今日の臨床サポート

肥大型心筋症

著者: 朝倉正紀1) 兵庫医科大学 循環器内科

著者: 北風政史2) 国立循環器病研究センター 心臓血管内科

監修: 伊藤浩 岡山大学循環器内科

著者校正/監修レビュー済:2020/03/12
参考ガイドライン:
日本循環器学会/日本心不全学会合同ガイドライン:心筋症診療ガイドライン(2018年改訂版)
患者向け説明資料

概要・推奨   

  1. 突然死の家族歴がある若年発症のHCM患者では、突然死のリスク評価を行うことが勧められる(推奨度1
  1. 肥大型心筋症は、サルコメアを構成する蛋白の遺伝子異常によって生じる。若年者では、常染色体優性遺伝の家族内発症がみられることが多く、家族を含めたスクリーニング検査や遺伝カウンセリングを行うことが強く勧められる(推奨度1)
  1. 肥大型心筋症は、自覚症状のない症例では、健診で発見されることが多い。聴診での音や駆出性収縮期雑音を認める際には、肥大型心筋症を疑い、心電図や心臓超音波検査を行うことが勧められる(推奨度1)
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
朝倉正紀 : 講演料(大塚製薬(株),小野薬品工業(株),アストラゼネカ(株),ノバルティスファーマ(株),第一三共(株),バイエル薬品(株)),研究費・助成金など(第一三共(株)),奨学(奨励)寄付など(大塚製薬(株))[2021年]
北風政史 : 未申告[2021年]
監修:伊藤浩 : 講演料(第一三共,興和,アストラゼネカ,小野,ノバルティスファーマ),研究費・助成金など(興和,Canon),奨学(奨励)寄付など(第一三共,田辺三菱,小野薬品,興和,Boston,武田,ベーリンガーインゲルハイム,持田,バイエル),企業などが提供する寄付講座(日本メドトロニック)[2021年]

改訂のポイント
  1. 心筋症診療ガイドライン(2018年改訂版)に基づき、診断や治療、アルゴリズムの修正を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 肥大型心筋症とは、高血圧などの明らかな原因がなく、心室壁の肥大を来す心筋疾患である。多くの場合左室壁の肥大が起こり、肥大した心筋の部位により血行動態や症状が変わる。
  1. 肥大型心筋症は、指定難病であり、中等症以上の場合などでは、申請し認定されると保険料の自己負担分の一部が公費負担として助成される。([平成27年1月施行])
  1.  難病法に基づく医療費助成制度 
  1. 肥大型心筋症の正確な有病率は明らかではないが、1998年の厚生労働省特定疾患特発性心筋症調査研究班による全国疫学調査では、全国推計患者数は21,900人とされ、有病率は17.3人/10万人であった[1][2][3][4]
  1. 調査対象者全員に心臓超音波検査を用いたスクリーニングでは、肥大型心筋症の診断における検出力が上がるため、わが国での有病率は374人/10万人(米国では170人/10万人)と報告されている[5][6]
  1. 肥大型心筋症患者の男女比は、2.3倍と男性に多い[1][2][3][4]
  1. 肥大型心筋症患者の年齢分布として、50歳以上が8割近くを占める一方、20歳までの患者も5%認める[1][2][3][4]
  1. 1982年の厚生省特定疾患特発性心筋症調査研究班の疫学調査では、肥大型心筋症患者の5年および10年生存率は、それぞれ91.5%と81.8%であった[7]。1999年に実施された全国疫学二次調査の2,155人の肥大型心筋症患者の5年生存率は86%であり、1年あたりの死亡率は2.2~3.0%であると報告されている[8]
  1. 肥大型心筋症患者における予後不良の独立した要因としては、高心胸比、低い左室駆出率、左脚ブロックであり、心尖部肥大は予後良好の因子であることが明らかにされている[8]
  1. わが国の家族性肥大型心筋症の40~50%に、遺伝子異常がみられる[9]
  1. 肥大型心筋症患者に観察される主な遺伝子異常を示す遺伝子は、心筋βミオシン重鎖遺伝子(MYH7)、心筋トロポニンT遺伝子(TNNT2)、心筋ミオシン結合蛋白C遺伝子(MYBPC3)、α-トロポミオシン(TPM1)などである[9][10]
問診・診察のポイント  
  1. 肥大型心筋症患者は、無症候性で、心電図異常などで発見されることが多い。

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文献 

著者: K Miura, H Nakagawa, Y Morikawa, S Sasayama, A Matsumori, K Hasegawa, Y Ohno, A Tamakoshi, T Kawamura, Y Inaba
雑誌名: Heart. 2002 Feb;87(2):126-30.
Abstract/Text OBJECTIVE: To estimate the total number of patients with idiopathic cardiomyopathy in Japan and the prevalence of the disorder.
DESIGN: A nationwide epidemiological survey.
SETTING: Hospitals selected randomly from among all hospitals in Japan.
PATIENTS: Patients presenting with any of the three types of idiopathic cardiomyopathy: dilated cardiomyopathy, hypertrophic cardiomyopathy, and restrictive cardiomyopathy.
MAIN OUTCOME MEASURES: The total number of patients in Japan was estimated using the sampling and response rates in each stratum with respect to hospital size. The second survey was conducted for patients reported in the first survey in order to obtain detailed information, including age, sex, and specific clinical data.
RESULTS: Estimated patient totals and 95% confidence intervals (CI) were 17 700 (95% CI 16 500 to 18 800) for dilated cardiomyopathy, 21 900 (95% CI 20 600 to 23 200) for hypertrophic cardiomyopathy, and 300 (95% CI 250 to 350) for restrictive cardiomyopathy. Crude prevalence per 100 000 population was estimated as 14.0 for dilated cardiomyopathy, 17.3 for hypertrophic cardiomyopathy, and 0.2 for restrictive cardiomyopathy; crude incidence per 100 000 person-years was estimated as 3.58, 4.14, and 0.06, respectively.
CONCLUSIONS: The total number and prevalence of patients with idiopathic cardiomyopathy in Japan are estimated for the first time in a nationwide survey. The prevalence of dilated cardiomyopathy in Japan appears to be about half that of Western populations, while that of hypertrophic cardiomyopathy is about the same.

PMID 11796547  Heart. 2002 Feb;87(2):126-30.
著者: B J Maron, J M Gardin, J M Flack, S S Gidding, T T Kurosaki, D E Bild
雑誌名: Circulation. 1995 Aug 15;92(4):785-9.
Abstract/Text BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetically transmitted disease and an important cause of morbidity and sudden cardiac death in young people, including competitive athletes. At present, however, few data exist to estimate the prevalence of this disease in large populations.
METHODS AND RESULTS: As part of the Coronary Artery Risk Development in (Young) Adults (CARDIA) Study, an epidemiological study of coronary risk factors, 4111 men and women 23 to 35 years of age selected from the general population of four urban centers had technically satisfactory echocardiographic studies during 1987 through 1988. Probable or definite echocardiographic evidence of HCM was present in 7 subjects (0.17%) on the basis of identification of a hypertrophied, nondilated left ventricle and maximal wall thickness > or = 15 mm that were not associated with systemic hypertension. Prevalence in men and women was 0.26:0.09%; in blacks and whites, 0.24:0.10%. Ventricular septal thickness was 15 to 21 mm (mean, 17 mm) in the 7 subjects. Only 1 of the 7 subjects had ever experienced important cardiac symptoms attributable to HCM, had previously been suspected of having cardiovascular disease, or had obstruction to left ventricular outflow; 4 other subjects had relatively mild systolic anterior motion of the mitral valve that was insufficient to produce dynamic basal outflow obstruction. ECGs were abnormal in 5 of the 7 subjects. Five other study subjects had left ventricular wall thicknesses of 15 to 21 mm that were a consequence of systemic hypertension.
CONCLUSIONS: HCM was present in about 2 of 1000 young adults. These unique population-based data will aid in assessments of the impact of HCM-related mortality and morbidity in the general population and the practicality of screening large populations for HCM, including those comprising competitive athletes.

