臨床検査部
研究活動の概要

　COVID-19感染拡大により2020年7月から入院患者を中心にCOVID-19の抗体検査、PCR検査、抗原検査を病院臨床検査部にて行っている。2021年3月までの検査実績は、PCR検査と抗原検査合計で9305件、COVID-19陽性は52件（0.56%）であった。月別の陽性率の推移を以下に示す。

COVID-19検査結果については予防医学・疫学情報部と共同で研究を継続している。

　臨床検査部の研究活動は、生理検査系では心電図、心磁図を用いた臨床診断、不整脈や突然死リスク層別化、さらに植込みデバイス関連の観察研究を報告した。長時間心電図（24時間ホルター心電図や1週間記録可能な心電図）を用いた心房細動の検出や、遺伝性不整脈の遺伝子型の推定なども行っている。
　一方、検体検査系では遺伝子検査室を中心に、遺伝性不整脈（QT延長症候群、ブルガダ症候群、カテコラミン誘発性多形性心室頻拍など）、マルファン症候群などの結合織病、家族性高コレステロール血症、さらにはオスラー病や先天性血栓症などの遺伝学的検査を積極的に実施し、臨床に応用できる体制を構築している。

主な研究成果

　心電図に関してはJ波症候群（ブルガダ症候群、早期再分極症候群）に関する長期観察結果から、複数の誘導でのJ波の存在が心室細動リスクに関連することを報告した1。さらに心臓再同期療法（CRT）に関して左室ペーシングによる心臓伝導障害の程度が、CRTの有効性を予測する指標として有用であることを報告した2。

　心磁図を用いた検討においても、J波症候群において心臓突然死のリスクが高いJ波とそうでないJ波の鑑別に役立つ指標が得られた3。さらに心磁図の左室伝導パターンから、CRTが有効な患者か否かを予測することが可能であった4。

　ゲノム関連の研究成果として、国際共同研究に参加し重要な成果が得られた。先天性QT延長症候群（LQTS）のうち比較的稀なLQT5に関する国際登録研究を発表した5。また日欧共同のゲノムワイド関連解析（GWAS）を用いた研究ではNOS1AP, KCNQ1, KLF12, KCNE1（D85N）などのcommon variantの存在がリスクに関係することを発表した6。さらに遺伝性不整脈の代表的な遺伝子において、欧米人と日本人において例えばSCN5Aのバリアントなどに大きな違いがあることも判明した7。

