Shinya Yamada

Adaptive servo ventilation improves Cheyne-Stokes respiration, cardiac function, and prognosis in chronic heart failure patients with cardiac resynchronization therapy

BACKGROUNDnCheyne-Stokes respiration (CSR-CSA) is often observed in patients with chronic heart failure (CHF). Although cardiac resynchronization therapy (CRT) is effective for CHF patients with left ventricular dyssynchrony, it is still unclear whether adaptive servo ventilation (ASV) improves cardiac function and prognosis of CHF patients with CSR-CSA after CRT.nnnMETHODS AND RESULTSnTwenty two patients with CHF and CSR-CSA after CRT defibrillator (CRTD) implantation were enrolled in the present study and randomly assigned into two groups: 11 patients treated with ASV (ASV group) and 11 patients treated without ASV (non-ASV group). Measurement of plasma B-type natriuretic peptide (BNP) levels (before 3, and 6 months later) and echocardiography (before and 6 months) were performed in each group. Patients were followed up to register cardiac events (cardiac death and re-hospitalization) after discharge. In the ASV group, indices for apnea-hypopnea, central apnea, and oxyhemoglobin saturation were improved on ASV. BNP levels, cardiac systolic and diastolic function were improved with ASV treatment for 6 months. Importantly, the event-free rate was significantly higher in the ASV group than in the non-ASV group.nnnCONCLUSIONSnASV improves CSR-CSA, cardiac function, and prognosis in CHF patients with CRTD. Patients with CSR-CSA and post CRTD implantation would get benefits by treatment with ASV.

Suppressive effects of adaptive servo-ventilation on ventricular premature complexes with attenuation of sympathetic nervous activity in heart failure patients with sleep-disordered breathing

Ventricular arrhythmias play a critical role in chronic heart failure (CHF) and are associated with adverse clinical outcomes. Sleep-disordered breathing (SDB) is associated with arrhythmias and/or a poor prognosis in CHF. Adaptive servo-ventilation (ASV) is a ventilatory support system designed to normalize ventilation in CHF patients with SDB. However, the effects of ASV on ventricular arrhythmias and sympathetic nervous activity are still unclear. Nineteen CHF patients with SDB were examined. We performed simultaneous overnight polysomnography and 24-h Holter ECG monitoring, and measured levels of daily urinary catecholamines for two consecutive days (baseline and on ASV). ASV significantly improved the apnea–hypopnea index (pxa0<xa00.01), arousal index (pxa0<xa00.01), and mean SpO2 (pxa0<xa00.01), and decreased daily urinary catecholamines (0.466–0.353xa0mg/day, pxa0=xa00.016) compared to baseline. Furthermore, power in the low to high frequency range as a marker of sympathetic nervous activity decreased across a 24-h period (24-h period: 2.8–1.9, pxa0=xa00.017; during daytime: 3.7–2.3, pxa0=xa00.013; and during sleep time: 1.5–1.3, pxa0=xa00.026). Importantly, ASV significantly decreased ventricular premature complexes not only during sleep time but also across a 24-h period (40.5–21.9xa0beats/h, pxa0=xa00.013). The short-term use of ASV reduced ventricular arrhythmias with the attenuation of sympathetic nervous activity, as demonstrated by urinary catecholamines and heart rate variability. ASV may have anti-sympathetic nervous and anti-arrhythmic effects for CHF with SDB.

Coronary Artery Spasm Related to Thiol Oxidation and Senescence Marker Protein-30 in Aging

BACKGROUNDnSenescence marker protein-30 (SMP30) decreases with aging, and SMP30 knockout (KO) mice show a short life with increased oxidant stress.nnnAIMSnWe assessed the effect of oxidant stress with SMP30 deficiency in coronary artery spasm and clarify its underlying mechanisms.nnnRESULTSnWe measured vascular responses to acetylcholine (ACh) and sodium nitroprusside (SNP) of isolated coronary arteries from SMP30 KO and wild-type (WT) mice. In SMP30 KO mice, ACh-induced vasoconstriction occurred, which was changed to vasodilation by dithiothreitol (DTT), a thiol-reducing agent. However, Nω-nitro-L-arginine-methyl ester, nitric oxide (NO) synthase inhibitor, or tetrahydrobiopterin did not change the ACh response. In isolated coronary arteries of WT mice, ACh-induced vasodilation occurred. Inhibition of glutathione reductase by 1, 3-bis(2-chloroethyl)-1-nitrosourea decreased ACh-induced vasodilation (n=10, p<0.01), which was restored by DTT. To evaluate the thiol oxidation, we measured the fluorescence of monochlorobimane (MCB) in coronary arteries, which covalently labels the total. The fluorescence level to MCB decreased in SMP30 KO mice, but with DTT treatment restored to a level comparable to that of WT mice. The reduced glutathione and total thiol levels were also low in the aorta of SMP30 KO mice compared with those of WT mice. Administration of ACh into the aortic sinus in vivo of SMP30 KO mice induced coronary artery spasm.nnnINNOVATIONnThe thiol redox state is a key regulator of endothelial NO synthase activity, and thiol oxidation was associated with endothelial dysfunction in the SMP30 deficiency model.nnnCONCLUSIONnThese results suggest that chronic thiol oxidation by oxidant stress is a trigger of coronary artery spasm, resulting in impaired endothelium-dependent vasodilation.