PMID 7641357  Circulation. 1995 Aug 15;92(4):785-9.
著者: Ali Nasermoaddeli, Katsuyuki Miura, Akira Matsumori, Yoshiyuki Soyama, Yuko Morikawa, Akira Kitabatake, Yutaka Inaba, Hideaki Nakagawa
雑誌名: Heart. 2007 Jun;93(6):711-5. doi: 10.1136/hrt.2006.095232. Epub 2006 Nov 3.
Abstract/Text OBJECTIVE: To investigate prognosis and prognostic factors in patients with hypertrophic cardiomyopathy (HCM) in Japan.
DESIGN: A nationwide epidemiological study.
SETTING: Hospitals selected randomly from among all hospitals in Japan.
PATIENTS: Clinical and epidemiological information for 2155 patients with HCM were collected in 1999.
MAIN OUTCOME MEASURES: Patients were classified on the basis of baseline prognostic factors. Survival rates up to 5 years were calculated by Cox's proportional hazard model for 1605 patients.
RESULTS: During the follow-up period, 241 deaths were recorded. The crude 5-year survival rate for the entire cohort was 86% (95% CI 84 to 88), and annual mortality ranged from 2.2% to 3.0%. A higher cardiothoracic ratio on chest x ray (HR 1.61; 95% CI 1.26 to 2.05, with 1 SD (6.2%) increase), a lower left ventricular ejection fraction (HR 1.42; 95% CI 1.20 to 1.69, with 1 SD (13%) decrease) and the presence of left bundle branch block (HR 3.14; 95% CI 1.28 to 7.71) were independently associated with a poorer prognosis, whereas the presence of apical hypertrophy at baseline (HR 0.58; 95%CI 0.36 to 0.92) predicted a better chance of survival.
CONCLUSIONS: The nationwide survey of patients with hypertrophic cardiomyopathy yielded important information on its prognosis and prognostic factors. These observations afford, for the first time, a measure of risk stratification in patients with HCM in Japan.

PMID 17085533  Heart. 2007 Jun;93(6):711-5. doi: 10.1136/hrt.2006.0952・・・
著者: Haruna Otsuka, Takuro Arimura, Tadaaki Abe, Hiroya Kawai, Yoshiyasu Aizawa, Toru Kubo, Hiroaki Kitaoka, Hiroshi Nakamura, Kazufumi Nakamura, Hiroshi Okamoto, Fukiko Ichida, Mamoru Ayusawa, Shinichi Nunoda, Mitsuaki Isobe, Masunori Matsuzaki, Yoshinori L Doi, Keiichi Fukuda, Taishi Sasaoka, Toru Izumi, Naoto Ashizawa, Akinori Kimura
雑誌名: Circ J. 2012;76(2):453-61. Epub 2011 Nov 23.
Abstract/Text BACKGROUND: Hypertrophic cardiomyopathy (HCM), which is inherited as an autosomal dominant trait, is the most prevalent hereditary cardiac disease. Although there are several reports on the systematic screening of mutations in the disease-causing genes in European and American populations, only limited information is available for Asian populations, including Japanese.
METHODS AND RESULTS: Genetic screening of disease-associated mutations in 8 genes for sarcomeric proteins, MYH7, MYBPC3, MYL2, MYL3, TNNT2, TNNI3, TPM1, and ACTC, was performed by direct sequencing in 112 unrelated Japanese proband patients with familial HCM; 37 different mutations, including 13 novel ones in 5 genes, MYH7, MYBPC3, TNNT2, TNNI3, and TPM1, were identified in 49 (43.8%) patients. Among them, 3 carried compound heterozygous mutations in MYBPC3 or TNNT2. The frequency of patients carrying the MYBPC3, MYH7, and TNNT2 mutations were 19.6%, 10.7%, and 8.9%, respectively, and the most frequently affected genes in the northeastern and southwestern parts of Japan were MYBPC3 and MYH7, respectively. Several mutations were found in multiple unrelated proband patients, for which the geographic distribution suggested founder effects of the mutations.
CONCLUSIONS: This study demonstrated the frequency and distribution of mutations in a large cohort of familial HCM in Japan.

PMID 22112859  Circ J. 2012;76(2):453-61. Epub 2011 Nov 23.
著者: Toru Kubo, Hiroaki Kitaoka, Makoto Okawa, Yuichi Baba, Takayoshi Hirota, Kayo Hayato, Naohito Yamasaki, Yoshihisa Matsumura, Haruna Otsuka, Takuro Arimura, Akinori Kimura, Yoshinori L Doi
雑誌名: Circ J. 2011;75(11):2654-9. Epub 2011 Jul 29.
Abstract/Text BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal-dominant pattern of inheritance mainly caused by single heterozygous mutations in sarcomere genes. Although multiple gene mutations have recently been reported in Western countries, clinical implications of multiple mutations in Japanese subjects are not clear.
METHODS AND RESULTS: A comprehensive genetic analysis of 5 sarcomere genes (cardiac β-myosin heavy chain gene [MYH7], cardiac myosin-binding protein C gene [MYBPC3], cardiac troponin T gene [TNNT2], α-tropomyosin gene [TPM1] and cardiac troponin I gene [TNNI3]) was performed in 93 unrelated patients and 14 mutations were identified in 28 patients. Twenty-six patients had single heterozygosity (20 in MYBPC3, 4 in MYH7, 1 in TNNT2, 1 in TNNI3), whereas 2 proband patients with familial HCM had double heterozygosity: 1 with P106fs in MYBPC3 and R869C in MYH7 and 1 with R945fs in MYBPC3 and E1049D in MYH7. From the results of the family survey and the previous literature on HCM mutations, P106fs, R945fs and R869C seemed to be pathological mutations and E1049D might be a rare polymorphism. The proband patient with P106fs and R869C double mutation was diagnosed as having HCM at an earlier age (28 years of age) than her relatives with single mutation, and had greater wall thickness with left ventricular outflow obstruction.
CONCLUSIONS: One double mutation was identified in a Japanese cohort of HCM patients. Further studies are needed to clarify the clinical significance of multiple mutations including phenotypic severity.

PMID 21799269  Circ J. 2011;75(11):2654-9. Epub 2011 Jul 29.
著者: Barry J Maron, Joseph J Doerer, Tammy S Haas, David M Tierney, Frederick O Mueller
雑誌名: Circulation. 2009 Mar 3;119(8):1085-92. doi: 10.1161/CIRCULATIONAHA.108.804617. Epub 2009 Feb 16.
Abstract/Text BACKGROUND: Sudden deaths in young competitive athletes are highly visible events with substantial impact on the physician and lay communities. However, the magnitude of this public health issue has become a source of controversy.
METHODS AND RESULTS: To estimate the absolute number of sudden deaths in US competitive athletes, we have assembled a large registry over a 27-year period using systematic identification and tracking strategies. A total of 1866 athletes who died suddenly (or survived cardiac arrest), 19+/-6 years of age, were identified throughout the United States from 1980 to 2006 in 38 diverse sports. Reports were less common during 1980 to 1993 (576 [31%]) than during 1994 to 2006 (1290 [69%], P<0.001) and increased at a rate of 6% per year. Sudden deaths were predominantly due to cardiovascular disease (1049 [56%]), but causes also included blunt trauma that caused structural damage (416 [22%]), commotio cordis (65 [3%]), and heat stroke (46 [2%]). Among the 1049 cardiovascular deaths, the highest number of events in a single year was 76 (2005 and 2006), with an average of 66 deaths per year (range 50 to 76) over the last 6 years; 29% occurred in blacks, 54% in high school students, and 82% with physical exertion during competition/training, whereas only 11% occurred in females (although this increased with time; P=0.023). The most common cardiovascular causes were hypertrophic cardiomyopathy (36%) and congenital coronary artery anomalies (17%).
CONCLUSIONS: In this national registry, the absolute number of cardiovascular sudden deaths in young US athletes was somewhat higher than previous estimates but relatively low nevertheless, with a rate of <100 per year. These data are relevant to the current debate surrounding preparticipation screening programs with ECGs and also suggest the need for systematic and mandatory reporting of athlete sudden deaths to a national registry.