　引用文献

  1. Kamakura T et al. Long-term prognosis of patients with J-wave syndrome. Heart. 2020, 106, 299-306.
  2. Ueda N, et al. Clinical impact of left ventricular paced conduction disturbance in cardiac resynchronization therapy. Heart Rhythm. 2020, 17, 1870-1877.
  3. Iwakami N, et al. Identification of malignant early repolarization pattern by late QRS activity in high-resolution magnetocardiography. Annals of Noninvasive Electrocardiology. 2020, 25, e12741.
  4. Nakashima, T et al. Novel Non-Invasive Index for Prediction of Responders in Cardiac Resynchronization Therapy Using High-Resolution Magnetocardiography. Circ J. 2020, 84(12), 2166-2174.
  5. Roberts JD, et al. An International Multi-Center Evaluation of Type 5 Long QT Syndrome: A Low Penetrant Primary Arrhythmic Condition. Circulation. 2020, 141(6), 429-439.
  6. Lahrouchi N, et al. Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome. Circulation. 2020, 142, 324-338.
  7. Walsh R, et al. Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls. Genetics in Medicine. 2021, 23, 47-58.
研究業績
  1. Iwakami N, Aiba T, Kamakura S, Takaki H, Furukawa TA, Sato T, Sun W, Shishido T, Nishimura K, Yamada-Inoue Y, Nagase S, Shimizu W, Yasuda S, Sugimachi M, Kusano K. Identification of malignant early repolarization pattern by late QRS activity in high-resolution magnetocardiography. Annals of Noninvasive Electrocardiology. 25, e12741, 2020.
  2. Roberts JD, Asaki SY, Mazzanti A, Bos JM, Tuleta I, Muir AR, Crotti L, Krahn AD, Kutyifa V, Shoemaker MB, Johnsrude CL, Aiba T, Marcondes L, Baban A, Udupa S, Dechert B, Fischbach P, Knight LM, Vittinghoff E, Kukavica D, Stallmeyer B, Giudicessi JR, Spazzolini C, Shimamoto K, Tadros R, Cadrin-Tourigny J, Duff HJ, Simpson CS, Roston TM, Wijeyeratne YD, El Hajjaji I, Yousif MD, Gula LJ, Leong-Sit P, Chavali N, Landstrom AP, Marcus GM, Dittmann S, Wilde AAM, Behr ER, Tfelt-Hansen J, Scheinman MM, Perez MV, Kaski JP, Gow RM, Drago F, Aziz PF, Abrams DJ, Gollob MH, Skinner JR, Shimizu W, Kaufman ES, Roden DM, Zareba W, Schwartz PJ, Schulze-Bahr E, Etheridge SP, Priori SG, Ackerman MJ. An International Multicenter Evaluation of Type 5 Long QT Syndrome: A Low Penetrant Primary Arrhythmic Condition. Circulation. 141, 429-439, 2020.
  3. Lahrouchi N, Tadros R, Crotti L, Mizusawa Y, Postema PG, Beekman L, Walsh R, Hasegawa K, Barc J, Ernsting M, Turkowski KL, Mazzanti A, Beckmann BM, Shimamoto K, Diamant UB, Wijeyeratne YD, Kucho Y, Robyns T, Ishikawa T, Arbelo E, Christiansen M, Winbo A, Jabbari R, Lubitz SA, Steinfurt J, Rudic B, Loeys B, Shoemaker MB, Weeke PE, Pfeiffer R, Davies B, Andorin A, Hofman N, Dagradi F, Pedrazzini M, Tester DJ, Bos JM, Sarquella-Brugada G, Campuzano O, Platonov PG, Stallmeyer B, Zumhagen S, Nannenberg EA, Veldink JH, van den Berg LH, Al-Chalabi A, Shaw CE, Shaw PJ, Morrison KE, Andersen PM, Muller-Nurasyid M, Cusi D, Barlassina C, Galan P, Lathrop M, Munter M, Werge T, Ribases M, Aung T, Khor CC, Ozaki M, Lichtner P, Meitinger T, van Tintelen JP, Hoedemaekers Y, Denjoy I, Leenhardt A, Napolitano C, Shimizu W, Schott JJ, Gourraud JB, Makiyama T, Ohno S, Itoh H, Krahn AD, Antzelevitch C, Roden DM, Saenen J, Borggrefe M, Odening KE, Ellinor PT, Tfelt-Hansen J, Skinner JR, van den Berg MP, Olesen MS, Brugada J, Brugada R, Makita N, Breckpot J, Yoshinaga M, Behr ER, Rydberg A, Aiba T, Kaab S, Priori SG, Guicheney P, Tan HL, Newton-Cheh C, Ackerman MJ, Schwartz PJ, Schulze-Bahr E, Probst V, Horie M, Wilde AA, Tanck MWT, Bezzina CR. Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome. Circulation. 142, 324-338, 2020.
