Obstructive Sleep Apnea as Possible Causal Factor for Visit-to-Visit Blood Pressure Variability.

BACKGROUND: Recent studies have shown that visit-to-visit blood pressure variability (BPV) is an independent risk factor for cardiovascular disease. However, it has not been clarified whether obstructive sleep apnea (OSA) is associated with visit-to-visit BPV. METHODS AND RESULTS: The 56 subjects with OSA and 26 control subjects without OSA were examined. Office BP was measured on 5 separate consecutive occasions prior to a polysomnography examination. The visit-to-visit BPV was expressed as the standard deviation and the coefficient of variation of the 5 systolic BP measurements. In subjects with an apnea-hypopnea index (AHI) of more than 20 episodes per hour, the visit-to-visit BPV was also measured after the start of continuous positive airway pressure (CPAP) therapy. Overall, the AHI positively correlated with the standard deviation and the coefficient of variation of systolic BP. In a multivariate analysis, the plasma noradrenaline level and the AHI were independently and positively correlated with the standard deviation and the coefficient of variation of the systolic BP. Among the patients who underwent CPAP therapy, good adherence with CPAP therapy significantly reduced the visit-to-visit BPV. CONCLUSIONS: OSA is associated with abnormal visit-to-visit BPV and sympathetic activation seems to be related in some way. (Circ J 2016; 80: 1787-1794).

Nocturnal Intermittent Hypoxia Is Associated With Left Ventricular Hypertrophy in Middle-Aged Men With Hypertension and Obstructive Sleep Apnea.

BACKGROUND: Obstructive sleep apnea (OSA) and left ventricular (LV) hypertrophy are considered to be closely associated. However, the relationship has not yet been fully demonstrated and is hence still controversial. The purpose of this study was to assess in hypertensive male patients the relationship between OSA and cardiac structure using a new index, namely, integrated area of desaturation (IAD), in addition to the apnea-hypopnea index (AHI) that is currently the most frequently used index of sleep-disordered breathing. METHODS: In our cross-sectional study, 223 hypertensive men younger than 65 years with sleep apnea and normal cardiac function were enrolled. All subjects were evaluated by fully attended polysomnography. Cardiac structure and function were evaluated by echocardiography. RESULTS: LV mass index significantly correlated with IAD (r = 0.203, P < 0.05), but not with AHI. Multivariate linear regression analyses showed that IAD, brain natriuretic peptide (BNP), and age are independent variables affecting the LV mass index (ß = 0.262, 0.237, and 0.173, respectively, P < 0.05). IAD was the one and only determinant among the indices of sleep-disordered breathing. CONCLUSIONS: Nocturnal intermittent hypoxia defined by IAD may be associated with LV hypertrophy in men with well-controlled hypertension and obstructive sleep apnea.

Continuous positive airway pressure treatment improves cardiovascular outcomes in elderly patients with cardiovascular disease and obstructive sleep apnea.

Obstructive sleep apnea (OSA) is associated with the progression of cardiovascular disease (CVD), particularly in the middle-aged population. However, the clinical importance of OSA as a risk for CVD in the elderly population remains controversial. Moreover, evidence for the effectiveness of continuous positive airway pressure (CPAP) treatment for the secondary prevention of CVD in elderly patients is lacking. We assessed whether CPAP treatment improves cardiovascular outcomes in elderly patients with OSA and CVD. In this retrospective cohort study, we enrolled 130 elderly patients aged 65-86 years with moderate to severe OSA (apnea-hypopnea index ≥15/h) and a history of hospitalization due to CVD, who underwent polysomnography between November 2004 and July 2011. Patients were divided into the CPAP group (n = 64) or untreated OSA group (n = 66). The main outcome measures were cardiovascular death and hospitalization due to CVD. During the mean follow-up period of 32.9 ± 23.8 (standard deviation) months, 28 (21.5 %) patients either died or were hospitalized. The Kaplan-Meier curves indicated that event-free survival was significantly lower in the untreated OSA group than in the CPAP group (P < 0.005). A multivariate analysis showed that the risk was significantly increased in the untreated OSA group (hazard ratio 5.13; 95 % confidence interval 1.01-42.0; P < 0.05). Moderate to severe OSA not treated with CPAP was an independent risk factor for relapse of a CVD event, and adequate CPAP treatment improved cardiovascular outcomes in elderly patients.

Baroreflex sensitivity of an arterial wall during rotary blood pump assistance.