PMID 19221222  Circulation. 2009 Mar 3;119(8):1085-92. doi: 10.1161/CI・・・
著者: Bernard J Gersh, Barry J Maron, Robert O Bonow, Joseph A Dearani, Michael A Fifer, Mark S Link, Srihari S Naidu, Rick A Nishimura, Steve R Ommen, Harry Rakowski, Christine E Seidman, Jeffrey A Towbin, James E Udelson, Clyde W Yancy, American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Thoracic Surgeons
雑誌名: Circulation. 2011 Dec 13;124(24):2761-96. doi: 10.1161/CIR.0b013e318223e230. Epub 2011 Nov 8.
Abstract/Text
PMID 22068435  Circulation. 2011 Dec 13;124(24):2761-96. doi: 10.1161/・・・
著者: A Selcuk Adabag, Michael A Kuskowski, Barry J Maron
雑誌名: Am J Cardiol. 2006 Dec 1;98(11):1507-11. doi: 10.1016/j.amjcard.2006.07.029. Epub 2006 Oct 12.
Abstract/Text Although hypertrophic cardiomyopathy (HC) occurs in 1 of 500 adults, most cardiology practices treat relatively few patients with HC, suggesting that many affected patients evade clinical recognition. Determining the clinical circumstances under which HC is identified will provide clues to its under-recognition. Clinical triggers leading to diagnostic echocardiograms were analyzed in 711 consecutive patients with HC. In most (384 [54%]), HC was initially suspected only after the onset of cardiac symptoms or acute cardiac events. In a substantial minority (327 [46%]), HC was recognized while patients were asymptomatic, including 225 (32%) by routine medical evaluations, in 27 of whom (4%) HC was recognized during preparticipation examinations for competitive sports or other activities. Women, older patients (age > or =50 years), and those with outflow obstruction at rest (gradient > or =30 mm Hg) were more likely suspected to have HC by virtue of cardiac symptoms or events (p <0.0001). Conversely, patients with extreme hypertrophy (wall thickness > or =30 mm) and those at high risk for sudden death were more often asymptomatic and identified by routine or family screenings (p <0.0001 and p = 0.004, respectively). Patients who subsequently died of heart failure or experienced embolic stroke were more often identified by virtue of symptoms or acute events (p = 0.03). In conclusion, although most patients with HC were recognized clinically only after overt disease manifestations, a substantial minority were diagnosed by routine examinations while asymptomatic, including an important subset of patients with HC recognized solely because of findings on sports preparticipation screening. These data underscore the need for heightened awareness and clinical suspicion of HC to increase the number of diagnosed patients, including many who may be at high risk for sudden death.

PMID 17126660  Am J Cardiol. 2006 Dec 1;98(11):1507-11. doi: 10.1016/j・・・
著者: K C Sze, P M Shah
雑誌名: Circulation. 1976 Sep;54(3):504-9.
Abstract/Text Phonoechocardiographic studies were performed in 23 patients with hypertrophic subaortic stenosis. In ten patients a distinct systolic sound was recorded, usually along the lower left sternal border. In eight of these cases the sound was low or medium frequency. Unlike the ejection click of valvular aortic stenosis, the sound began 40-100 msec after the upstroke of the indirect carotid pulse and occurred close to the initial peak of the carotid pulse. This sound, termed pseudoejection sound, was associated with systolic anterior movement (SAM) of the anterior mitral leaflet on the echocardiogram. In all six patients studied with simultaneous phonoechocardiograms, the pseudoejection sound coincided with the sudden halting of SAM of the anterior mitral leaflet. Following provocative maneuvers the sound became louder, and its timing, as well as the sharp halting of SAM of the mitral leaflet, occurred earlier in systole. The pseudoejection sound probably results either from impact of the anterior mitral leaflet against the interventricular septum or more likely from deceleration of blood flow in the left ventricular outflow tract. The echo data support the association of the pseudoejection sound with significant left aventricular outflow obstruction,

PMID 985739  Circulation. 1976 Sep;54(3):504-9.
著者: P Spirito, P Bellone, K M Harris, P Bernabo, P Bruzzi, B J Maron
雑誌名: N Engl J Med. 2000 Jun 15;342(24):1778-85. doi: 10.1056/NEJM200006153422403.
Abstract/Text BACKGROUND: Sudden death is known to be a possible consequence of hypertrophic cardiomyopathy. Quantification of the risk of sudden death, however, remains imprecise for most patients with this disease.
METHODS: We assessed the relation between the magnitude of left ventricular hypertrophy and mortality in 480 consecutive patients with hypertrophic cardiomyopathy. The patients were categorized into five subgroups according to maximal wall thickness: 15 mm or less, 16 to 19 mm, 20 to 24 mm, 25 to 29 mm, and 30 mm or more. Their ages ranged from 1 to 89 years (median, 47).
RESULTS: Over a mean follow-up period of 6.5 years, 65 of the 480 patients (14 percent) died: 23 suddenly, 15 of heart failure, and 27 of noncardiac causes or stroke. The risk of sudden death increased progressively and in direct relation to wall thickness (P=0.001), ranging from 0 per 1000 person-years (95 percent confidence interval, 0 to 14.4) for a wall thickness of 15 mm or less to 18.2 per 1000 person-years (95 percent confidence interval, 7.3 to 37.6) for a wall thickness of 30 mm or more and almost doubling from each wall-thickness subgroup to the next. The cumulative risk 20 years after the initial evaluation was close to zero for patients with a wall thickness of 19 mm or less but almost 40 percent for wall thicknesses of 30 mm or more. As compared with the other subgroups, patients with extreme hypertrophy were the youngest (mean age, 31 years), and most (41 of 43) had mild symptoms or no symptoms; of the 12 patients who were less than 18 years old at the initial evaluation, 5 died suddenly.
CONCLUSIONS: In hypertrophic cardiomyopathy, the magnitude of hypertrophy is directly related to the risk of sudden death and is a strong and independent predictor of prognosis. Young patients with extreme hypertrophy, even those with few or no symptoms, appear to be at substantial long-term risk and deserve consideration for interventions to prevent sudden death. The majority of patients with mild hypertrophy are at low risk and can be reassured regarding their prognosis.