  4. Ueda N, Noda T, Ishibashi K, Nakajima K, Kataoka N, Kamakura T, Wada M, Yamagata K, Inoue Y, Miyamoto K, Nagase S, Aiba T, Kanzaki H, Izumi C, Noguchi T, Yasuda S, Kusano K. Efficacy of a Device-Based Continuous Optimization Algorithm for Patients With Cardiac Resynchronization Therapy. Circulation Journal. 84, 18-25, 2020.
  5. Ishikawa T, Mishima H, Barc J, Takahashi MP, Hirono K, Terada S, Kowase S, Sato T, Mukai Y, Yui Y, Ohkubo K, Kimoto H, Watanabe H, Hata Y, Aiba T, Ohno S, Chishaki A, Shimizu W, Horie M, Ichida F, Nogami A, Yoshiura KI, Schott JJ, Makita N. Cardiac Emerinopathy: A Nonsyndromic Nuclear Envelopathy With Increased Risk of Thromboembolic Stroke Due to Progressive Atrial Standstill and Left Ventricular Noncompaction. Circulation: Arrhythmia and Electrophysiology. 13, 1165-1174, 2020.
  6. Funabashi S, Omote K, Nagai T, Honda Y, Nakano H, Honda S, Iwakami N, Hamatani Y, Nakai M, Nishimura K, Asaumi Y, Aiba T, Noguchi T, Kusano K, Yokoyama H, Yasuda S, Ogawa H, Anzai T. Elevated admission urinary N-acetyl-β-D-glucosamidase level is associated with worse long-term clinical outcomes in patients with acute heart failure. European Heart Journal: Acute Cardiovascular Care. 9, 429-436, 2020.
  7. Nakano H, Nagai T, Honda Y, Honda S, Iwakami N, Matsumoto C, Asaumi Y, Aiba T, Noguchi T, Kusano K, Yokoyama H, Ogawa H, Yasuda S, Chikamori T, Anzai T. Prognostic value of base excess as indicator of acid-base balance in acute heart failure. European Heart Journal: Acute Cardiovascular Care. 9, 399-405, 2020.
  8. Kamakura T, Shinohara T, Yodogawa K, Murakoshi N, Morita H, Takahashi N, Inden Y, Shimizu W, Nogami A, Horie M, Aiba T, Kusano K. Long-term prognosis of patients with J-wave syndrome. Heart. 106, 299-306, 2020.
  9. Ueda N, Noda T, Nakajima I, Ishibashi K, Nakajima K, Kamakura T, Wada M, Yamagata K, Inoue Y, Miyamoto K, Nagase S, Aiba T, Kiso K, Kanzaki H, Izumi C, Noguchi T, Yasuda S, Kusano K. Clinical impact of left ventricular paced conduction disturbance in cardiac resynchronization therapy. Heart Rhythm. 17, 1870-1877, 2020.
  10. Kakehashi S, Kamakura T, Aiba T, Kusano K. Two Forms of Monomorphic Ventricular Tachycardia in a Patient with Brugada Syndrome. Internal Medicine. 59, 1287-1290, 2020.
  11. Otsuki S, Aiba T, Tahara Y, Nakajima K, Kataoka N, Kamakura T, Wada M, Ishibashi K, Yamagata K, Inoue Y, Miyamoto K, Nagase S, Noda T, Izumi C, Noguchi T, Nishimura K, Yonemoto N, Nonogi H, Nagao K, Ikeda T, Sato N, Tsutsui H, Yasuda S, Kusano K; Japanese Circulation Society With Resuscitation Science Study (JCS-ReSS) Group. Intra-day change in occurrence of out-of-hospital ventricular fibrillation in Japan: The JCS-ReSS study. International Journal of Cardiology. 318, 54-60, 2020.
