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Efficacy of Insominia and Benzodiazepines in Heart Failure Patients
The 20th Annual Scientific Meeting chronic heart failure. Methods: We measured blood pressure, oxygen saturation, heart rate valiability and respiratory rate at basline and after the10minute application of ASV. We measured the same parameters again at baseline and after the 10minute application of CPAP in 14 patients (12men, average EF = 35%, age = 69, BNP = 429) with chronic heart failure. Results: There were no significant difference in baseline parameters between ASV and CPAP. There were no effect of CPAP and ASV on blood pressure (ASV:113.5/67.9 to 116.2/67.5 mmHg, P = .29, CPAP:111.3/65.8 to 115.0/66.5 mmHg, P = .13), oxygen saturation(ASV:96.6 to 97.1%, P = .08, CPAP:96.4 to 96.7%, P = .26) and R-R interval(ASV:886 to 903 msec, P = .09, CPAP:872 to 827 msec, P = .44). ASV significantly reduced the ratio of low frequency to high frequency power(LF/HF) ratio(1.64 to 0.98, P = .04) and decreased resipiratory rate(17.8 to 15.6, P = .03). But there were no signicant effect of CPAP on LF/HF ratio(1.29 to 1.00, P = .28) and resipiratory rate(17.1 to16.7, P = .37). Conclusion: In patients with chronic heart failure, ASV more effectively reduced sympathetic nerve activity than CPAP.
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clarify the clinical significance of PLMS on prognosis of heart failure (HF) and the associations between PLMS and clinical background in HF patients. Methods and Results: We enrolled 114 patients with HF who underwent polysomnography, and divided into two groups based on PLM index: severe PLMS group (PLM index ≥ 30/h, n = 18) and non-severe PLMS group (PLM index < 30/h, n = 96). In the multiple regression analysis to determine PLM index, among considerable clinical risk variables, the presence of chronic kidney disease was an independent predictor of PLM index (ß = 0.235, P = .010). In Kaplan-Meier analysis, cardiac mortality was significantly higher in severe PLMS group than in non-severe PLMS group (33.3% vs. 7.3%, P = .003). The severe PLMS group patients had lower levels of estimated glomerular filtration rate and peak oxygen uptake. In the Cox proportional hazard analysis, severe PLMS was an independent predictor of cardiac mortality (HR 3.780, P = .021). PLMS was the predictor of adverse cardiac mortality in HF patients. Conclusion: The presence of PLMS exhibited impaired renal function and exercise capacity, and may be a potential marker of adverse prognosis in HF patients.
EP17-2 Novel Parametric Method to Identify the System Characteristics of Respiratory Central Chemoreflex in Human Keimei Yoshida1, Takeshi Tohyama1, Keita Saku2, Akiko Nishizaki1, Takuya Nishikawa1, Tadayoshi Miyamoto3, Takuya Kishi2, Hiroyuki Tsutsui1, Kenji Sunagawa2; 1Departments of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; 2Center for Disruptive Cardiovascular Medicine, Kyushu University, Fukuoka, Japan; 3Graduate school of Health Sciences, Morinomiya University of Medical Sciences, Osaka, Japan Background: Central chemoreflex (CR) is the principal system responsible for respiratory homeostasis. The hyper-activity and -sensitivity of CR in heart failure lead to respiratory abnormalities, and are a strong predictor of the mortality. The aim of this study is to develop a quantitative and less invasive method to characterize CR. Methods: In 4 healthy volunteers, we measured end tidal CO2 (EtCO2), and minute ventilation (VE). We divided the respiratory system into two components: the controller (EtCO2 to VE) and plant (VE to EtCO2). To identify the controller, we randomly switched inhaled gas from 0% to 5% CO2. To evaluate the plant, subjects randomly switched their respiration from spontaneous breathing to hyperventilation. We modeled both systems as G(t) = K/τ*exp(−(t − Td)/τ) (K = gain, τ = time constant and Td = lag) and identified parameters by fitting the model to the time-series. Results: We found the parameters of the controller as K = 0.4 ± 0.2 L/min/mmHg, τ = 41 ± 22 sec and Td = 8.3 ± 8.5 sec, and the plant as K=-1.4 ± 0.5 mmHg/L/min, τ = 16 ± 16 sec and Td = 0.3 ± 0.6 sec. Time series back calculated from parameters in each subject matched well with those measured (R2 = 0.91 ± 0.05 in the controller and 0.90 ± 0.02 in the plant), indicating the accuracy of the models and parameter estimations. Conclusions: The proposed method accurately characterizes the chemoreflex function and may serve as a clinical tool to evaluate respiratory abnormalities in heart failure.
