Dilated cardiomyopathy

Japanese: 拡張型心筋症

(2) Dilated cardiomyopathy
Concept/Definition: In the WHO/ISFC classification, dilated cardiomyopathy is a type of cardiomyopathy, along with hypertrophic cardiomyopathy, and is accompanied by dilation of the left ventricular cavity and reduced contractility. In the WHO/ISFC classification, myocardial diseases with a clear cause or connection to a systemic disease are excluded as "specific myocardial diseases" (Table 5-13-1).
The pathology of dilated cardiomyopathy is a decrease in left ventricular systolic function, resulting in symptoms of heart failure. In Japan, it accounts for approximately 20% of causes of heart failure and is one of the main causes of so-called "non-ischemic" heart failure.
Etiology Dilated cardiomyopathy is thought to have a variety of causes, including genetic predisposition and viral infection. Familial dilated cardiomyopathy is reported in 20-30% of cases overseas, and in Japan, in a survey by the Ministry of Health, Labor and Welfare, it accounted for 5%. As with hypertrophic cardiomyopathy, a link with various genetic abnormalities in myocardial contraction-related proteins has been suggested, and abnormalities have been reported in the cardiac actin gene, desmin gene, lamin gene, δ-sarcoglycan gene, cardiac β-myosin heavy chain gene, cardiac troponin Τ gene, and α-tropomyosin gene. Meanwhile, a link with viral infection has also attracted attention, and viral genomes such as coxsackievirus, adenovirus, and hepatitis C virus have been detected in the myocardium of patients with this disease.
There is little data on prognosis for dilated cardiomyopathy alone, and in terms of the prognosis for all heart failure based on reduced left ventricular systolic function, data from a reliable heart failure registry study in Japan shows an annual mortality rate of 7-8%, but the prognosis for non-ischemic cardiomyopathy is better than that for so-called ischemic cardiomyopathy. The majority of deaths are due to heart failure caused by the worsening of heart failure itself, or sudden death, but thromboembolism can also be a cause of death.
Pathology (Figure 5-13-11)
There are no pathological findings characteristic of dilated cardiomyopathy. Basically, degeneration, loss, and fibrosis of cardiomyocytes are observed. Individual cardiomyocytes also become hypertrophied, and there is also variation in the size of muscle fibers.
Symptoms There are no symptoms specific to dilated cardiomyopathy, and symptoms of heart failure are the main symptom, but there are also symptoms associated with arrhythmia.
Symptoms of heart failure include shortness of breath on exertion, edema, fatigue, and insomnia. In cases where the condition rapidly worsens, orthopnea and nocturnal dyspnea may occur. If tachyarrhythmias such as atrial fibrillation and ventricular tachycardia are also present, the patient will be aware of palpitations, and if sustained ventricular tachycardia is present, consciousness may be lost, leading to sudden death. In severe cases, physical examination often reveals a third and fourth heart sound, a galloping rhythm, and a pansystolic murmur caused by secondary mitral regurgitation due to left ventricular enlargement. The apical beat is shifted to the left and below the midclavicular line. In cases with right-sided heart failure, the jugular vein is distended, and pleural effusion and ascites can be seen. If pulmonary congestion becomes severe and pulmonary edema occurs, moist rales can be heard, mainly in the lower lung fields.
Examination findings Chest X-ray (Figure 5-13-12) shows enlargement of the cardiac shadow. The left ventricle is mainly enlarged, but the left atrium is also enlarged reflecting an increase in filling pressure. Myocardial damage often extends to the right heart system, and left-sided heart failure also causes pulmonary venous hypertension, which results in enlargement of the right heart system. Unlike hypertensive heart disease, the aortic arch (left first arch) does not generally enlarge. There is an increase in the pulmonary vascular shadow due to pulmonary congestion, and in cases of acute cardiogenic pulmonary edema, a so-called butterfly shadow is seen, which spreads from the hilum to the periphery. Pleural effusion is seen due to the accumulation of fluid. An electrocardiogram (Figure 5-13-13) shows left ventricular hypertrophy with ST depression, left atrial overload (the negative part of the latter half of the P wave of _V1 ), abnormal Q waves, negative T waves, and left bundle branch block. A Holter electrocardiogram shows ventricular premature contractions and ventricular tachycardia. Atrial fibrillation also occurs in 20 to 30 percent of cases.
