Yoshitaka Oda

Short term effect of adaptive servo-ventilation on muscle sympathetic nerve activity in patients with heart failure.

Chronic heart failure (HF) is characterized by sympathetic overactivation and periodic breathing. We examined whether adaptive servo-ventilation (ASV) exerts a sympathoinhibitory effect in patients with HF via normalizing respiratory pattern. Muscle sympathetic nerve activity (MSNA), heart rate, blood pressure, respiratory pattern and oxygen saturation were examined in 29 HF patients without obstructive sleep apnea (age, 61±15years; ejection fraction, 0.32±0.09; obstructive apnea index, <5/h) before (10 min), during (30 min) and after (10 min) the application of ASV. Periodic breathing was defined as a repeated oscillation of tidal volume with regularly recurring hyperpnea and hypopnea with a variation in tidal volume of greater than 25%. The severity of respiratory instability was determined using the coefficient of variation of tidal volume (CV-TV). Of 29 patients with HF, 11 had periodic breathing and 18 did not. There was a modest positive correlation between MSNA and CV-TV (n=29, p<0.05). ASV reduced respiratory rate, CV-TV and MSNA only in the group with periodic breathing (p<0.01). Change in MSNA significantly correlated with changes in respiratory rate, CV-TV and presence of periodic breathing. However, multivariate analyses revealed that respiratory rate and CV-TV were independent predictors of change in MSNA. ASV reduces MSNA by slowing respiratory rates and stabilizing respiratory patterns in patients with HF.

Impact of sleeping position on central sleep apnea/Cheyne-Stokes respiration in patients with heart failure.

BACKGROUND The present study determines the influence of sleeping position on central sleep apnea (CSA) in patients with heart failure (HF). METHODS The apnea/hypopnea index (AHI) during different body positions while asleep was examined by cardiorespiratory polygraphy in 71 patients with HF (ejection fraction <45%). RESULTS Twenty-five of the patients having predominantly CSA (central apnea index 10/h) with a lower obstructive apnea index (<5/h) were assigned to groups with positional (lateral to supine ratio of AHI <50%, n=12) or non-positional (ratio > or = 50%, n=13) CSA. In the non-positional group the BNP level was higher, the ejection fraction was lower and the trans-tricuspid pressure gradient was higher than in the positional group. Multiple regression analysis revealed more advanced age (p=0.006), log(10)BNP (p=0.017) and lung-to-finger circulation time (p=0.020) as independent factors of the degree of positional CSA. Intensive treatment for HF changed CSA from non-positional to positional in all eight patients tested. Single night of positional therapy reduced CSA (p<0.05) and BNP level (p=0.07) in seven positional patients. CONCLUSION As cardiac dysfunction progresses, severity of CSA also increases and positional CSA becomes position-independent. Positional therapy could decrease CSA, thereby having a valuable effect on HF.

Slow and deep respiration suppresses steady-state sympathetic nerve activity in patients with chronic heart failure: from modeling to clinical application

Influences of slow and deep respiration on steady-state sympathetic nerve activity remain controversial in humans and could vary depending on disease conditions and basal sympathetic nerve activity. To elucidate the respiratory modulation of steady-state sympathetic nerve activity, we modeled the dynamic nature of the relationship between lung inflation and muscle sympathetic nerve activity (MSNA) in 11 heart failure patients with exaggerated sympathetic outflow at rest. An autoregressive exogenous input model was utilized to simulate entire responses of MSNA to variable respiratory patterns. In another 18 patients, we determined the influence of increasing tidal volume and slowing respiratory frequency on MSNA; 10 patients underwent a 15-min device-guided slow respiration and the remaining 8 had no respiratory modification. The model predicted that a 1-liter, step increase of lung volume decreased MSNA dynamically; its nadir (-33 ± 22%) occurred at 2.4 s; and steady-state decrease (-15 ± 5%), at 6 s. Actually, in patients with the device-guided slow and deep respiration, respiratory frequency effectively fell from 16.4 ± 3.9 to 6.7 ± 2.8/min (P < 0.0001) with a concomitant increase in tidal volume from 499 ± 206 to 1,177 ± 497 ml (P < 0.001). Consequently, steady-state MSNA was decreased by 31% (P < 0.005). In patients without respiratory modulation, there were no significant changes in respiratory frequency, tidal volume, and steady-state MSNA. Thus slow and deep respiration suppresses steady-state sympathetic nerve activity in patients with high levels of resting sympathetic tone as in heart failure.