  12. Ueda N, Kamakura T, Noda T, Nakajima K, Kataoka N, Wada M, Yamagata K, Ishibashi K, Inoue Y, Miyamoto K, Nagase S, Aiba T, Izumi C, Noguchi T, Yasuda S, Kusano K. Efficacy and safety of new-generation atrial antitachycardia pacing for atrial tachyarrhythmias in patients implanted with cardiac resynchronization therapy devices. Journal of Cardiology. 75, 559-566, 2020.
  13. Tada A, Omote K, Nagai T, Honda Y, Nakano H, Honda S, Iwakami N, Hamatani Y, Nakai M, Nishimura K, Asaumi Y, Aiba T, Noguchi T, Kusano K, Yokoyama H, Yasuda S, Ogawa H, Anzai T. Prevalence, Determinants, and Prognostic Significance of Hospital Acquired Pneumonia in Patients with Acute Heart Failure. Journal of Clinical Medicine. 9, 2219, 2020.
  14. Shimoyama T, Hayashi H, Suzuki F, Nishiyama Y, Miyamoto Y, Aiba T, Shimizu W, Kimura K. Idiopathic ventricular fibrillation and the V1764fsX1786 frameshift mutation of the SCN5A gene in a myotonic dystrophy type 1 patient. Journal of Clinical Neuroscience. 74, 242-244, 2020.
  15. Kashiwa A, Aiba T, Makimoto H, Shimamoto K, Yamagata K, Kamakura T, Wada M, Miyamoto K, Inoue-Yamada Y, Ishibashi K, Noda T, Nagase S, Miyazaki A, Sakaguchi H, Shiraishi I, Yagihara N, Watanabe H, Aizawa Y, Makiyama T, Itoh H, Hayashi K, Yamagishi M, Sumitomo N, Yoshinaga M, Morita H, Ohe T, Miyamoto Y, Makita N, Yasuda S, Kusano K, Ohno S, Horie M, Shimizu W. Systematic Evaluation of KCNQ1 Variant Using ACMG/AMP Guidelines and Risk Stratification in Long QT Syndrome Type 1. Circulation: Genomic and Precision Medicine. Epub, 2020.
  16. Wakamiya A, Kamakura T, Shinohara T, Yodogawa K, Murakoshi N, Morita H, Takahashi N, Inden Y, Shimizu W, Nogami A, Horie M, Nakajima K, Kataoka N, Wada M, Yamagata K, Ishibashi K, Inoue Y, Miyamoto K, Nagase S, Noda T, Aiba T, Yasuda S, Ieda M, Kusano K. Improved Risk Stratification of Patients With Brugada Syndrome by the New Japanese Circulation Society Guideline - A Multicenter Validation Study. Circulation Journal. 84, 2158-2165, 2020.
  17. Nakashima T, Usami S, Aiba T, Oishi S, Kimura Y, Kawakami S, Yamada-Inoue Y, Ogata S, Ueda N, Nakajima K, Kamakura T, Wada M, Yamagata K, Ishibashi K, Miyamoto K, Noda T, Nagase S, Kanzaki H, Izumi C, Yasuda S, Kamakura S, Takaki H, Sugimachi M, Kusano K. Novel Non-Invasive Index for Prediction of Responders in Cardiac Resynchronization Therapy Using High-Resolution Magnetocardiography. Circulation Journal. 84, 2166-2174, 2020.
  18. Yokoyama Y, Aiba T, Ueda N, Nakajima K, Kamakura T, Wada M, Yamagata K, Ishibashi K, Inoue Y, Miyamoto K, Nagase S, Noda T, Yasuda S, Shimizu W, Kusano K. Subcutaneous and transvenous implantable cardioverter defibrillator in high-risk long-QT syndrome type 3 associated with Val411Met mutation in SCN5A. Journal of Cardiology Cases. 22, 238-241, 2020.
  19. Miki T, Senoo K, Okura T, Shiraishi H, Shirayama T, Aiba T, Matoba S. First episode of ventricular fibrillation in an 84-year-old man with long-QT type 2 syndrome: A case report. Journal of Cardiology Cases. 22, 257-259, 2020.
  20. Tse G, Zhou J, Lee S, Liu T, Bazoukis G, Mililis P, Wong ICK, Chen C, Xia Y, Kamakura T, Aiba T, Kusano K, Zhang Q, Letsas KP. Incorporating Latent Variables Using Nonnegative Matrix Factorization Improves Risk Stratification in Brugada Syndrome. Journal of the American Heart Association. 9, e012714, 2020.
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