PMID 10853000  N Engl J Med. 2000 Jun 15;342(24):1778-85. doi: 10.1056・・・
著者: Barry J Maron, N A Mark Estes, Martin S Maron, Adrian K Almquist, Mark S Link, James E Udelson
雑誌名: Circulation. 2003 Jun 17;107(23):2872-5. doi: 10.1161/01.CIR.0000072343.81530.75.
Abstract/Text
PMID 12814983  Circulation. 2003 Jun 17;107(23):2872-5. doi: 10.1161/0・・・
著者: Pawel Petkow Dimitrow, Lidia Chojnowska, Tomasz Rudzinski, Walerian Piotrowski, Lidia Ziólkowska, Andrzej Wojtarowicz, Anna Wycisk, Alicja Dabrowska-Kugacka, Ewa Nowalany-Kozielska, Bozena Sobkowicz, Wojciech Wróbel, Janina Aleszewicz-Baranowska, Andrzej Rynkiewicz, Krystyna Loboz-Grudzien, Michal Marchel, Andrzej Wysokinski
雑誌名: Eur Heart J. 2010 Dec;31(24):3084-93. doi: 10.1093/eurheartj/ehq308. Epub 2010 Sep 15.
Abstract/Text AIMS: in hypertrophic cardiomyopathy (HCM), the following five risk factors have a major role in the primary prevention of sudden death (SD): family history of SD (FHSD), syncope, massive wall thickness (MWTh) >30 mm, non-sustained ventricular tachycardia (nsVT) in Holter monitoring of electrocardiography, and abnormal blood pressure response to exercise (aBPRE). In HCM, as a genetic cardiac disease, the risk for SD may also exist from birth. The aim of the study was to compare the survival curves constructed for each of the five risk factors in a traditional follow-up model (started at the first presentation of a patient at the institution) and in a novel follow-up model (started at the date of birth). In an additional analysis, we compared the survival rate in three subgroups (without FHSD, with one SD, and with two or more SDs in a family).
METHODS AND RESULTS: a total of 1306 consecutive HCM patients (705 males, 601 females, mean age of 47 years, and 193 patients were <18 years) evaluated at 15 referral centres in Poland were enrolled in the study. In a novel method of follow-up, all the five risk factors confirmed its prognostic power (FHSD: P = 0.0007; nsVT: P < 0.0001; aBPRE: P = 0.0081; syncope: P < 0.0001; MWTh P> 0.0001), whereas in a traditional method, only four factors predicted SD (except aBPRE). In a novel model of follow-up, FHSD in a single episode starts to influence the prognosis with a delay to the fifth decade of life (P = 0.0007). Multiple FHSD appears to be a very powerful risk factor (P < 0.0001), predicting frequent SDs in childhood and adolescence.
CONCLUSION: the proposed concept of a lifelong calculated follow-up is a useful strategy in the risk stratification of SD. Multiple FHSD is a very ominous risk factor with strong impact, predicting frequent SD episodes in the early period of life.

PMID 20843960  Eur Heart J. 2010 Dec;31(24):3084-93. doi: 10.1093/eurh・・・
著者: B J Maron, J K Wolfson, E Ciró, P Spirito
雑誌名: Am J Cardiol. 1983 Jan 1;51(1):189-94.
Abstract/Text Distribution of left ventricular (LV) hypertrophy was assessed by wide-angle, 2-dimensional (2-D) echocardiography in 153 patients with hypertrophic cardiomyopathy and compared with the scalar electrocardiogram in the same patients. The most common electrocardiographic alterations were S-T segment changes and T-wave inversion (61%), LV hypertrophy (47%), abnormal Q waves (25%), and left atrial enlargement (24%). LV hypertrophy on the electrocardiogram was significantly more common in patients with the most extensive distribution of LV hypertrophy on 2-D echocardiogram involving substantial portions of both the ventricular septum and LV free wall (type III; 51 of 69, 74%) than in those with more limited distribution of LV hypertrophy (21 of 84, 25%; p less than 0.001). Most patients with hypertrophic cardiomyopathy and normal electrocardiograms (13 of 23) had localized (type I) hypertrophy, but only 4 had the extensive type III pattern of hypertrophy. Abnormal Q waves were significantly more common in those patients without hypertrophy of the anterior, basal septum (type IV; 15 of 27, 56%) than in those with basal septal hypertrophy (23 of 126, 18%; p less than 0.001); abnormal Q waves were uncommon in extensive type III distribution of hypertrophy (13 of 69, 19%). Thus, although no single electrocardiographic abnormality is characteristic of hypertrophic cardiomyopathy, 2-D echocardiography clarifies the significance of certain electrocardiographic patterns: (1) LV hypertrophy on the electrocardiogram, although present in only about half of the study group, was a relatively sensitive (74%) marker for extensive (type III) LV hypertrophy; (2) abnormal Q waves cannot be explained by ventricular septal hypertrophy alone; and (3) a normal electrocardiogram was most commonly a manifestation of localized LV hypertrophy.

PMID 6217739  Am J Cardiol. 1983 Jan 1;51(1):189-94.
著者: L M Shapiro, W J McKenna
雑誌名: J Am Coll Cardiol. 1983 Sep;2(3):437-44.
Abstract/Text The distribution of left ventricular hypertrophy was assessed by M-mode and two-dimensional echocardiography in 89 patients with hypertrophic cardiomyopathy. Myocardial thickness was measured in the septum and the free and posterior wall in both the proximal and distal left ventricle. All patients had at least one myocardial region that was hypertrophied. The predominant pattern of hypertrophy was defined as symmetric (31%), asymmetric septal (55%) and distal ventricular (14%). The spectrum of wall thickness measurements between patients with symmetric hypertrophy was wide (1.5 to 4.5 cm) and was not related to age. In patients with asymmetric septal hypertrophy, the distribution of hypertrophy conformed to previously described patterns; hypertrophy was localized to the anterior septum (14%) or the anterior and posterior septum (35%) or involved both the septum and the left ventricular free wall (51%). The patients with distal ventricular hypertrophy had marked papillary muscle thickening, and only 1 of 12 patients could be correctly diagnosed using M-mode echocardiography. The proportion of patients with symmetric and distal ventricular hypertrophy was greater than that reported when patients are selected on the basis of M-mode diagnostic criteria. This reflects the limitations of the M-mode technique in the assessment of left ventricular hypertrophy and suggests that the recognition and understanding of hypertrophic cardiomyopathy have been biased by patients with asymmetric septal hypertrophy who previously were most readily identified.

PMID 6683731  J Am Coll Cardiol. 1983 Sep;2(3):437-44.
著者: Luis C Afonso, Juan Bernal, Jeroen J Bax, Theodore P Abraham
雑誌名: JACC Cardiovasc Imaging. 2008 Nov;1(6):787-800. doi: 10.1016/j.jcmg.2008.09.002. Epub 2008 Nov 18.
Abstract/Text Hypertrophic cardiomyopathy is a relatively common inherited cardiomyopathy that is occasionally challenging to differentiate from hypertensive heart disease and athlete hearts on the basis of morphologic or functional abnormalities alone. Echocardiography has traditionally played a preeminent role in the diagnosis, formulation of management strategies, and the prognostication of this complex disease. In this review, we briefly profile the utility and pitfalls of established echocardiographic modalities and discuss the evolving role of novel echocardiographic imaging modalities such as tissue Doppler, Doppler-based strain, 2-dimensional strain (speckle tracking imaging), and 3-dimensional imaging in the assessment of hypertrophic cardiomyopathy.

PMID 19356516  JACC Cardiovasc Imaging. 2008 Nov;1(6):787-800. doi: 10・・・
著者: James C C Moon, Emma Reed, Mary N Sheppard, Andrew G Elkington, Siew Yen Ho, Margaret Burke, Mario Petrou, Dudley J Pennell
雑誌名: J Am Coll Cardiol. 2004 Jun 16;43(12):2260-4. doi: 10.1016/j.jacc.2004.03.035.
Abstract/Text OBJECTIVES: We sought to identify the histologic basis of myocardial late gadolinium enhancement cardiovascular magnetic resonance (CMR) in hypertrophic cardiomyopathy (HCM).
BACKGROUND: The histologic basis of late gadolinium CMR in patients with HCM is unknown.
METHODS: A 28-year-old male patient with HCM and heart failure underwent late gadolinium enhancement CMR and, 49 days later, heart transplantation. The explanted heart was examined histologically for the extent of collagen and disarray, and the results were compared with a previous in vivo CMR scan.
RESULTS: Overall, 19% of the myocardium was collagen, but the amount per segment varied widely (SD +/- 19, range 0% to 71%). Both disarray and collagen were more likely to be found in the mesocardium than in the endo- or epicardium. There was a significant relationship between the extent of late gadolinium enhancement and collagen (r = 0.7, p < 0.0001) but not myocardial disarray (p = 0.58). Segments containing >15% collagen were more likely to have late gadolinium enhancement. Regional wall motion was inversely related to the extent of myocardial collagen and late gadolinium enhancement but not disarray (p = 0.0003, 0.04, and NS, respectively).
CONCLUSIONS: In this patient with HCM and heart failure, regions of myocardial late gadolinium enhancement by CMR represented regions of increased myocardial collagen but not disarray.