Association of Serum n-3/n-6 Polyunsaturated Fatty Acid Ratio With T-Wave Alternans in Patients With Ischemic Heart Disease

Several studies have demonstrated that oral intake of n-3 polyunsaturated fatty acids, specifically eicosapentaenoic acid (EPA), prevents ventricular tachyarrhythmias (VT) with ischemic heart disease, but the underlying mechanisms still remain unclear. Thus, we examined the relation between the serum EPA/arachidonic acid (AA) ratio and electrophysiological properties in patients with ischemic heart disease. The study subjects consisted of 57 patients (46 males, mean age, 66 ± 13 years) with ischemic heart disease. T-wave alternans (TWA) and heart rate variability were assessed by 24hour Holter ECG, and left ventricular ejection fraction (LVEF) was determined by echocardiography. Fasting blood samples were collected, and the serum EPA/AA ratio was determined. Based on a median value of the serum EPA/AA ratio, all subjects were divided into two groups: serum EPA/AA ratio below 0.33 (Group-L, n = 28) or not (Group-H, n = 29). We compared these parameters between the two groups. LVEF was not different between the two groups. The maximum value of TWA was significantly higher in Group-L than in Group-H (69.5 ± 22.8 μV versus 48.7 ± 12.0 μV, P = 0.007). In addition, VT defined as above 3 beats was observed in 7 cases (25%) in Group-L, but there were no cases of VT in Group-H (P = 0.004). However, low-frequency (LF) component, high-frequency (HF) component, LF to HF ratio, and standard deviation of all R-R intervals were not different between the two groups. These results suggest that a low EPA/AA ratio may induce cardiac electrical instability, but not autonomic nervous imbalance, associated with VT in patients with ischemic heart disease.

Senescence marker protein-30 deficiency impairs angiogenesis under ischemia

Aging decreases collateral-dependent flow recovery following acute arterial obstruction. However, the mechanisms are partially understood, therefore critical management has been lacked in clinical setting. Senescence marker protein-30 (SMP30) is a novel aging marker, which is assumed to act as an anti-aging factor in various organs. Therefore, we studied the effect of SMP30 on ischemia-induced collateral growth in SMP30 knockout (KO) mice, young and old C57BL/6 mice. The SMP30 expression in gastrocnemius tissue was decreased in old mice compared to that of young mice. The recovery of cutaneous blood flow in hind limb after femoral artery ligation and tissue capillary density recoveries were suppressed in SMP30 KO and old mice compared to those in young mice. Nitric oxide generation induced by l-arginine and GSH/GSSG in aorta of SMP30 KO and old mice were lower than those in young mice. The levels of NADPH oxidase activity and superoxide production in the ischemic tissue were higher in SMP30 KO and old mice than in young mice. The phosphorylated eNOS and Akt levels and VEGF levels in ischemic muscle were lower in SMP30 KO and old mice than in young mice. Deficiency of SMP30 exacerbates oxidative stress related to NADPH oxidase activity enhancement and impairs eNOS activity, which leads to rarefaction of angiogenesis induced by ischemia. These results suggest that SMP30 plays a key role in disrupting collateral growth under ischemia in aging.

Serum phosphate levels reflect responses to cardiac resynchronization therapy in chronic heart failure patients.

Recent studies have shown that high levels of serum phosphate are associated with adverse cardiovascular events. However, little is known about the relation between phosphate levels and improvement of cardiac function in chronic heart failure (CHF) patients who underwent cardiac resynchronization therapy (CRT). The purpose of this study was to examine whether serum phosphate levels were able to predict responders to CRT and adverse cardiac events.

Age-related oxidant stress with senescence marker protein-30 deficiency plays a pivotal role in coronary artery spasm.

