Flow-mediated dilation normalization predicts outcome in chronic heart failure patients.

Background: Reduced flow-mediated dilation (FMD) is a known prognostic marker in heart failure (HF), but may be influenced by the brachial artery (BA) diameter. Aiming to adjust for this influence, we normalized FMD (nFMD) by the peak shear rate (PSR) and tested its prognostic power in HF patients. Methods and Results: BA diameter, FMD, difference in hyperemic versus rest brachial flow velocity (FVD), PSR (FVD/BA), and nFMD (FMD/PSR × 1000) were assessed in 71 HF patients. At follow-up (mean 512 days), 19 HF (27%) reached the combined endpoint (4 heart transplantations [HTs], 1 left ventricle assist device implantation [LVAD], and 14 cardiac deaths [CDs]). With multivariate Cox regression analysis, New York Heart Association functional class ≥III (hazard ratio [HR] 9.36, 95% confidence interval [CI] 2.11-41.4; P =.003), digoxin use (HR 6.36, 95% CI 2.18-18.6; P =.0010), FMD (HR 0.703, 95% CI 0.547-0.904; P =.006), PSR (HR 1.01, 95% CI 1.005-1.022; P =.001), FVD (HR 1.04, 95% CI 1.00-1.06; P =.02), and nFMD (HR 0.535, 95% CI 0.39-0.74; P =.0001) were predictors of unfavorable outcome. Receiver operating characteristic curve for nFMD showed that patients with nFMD >5 seconds had significantly better event-free survival than patients with nFMD ≤5 seconds (log-rank test: P 5 seconds have a better prognosis than those with lower values

Prognostic relevance of a non-invasive evaluation of right ventricular function and pulmonary artery pressure in patients with chronic heart failure.

AIM: To determine the prognostic relevance of the echocardiographic evaluation of pulmonary artery systolic pressure (PASP) and tricuspid annular plane systolic excursion (TAPSE) in patients with chronic heart failure (CHF). Pulmonary hypertension (PH) and right ventricular (RV) dysfunction have both been associated with poor prognosis in CHF. METHODS AND RESULTS: A complete echocardiographic examination was performed in 658 outpatients with CHF and LVEF <45%. PASP was available in 544 (83%) patients, TAPSE in all patients, and E wave deceleration time (DT) in 643 (98%) patients. During a median follow-up period of 38 months, 125 patients died, 5 underwent urgent heart transplantation, and 5 had an appropriately detected and treated episode of ventricular fibrillation. At Cox survival analysis (composite endpoint was death, urgent heart transplantation, and ventricular fibrillation), patients with PASP ≥40 mmHg plus TAPSE ≤14 mm had a poorer prognosis than those with high PASP but preserved TAPSE; RV dysfunction associated with normal PASP did not carry additional risks. Similar results were obtained when patients were grouped on the basis of DT (restrictive vs. non restrictive) and TAPSE. CONCLUSIONS: A simple echocardiographic evaluation of PASP and RV function with TAPSE may improve risk stratification in patients with CHF. Importantly, if PASP cannot be recorded at echocardiography, a restrictive DT, measurable in the vast majority of patients, may be coupled with TAPSE to stratify patients

Role of oxidative and nitrosative stress biomarkers in chronic heart failure

In this review, we present recent insights on chronic heart failure (CHF) and the potential role of tumor necrosis factor (TNF)-alpha, interleukins, myeloperoxidase (MPO), and nitrosative stress in the progression of this disease process. Reactive oxygen species (ROS) are produced as a consequence of aerobic metabolism. Under physiologic conditions, their unfavourable effect in causing oxidative damage is counteracted by antioxidants. An imbalance in favour of oxidants leads to oxidative stress, and contributes to myocyte apoptosis, direct negative inotropic effects, and reduced bioavailability of nitric oxide (NO). Together, these effects lead to impaired vasodilatation of the coronary, pulmonary and peripheral vascular beds. In patients with moderate to severe forms of CHF, TNF-alpha leads to the formation of nitrotyrosine and consumption of nitric oxide by virtue of activation of myeloperoxidase. Further studies are required to better elucidate the complex interaction of oxidative stress, endothelial dysfunction and inflammatory activation in CHF. Such insights would likely lead to development of better strategies for the assessment of the disease severity by monitoring of new bio-humoral indices and better treatment approaches

INCREASED NITROTYROSINE PLASMA LEVELS IN RELATION TO SYSTEMIC MARKERS OF INFLAMMATION AND MYELOPEROXIDASE IN CHRONIC HEART FAILURE.

The presence of a reciprocal link between inflammation and oxidative/nitrosative stress has been postulated in chronic heart failure (CHF). We aimed to determine signs of nitrosative stress in serum/plasma of CHF patients. ELISA tests were used for quantification of serum/plasma levels of Nitrotyrosine (NT), H2O2, total NO, nitrite (NO2 −), myeloperoxidase (MPO), Tumor Necrosis Factor-alpha (TNFα) and pro-Brain Natriuretic Peptide (proBNP) in 66 CHF patients (9 in NYHA I, 34 NYHA II, 23 NYHA III) and in 14 age-matched healthy subjects. NT levels were higher in NYHA III CHF patients compared to NYHA II (pb0.05), NYHA I (pb0.03) and controls (pb0.02), whereas NO2 − and total NO were higher in NYHA III compared to I (pb0.05 and pb0.04, respectively) and controls (pb0.004 and 0.002) and in NYHA II compared to controls (pb0.04 and pb0.009). NT levels correlated significantly with MPO (r=0.37, pb0.003), TNFα (r=0.32, pb0.01) and proBNP (r=0.32, pb0.01). These data demonstrate an increased NT plasma level in patients with moderate/severe CHF which is associated to increased levels of markers of systemic inflammation

Lower extremities peripheral arterial disease among patients admitted to cardiac rehabilitation: the THINKPAD registry

BACKGROUND/OBJECTIVES: Lower extremities peripheral arterial disease (LE-PAD) across the wide range of conditions for Cardiac Rehabilitation (CR) is poorly understood. The "ATHerosclerosis of the lower extremIties as a liNKed comorbidity in Patients Admitted for carDiac rehabilitation" (THINKPAD) registry explored LE-PAD in CR patients in terms of prevalence and interventions delivered. METHODS: Multicenter, consecutive case series of 1506 patients discharged from 16 CR Units in Italy from May 1 to June 30, 2012. RESULTS: LE-PAD constituted a primary indication for CR and a comorbidity on admission in 2.6% and 9.3% of patients respectively. LE-PAD patients were significantly older (72 ± 9 vs. 67 ± 12 years, p<0.001) and displayed a worse cardiovascular risk profile (diabetes 38% vs. 23%, hypertension 86% vs. 63%, hypercholesterolemia 74% vs. 52%, smoking 72% vs. 50%, low level of physical activity 84% vs. 69%, impaired diet habits 69% vs. 55%, p<0.01 for all). COPD (17% vs. 11%, p<0.05), CKD (20% vs. 10%, p<0.01), and past history of coronary revascularization (29% vs. 14%, p<0.001) were also more represented in the LE-PAD group. Half of LE-PAD patients received a formal staging, with low provision of ABI (18%) and color Doppler (48%) investigation. Secondary prevention targets at the end of CR for blood pressure and lipid control were accomplished in 83% and 46% of patients respectively (strongly correlated with the presence of CAD), while other guideline-recommended drugs for LE-PAD were prescribed in less than 4% of cases. CONCLUSION: LE-PAD represents an uncommon referral indication for CR. Our data confirm its systematic underassessment and undertreatmen