries and arterioles, often admixed with fibrin thrombi. The involved and noninvolved arteries also demonstrated fibrocellular intimal proliferation causing marked luminal stenosis and occlusion. These pathological features were characteristic of PTTM, which should be distinguished from microscopic tumor embolism and should be considered in the differential diagnosis of acute/subacute cor pulmonale and pulmonary hypertension in cancer as well as in noncancer patients. We propose a review of the literature and an algorithm to improve PTTM antemortem diagnosis.

10-year exercise training in chronic heart failure: a randomized controlled trial.

OBJECTIVES: This study investigated the effect of a very long-term exercise training program is not known in chronic heart failure (CHF) patients. BACKGROUND: We previously showed that long-term moderate exercise training (ET) improves functional capacity and quality of life in New York Heart Association class II and III CHF patients. METHODS: We studied 123 patients with CHF whose condition was stable over the previous 3 months. After randomization, a trained group (T group, n = 63) underwent a supervised ET at 60% of peak oxygen consumption (Vo(2)), 2 times weekly for 10 years, whereas a nontrained group (NT group, n = 60) did not exercise formally. The ET program was supervised and performed mostly at a coronary club with periodic control sessions twice yearly at the hospital's gym. RESULTS: In the T group, peak Vo(2) was more than 60% of age- and gender-predicted maximum Vo(2) each year during the 10-year study (p < 0.05 vs. the NT group). In NT patients, peak Vo(2) decreased progressively with an average of 52 ± 8% of maximum Vo(2) predicted. Ventilation relative to carbon dioxide output (VE/Vco(2)) slope was significantly lower (35 ± 9) in T patients versus NT patients (42 ± 11, p < 0.01). Quality-of-life score was significantly better in the T group versus the NT group (43 ± 12 vs. 58 ± 14, p < 0.05). During the 10-year study, T patients had a significant lower rate of hospital readmission (hazard ratio: 0.64, p < 0.001) and cardiac mortality (hazard ratio: 0.68, p < 0.001) than controls. Multivariate analysis selected peak Vo(2) and resting heart rate as independent predictors of events. CONCLUSIONS: Moderate supervised ET performed twice weekly for 10 years maintains functional capacity of more than 60% of maximum Vo(2) and confers a sustained improvement in quality of life compared with NT patients. These sustained improvements are associated with reduction in major cardiovascular events, including hospitalizations for CHF and cardiac mortality.

Trimetazidine improves endothelial dysfunction in chronic heart failure: an antioxidant effect.

AIMS: To determine whether trimetazidine (TMZ) improves the endothelium-dependent relaxation (EDR) in chronic heart failure (CHF) and whether this effect is associated with its antioxidant properties. METHODS AND RESULTS: We studied 51 patients (mean age 51.4 +/- 6 years) with CHF secondary to ischaemic cardiomyopathy (ejection fraction 32.5 +/- 4.5%). Plasma malondialdehyde (MDA) and lipid hydroperoxides (LOOHs) were measured from an antecubital vein on study entry and after a 4 week treatment with oral TMZ (20 mg tid) (group T, n = 23) or placebo (group C, n = 22) given randomly. Endothelium-dependent vasodilation of the radial artery (RA) was determined by intra-arterial infusion of acetylcholine (7.5, 15 and 30 microg/min). Patients receiving TMZ had an increased radial artery diameter (RAD) in response to each dose of acetylcholine infusion and a greater peak oxygen uptake (P < 0.01 vs. placebo). Plasma MDA and LOOHs levels were reduced at 4 weeks only in patients receiving TMZ (P < 0.001 for both vs. placebo). The improvement in ED-vasodilation was correlated with changes in peak VO(2) (r = 0.68; P = 0.0001), MDA (r = -0.61; P = 0.0002) and LOOHs (r = -0.59; P = 0.005). CONCLUSION: TMZ improves the ED-relaxation in patients with ischaemic cardiomyopathy. The antioxidant properties of TMZ may play a role.

Effects of short-term moderate exercise training on sexual function in male patients with chronic stable heart failure.

BACKGROUND: Patients with chronic heart failure (CHF) have sexual dysfunction that impairs quality of life. Recent trials have demonstrated that exercise training (ET) improves quality of life (QOL) of CHF patients, but it is not established whether this benefit may be associated with an improvement in sexual dysfunction. OBJECTIVE: To determine whether ET can improve sexual dysfunction in patients with CHF. METHODS: We prospectively studied 59 male patients (57+/-9 years) with stable CHF in sinus rhythm and without prostatic disease. Patients were randomized into two groups. A group (T, n = 30) underwent supervised cycle ergometer ET at 60% of peak VO2, three times a week, 60 min each session, for 8 weeks. A group (NT, n = 29) was not exercised. Medications were not changed during the study. On study entry and at 8 weeks all patients underwent a symptom-limited cardiopulmonary exercise testing, brachial artery endothelium-dependent (ED) and endothelium-independent (EI) vasomotor responses, QOL and sexual activity profile assessment (SAP) by questionnaire. RESULTS: At 8 weeks, no changes were observed in control patients. In trained patients, however, peak VO2 improved by 18% (P < 0.005) and was correlated with QOL (r = 0.80; P < 0.001). Flow-mediated dilation improved in trained patients (from 2.29+/-1.13% to 5.04+/-1.7%, P = 0.0001), while EI dilation (after 0.3 mg sublingual NTG) did not. In group T, all three domains (i.e. Domain 1=relationship with the partner; Domain 2 = quality of penile erection; Domain 3 = personal wellness) were significantly improved from baseline (total score patients: from 3.49+/-3.4 to 6.17+/-3.2, P < 0.001; partners: from 2.47+/-2.7 to 4.87+/-2.5, P < 0.001). Pre-post training change in SAP total score was correlated with changes in coronary risk profile (r = -0.49; P = 0.01), peak VO2 (r = 0.67; P < 0.001) and QOL (r = 0.73; P = 0.01). Multivariate analysis selected the improvement in ED-vasomotor response as the strongest independent predictor of SAP improvement (r = 0.63, P < 0.001). CONCLUSIONS: In stable CHF, cycle ergometer ET significantly improves brachial artery endothelial dysfunction, suggesting a systemic effect of leg exercise. This benefit was correlated with improvements in sexual activity.