Experimental heart rate regulation in cycle-ergometer exercises.

The heart rate can be effectively used as a measure of the exercise intensity during long duration cycle-ergometer exercises: precisely controlling the heart rate (HR) becomes crucial especially for athletes or patients with cardiovascular/obesity problems. The aim of this letter is to experimentally show how the nonlocal and nonswitching nonlinear control that has been recently proposed in the literature for the HR regulation in treadmill exercises can be effectively applied to cycle-ergometer exercises at constant cycling speed. The structure of the involved nonlinear model for the HR dynamics in cycle-ergometer exercises is mathematically inspired by the structure of a recently identified and experimentally validated nonlinear model for the HR dynamics in treadmill exercises: the role played by the treadmill speed is played here by the work load while the zero speed case for the treadmill exercise is here translated into the cycling operation under zero work load. Experimental results not only validate the aforementioned nonlinear model but also demonstrate the effectiveness--in terms of precise HR regulation--of an approach which simply generalizes to the nonlinear framework the classical proportional-integral control design. The possibility of online modifying the HR reference on the basis of the heart rate variability (HRV) is also suggested and experimentally motivated.

Biological drug treatment of rheumatoid arthritis and spondyloarthritis: effects on QT interval and QT dispersion.

OBJECTIVE: Tumor necrosis factor-α (TNF-α) antagonists bring about significant improvement in chronic inflammatory diseases such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). There is some evidence that they can also have negative myocardial effects, but to date this issue has not been clarified. We evaluated changes in electrocardiographic measures [QT interval, corrected, dispersion, and dispersion corrected (QT, QTc, QTd, QTdc, respectively)] in patients with RA or SpA treated with anti-TNF agents (infliximab and etanercept), those treated with other biological agents (rituximab), and with methotrexate. METHODS: We studied 38 consecutive patients with RA (21 patients) or SpA (19 patients) being treated with TNF-α antagonists, 8 patients with RA being treated with rituximab, and 13 patients (8 with RA and 5 with SpA) taking methotrexate. Electrocardiographs (ECG) were performed on all participants at baseline and 12 months after initiation of treatment, and the QT, QTc, and QTd were calculated with standard procedures. RESULTS: After 12 months of treatment, significant increases over baseline values were observed in the mean QT (p < 0.009), QTd (p < 0.0001), and QTdc (p < 0.0001) of the anti-TNF group, but no significant changes were observed in those taking rituximab. QT changes in the anti-TNF group were unrelated to the disease (RA vs SpA) or drug (infliximab vs etanercept), and none were associated with clinical manifestations of cardiac disease. CONCLUSION: In patients with RA and SpA, TNF-α antagonists seem to increase the QT and QTd measures. Although these changes were completely asymptomatic, ECG may be indicated in patients being considered for anti-TNF therapy to identify those at risk for cardiac complications.

Autonomic dysfunction and microvascular damage in systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease characterized by vascular damage and interstizial fibrosis of many organs. Our interest was focused on the evaluation of cardiac autonomic function by measurements of heart rate variability (HRV) and microvascular damage detected by nailfold capillaroscopy (NC) in SSc patients. We examined 25 consecutive outpatients affected by systemic sclerosis and 25 healthy controls. Exclusion criteria were the presence of cardiac disease, hypertension, diabetes mellitus, or neurological diseases. All subjects underwent 24-h ambulatory ECG Holter recording and NC examination. Heart rate variability was evaluated in the time domain, using appropriate software, computing the time series of all normal-to-normal (NN) QRS intervals throughout the 24-h recording period. A semiquantitative rating scale was adopted to score the NC abnormalities, as well as a rating system for avascular areas and morphological NC patterns. In SSc patients, HRV analysis showed significantly lower values of SDNN (standard deviation of all NN intervals) (p=0.009), SDANN (standard deviation of the averages of NN intervals in all 5-min segments of the entire recording) (p=0.01), and pNN50 (the percentage of adjacent NN intervals that differed by more than 50 ms) (p=0.02), compared to the control group. These parameters in SSc patients significantly decreased with the worsening of semiquantitative capillaroscopy score. In conclusion, an abnormal autonomic nervous control of the heart might contribute to identify subclinical cardiac involvement in SSc patients. The coexistence of autonomic dysfunction with a more severe microvascular damage could be considered a potential prognostic tool in the identification of those patients particularly at risk for cardiac mortality.