EP17-5 Prognostic Impact of Quantitative Index of Diurnal Respiratory Instability on Cardiovascular Events in Patients with Heart Failure Naoto Kumagai1, Kaoru Dohi1, So Miyahara1, Syusuke Fukuoka1, Taku Omori1, Keishi Moriwaki1, Emiyo Sugiura1, Naoki Fujimoto2, Norikazu Yamada1, Masaaki Ito1; 1 Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Mie, Japan; 2Department of Molecular and Laboratory Medicine, Mie University Graduate School of Medicine, Mie, Japan Background: There is no established method to quantify diurnal respiratory instability (RI) of heart failure (HF). Methods: We prospectively enrolled 60 patients with symptomatic HF (70 ± 14 years, 75% male, and NYHA functional classes II-IV), and follow-up after hospital discharge. Non-uniformity of the breath-by-breath respiratory slopes during 15 minutes calculated as the ratio of peak inspiratory amplitude to corresponding peak-to-peak interval was assessed by histogram-based frequency distribution measurement, and was defined as the “RI-index”. Results: The high RIindex above the median value group had significantly higher cumulative clinical events rate compared with the low RI-index group (Log-Rank test; P < .01). On Cox’s proportional hazard model, the high RI-index was the independent predictor of the poor outcomes. Conclusion: The RI-index can be a useful predictive marker of patients with HF.
EP17-3 Efficacy of Insominia and Benzodiazepines in Heart Failure Patients Yoshiaki Kubota, Kuniya Asai, Aya Yoshinaga, Yuuki Izumi, Kouji Murai, Yukichi Tokita, Masatomo Yoshikawa, Yayoi Tsukada, Wataru Shimizu; Department of Cardiovascular Medicine, Nippon Medical School Hospital, Tokyo, Japan Background: Insomnia is concomitantly present in the heart failure (HF). We investigated the differences in the hospitalization rates for HF between the HF patients with and without insomnia. Methods: Consecutive 837 HF patients, who had history of hospitalization at our institute between January 2011 and December 2015 were evaluated. Finally 95 HF patients with insomnia (group A), and 505 age-and sexmatched HF patients without insomnia (group B) were enrolled. Results: The mean age of the patients was 76.7 p < 9.2 years, and 64.2% were male. The mean followup period was 17.6 months. Clinical characteristics including hypertension, renal insufficiency, left ventricular function, vascular disease, arrhythmias, and medication for CHF were not different between two groups. The rate of rehospitalization by HF was not significantly different between group A compared with group B (log-rank P = .188), whereas, hospitalization days were significantly longer in group A than in group B (36.3 ± 33.0 vs. 23.8 ± 20.9 days; P < .05). Benzodiazepines were associated with the comorbidity of night delirium (odds ratio, 3.99; 95% confidence interval, 1.20–13.34; P = .024). Conclusions: Insomnia is associated with longer hospitalization days in the heart failure patients. Benzodiazepines are associated with an increased risk of incident night delirium.
EP17-4 Association between Periodic Leg Movements during Sleep and Heart Failure Patients Yuki Kanno, Akiomi Yoshihisa, Shunsuke Watanabe, Shunsuke Miura, Tetsuro Yokokawa, Takamasa Sato, Satoshi Suzuki, Masayoshi Oikawa, Atushi Kobayashi, Yasuchika Takeishi; Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan Background: Periodic limb movements during sleep (PLMS) consist of recurring muscular activations of legs which occur repetitively in the sleeping period. We aimed to
EP17-6 Frequent Periodic Leg Movements during Sleep Is an Unrecognized Sleep Disorder in Heart Failure: A Case Report Masayuki Goto, Yoshifumi Takata, Tasuku Yamaguchi, Kazuki Shiina, Yasuhiro Usui, Kota Kato, Akira Yamashina; Department of Cardiology, Tokyo Medical University, Tokyo, Japan A 48-year-old man was admitted to our hospital due to acute decompensated hear failure (HF). He had untreated hypertension, diabetes, dyslipidemia. Echocardiography revealed diffuse hypo-kinesis of left ventricle with 20% of left ventricular ejection fraction (LVEF). The lung congestion and low output state in this patient were improved by treatment using vasodilators and inotropic agents. However, discomfort of the lower extremities before sleep, frequent arousal during sleep and daytime sleepiness had been bothering him. Polysomnography showed moderate sleep disordered breathing (SDB) with 23.1/h of apnea-hypopnea index (AHI) and frequent periodic leg movements (PLM) during sleep with 97.9/h of PLM index with microarousal. He was consistent with the diagnostic criteria for restless legs syndrome (RLS). Coronary angiography showed severe stenosis of triple coronary vessels and he underwent coronary artery bypass surgery. After 3 months, his LVEF improved to 49%. Second polysomnography showed improvement of AHI with 9.4/h and no improvement of PLMI. Therefore, he was treated by dopamine agonist (rotigotine) and his symptoms on the RLS were clearly improved. We have to recognize not only SDB, but also PLM during sleep in HF patients using polysomnography.