Echocardiogram (Figure 5-13-14) shows left ventricular enlargement, decreased contractility, thinning of the ventricular wall, and enlargement of the left atrium. Decreased left ventricular contractility is often diffuse, but dyssynchrony due to a time phase shift in localized contraction is often observed. The Doppler left ventricular inflow velocity waveform changes from impaired relaxation to pseudo-normalization and then to a restrictive pattern as the left ventricular filling pressure increases. Left ventricular enlargement is also associated with various degrees of functional mitral regurgitation (Figure 5-13-15) due to tethering of the mitral valve (a phenomenon in which the papillary muscles pull on the mitral valve leaflets as the left ventricle expands, preventing them from closing).
Nuclear medicine examinations and MRI findings Myocardial perfusion scintigraphy using thallium or technetium is useful in differentiating from ischemic cardiomyopathy. MIBG scintigraphy shows an increase in the washout rate from the myocardium and a decrease in the H/M ratio (heart/mediastinum ratio). Evaluation of delayed enhancement by gadolinium-enhanced MRI is useful in differentiating from ischemic cardiomyopathy, and is also useful in differentiating from specific myocardial diseases.
Cardiac catheterization findings: Cardiac catheterization, including right heart catheterization, is necessary to evaluate cardiac function, and coronary angiography is useful for ruling out coronary artery disease.
Reflecting left ventricular dysfunction, there are increased left ventricular end-diastolic pressure, increased pulmonary artery wedge pressure, increased pulmonary artery pressure, and decreased cardiac output. Left ventricular systolic pressure is low, and in severe cases, pulsus alternans, in which systolic pressure repeatedly rises and falls after premature contractions, is observed. Cardiac output is normal or decreased, and systemic vascular resistance is increased. Left ventricular angiography (Figure 5-13-16) shows increased left ventricular end-diastolic volume, decreased left ventricular ejection fraction, diffuse decreased left ventricular wall motion, and occasionally impaired left ventricular motor coordination and mitral regurgitation. No significant stenosis is observed in the coronary arteries, and the left ventricular dilation gives an overall impression of being "stretched." A myocardial biopsy is recommended to rule out myocarditis and specific myocardial diseases. A bitom is used to perform a subendocardial biopsy of the right ventricular septum or left ventricle.
Biomarkers BNP or NT Pro-BNP are widely used as biomarkers reflecting the severity of heart failure, and are used to predict prognosis and evaluate the effectiveness of treatment. In addition, cases in which troponin T is positive are considered to indicate ongoing myocardial damage and are a predictor of poor prognosis.
Treatment The main focus of treatment is on heart failure due to decreased left ventricular systolic function. In other words, loop diuretics and other diuretics are used to reduce exertional dyspnea and edema due to congestion, and angiotensin-converting enzyme (ACE) inhibitors (angiotensin II receptor blockers if intolerance is not possible), beta-blockers, and anti-aldosterone drugs are used to improve life prognosis. Implantable cardioverter defibrillators (ICDs) are effective non-pharmacological therapies for preventing sudden death. Cardiac resynchronization therapy (CRT) is best suited for patients who have symptoms of NYHA class III or higher heart failure despite optimal medical treatment, a left ventricular ejection fraction of 35% or less, and a QRS width of 120 seconds or more.
Waon therapy, developed in Japan, has been shown to reduce the death or hospitalization rate in patients with heart failure, including dilated cardiomyopathy. Waon therapy is a treatment method developed by Tei Chuwa and others. It involves heating and keeping the whole body warm at 60°C for 15 minutes, followed by a further 30 minutes of rest to maintain the effect of the warmth, and at the end of the treatment, rehydration is provided in proportion to sweating. This treatment raises the core body temperature by approximately 1.0°C. Meta-analyses and other studies have shown that cardiac rehabilitation improves the exercise tolerance and quality of life of patients with heart failure, and also improves their prognosis. Treatment of the associated sleep-disordered breathing has also been reported to improve cardiac function and exercise tolerance. As for surgical treatment, in cases of severe mitral regurgitation, mitral valve repair or replacement may be performed. If all other treatments are ineffective, heart transplantation may be considered. [Hyakumura Shinichi and Wada Hiroshi]
■ References <br /> Tomoike, Hitoshi, et al.: Guidelines for the management of dilated cardiomyopathy and related secondary cardiomyopathies, Japanese Circulation Society. http://www.j-circ.or.jp/guideline/pdf/JCS2011_tomoike_h.pdf
Ministry of Health, Labor and Welfare Intractable Disease Overcoming Project Idiopathic Cardiomyopathy Research Group: Cardiomyopathy, Diagnosis Guide and Commentary (Kitahata Akira et al. eds.), Karinsha, Sapporo, 2005.
McKenna WJ, et al: Report of the 1995 World Health Organization/International Society and Federation of Cardiology task force on the definition and classification of cardiomyopathies. Circulation, 93: 841, 1996.

