Pulse rate variability: a new biomarker, not a surrogate for heart rate variability.

With the popularization of pulse wave signals by the spread of wearable watch devices incorporating photoplethysmography (PPG) sensors, many studies are reporting the accuracy of pulse rate variability (PRV) as a surrogate of heart rate variability (HRV). However, the authors are concerned about their research paradigm based on the assumption that PRV is a biomarker that reflects the same biological properties as HRV. Because PPG pulse wave and ECG R wave both reflect the periodic beating of the heart, pulse rate and heart rate should be equal, but it does not guarantee that the respective variabilities are also the same. The process from ECG R wave to PPG pulse wave involves several transformation steps of physical properties, such as those of electromechanical coupling and conversions from force to volume, volume to pressure, pressure impulse to wave, pressure wave to volume, and volume to light intensity. In fact, there is concreate evidence that shows discrepancy between PRV and HRV, such as that demonstrating the presence of PRV in the absence of HRV, differences in PRV with measurement sites, and differing effects of body posture and exercise between them. Our observations in adult patients with an implanted cardiac pacemaker also indicate that fluctuations in R-R intervals, pulse transit time, and pulse intervals are modulated differently by autonomic functions, respiration, and other factors. The authors suggest that it is more appropriate to recognize PRV as a different biomarker than HRV. Although HRV is a major determinant of PRV, PRV is caused by many other sources of variability, which could contain useful biomedical information that is neither error nor noise.

Ultrasound cardiography examinations detect victims' long-term realized and potential consequences after major disasters: a case-control study.

BACKGROUND: An increase in cardiovascular diseases has been reported following major disasters. Previous work has shown that ultrasonographic findings from ultrasound cardiography examination (UCG) increased until the 44th month after the tsunami caused by the Great East Japan Earthquake. The present study conducted UCG among victims in the tsunami disaster area and investigated the frequency of disaster-related cardiovascular diseases and changes over time until the 55th month after the disaster. METHODS: The subjects were residents of temporary housing complexes and neighboring housing in Watari-gun, Miyagi Prefecture, Japan. There were 207 subjects in the 18th month, 125 in the 30th month, 121 in the 44th month, and 106 in the 55th month after the disaster. Data were collected through UCG and self-report questionnaire. RESULTS: Significant changes were observed among subjects with clinical findings from the UCG, which increased over the study period-from 42.0 to 60.8, 72.7, and 73.6% beginning in the 18th month after the disaster (p < 0.0001). CONCLUSIONS: It is possible that the UCG can become a useful examination to visualize the potential impact of a major disaster on the cardiac function of victims. Victims with clinical findings continued increasing not only during the acute phase after a disaster but also in the long term. We therefore need to keep this in mind, and note that it is important to establish a support system to control cardiovascular diseases from the early stage of disaster. TRIAL REGISTRATION: UMIN; ID000029802. R000034050 . 2 November 2017.

The utility of on-site ultrasound screening in population at high risk for deep venous thrombosis in temporary housing after the great East Japan Earthquake.

BACKGROUND: To evaluate the diagnostic performance of ultrasonography for screening of a population at risk for deep vein thrombosis (DVT) in a post-disaster setting. METHODS: Ultrasonography was applied as a screening technique to the residents of a temporary housing facility who were displaced following the Great East Japan Earthquake. Thirty DVT screening sessions were held from April 2013 to June 2015. Individuals were invited to participate if they were identified as "high risk" for DVT, defined as those with low activity levels, a history of lower limb trauma, baseline lower limb pain or swelling, a cancer-bearing status, or a history of venous thromboembolic event. Ultrasonographic examinations were performed from the calf to the popliteal veins using portable devices. RESULTS: Of the 3,316 subjects screened (682 men and 2,634 women) with a mean age of 71 ± 9.7 years, DVT was diagnosed in 382 (11.5%). DVT was more likely in older, symptomatic, or female patients with a history of venous thromboembolism and attempting to perform daily exercise. The rate of DVT diagnosis increased from 9.9% in 2013 to 13.5% in 2015. CONCLUSIONS: Ultrasonography is efficient for screening at-risk populations in challenging settings. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:566-574, 2017.

Numerical analysis of hemodynamic changes in the left atrium due to atrial fibrillation.

Atrial fibrillation (AF) disrupts movement of the left atrium (LA) and worsens the vital prognosis by causing thromboembolism. Ultrasound Doppler measurement, phase-contrast magnetic resonance imaging (PC MRI), as well as computational fluid dynamics (CFD) have revealed hemodynamic changes in the LA due to AF, such as stagnation of blood flow in the left atrial appendage (LAA). However, quantitative evaluation of the hemodynamics during AF has not been conducted, and the effects of important AF characteristics, such as a lack of active contraction of the LA (atrial kick) in late diastole and the occurrence of high-frequency fibrillation (>400bpm) of the atrial wall, on blood flow field and concomitant hemodynamic stresses have not been completely understood. In this study, the effects of the above-mentioned two characteristic phenomena of AF on blood flow and hemodynamic parameters were quantitatively investigated. Based on MRI of a healthy volunteer heart, one healthy LA model and two AF models (one without atrial kick, and one without atrial kick and with high-frequency fibrillation) were constructed to perform hemodynamic analysis, and the computational results were compared. The results revealed that each characteristic phenomenon of AF influenced hemodynamics. Especially, atrial wall movement by high-frequency fibrillation had a large impact on the stagnation of blood flow. The relative residence time (RRT), which is an indicator of stagnation of blood flow, increased in the upper part of the LAA during AF. This result implies that there is a local thrombus-prone site in LAA when AF occurs.