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JHFS
S215
clarify the clinical significance of PLMS on prognosis of heart failure (HF) and the associations between PLMS and clinical background in HF patients. Methods and Results: We enrolled 114 patients with HF who underwent polysomnography, and divided into two groups based on PLM index: severe PLMS group (PLM index ≥ 30/h, n = 18) and non-severe PLMS group (PLM index < 30/h, n = 96). In the multiple regression analysis to determine PLM index, among considerable clinical risk variables, the presence of chronic kidney disease was an independent predictor of PLM index (ß = 0.235, P = .010). In Kaplan-Meier analysis, cardiac mortality was significantly higher in severe PLMS group than in non-severe PLMS group (33.3% vs. 7.3%, P = .003). The severe PLMS group patients had lower levels of estimated glomerular filtration rate and peak oxygen uptake. In the Cox proportional hazard analysis, severe PLMS was an independent predictor of cardiac mortality (HR 3.780, P = .021). PLMS was the predictor of adverse cardiac mortality in HF patients. Conclusion: The presence of PLMS exhibited impaired renal function and exercise capacity, and may be a potential marker of adverse prognosis in HF patients.
EP17-2 Novel Parametric Method to Identify the System Characteristics of Respiratory Central Chemoreflex in Human Keimei Yoshida1, Takeshi Tohyama1, Keita Saku2, Akiko Nishizaki1, Takuya Nishikawa1, Tadayoshi Miyamoto3, Takuya Kishi2, Hiroyuki Tsutsui1, Kenji Sunagawa2; 1Departments of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; 2Center for Disruptive Cardiovascular Medicine, Kyushu University, Fukuoka, Japan; 3Graduate school of Health Sciences, Morinomiya University of Medical Sciences, Osaka, Japan Background: Central chemoreflex (CR) is the principal system responsible for respiratory homeostasis. The hyper-activity and -sensitivity of CR in heart failure lead to respiratory abnormalities, and are a strong predictor of the mortality. The aim of this study is to develop a quantitative and less invasive method to characterize CR. Methods: In 4 healthy volunteers, we measured end tidal CO2 (EtCO2), and minute ventilation (VE). We divided the respiratory system into two components: the controller (EtCO2 to VE) and plant (VE to EtCO2). To identify the controller, we randomly switched inhaled gas from 0% to 5% CO2. To evaluate the plant, subjects randomly switched their respiration from spontaneous breathing to hyperventilation. We modeled both systems as G(t) = K/τ*exp(−(t − Td)/τ) (K = gain, τ = time constant and Td = lag) and identified parameters by fitting the model to the time-series. Results: We found the parameters of the controller as K = 0.4 ± 0.2 L/min/mmHg, τ = 41 ± 22 sec and Td = 8.3 ± 8.5 sec, and the plant as K=-1.4 ± 0.5 mmHg/L/min, τ = 16 ± 16 sec and Td = 0.3 ± 0.6 sec. Time series back calculated from parameters in each subject matched well with those measured (R2 = 0.91 ± 0.05 in the controller and 0.90 ± 0.02 in the plant), indicating the accuracy of the models and parameter estimations. Conclusions: The proposed method accurately characterizes the chemoreflex function and may serve as a clinical tool to evaluate respiratory abnormalities in heart failure.