Table 5-13-1
Specific myocardial diseases (WHO/ISFC, 1995) ">

Table 5-13-1

Source : Internal Medicine, 10th Edition About Internal Medicine, 10th Edition Information

Japanese:

（2）拡張型心筋症（dilated cardiomyopathy）
概念・定義
　拡張型心筋症はWHO/ISFC分類では肥大型心筋症などと並ぶ心筋症の1つのタイプで左室内腔の拡張と収縮の低下を伴う．WHO/ISFC分類では原因または全身疾患との関連が明らかな心筋疾患は「特定心筋疾患」として除外される（表5-13-1）．
　拡張型心筋症の病態は左室収縮機能低下であり，その結果心不全症状を呈する．わが国においては心不全の原因疾患の約20％を占め，いわゆる「非虚血性」心不全の主要原因疾患の1つである．
病因
　拡張型心筋症は遺伝的素因，ウイルス感染などさまざまな病因によるものが含まれると考えられる．家族性の拡張型心筋症は，外国での報告は20～30％，わが国の厚生省の調査では5％であった．肥大型心筋症のように心筋収縮関連蛋白のさまざまな遺伝子異常との関連が示唆され，心筋アクチン遺伝子，デスミン遺伝子，ラミン遺伝子，δ-サルコグリカン遺伝子，心筋βミオシン重鎖遺伝子，心筋トロポニンΤ遺伝子，αトロポミオシン遺伝子の異常が報告されている．一方，ウイルス感染との関連も注目されており，本症の心筋からコクサッキーウイルス，アデノウイルスやC型肝炎ウイルスなどのウイルスゲノムが検出されている．
　予後については拡張型心筋症のみについてのデータは少なく，左室収縮機能低下に基づく心不全全体の予後については，わが国の信頼できる心不全登録研究のデータでは年間死亡率が7～8％であるが，非虚血性心筋症の予後はいわゆる虚血性心筋症よりも予後は良好である．死因は心不全自体の悪化による心不全死と突然死が大半を占めるが，血栓塞栓症も死因となる．
病理（図5-13-11）
　拡張型心筋症に特徴的な病理所見はない．基本的には心筋細胞の変性，脱落，線維化などがみられる．また個々の心筋細胞は肥大し，筋線維の大小不同もみられる．
症状
　拡張型心筋症に特異的な症状はなく心不全症状が主体となるが，不整脈に伴う症状もある．
　心不全症状としては労作時息切れ，浮腫，倦怠感，不眠等である．急激に悪化する場合には起坐呼吸，夜間呼吸困難などがみられる．心房細動や心室頻拍などの頻脈性不整脈を合併すれば動悸を自覚し，持続性心室頻拍であれば意識消失をきたすこともあり，突然死につながる．身体所見では重症例では聴診上Ⅲ音，Ⅳ音をしばしば聴取し奔馬調律（ギャロップ）となり，左室拡大に伴う二次性僧帽弁閉鎖不全に起因する汎収縮期雑音を聴取する．心尖拍動は鎖骨中線より左側かつ下方に偏移する．右心不全がある場合には頸静脈は怒張し，胸水や腹水を認める．肺うっ血が高度となり肺浮腫をきたせば下肺野を中心に湿性ラ音を聴取する．
検査所見
　胸部X線（図5-13-12）では心陰影の拡大がみられる．おもに左室が拡大するが，充満圧の上昇を反映して左房も拡大する．心筋障害はしばしば右心系にも及び，また左心不全でも肺静脈性肺高血圧をきたす結果，右心系も拡大する．高血圧性心疾患と異なり一般に大動脈弓（左第1弓）は拡大しない．肺うっ血に基づく肺血管影の増強があり，また急性心原性肺水腫の病態を呈する場合には肺門から末梢に広がるいわゆるbutterfly shadowを呈する．体液の貯留に伴い胸水がみられる．心電図（図5-13-13）ではST低下を伴う左室肥大，左房負荷（V₁のP波の後半の陰性部分），異常Q波，陰性T波，左脚ブロックなどがみられる．Holter心電図では心室性期外収縮，心室頻拍などがみられる．心房細動も2～3割に合併する．
　心エコー（図5-13-14）では左室の拡大と収縮低下，心室壁の菲薄化，左房の拡大がみられる．左室収縮の低下はびまん性のことが多いが，局所の収縮の時相のずれによる協調運動障害（dyssynchrony）をしばしば認める．ドプラの左室流入速度波形は左室充満圧の上昇に伴ってimpaired relaxation（弛緩障害）から pseudo-normalization（偽正常化），さらにはrestrictive pattern（拘束パターン）へと変化する．左室拡大に伴い僧帽弁のtethering（テザリング：左室の拡大に伴い，乳頭筋により僧帽弁尖がひっぱられ閉鎖が妨げられる現象）によるさまざまな程度の機能性僧帽弁閉鎖不全（図5-13-15）もみられる．