Renal insufficiency coexisting with heart failure is related to elevated sympathetic nerve activity

We investigated whether coexisting renal insufficiency (RI) is associated with elevated sympathetic activity in patients with heart failure (HF). Resting muscle sympathetic nerve activity (MSNA) was determined in 101 patients with HF (ejection fraction<0.45) and 8 patients with RI but without HF (RI group). Diagnosis of RI was made of glomerular filtration rates <60ml/min/1.73m(2) estimated using the simplified Modification of Diet in Renal Disease equation. Of 101 patients, 45 had RI (HFRI group) and 56 did not (HF group). HFRI group was older (p<0.05) and given loop diuretics more frequently (p<0.05), and had a lower specific activity scale (p<0.05) than HF group. HFRI group exhibited significantly greater MSNA indices than either HF group or RI group (burst rate, p<0.05; burst incidence, p<0.01). Univariate analysis showed that RI, age, specific activity scale level and dose of furosemide were significant predictors of increased burst incidence of MSNA in patients with HF. Notably, multivariate analysis revealed that RI was the only independent factor for increased MSNA indices. These findings suggest that coexisting RI is associated with elevated sympathetic activity in patients with HF.

A Rare Case of Sarcoidosis with Bilateral Leg Lymphedema as an Initial Symptom

A 55-year-old man was admitted to our hospital because of bilateral leg lymphedema. He also showed subcutaneous nodules and CT scan disclosed multiple enlarged lymph nodes at thoracic, abdominal, and inguinal areas. Biopsy of the inguinal lymph node and the subcutaneous nodule revealed noncaseating epithelioid cell granuloma, a finding consistent with sarcoidosis. Lymphedema was attributed to the blockade of lymph flow by the systemic lymph node involvement of the disease. Within 1 week after the initiation of steroid therapy, his leg edema disappeared. Lymphedema could be the initial symptom of systemic sarcoidosis.

Independent prognostic importance of respiratory instability and sympathetic nerve activity in patients with chronic heart failure

BACKGROUND Respiratory instability in chronic heart failure (CHF) is characterized by irregularly rapid respiration or non-periodic breathing rather than by Cheyne-Stokes respiration. We developed a new quantitative measure of respiratory instability (RSI) and examined its independent prognostic impact upon CHF. METHODS In 87 patients with stable CHF, respiratory flow and muscle sympathetic nerve activity (MSNA) were simultaneously recorded. RSI was calculated from the frequency distribution of respiratory spectral components and very low frequency components. RESULTS During a mean follow-up of 85±38 months, 24 patients died. Sixteen patients who died of cardiac causes had a lower RSI (16±6 vs. 30±21, p<0.01), a lower specific activity scale (4.3±1.4 Mets vs. 5.7±1.4 Mets, p<0.005), a higher MSNA burst area (16±5% vs. 11±4%, p<0.001), and a higher brain natriuretic peptide (BNP) level (514±559pg/ml vs. 234±311pg/ml, p<0.05) than 71 patients who did not die of cardiac causes. Multivariate analysis revealed that RSI (p=0.015), followed by MSNA burst area (p=0.033), was an independent predictor of subsequent all-cause deaths and that RSI (p=0.026), MSNA burst area (p=0.001), and BNP (p=0.048) were independent predictors of cardiac deaths. Patients at very high risk of fatal outcome could be identified by an RSI<20. CONCLUSIONS The daytime respiratory instability quantified by a new measure of RSI has prognostic importance independent of sympathetic nerve activation in patients with clinically stable CHF. An RSI of <20 identifies patients at very high risk for subsequent all-cause and cardiovascular death.

DIFFERING EFFECTS OF ADAPTIVE SERVO-VENTILATION AND CONTINUOUS POSITIVE AIRWAY PRESSURE ON MUSCLE SYMPATHETIC NERVE ACTIVITY IN PATIENTS WITH HEART FAILURE

Long-term adaptive servo-ventilation (ASV) increases cardiac function more effectively than continuous positive airway pressure (CPAP), possibly via alleviating sympathetic overactivation by respiratory stabilization. The present study evaluated the effect of ASV and CPAP at comparable pressure on