It is well known that the baroreflex system is one of the most important indicators of the pathophysiology in hypertensive patients. We can check the sensitivity of the baroreflex by observing heart rate (HR) responses; however, there is no simple diagnostic method to measure the arterial behavior in the baroreflex system. Presently, we report the development of a method and associated hardware that enables the diagnosis of baroreflex sensitivity by measuring the responses of both the heart and the artery. In this system, the measurements are obtained by monitoring an electrocardiogram and a pulse wave recorded from the radial artery or fingertip. The arterial responses were measured in terms of the pulse wave velocity (PWV) calculated from the pulse wave transmission time (PTT) from the heart to the artery. In this system, the HR change corresponding to the blood pressure change in time series sequence was observed. Slope of the changes in blood pressure and HR indicated the sensitivity of the baroreflex system of the heart. This system could also measure the sensitivity of the baroreflex system of an artery. Changes in the PWV in response to the blood pressure changes were observed. Significant correlation was observed in the time sequence between blood pressure change and PWV change after calculating the delay time by cross-correlation. The slope of these parameter changes was easily obtained and it demonstrated the sensitivity of the baroreflex system of an artery. We evaluated this method in animal experiments using rotary blood pump (RBP) with undulation pump ventricular assist device, and PTT elongation was observed in response to increased blood pressure with RBP assistance. Furthermore, when tested clinically, decreased sensitivity of the baroreflex system in hypertensive patients was observed. This system may be useful when we consider the ideal treatment and follow-up of patients with hypertension.

Development of the pulsation device for rotary blood pumps.

A rotary blood pump (RP) is desirable as a small ventricular assist device (VAD). However, an RP is nonpulsatile. We tried to develop a device that attaches a pulse to the RP. We also tried to develop a pulse-generating equipment that was not air-pressure driven. The ball screw motor was considered a candidate. The application of a small-sized shape memory alloy was also attempted. An electrohydraulic system was adopted, and actuator power was connected to the diaphragm. The diaphragm was placed on the outer side of the ventricle. Most RPs that have been developed all over the world drain blood from the ventricle. The wave of a pulse should be generated if a pulse is added by the drawn part. The output assistance from the outer side of the ventricle was attempted in animal experiments, and the device operated effectively. This device can be used during implantable operation of RP. This may serve as an effective device in patients experiencing problems in peripheral circulation and in the function of internal organs.

Development of an implantable undulation type ventricular assist device for control of organ circulation.

It is well known that a rotary blood pump (RP) is effective as a small ventricular assist device (VAD). It might be still more effective if pulsation was available. The undulation pump (UP), which is a type of small RP, can also produce pulsation. In Japan, a development project for an implantable type UP ventricular assist device (UPVAD) is now advanced. Six universities and some companies together have been in charge of the development project for 5 years. In this study, the influence which the UP under development has on circulation in internal organs was investigated. Goats with the same weight as an average Asian person were used for the experiment. The left chest cavity was opened after resection of the fourth rib and the heart was approached. A cannula was inserted in the left ventricle from the apex. An outflow cannula was inserted into the left descending aorta. Heart muscle was excised using a newly developed puncher. The UPVAD was implanted using a left-heart bypass system. The myocardial blood flow, carotid arterial blood flow, and the kidney blood flow were recorded together with an electrocardiogram, blood pressure, and the flow rate. In these animal experiments, the blood circulation dynamic state was stabilized and sufficient support of the left heart was observed. Myocardial blood flow, carotid arterial flow, and a kidney blood flow increase resulting from UPVAD support was observed. Often the problem of multiple organ failure is important at the time of clinical application of a ventricular assist device. Assisting circulation to internal organs is important for prevention of multiple organ failure. It was concluded that the UPVAD might be useful for prevention of multiple organ failure.

A Japanese-Russian collaborative study on aging and atherosclerosis.

In Russia, the average life span is decreasing. This phenomenon has not been previously observed in the western hemisphere during periods of relative peace. Although this trend can be attributed to various causes, the available statistics suggest that approximately 55% of the total mortality in Russia at the present time is due to cardiovascular events. Similarly, cardiovascular events are also increasing in Japan and are associated with changes in eating habits. A Japanese-Russian international collaborative study was therefore initiated to investigate this. Data on 102 normal Russian subjects were obtained from a total of 345 patients treated at the Smolensk State Medical Academy outpatients' clinic. The data on the Japanese patients were collected at Tohoku University, Tohoku Rosai Hospital, and Fukuda Denshi Company. Sixty-seven healthy male Japanese volunteers were compared with 44 healthy male Russian patients. In this study, Vasera VS1000 (Fukuda Denshi, Tokyo) was utilized to measure pulse wave velocity (PWV). Linear regression analysis was performed, and the results showed that brachial-ankle PWV (baPWV) was significantly higher in the Russian compared with the Japanese study group. With regard to aging, PWV was found to increase both in the Japanese and Russian subjects, with a significant increase in the latter group during their 40s compared with the Japanese, and with this tendency being carried forward into the 50s. This may be the principal cause for the higher incidence of cardiovascular events reported among Russians. Furthermore, when a straight line regression analysis was performed, the zero axis intercept in both cases showed almost the same value. These results indicated that the PWV may be almost the same in Japanese and Russian populations at the time of birth. In conclusion, at the time of birth, there is no difference in the atherosclerotic status of Japanese and Russian infants. However, over time atherosclerosis becomes more apparent and progresses significantly in the case of Russian subjects. This finding is observed through the analysis of PWV. The present authors intend to continue their study aimed at preventing the further development of atherosclerosis through medical intervention.