核医学検査，MRI所見
　タリウムやテクネシウムなどを用いた心筋血流シンチグラフィは虚血性心筋症との鑑別に有用である．MIBGシンチグラフィでは心筋からの洗い出し率（washout rate）の増加とH/M比（心臓/縦隔の比）の低下とがみられる．ガドリニウムを用いた造影MRI検査による遅延造影の評価は虚血性心筋症との鑑別に有用であり，また特定心筋疾患との鑑別にも役立つ．
心臓カテーテル所見
　右心カテーテルを含む心臓カテーテル検査は心機能の評価のため必要であり，また冠動脈造影は冠動脈疾患の除外のため有用である．
　左心機能不全を反映して左室拡張末期圧の上昇，肺動脈楔入圧の上昇，肺動脈圧の上昇，心拍出量の低下がみられる．左室収縮期圧は低めで，重症例では期外収縮の後などに収縮期圧が高低を繰り返す交互脈（pulsus alternans）がみられる．心拍出量は正常または低下し，体血管抵抗は上昇する．左室造影（図5-13-16）では左室拡張末期容積の増大，左室駆出率の低下，びまん性の左室壁運動低下，ときに左室運動協調障害，僧帽弁逆流などがみられる．冠動脈には有意狭窄を認めず，左室拡大に伴い全体に“引き伸ばされた”印象をうける．　心筋生検は心筋炎や特定心筋疾患の除外のため行われることが望ましい．バイトームを用いて右心側心室中隔あるいは左心室の心内膜下生検が行われる．
バイオマーカー
　心不全の重症度を反映するバイオマーカーとしてBNPあるいはNT Pro-BNPが汎用され，予後予測，治療効果の判定などに用いられる．そのほかにトロポニンTが陽性となる症例ではongoing myocardial damageがあると考えられ予後不良の予測因子となる
治療
　治療は左室収縮機能の低下に基づく心不全の治療が主体となる．つまりうっ血に基づく労作時呼吸困難や浮腫を軽減するためにはループ利尿薬をはじめとする利尿薬，生命予後の改善のためにはアンジオテンシン変換酵素（ACE）阻害薬（忍容性がない場合はアンジオテンシンⅡ受容体拮抗薬），β遮断薬，抗アルドステロン薬が用いられる．　非薬物療法としては突然死の予防のための植え込み型除細動器（ICD）が効果的である．心臓再同期療法（CRT）は内科治療の最適化を行ってもNYHAⅢ度以上の心不全症状があり，左室駆出率は35％以下，QRS幅が120 sec以上の症例が良い適応となる．
　わが国で開発された和温療法は拡張型心筋症を含む心不全患者の死亡または入院を減少させることがわかっている．和温療法とは，鄭忠和らによって開発された治療法で，全身を摂氏60 ℃で15分間加温・保温の後，さらに30分の安静保温で和温効果を持続させ，終了時に発汗に見合う水分補給を行うものである．この処置により，深部体温が約1.0 ℃上昇する．心臓リハビリテーションは心不全患者の運動耐容能，QOLを改善しさらには予後も改善することがメタ解析などで明らかになっている．合併する睡眠呼吸障害の治療も心機能，運動耐容能などを改善することが報告されている．　外科的治療法としては僧帽弁閉鎖不全が高度の場合，僧帽弁形成術もしくは僧帽弁置換術が行われることもある．あらゆる治療が奏効しない場合には心臓移植を考慮する．［百村伸一・和田　浩］
■文献
友池仁暢，他：拡張型心筋症ならびに関連する二次性心筋症の診療に関するガイドライン，日本循環器学会．http://www.j-circ.or.jp/guideline/pdf/JCS2011_tomoike_h.pdf
厚生労働省難治性疾患克服事業特発性心筋症調査研究班：心筋症，診断の手引きとその解説（北畠顕他編），かりん舎，札幌， 2005.
McKenna WJ, et al: Report of the 1995 World Health Organization/International Society and Federation of Cardiology task force on the definition and classification of cardiomyopathies. Circulation, 93: 841, 1996.

表5-13-1
特定心筋疾患（1995 年WHO/ISFC）">

表5-13-1

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