EP17-5 Prognostic Impact of Quantitative Index of Diurnal Respiratory Instability on Cardiovascular Events in Patients with Heart Failure Naoto Kumagai1, Kaoru Dohi1, So Miyahara1, Syusuke Fukuoka1, Taku Omori1, Keishi Moriwaki1, Emiyo Sugiura1, Naoki Fujimoto2, Norikazu Yamada1, Masaaki Ito1; 1 Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Mie, Japan; 2Department of Molecular and Laboratory Medicine, Mie University Graduate School of Medicine, Mie, Japan Background: There is no established method to quantify diurnal respiratory instability (RI) of heart failure (HF). Methods: We prospectively enrolled 60 patients with symptomatic HF (70 ± 14 years, 75% male, and NYHA functional classes II-IV), and follow-up after hospital discharge. Non-uniformity of the breath-by-breath respiratory slopes during 15 minutes calculated as the ratio of peak inspiratory amplitude to corresponding peak-to-peak interval was assessed by histogram-based frequency distribution measurement, and was defined as the “RI-index”. Results: The high RIindex above the median value group had significantly higher cumulative clinical events rate compared with the low RI-index group (Log-Rank test; P < .01). On Cox’s proportional hazard model, the high RI-index was the independent predictor of the poor outcomes. Conclusion: The RI-index can be a useful predictive marker of patients with HF.
EP17-3 Efficacy of Insominia and Benzodiazepines in Heart Failure Patients Yoshiaki Kubota, Kuniya Asai, Aya Yoshinaga, Yuuki Izumi, Kouji Murai, Yukichi Tokita, Masatomo Yoshikawa, Yayoi Tsukada, Wataru Shimizu; Department of Cardiovascular Medicine, Nippon Medical School Hospital, Tokyo, Japan Background: Insomnia is concomitantly present in the heart failure (HF). We investigated the differences in the hospitalization rates for HF between the HF patients with and without insomnia. Methods: Consecutive 837 HF patients, who had history of hospitalization at our institute between January 2011 and December 2015 were evaluated. Finally 95 HF patients with insomnia (group A), and 505 age-and sexmatched HF patients without insomnia (group B) were enrolled. Results: The mean age of the patients was 76.7 p < 9.2 years, and 64.2% were male. The mean followup period was 17.6 months. Clinical characteristics including hypertension, renal insufficiency, left ventricular function, vascular disease, arrhythmias, and medication for CHF were not different between two groups. The rate of rehospitalization by HF was not significantly different between group A compared with group B (log-rank P = .188), whereas, hospitalization days were significantly longer in group A than in group B (36.3 ± 33.0 vs. 23.8 ± 20.9 days; P < .05). Benzodiazepines were associated with the comorbidity of night delirium (odds ratio, 3.99; 95% confidence interval, 1.20–13.34; P = .024). Conclusions: Insomnia is associated with longer hospitalization days in the heart failure patients. Benzodiazepines are associated with an increased risk of incident night delirium.
EP17-4 Association between Periodic Leg Movements during Sleep and Heart Failure Patients Yuki Kanno, Akiomi Yoshihisa, Shunsuke Watanabe, Shunsuke Miura, Tetsuro Yokokawa, Takamasa Sato, Satoshi Suzuki, Masayoshi Oikawa, Atushi Kobayashi, Yasuchika Takeishi; Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan Background: Periodic limb movements during sleep (PLMS) consist of recurring muscular activations of legs which occur repetitively in the sleeping period. We aimed to
EP17-6 Frequent Periodic Leg Movements during Sleep Is an Unrecognized Sleep Disorder in Heart Failure: A Case Report Masayuki Goto, Yoshifumi Takata, Tasuku Yamaguchi, Kazuki Shiina, Yasuhiro Usui, Kota Kato, Akira Yamashina; Department of Cardiology, Tokyo Medical University, Tokyo, Japan A 48-year-old man was admitted to our hospital due to acute decompensated hear failure (HF). He had untreated hypertension, diabetes, dyslipidemia. Echocardiography revealed diffuse hypo-kinesis of left ventricle with 20% of left ventricular ejection fraction (LVEF). The lung congestion and low output state in this patient were improved by treatment using vasodilators and inotropic agents. However, discomfort of the lower extremities before sleep, frequent arousal during sleep and daytime sleepiness had been bothering him. Polysomnography showed moderate sleep disordered breathing (SDB) with 23.1/h of apnea-hypopnea index (AHI) and frequent periodic leg movements (PLM) during sleep with 97.9/h of PLM index with microarousal. He was consistent with the diagnostic criteria for restless legs syndrome (RLS). Coronary angiography showed severe stenosis of triple coronary vessels and he underwent coronary artery bypass surgery. After 3 months, his LVEF improved to 49%. Second polysomnography showed improvement of AHI with 9.4/h and no improvement of PLMI. Therefore, he was treated by dopamine agonist (rotigotine) and his symptoms on the RLS were clearly improved. We have to recognize not only SDB, but also PLM during sleep in HF patients using polysomnography.