Brachio-ankle pulse wave velocity and cardio-ankle vascular index (CAVI).

In order to diagnose arteriosclerosis in any part of the body, pulse wave velocity (PWV) measurement is a useful approach. However, it is considered that the technique of PWV measurement should be simplified. A new method for measuring PWV has therefore been proposed in Japan. The PWV of the brachial artery (ba) and the ankle was measured by applying air pressure with the aid of a volume plethysmograph. Comparisons between the baPWV measurement method and the conventional method are currently being performed. Since satisfactory results have been obtained to date, baPWV has gained popularity throughout Japan. Since this method measures PWV in the arm and foot, it may be said that aortic PWV is not reflected though a large amount of past PWV measurements. BaPWV is influenced by blood pressure. With the baPWV technique, blood pressure compensation is not carried out. Furthermore, the pulse pressure is measured by air pressure; therefore any stimulus that exerts pressure on an artery may influence these results. Due to these reasons, a cardie-ankle vascular index (CAVI) has been proposed in which the pressure wave form indicating the closing of the aortic valve appears in the form of an arterial pressure wave after a fixed delay time. This delay is the time difference between the actual closing of the aortic valve and the measuring point. Prior to the introduction of baPWV, PWV was measured in the carotid artery and foot. As in traditional PWV, baPWV uses the delay time, but between the brachial artery and the ankle artery. However, the carotid artery differs from the brachial artery, and the measured value differs depending on whether the arteriosclerosis is present in the carotid artery or the brachial artery. CAVI is calculated from the ECG, PCG, brachial artery waveform and ankle artery waveform using a special algorithm. This new method represents a breakthrough in the diagnosis of atherosclerosis.

Addition of rhythm to non-pulsatile circulation.

The development of a rotary blood pump (RP) is desirable as it can be used as a small ventricular assistance device (VAD). However, a RP does not generate any pulse. It may be physiologically better for the patient if the RP could generate a pulse. We have attempted to develop a device that produces a pulse in the RP. Intra-aortic balloon pumping (IABP) is effective in producing a pulse. However, the IABP cannot be implanted inside the body. Therefore, an attempt was made to develop pulse-generating equipment that was not driven by air pressure. The ball screw motor was considered as a possible candidate. In the future, we plan to apply small shape memory alloys. An electrohydraulic system was adopted, and actuator power output was connected to the diaphragm. The diaphragm was placed outside the ventricle. Most RPs developed throughout the world drain blood from the ventricle. The pulse wave should be generated if a pulse is added by the part from which blood is being drawn. In this study, animal experiments were conducted and the output assistance was tested from outside the ventricle. The device operated effectively in the animal experiment. The RP can easily be equipped with this device at the time of performing the implant operation. For a patient with problems of peripheral circulation and the internal organ function, it may prove to be an effective device.

Artificial myocardium with an artificial baroreflex system using nano technology.

Where is the place which should be helped in a patient with congestive heart failure? The answer may be contraction of the heart. At Tohoku University, development research of "the artificial myocardium" has been conducted, using a ball screw type electromagnetic motor. Furthermore, super-miniaturization is being attempted at present. Thus, a system with shape memory alloy is being developed. The cooling speed problem was solved by the application of the Peltier element. A drive at a speed equal to that of a heartbeat was realized by the application of this system. At present, a ventricular assist device is used for patients waiting for a heart transplant in Japan. An air driven type system disturbs a patient's QOL remarkably because it is connected to the drive device. With our concept, energy is provided by using the electromagnetic force from outside of the body by the use of transcutaneous energy transmission system. Magnetic shielding by amorphous fibers was used at Tohoku University to improve the total efficiency. A natural heart can alter the cardiac output corresponding to the demand. Artificial internal organs must participate in the system of the living body, too. Tohoku University has developed a resistance based artificial heart control algorithm, which simulated a baroreflex system to cope with every demand. Nano level sensing equipment is now under development at Tohoku University. At present, development is being conducted aiming at an "intelligent artificial myocardium".