PMID 15193690  J Am Coll Cardiol. 2004 Jun 16;43(12):2260-4. doi: 10.1・・・
著者: B J Maron, V J Ferrans, W L Henry, C E Clark, D R Redwood, W C Roberts, A G Morrow, S E Epstein
雑誌名: Circulation. 1974 Sep;50(3):436-46.
Abstract/Text
PMID 4278057  Circulation. 1974 Sep;50(3):436-46.
著者: J W Mason, J B O'Connell
雑誌名: Circulation. 1989 May;79(5):971-9.
Abstract/Text At this time, endomyocardial biopsy has proven validity as a diagnostic method in few circumstances. However, it is overused. In the near term, the extent of its use should be modified by knowledge of its therapeutic relevance in patients with myocarditis. In the long term, numerous new techniques for studying pathophysiology at the subcellular and molecular levels will demand a central role for endomyocardial biopsy in the diagnosis, treatment and fundamental understanding of myocardial diseases. We believe that endomyocardial biopsy will serve as an indispensible link between basic scientists and clinicians in the effort to describe disease mechanisms.

PMID 2653662  Circulation. 1989 May;79(5):971-9.
著者: Kevin M Harris, Paolo Spirito, Martin S Maron, Andrey G Zenovich, Francesco Formisano, John R Lesser, Shannon Mackey-Bojack, Warren J Manning, James E Udelson, Barry J Maron
雑誌名: Circulation. 2006 Jul 18;114(3):216-25. doi: 10.1161/CIRCULATIONAHA.105.583500. Epub 2006 Jul 10.
Abstract/Text BACKGROUND: End stage (ES) is a recognized part of the hypertrophic cardiomyopathy (HCM) disease spectrum. Frequency, clinical profile and course, and treatment strategies in these patients remain incompletely defined.
METHODS AND RESULTS: Three HCM cohorts comprised 1259 patients, including 44 (3.5%) characterized as ES with systolic dysfunction (ejection fraction <50% at rest; range 15% to 49%). ES developed at a wide age range (14 to 74 years), with 45% of patients < or = 40 years old. Although 29 patients (66%) died of progressive heart failure, had sudden death events, or underwent heart transplantation, 15 (34%) survived with medical management over 3+/-3 years. Duration from onset of HCM symptoms to ES identification was considerable (14+/-10 years), but ES onset to death/transplantation was brief (2.7+/-2 years). ES occurred with similar frequency in patients with or without prior myectomy (P=0.84). Appropriate defibrillator interventions were 10% per year in patients awaiting donor hearts. Most ES patients (n=23; 52%) showed substantial left ventricular (LV) remodeling with cavity dilatation. Less complete remodeling occurred in 21 patients (48%), including 5 with persistence of a nondilated and markedly hypertrophied LV. Pathology and magnetic resonance imaging showed extensive (transmural) fibrosis in 9 of 11 ES patients. At initial evaluation, patients who developed ES were younger with more severe symptoms, had a larger LV cavity, and more frequently had a family history of ES than other HCM patients.
CONCLUSIONS: ES of nonobstructive HCM has an expanded and more diverse clinical expression than previously appreciated, including occurrence in young patients, heterogeneous patterns of remodeling, frequent association with atrial fibrillation, and impaired LV contractility that precedes cavity dilatation, wall thinning, and heart failure symptoms. ES is an unfavorable complication (mortality rate 11% per year) and a sudden death risk factor; it requires vigilance to permit timely recognition and the necessity for defibrillator implantation and heart transplantation.

PMID 16831987  Circulation. 2006 Jul 18;114(3):216-25. doi: 10.1161/CI・・・
著者: Tomoyuki Hamada, Toru Kubo, Hiroaki Kitaoka, Takayoshi Hirota, Eri Hoshikawa, Kayo Hayato, Yuji Shimizu, Makoto Okawa, Naohito Yamasaki, Yoshihisa Matsumura, Toshikazu Yabe, Jun Takata, Yoshinori L Doi
雑誌名: Clin Cardiol. 2010 Jul;33(7):E24-8. doi: 10.1002/clc.20533.
Abstract/Text BACKGROUND: Although the dilated phase of hypertrophic cardiomyopathy (D-HCM) characterized by left ventricular (LV) systolic dysfunction and cavity dilatation has been reported to be a poor prognosis, this is now in contrast to the improved prognosis of dilated cardiomyopathy (DCM) in the era of advancements in heart failure management. There has been no investigation of the clinical features of D-HCM compared with those of DCM from the point of management of systolic dysfunction.
HYPOTHESIS: The aim of this study was to investigate the clinical features of D-HCM in comparison with those of DCM in a single institute.
METHODS: We studied 20 consecutive patients with D-HCM (global ejection fraction < 50%) and 115 consecutive patients with DCM.
RESULTS: At diagnosis of D-HCM, 8 (40%) of the D-HCM patients already experienced dyspnea (New York Heart Association [NYHA] class >or= III). Left atrial diameter was larger and prevalence of atrial fibrillation was higher in the D-HCM group, although LV size was larger and LV ejection fraction was lower in the DCM group. During the follow-up period (4.0 years), 11 (55%) of the patients with D-HCM died. The 5-year survival rate from all-cause mortality including cardiac transplantation was 45.6% in patients with D-HCM vs 81.6% in patients with DCM (log-rank P = .0001).
CONCLUSIONS: Patients with D-HCM were more symptomatic at diagnosis, although LV dilatation and impaired fractional shortening seemed more severe in patients with DCM. The prognosis for D-HCM patients was worse than that for patients with DCM despite similar or even more intensive treatment for heart failure.

Copyright (c) 2010 Wiley Periodicals, Inc.
PMID 20641106  Clin Cardiol. 2010 Jul;33(7):E24-8. doi: 10.1002/clc.20・・・
著者: Martin S Maron, Iacopo Olivotto, Andrey G Zenovich, Mark S Link, Natesa G Pandian, Jeffery T Kuvin, Stefano Nistri, Franco Cecchi, James E Udelson, Barry J Maron
雑誌名: Circulation. 2006 Nov 21;114(21):2232-9. doi: 10.1161/CIRCULATIONAHA.106.644682. Epub 2006 Nov 6.
Abstract/Text BACKGROUND: Nonobstructive hypertrophic cardiomyopathy (HCM) has been regarded as the predominant hemodynamic form of the disease on the basis of assessment of outflow gradient under resting conditions. We sought to prospectively define the prevalence, clinical profile, and significance of left ventricular (LV) outflow tract obstruction under resting conditions and with physiological exercise in a large HCM cohort.
METHODS AND RESULTS: We prospectively analyzed 320 consecutive HCM patients (age, 47+/-17 years), measuring LV outflow gradient at rest, with Valsalva maneuver, and with exercise echocardiography. LV outflow obstruction was present at rest and/or with exercise in 225 patients (70%); 119 had rest gradients > or = 50 mm Hg and were not exercised. Of the other 201 patients with gradients < 50 mm Hg at rest (average, 4+/-9 mm Hg), 106 developed mechanical obstruction to LV outflow resulting from mitral valve-septal contact after exercise (80+/-43 mm Hg), including 76 with marked gradients > or = 50 mm Hg and 46 with heart failure symptoms. The remaining 95 patients (30%) had no or small gradients (< 30 mm Hg) both at rest and with exercise. Valsalva maneuver underestimated the presence and magnitude of exercise-induced obstruction.
CONCLUSIONS: Among those patients who come to clinical evaluation, HCM is a predominantly obstructive disease in which LV outflow gradients, frequently associated with heart failure symptoms and often identified only with exercise, are evident in most patients (ie, 70%). Identification of LV outflow obstruction with exercise echocardiography may broaden management options in HCM by identifying symptomatic patients not otherwise regarded as potential candidates for septal reduction therapy. Assessment of subaortic gradients with exercise should be a routine component of the evaluation of HCM patients without outflow obstruction under resting conditions.