ObjectivesWe examined the mechanism of coronary artery spasm related to oxidant stress with aging in senescence marker protein-30 (SMP30)-deficient mice because SMP30 decreases with aging and SMP30 knockout (KO) mice show a short life with increased oxidant stress. MethodsTo examine the effect of SMP30 on coronary artery vasomotor tone, we measured the endothelium-dependent [5-hydroxytryptamine (5-HT)] response of isolated, pressurized coronary arteries from SMP30 KO and wild-type (WT) mice (n=10 each). ResultsIn SMP30 KO mice, 5-HT-induced vasoconstriction occurred, which altered vasodilation with dithiothreitol, a thiol-reducing agent. In WT mice, 5-HT-induced vasodilation occurred. Administration of 5-HT from the aortic sinus induced a coronary artery spasm in SMP30 KO mice, which was prevented by the intravenous administration of Y-27632, rho-kinase inhibitor. The fluorescence level of monochlorobimane in coronary arteries, which covalently labels the reduced total thiols, decreased in SMP30 KO mice, but reverted to a level comparable with that of WT mice on treatment with Y-27632. From these results, SMP30 provides protection against coronary artery spasm. ConclusionChronic oxidant stress associated with aging plays an important role in coronary artery spasm related to thiol oxidation and rho-kinase signaling.

Utility of heart rate turbulence and T-wave alternans to assess risk for readmission and cardiac death in hospitalized heart failure patients

Heart failure (HF) patients have a higher risk of recurrent HF and cardiac death, and electrical remodeling is considered to be an important factor for HF progression. The present study aimed to validate the utility of electrocardiogram and Holter monitoring for the risk stratification of HF patients.

Predictive impact of the decreasing rate of intrathoracic impedance in worsening chronic heart failure

PurposeIntrathoracic impedance monitoring is useful for heart failure (HF) management in patients with cardiac resynchronization therapy (CRT). However, more accurate identification of worsening chronic HF (CHF) is required in the clinical setting. We investigated this issue by estimating changes in impedance.MethodsWe studied 38 CHF patients (29 males, mean age 67xa0years) with CRT-defibrillator capable of impedance monitoring. During the follow-up period (20.7u2009±u20097.8xa0months), the subjects experienced a total of 129 fluid index threshold (60xa0ohm·days) crossing events. These events were divided into two groups: HF events (nu2009=u200970) and no HF events (nu2009=u200959). Based on the impedance at the beginning of increasing fluid index (S) and at the crossing of 60xa0ohm·days (E), the rate of impedance change (Su2009−u2009Eu2009/u2009S) was estimated. In addition, the elapsed time from S to E (T) was evaluated. Then, we calculated the rate of impedance change per day (Su2009−u2009Eu2009/u2009Su2009×u2009T) in each group.ResultsThe rate of impedance change per day was significantly higher in HF events than in no HF events (0.86u2009±u20090.48 vs. 0.37u2009±u20090.22xa0%/day, Pu2009<u20090.01). By receiver operating characteristic curve for identification of HF events, the best cutoff value of the rate of impedance change was 0.48xa0%/day (sensitivity 80xa0%, specificity 81xa0%, and area under the curve 0.85).ConclusionsThese results suggest that a faster drop in intrathoracic impedance reflected worsening CHF in patients with CRT-defibrillator. Thus, intrathoracic impedance monitoring based on the rate of impedance change may provide a more accurate identification of worsening CHF.

Predicting factors of transmural thermal injury after cryoballoon pulmonary vein isolation

PurposeTransmural thermal injury (TTI), such as esophageal erosion/ulcer and periesophageal nerve injury leading to gastric hypomotility, is not rare complications associated with pulmonary vein isolation (PVI). However, the mechanism and predicting factors of TTI have not yet been fully elucidated with second-generation cryoballoon (CB) PVI.MethodsOne hundred ten consecutive patients, who underwent CB PVI for atrial fibrillation and received esophagogastroduodenoscopy 2xa0days later, were investigated. The relationships between TTI and both clinical and anatomical parameters were examined. We measured the following parameters based on the computed tomography data: the angle of the left atrial (LA) posterior wall to the descending aorta (Ao) (LA-Ao angle); the branching angle of the left inferior pulmonary vein (LIPV) to the coronal plane (LIPV angle); and the minimum distance between the LA posterior wall and descending Ao enclosing the esophagus (LA-Ao distance).ResultsTTIs occurred in 19 patients (esophageal erosion in 2 and gastric hypomotility in 17). The patients with TTI were significantly older than those without TTI. In the anatomical parameters, the LIPV angle was larger and the LA-Ao distance was shorter in the TTI (+) group compared to the TTI (−) group. With the multivariate logistic regression analysis, the age (odds ratio [OR] 2.148, Pu2009=u20090.022) and LA-Ao distance (OR 0.430, Pu2009=u20090.013) were independent predictors of TTI.ConclusionsThe occurrence of TTI in CB PVI was associated with aging, suggesting compromised periesophageal circulation, and the anatomical proximities between the LA and the descending Ao, which enclose the esophagus.