One-year overview of deep vein thrombosis prevalence in the ishinomaki area since the great East Japan earthquake.

After the Great East-Japan Earthquake, the prevalence of deep vein thrombosis (DVT) in disaster shelters in Ishinomaki (Pacific coast, Miyagi, Japan) was found much higher than that ever reported in Japan. In Ishinomaki, twelve patients were found to have pulmonary thromboembolism for one month since the earthquake and DVT was found in 10 of those patients. The calf DVT was examined using ultrasonography in the shelters (from March to July 2011) and in temporary emergency housings (from August to December 2011). Calf DVT was found in 190 of 701 evacuees. DVT prevalence was higher in the tsunami-flooded shelters (34.2%) than in that in the non-flooded shelters (19.1%). This indicated that deteriorated and crowded condition in the tsunami-flooded shelters might induce thrombogenesis in calf veins. Therefore, evacuees were recommended to leave tsunami-flooded areas. DVT prevalence in the shelters was gradually reduced, however, that was still higher in the temporary emergency housings (8.9%) than in the non-disaster area in Japan (2.2% in Yokohama city). The risk of calf DVT in the temporary emergency housings was increased because of reduced blood flow in the calf veins caused by immobility. The residents of the housings were required to be physically active to avoid calf DVT. (English translation of Jpn J Phlebol 2013; 24: 380-384).

Percutaneous coronary intervention by retrograde approach for chronic total occlusion of the proximal left anterior descending artery via a gastroepiploic artery graft.

Coronary arteries connecting to septal branch are often occluded in post-coronary artery bypass graft cases. A 70-year-old male had undergone CABG; radial artery graft to the LCX, and gastroepiploic artery (GEA) graft to the RCA. Coronary angiography revealed total occlusion in proximal LAD, while both graft vessels had good flow. Retrograde percutaneous coronary intervention (PCI) procedure from the septal channel via GEA graft to the RCA was performed for total occlusion of LAD. Despite the tortuous GEA, deep engagement with a 4-french guiding catheter ensured powerful back-up force. After retrograde wire crossing, two drug-eluting stents were implanted, successfully.

High prevalence of deep vein thrombosis in tsunami-flooded shelters established after the great East-Japan earthquake.

High prevalence of deep vein thrombosis (DVT) in disaster shelters has been reported in the aftermath of earthquakes in Japan. Calf DVT was examined using sonography in the shelters after the Great East Japan earthquake on March 11, 2011. By the end of July 2011, 701 out of 8,630 evacuees suspected with calf DVT, judged by inspections or medical interviews, were examined in 32 shelters, and 190 evacuees were confirmed to have calf DVT. The prevalence of DVT was 2.20%, which was 200 times higher than the usual incidence in Japan. The DVT prevalence seemed to decrease with time. By the end of May, a significantly higher prevalence of DVT was found in tsunami-flooded shelters (109 of 3,871 evacuees; 2.82%) than in non-flooded shelters (53 of 3,155 evacuees; 1.68%). After June, its prevalence was still higher (18/541; 3.33%) in tsunami-flooded shelters than in non-flooded shelters (10/1063; 0.94%). The cause of the high prevalence of DVT was supposed to be dehydration due to the delay in supplying drinking water, vomiting, and diarrhea experienced by the evacuees because of a shortage of clean water to wash their hands. Dehydration was especially noticed in women because they restricted themselves of water intake to avoid using unsanitary toilet facilities. Moreover, crowded shelters restricted the mobility of elderly people, which would exacerbate the prevalence of DVT. Those deteriorated and crowded shelters were observed in tsunami-flooded areas. Therefore, long-term shelters should not be set up in flooded areas after tsunami.

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".

Surgical management of localized left ventricular aneurysm associated with acute myocarditis.

We present a case of a localized left ventricular (LV) aneurysm in a 72-year-old woman with sudden onset of severe chest pain. A left ventriculogram revealed a small saccular outpouching protruding from the apex accompanied with narrow neck connection to the ventricular cavity. Both coronary arteries and global function were normal. We preoperatively diagnosed her as having an impending rupture in the congenital LV diverticulum because no inflammatory myocardial disease was suggested by general laboratory tests. After successful surgical treatment, microscopic examination for the myocardial specimens was performed and revealed diffuse lymphocytic infiltration associated with focal necrosis of myocardium. Histological findings were consistent with those of acute lymphocytic myocarditis. Without histological confirmation, an aneurysm caused by silent myocarditis might be misdiagnosed as a diverticulum.

Recent progress in artificial organ research at Tohoku University.

Tohoku University has developed various artificial organs over the last 30 years. Pneumatic driven ventricular assist devices with a silicone ball valve have been designed by the flow visualization method, and clinical trials have been performed in Tohoku University Hospital. On the basis of these developments, a pneumatic driven total artificial heart has been developed and an animal experimental evaluation was conducted. The development of artificial organs in Tohoku University has now progressed to the totally implantable type using the transcutaneous energy transmission system with amorphous fibers for magnetic shielding. Examples of implantable systems include a vibrating flow pump for ventricular assist device, an artificial myocardium by the use of shape memory alloy with Peltier elements, and an artificial sphincter for patients with a stoma. An automatic control system for artificial organs had been developed for the ventricular assist devices including a rotary blood pump to avoid suction and to maintain left and right heart balance. Based upon the technology of automatic control algorithm, a new diagnostic tool for evaluating autonomic nerve function has been developed as a branch of artificial organ research and this new machine has been tested in Tohoku University Hospital. Tohoku University is following a variety of approaches aimed at innovation in artificial organs and medical engineering fields.