PMID 17088454  Circulation. 2006 Nov 21;114(21):2232-9. doi: 10.1161/C・・・
著者: Steve R Ommen, Barry J Maron, Iacopo Olivotto, Martin S Maron, Franco Cecchi, Sandro Betocchi, Bernard J Gersh, Michael J Ackerman, Robert B McCully, Joseph A Dearani, Hartzell V Schaff, Gordon K Danielson, A Jamil Tajik, Rick A Nishimura
雑誌名: J Am Coll Cardiol. 2005 Aug 2;46(3):470-6. doi: 10.1016/j.jacc.2005.02.090.
Abstract/Text OBJECTIVES: This study sought to determine the impact of surgical myectomy on long-term survival in hypertrophic cardiomyopathy (HCM).
BACKGROUND: Left ventricular (LV) outflow tract obstruction in HCM increases the likelihood of heart failure and cardiovascular death. Although surgical myectomy is the primary treatment for amelioration of outflow obstruction and advanced drug-refractory heart failure symptoms, its impact on long-term survival remains unresolved.
METHODS: Total and HCM-related mortality were compared in three subgroups comprised of 1,337 consecutive HCM patients evaluated from 1983 to 2001: 1) surgical myectomy (n = 289); 2) LV outflow obstruction without operation (n = 228); and 3) nonobstructive (n = 820). Mean follow-up duration was 6 +/- 6 years.
RESULTS: Including two operative deaths (procedural mortality, 0.8%), 1-, 5-, and 10-year overall survival after myectomy was 98%, 96%, and 83%, respectively, and did not differ from that of the general U.S. population matched for age and gender (p = 0.2) nor from patients with nonobstructive HCM (p = 0.8). Compared to nonoperated obstructive HCM patients, myectomy patients experienced superior survival free from all-cause mortality (98%, 96%, and 83% vs. 90%, 79%, and 61%, respectively; p < 0.001), HCM-related mortality (99%, 98%, and 95% vs. 94%, 89%, and 73%, respectively; p < 0.001), and sudden cardiac death (100%, 99%, and 99% vs. 97%, 93%, and 89%, respectively; p = 0.003). Multivariate analysis showed myectomy to have a strong, independent association with survival (hazard ratio 0.43; p < 0.001).
CONCLUSIONS: Surgical myectomy performed to relieve outflow obstruction and severe symptoms in HCM was associated with long-term survival equivalent to that of the general population, and superior to obstructive HCM without operation. In this retrospective study, septal myectomy seems to reduce mortality risk in severely symptomatic patients with obstructive HCM.

PMID 16053960  J Am Coll Cardiol. 2005 Aug 2;46(3):470-6. doi: 10.1016・・・
著者: R Patel, S F Nagueh, N Tsybouleva, M Abdellatif, S Lutucuta, H A Kopelen, M A Quinones, W A Zoghbi, M L Entman, R Roberts, A J Marian
雑誌名: Circulation. 2001 Jul 17;104(3):317-24.
Abstract/Text BACKGROUND: Hypertrophic cardiomyopathy is a genetic disease characterized by cardiac hypertrophy, myocyte disarray, interstitial fibrosis, and left ventricular (LV) dysfunction. We have proposed that hypertrophy and fibrosis, the major determinants of mortality and morbidity, are potentially reversible. We tested this hypothesis in beta-myosin heavy chain-Q(403) transgenic rabbits.
METHODS AND RESULTS: We randomized 24 beta-myosin heavy chain-Q(403) rabbits to treatment with either a placebo or simvastatin (5 mg. kg(-1). d(-1)) for 12 weeks and included 12 nontransgenic controls. We performed 2D and Doppler echocardiography and tissue Doppler imaging before and after treatment. Demographic data were similar among the groups. Baseline mean LV mass and interventricular septal thickness in nontransgenic, placebo, and simvastatin groups were 3.9+/-0.7, 6.2+/-2.0, and 7.5+/-2.1 g (P<0.001) and 2.2+/-0.2, 3.1+/-0.5, and 3.3+/-0.5 mm (P=0.002), respectively. Simvastatin reduced LV mass by 37%, interventricular septal thickness by 21%, and posterior wall thickness by 13%. Doppler indices of LV filling pressure were improved. Collagen volume fraction was reduced by 44% (P<0.001). Disarray was unchanged. Levels of activated extracellular signal-regulated kinase (ERK) 1/2 were increased in the placebo group and were less than normal in the simvastatin group. Levels of activated and total p38, Jun N-terminal kinase, p70S6 kinase, Ras, Rac, and RhoA and the membrane association of Ras, RhoA, and Rac1 were unchanged.
CONCLUSIONS: Simvastatin induced the regression of hypertrophy and fibrosis, improved cardiac function, and reduced ERK1/2 activity in the beta-myosin heavy chain-Q(403) rabbits. These findings highlight the need for clinical trials to determine the effects of simvastatin on cardiac hypertrophy, fibrosis, and dysfunction in humans with hypertrophic cardiomyopathy and heart failure.

PMID 11457751  Circulation. 2001 Jul 17;104(3):317-24.
著者: Christopher Semsarian, Imran Ahmad, Michael Giewat, Dimitrios Georgakopoulos, Joachim P Schmitt, Bradley K McConnell, Steven Reiken, Ulrike Mende, Andrew R Marks, David A Kass, Christine E Seidman, J G Seidman
雑誌名: J Clin Invest. 2002 Apr;109(8):1013-20. doi: 10.1172/JCI14677.
Abstract/Text Dominant mutations in sarcomere protein genes cause hypertrophic cardiomyopathy, an inherited human disorder with increased ventricular wall thickness, myocyte hypertrophy, and disarray. To understand the early consequences of mutant sarcomere proteins, we have studied mice (designated alphaMHC(403/+)) bearing an Arg403Gln missense mutation in the alpha cardiac myosin heavy chain. We demonstrate that Ca(2+) is reduced in the sarcoplasmic reticulum of alphaMHC(403/+) mice, and levels of the sarcoplasmic reticulum Ca(2+)-binding protein calsequestrin are diminished in advance of changes in cardiac histology or morphology. Further evidence for dysregulation of sarcoplasmic reticulum Ca(2+) in these animals is seen in their decreased expression of the ryanodine receptor Ca(2+)-release channel and its associated membrane proteins and in an increase in ryanodine receptor phosphorylation. Early administration of the L-type Ca(2+) channel inhibitor diltiazem restores normal levels of these sarcoplasmic reticular proteins and prevents the development of pathology in alphaMHC(403/+) mice. We conclude that disruption of sarcoplasmic reticulum Ca(2+) homeostasis is an important early event in the pathogenesis of this disorder and suggest that the use of Ca(2+) channel blockers in advance of established clinical disease could prevent hypertrophic cardiomyopathy caused by sarcomere protein gene mutations.