Variation in the dopaminergic response during the day in Parkinson disease.

OBJECTIVE: In many parkinsonian patients with fluctuating disease the early morning levodopa dose is more effective than the following dose on the same day. In this study we investigated whether the poor responsiveness to the early afternoon dose of levodopa depends only on peripheral and central levodopa pharmacokinetics or also on pharmacodynamic factors. METHODS: Ten parkinsonian patients experiencing postprandial drug-resistant off periods received two boluses of apomorphine by subcutaneous injection at 8 am and 3 pm on two nonconsecutive days. On day 2, therapy was stopped at 11 am. For each bolus we determined time to on, duration of the on state, magnitude of benefit, and levodopa and apomorphine plasma levels at baseline and immediately after patients reached the on state. RESULTS: The mean duration of on phases was significantly shorter and the apomorphine plasma level needed to reach the on state was significantly higher in the afternoon than in the morning (P<0.01 by paired t test). CONCLUSIONS: This study suggest that there is a change in responsiveness to dopaminergic stimulation during the day. The less effective dopaminergic response in afternoon depends on pharmacodynamic factors and not only on peripheral and central levodopa pharmacokinetic.

Tumor necrosis factor-alpha and myocardial function in patients with myotonic dystrophy type 1.

An imbalance of TNF system activity has been reported in patients with myotonic dystrophy type 1 (DM1). Nevertheless, the question whether TNF-alpha action is directly implicated in the pathogenesis of DM1 or is a simple marker of disease activity is still open. Therefore, the present study was aimed to investigate serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 levels in association with the disease stage, cytosine-thymine-guanine (CTG) expansion and cardiac function of 56 patients with DM1 (40+/-14 years) and 28 healthy controls (42+/-12 years). All subjects were submitted to resting electrocardiogram (EKG), Signal-averaged EKG (SA-EKG), and M-mode/2-D echocardiography. TNF-alpha levels were higher in patients compared to controls (p<0.0003) and were associated to disease stage (p<0.02). Significant correlation were observed between TNF and CTG expansion (p<0.005) or PQ intervals (p<0.0005). Ventricular late potentials (VLPs) occurred in 54% of cases. In these patients, TNF-alpha levels were higher compared to those without VLPs (p<0.05). We may conclude that TNF-alpha levels might represent and adjunctive criterion for disease staging in patients with myotonic dystrophy type 1, and that elevated TNF levels in DM1 may lead to cardiac fibrosis affecting diastolic function, conduction, and automaticity.

Ventricular late potentials in systemic sclerosis: relationship with skin involvement.

OBJECTIVE: To detect the myocardial involvement in patients with systemic sclerosis (SSc) by signal averaged electrocardiography method (SA-ECG) in relationship to the skin changes. METHODS: We selected 24 SSc outpatients according to American Rheumatism Association criteria, without clinical and instrumental evidence of cardiac disease, and compared them with 24 control subjects. All patients and controls underwent SA-ECG to detect ventricular late potentials (LP). The extent and severity of skin involvement in SSc patients was detected by modified Rodnan (m-Rodnan) skin score. RESULTS: SSc patients had higher prevalence of LP compared to controls (46 versus 8%, p < 0.003). Median skin score value in the overall SSc population was 7 [mean, SD (range): 7.8, 3.2, (4-18)]. Patients with LP had a higher median skin score value compared to SSc patients without LP [median (range): 10 (6-18) versus 6 (4-9); Mann-Whitney U test 22.5, p < 0.005]. A subset analysis was also performed to verify the correlation of antibodies positivity (anti-centromere and Scl 70) pattern and the presence of LP. Our findings showed that higher values of skin score correlated with the presence of LP independent of antibody subsets. CONCLUSIONS: Our data suggest that diffuse abnormalities of the cardiac tissue detected by SA-ECG may be present, even in patients without cardiac symptoms. The relationship between LP and skin involvement in patients without clinical evidence of cardiac involvement may help detect of a subset of patients who may develop scleroderma heart disease.