PMID 11956238  J Clin Invest. 2002 Apr;109(8):1013-20. doi: 10.1172/JC・・・
著者: Vinitha Senthil, Suet N Chen, Natalie Tsybouleva, Tripti Halder, Sherif F Nagueh, James T Willerson, Robert Roberts, A J Marian
雑誌名: Circ Res. 2005 Aug 5;97(3):285-92. doi: 10.1161/01.RES.0000177090.07296.ac. Epub 2005 Jul 14.
Abstract/Text Cardiac hypertrophy, a major determinant of morbidity and mortality in hypertrophic cardiomyopathy (HCM), is considered a secondary phenotype and potentially preventable. To test this hypothesis, we screened 30 5- to 6-month-old beta-myosin heavy chain Q403 transgenic rabbits by echocardiography and selected 26 without cardiac hypertrophy. We randomized the transgenic rabbits to treatment with atorvastatin (2.5 mg/Kg/d), known to block hypertrophic signaling or a placebo. We included 15 nontransgenic rabbits as controls. Cardiac phenotype was analyzed serially before, 6 and 12 months after randomization. Serum total cholesterol levels were reduced by 49% with atorvastatin administration. Left-ventricular mass, wall thickness; myocyte size, myocardial levels of molecular markers of hypertrophy, lipid peroxides, and oxidized mitochondrial DNA; and the number of terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive myocytes were increased significantly in the placebo but not in the atorvastatin group. Myocardium catalase mRNA levels were decreased by 5-fold in the placebo but were normal in the atorvastatin group. Catalase protein level and activity were not significantly changed. Levels of membrane-bound Ras and phospho-p44/42 mitogen-activated-protein kinase (MAPK) were increased in the placebo group (approximately 2.5 fold) but were reduced in the atorvastatin group. Levels of GTP- and membrane-bound RhoA and Rac1, phospho-p38, and phospho-c-Jun NH2-terminal kinases were unchanged. Thus, atorvastatin prevented development of cardiac hypertrophy; determined at organ, cellular, and molecular levels, partly through reducing active Ras and p44/42 MAPK. The results indicate potential beneficial effects of atorvastatin in prevention of cardiac hypertrophy, a major determinant of morbidity in all forms of cardiovascular diseases, and beckon clinical studies in humans with HCM.

PMID 16020756  Circ Res. 2005 Aug 5;97(3):285-92. doi: 10.1161/01.RES.・・・
著者: Mark V Sherrid, Ivan Barac, William J McKenna, Perry M Elliott, Shaughan Dickie, Lidia Chojnowska, Susan Casey, Barry J Maron
雑誌名: J Am Coll Cardiol. 2005 Apr 19;45(8):1251-8. doi: 10.1016/j.jacc.2005.01.012.
Abstract/Text OBJECTIVES: In this study we assessed the long-term efficacy and safety of disopyramide for patients with obstructive hypertrophic cardiomyopathy (HCM).
BACKGROUND: It has been reported that disopyramide may reduce left ventricular outflow gradient and improve symptoms in patients with HCM. However, long-term efficacy and safety of disopyramide has not been shown in a large cohort.
METHODS: Clinical and echocardiographic data were evaluated in 118 obstructive HCM patients treated with disopyramide at 4 HCM treatment centers. Mortality in the disopyramide-treated patients was compared with 373 obstructive HCM patients not treated with disopyramide.
RESULTS: Patients were followed with disopyramide for 3.1 +/- 2.6 years; dose 432 +/- 181 mg/day (97% also received beta-blockers). Seventy-eight patients (66%) were maintained with disopyramide without the necessity for major non-pharmacologic intervention with surgical myectomy, alcohol ablation, or pacing; outflow gradient at rest decreased from 75 +/- 33 to 40 +/- 32 mm Hg (p < 0.0001) and mean New York Heart Association functional class from 2.3 +/- 0.7 to 1.7 +/- 0.6 (p < 0.0001). Forty other patients (34%) could not be satisfactorily managed with disopyramide and required major invasive interventions because of inadequate symptom and gradient control or vagolytic side effects. All-cause annual cardiac death rate between disopyramide and non-disopyramide-treated patients did not differ significantly, 1.4% versus 2.6%/year (p = 0.07). There was also no difference in sudden death rate, 1.0%/year versus 1.8%/year (p = 0.08).
CONCLUSIONS: Two-thirds of obstructed HCM patients treated with disopyramide could be managed medically with amelioration of symptoms and about 50% reduction in subaortic gradient over >/=3 years. Disopyramide therapy does not appear to be proarrhythmic in HCM and should be considered before proceeding to surgical myectomy or alternate strategies.

PMID 15837258  J Am Coll Cardiol. 2005 Apr 19;45(8):1251-8. doi: 10.10・・・
著者: B J Maron, W K Shen, M S Link, A E Epstein, A K Almquist, J P Daubert, G H Bardy, S Favale, R F Rea, G Boriani, N A Estes, P Spirito
雑誌名: N Engl J Med. 2000 Feb 10;342(6):365-73. doi: 10.1056/NEJM200002103420601.
Abstract/Text BACKGROUND: Hypertrophic cardiomyopathy is a genetic disease associated with a risk of ventricular tachyarrhythmias and sudden death, especially in young patients.
METHODS: We conducted a retrospective multicenter study of the efficacy of implantable cardioverter-defibrillators in preventing sudden death in 128 patients with hypertrophic cardiomyopathy who were judged to be at high risk for sudden death.
RESULTS: At the time of the implantation of the defibrillator, the patients were 8 to 82 years old (mean [+/-SD], 40+/-16), and 69 patients (54 percent) were less than 41 years old. The average follow-up period was 3.1 years. Defibrillators were activated appropriately in 29 patients (23 percent), by providing defibrillation shocks or antitachycardia pacing, with the restoration of sinus rhythm; the average age at the time of the intervention was 41 years. The rate of appropriate defibrillator discharge was 7 percent per year. A total of 32 patients (25 percent) had episodes of inappropriate discharges. In the group of 43 patients who received defibrillators for secondary prevention (after cardiac arrest or sustained ventricular tachycardia), the devices were activated appropriately in 19 patients (11 percent per year). Of 85 patients who had prophylactic implants because of risk factors (i.e., for primary prevention), 10 had appropriate interventions (5 percent per year). The interval between implantation and the first appropriate discharge was highly variable but was substantially prolonged (four to nine years) in six patients. In all 21 patients with stored electrographic data and appropriate interventions, the interventions were triggered by ventricular tachycardia or fibrillation.
CONCLUSIONS: Ventricular tachycardia or fibrillation appears to be the principal mechanism of sudden death in patients with hypertrophic cardiomyopathy. In high-risk patients with hypertrophic cardiomyopathy, implantable defibrillators are highly effective in terminating such arrhythmias, indicating that these devices have a role in the primary and secondary prevention of sudden death.

PMID 10666426  N Engl J Med. 2000 Feb 10;342(6):365-73. doi: 10.1056/N・・・
著者: Barry J Maron, Paolo Spirito, Win-Kuang Shen, Tammy S Haas, Francesco Formisano, Mark S Link, Andrew E Epstein, Adrian K Almquist, James P Daubert, Thorsten Lawrenz, Giuseppe Boriani, N A Mark Estes, Stefano Favale, Marco Piccininno, Stephen L Winters, Massimo Santini, Sandro Betocchi, Fernando Arribas, Mark V Sherrid, Gianfranco Buja, Christopher Semsarian, Paolo Bruzzi
雑誌名: JAMA. 2007 Jul 25;298(4):405-12. doi: 10.1001/jama.298.4.405.
Abstract/Text CONTEXT: Recently, the implantable cardioverter-defibrillator (ICD) has been promoted for prevention of sudden death in hypertrophic cardiomyopathy (HCM). However, the effectiveness and appropriate selection of patients for this therapy is incompletely resolved.
OBJECTIVE: To study the relationship between clinical risk profile and incidence and efficacy of ICD intervention in HCM.
DESIGN, SETTING, AND PATIENTS: Multicenter registry study of ICDs implanted between 1986 and 2003 in 506 unrelated patients with HCM. Patients were judged to be at high risk for sudden death; had received ICDs; underwent evaluation at 42 referral and nonreferral institutions in the United States, Europe, and Australia; and had a mean follow-up of 3.7 (SD, 2.8) years. Measured risk factors for sudden death included family history of sudden death, massive left ventricular hypertrophy, nonsustained ventricular tachycardia on Holter monitoring, and unexplained prior syncope.
MAIN OUTCOME MEASURE: Appropriate ICD intervention terminating ventricular tachycardia or fibrillation.
RESULTS: The 506 patients were predominately young (mean age, 42 [SD, 17] years) at implantation, and most (439 [87%]) had no or only mildly limiting symptoms. ICD interventions appropriately terminated ventricular tachycardia/fibrillation in 103 patients (20%). Intervention rates were 10.6% per year for secondary prevention after cardiac arrest (5-year cumulative probability, 39% [SD, 5%]), and 3.6% per year for primary prevention (5-year probability, 17% [SD, 2%]). Time to first appropriate discharge was up to 10 years, with a 27% (SD, 7%) probability 5 years or more after implantation. For primary prevention, 18 of the 51 patients with appropriate ICD interventions (35%) had undergone implantation for only a single risk factor; likelihood of appropriate discharge was similar in patients with 1, 2, or 3 or more risk markers (3.83, 2.65, and 4.82 per 100 person-years, respectively; P = .77). The single sudden death due to an arrhythmia (in the absence of advanced heart failure) resulted from ICD malfunction. ICD complications included inappropriate shocks in 136 patients (27%).
CONCLUSIONS: In a high-risk HCM cohort, ICD interventions for life-threatening ventricular tachyarrhythmias were frequent and highly effective in restoring normal rhythm. An important proportion of ICD discharges occurred in primary prevention patients who had undergone implantation for a single risk factor. Therefore, a single marker of high risk for sudden death may be sufficient to justify consideration for prophylactic defibrillator implantation in selected patients with HCM.

PMID 17652294  JAMA. 2007 Jul 25;298(4):405-12. doi: 10.1001/jama.298.・・・
著者: Uma S Valeti, Rick A Nishimura, David R Holmes, Philip A Araoz, James F Glockner, Jerome F Breen, Steve R Ommen, Bernard J Gersh, A Jamil Tajik, Charanjit S Rihal, Hartzell V Schaff, Barry J Maron
雑誌名: J Am Coll Cardiol. 2007 Jan 23;49(3):350-7. doi: 10.1016/j.jacc.2006.08.055. Epub 2007 Jan 4.
Abstract/Text OBJECTIVES: This study sought to describe the acute morphologic differences that result from septal myectomy and alcohol septal ablation using cardiac magnetic resonance (CMR) imaging.
BACKGROUND: Surgical septal myectomy and alcohol septal ablation relieve left ventricular outflow tract obstruction in severely symptomatic patients with hypertrophic cardiomyopathy (HCM).
METHODS: Cine and contrast-enhanced CMR images were obtained in HCM patients before and after septal myectomy (n = 24) and alcohol septal ablation (n = 24). Location of septal reduction, extent of myocardial necrosis, and conduction system abnormalities with each technique were compared.
RESULTS: With septal myectomy, there was a discrete area of resected tissue consistently localized to anterior septum. In contrast, alcohol septal ablation resulted in a more variable effect. In most patients, alcohol septal ablation caused a transmural region of tissue necrosis, located more inferiorly in the basal septum than myectomy and usually extending into the right ventricular side of the septum at the midventricular level. However, there were 6 patients after alcohol septal ablation in whom there was sparing of the basal septum with residual gradients at follow-up. After the procedure, left bundle branch block developed in 46% of septal myectomy patients, and right bundle branch block was evident in 58% of alcohol septal ablation patients.
CONCLUSIONS: Septal myectomy and alcohol septal ablation for severely symptomatic, drug-refractory patients with obstructive HCM have different morphologic effects and location sites on left ventricular septal myocardium. Septal myectomy provides consistent resection of the obstructing portion of the anterior basal septum, whereas the effect of ethanol septal ablation is more variable. These findings may have important implications for patient selection and management as well as long-term outcome.

PMID 17239717  J Am Coll Cardiol. 2007 Jan 23;49(3):350-7. doi: 10.101・・・
著者: Paul Sorajja, Uma Valeti, Rick A Nishimura, Steve R Ommen, Charanjit S Rihal, Bernard J Gersh, David O Hodge, Hartzell V Schaff, David R Holmes
雑誌名: Circulation. 2008 Jul 8;118(2):131-9. doi: 10.1161/CIRCULATIONAHA.107.738740.
Abstract/Text BACKGROUND: The clinical efficacy of alcohol septal ablation for drug-refractory hypertrophic cardiomyopathy remains unclear. This study examines the outcome of alcohol septal ablation performed at a tertiary hypertrophic cardiomyopathy referral center.
METHODS AND RESULTS: Among 601 patients with severely symptomatic obstructive hypertrophic cardiomyopathy referred for alcohol septal ablation or myectomy from 1998 to 2006, 138 patients (median age, 64 years; 39% men) chose to undergo ablation. Procedural complications included death in 1.4%, sustained ventricular arrhythmias in 3%, tamponade in 3%, and pacemaker implantation in 20%. This rate was higher than a combined complication rate of 5% in age- and gender-matched patients who had undergone septal myectomy at Mayo Clinic (P<0.0001). Four-year survival free of all mortality was 88.0% (95% confidence interval, 79.4 to 97.5%), which was similar to that of the age- and gender-matched patients who had undergone myectomy (P=0.18). Six patients had documented ventricular arrhythmias after ablation, 4 of whom had successful intervention. Four-year survival free of death and severe New York Heart Association class III/IV symptoms after septal ablation was 76.4%, and 71 patients (51%) became asymptomatic. Myectomy patients CONCLUSIONS: Alcohol septal ablation is an efficacious procedure if performed in an experienced institution and may resolve symptoms in a subset of patients with obstructive hypertrophic cardiomyopathy. However, the procedural complication rate exceeds that of myectomy. Patients 65 years of age have better symptom resolution with myectomy. No impairment in short-term survival was noted in this nonrandomized study, but the long-term outcome remains unknown.

PMID 18591440  Circulation. 2008 Jul 8;118(2):131-9. doi: 10.1161/CIRC・・・
著者: Folkert J ten Cate, Osama I I Soliman, Michelle Michels, Dominic A M J Theuns, Peter L de Jong, Marcel L Geleijnse, Patrick W Serruys
雑誌名: Circ Heart Fail. 2010 May;3(3):362-9. doi: 10.1161/CIRCHEARTFAILURE.109.862359. Epub 2010 Mar 23.
Abstract/Text BACKGROUND: The impact of alcohol septal ablation (ASA)-induced scar is not known. This study sought to examine the long-term outcome of ASA among patients with obstructive hypertrophic cardiomyopathy.
METHODS AND RESULTS: Ninety-one consecutive patients (aged 54+/-15 years) with obstructive hypertrophic cardiomyopathy underwent ASA. Primary study end point was a composite of cardiac death and aborted sudden cardiac death including appropriate cardioverter-defibrillator discharges for fast ventricular tachycardia/ventricular fibrillation. Secondary end points were noncardiac death and other nonfatal complications. Outcomes of ASA patients were compared with 40 patients with hypertrophic cardiomyopathy who underwent septal myectomy. During 5.4+/-2.5 years, primary and/or secondary end points were seen in 35 (38%) ASA patients of whom 19 (21%) patients met the primary end point. The 1-, 5-, and 8-year survival-free from the primary end point was 96%, 86%, and 67%, respectively in ASA patients versus 100%, 96%, and 96%, respectively in myectomy patients during 6.6+/-2.7 years (log-rank, P=0.01). ASA patients had a approximately 5-fold increase in the estimated annual primary end point rate (4.4% versus 0.9%) compared with myectomy patients. In a multivariable model including a propensity score, ASA was an independent predictor of the primary end point (unadjusted hazard ratio, 5.2; 95% CI, 1.2 to 22.1; P=0.02 and propensity score-adjusted hazard ratio, 6.1; 95% CI, 1.4 to 27.1; P=0.02).
CONCLUSIONS: This study shows that ASA has potentially unwanted long-term effects. This poses special precaution, given the fact that ASA is practiced worldwide at increasing rate. We recommend myectomy as the preferred intervention in patients with obstructive hypertrophic cardiomyopathy.

PMID 20332420  Circ Heart Fail. 2010 May;3(3):362-9. doi: 10.1161/CIRC・・・

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