KSHF guideline for the management of CHRONIC HEART FAILURE 2016 만성심부전 진료지침 대한심장학회심부전연구회

Transcription

1 KSHF guideline for the management of CHRONIC HEART FAILURE 2016 만성심부전 진료지침 대한심장학회심부전연구회

2 KSHF guideline for the management of CHRONIC HEART FAILURE 2016 만성심부전 진료지침 대한심장학회심부전연구회

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4 서문 심부전의적절하고효과적인치료를위해서는의료진이각각의환자에게적정한최상의진료계획을수립하는것이가장중요하다. 만성심부전진료지침서는제정당시가용한모든증거를수집하고평가하여심부전의진단및치료에관한내용을정리하였다. 수집된증거들의철저한분석과고찰을기반으로제정된본지침서는의료진에게최적의심부전진료방향을제공할뿐아니라, 심부전진료의현황과적정성등을평가하여향후진료의질개선과진료전략개발도구의발굴에도움이될것이다. 본지침서는심부전교과서의내용을대신하는것이아니라보조하는것이며, 실제심부전환자진료의최종판단은의료진의권리이자책임이다. 한국형만성심부전진료지침서의제정은 2012년 3월구성된대한심장학회심부전연구회의제정위원회에서한국형심부전진료지침에대한제정이처음논의되었다. 진료지침제정에대한일반적인원칙들을검토후각국의진료지침을비롯한심부전관련문헌을고찰함과동시에우리나라심부전환자진료와관련된증거들을수집하고분석하여만성심부전에대한진료지침제정을진행하게되었다. 본진료지침은수용개작의형식을따랐으나, 가능한많은국내의데이터를포함시키고자하였다. 국내심부전환자들을대상으로한국내연구진들의연구논문을찾아검토하였고, 이를인용하였다. 본진료지침제정과관련하여주제선정, 근거검토및권고안결정에대한모든과정들을별도로기록하였다. 이는진료지침제정에대한투명성을확보하고, 추후진료지침제정을좀더용이하게하기위함이다. 본진료지침은진료를돕기위한지침으로사용되는것이지, 의료행위의옳고그름을판단하는잣대가될수없음을밝힌다. 개별환자의진료는담당의료진의개인적인견해및판단이우선하며본진료지침은이판단을뒷받침해주기위한것으로사용되어야하겠다. 수집된자료를분석하여지침의권고안을정하는일련의과정은근거에기반을둔방법으로제정위원회에서작성하였다. 권고종류 (COR, Class of Recommendation) 의평가와결정은치료효과의정도를양적으로분석하여수립하였는데, 이는현재인정되고있는치료혹은진단방법의유용성과유해성을평가하여그차이에대한이익의크기를기준으로하였다. 이러한치료효과에대한평가및결정에대한권고안의확실성을나타내는증거수준 (LOE, Level of Evidence) 은제정위원회에서그등급을분류하여 LOE A, B, C로순위를나누었다 ( 표 1, 2). 서문 iii

5 표 1. 권고종류 (COR, Class of Recommendation) 기준표 Class I Class IIa Class IIb Class III 이익 >>> 위험 이익 >> 위험 이익 위험 무익또는위험 시술혹은치료를해야한다. 필요목적에따른추가연구들시술혹은치료수행이타당하다. 필요목적이광범위한추가연구들 ( 레지스트리데이터 ) 시술혹은치료가도움이될것이다. 이롭지않거나해가될수있기때문에시술혹은치료를하면안된다, 해가된다. Level A 다수의환자군대상, 다수의무작위연구혹은메타분석데이터를근거 시술혹은치료가유용하거나효과적인경우 다수의무작위연구나메타분석에충분한증거가있는경우 시술혹은치료가유용하거나효과적임을시사하는경우 다수의무작위연구나메타분석에서일부상충하는증거가있는경우 권고사항의유용성과효과가덜확립된경우 다수의무작위연구나메타분석에크게상충하는증거가있는경우 시술혹은치료를위한사항이유용하거나효과적이지않고해가되는경우 다수의무작위연구나메타분석에충분한증거가있는경우 Level B 제한된환자군대상, 하나의무작위연구혹은비무작위연구데이터를근거 시술혹은치료가유용하거나효과적인경우 하나의무작위연구또는비무작위연구에증거가있는경우 시술혹은치료가유용하거나효과적임을시사하는경우 하나의무작위연구또는비무작위연구에일부상충하는증거가있는경우 권고사항의유용성과효과가덜확립된경우 하나의무작위연구또는비무작위연구들에크게상충하는증거가있는경우 시술혹은치료를위한사항이유용하거나효과적이지않고해가되는경우 하나의무작위연구또는비무작위연구들에증거가있는경우 Level C 매우제한된환자군대상, 전문가견해, 사례연구또는치료의기준 시술혹은치료가유용하거나효과적인경우 하나의무작위연구또는비무작위연구에증거가있는경우 시술혹은치료가유용하거나효과적임을시사하는경우 전문가견해, 사례연구또는치료의기준에대한견해가일치하지않는경우 권고사항의유용성과효과가덜확립된경우 전문가견해, 사례연구또는치료의기준에대한견해가일치하지않는경우 시술혹은치료를위한사항이유용하거나효과적이지않고해가되는경우 전문가견해, 사례연구또는치료의기준 iv 만성심부전진료지침

6 표 2. 권고종류 (COR, Class of Recommendation) 한글표현 I OO 해야한다. 권고한다. IIa OO 하는것은타당하다. 도움이될수있다. IIb OO 하는것을고려할수있다. III OO 하면안된다. 해가된다. 추천되지않는다. 제정위원회는만성심부전진료지침제정에영향을미칠수있는어떤외부의영향도받지않고, 이해상충을배제하려최선의노력을다하였다. 본진료지침의진료권고안들이실제임상에유용하게적용되기위해서는지침서의광범위한발의및확산유지가중요하다. 향후진료권고안의발전적개정은물론심부전치료의발전을위해서는설문이나등록사업등을통해진료지침이실제임상진료에서의유용성을알아보는사업이수반되어야할것이다. 만성심부전진료지침제정위원회위원장 서문 v

7 집필진 제정위원회 위원장 최동주서울대학교의과대학분당서울대학교병원순환기내과 위원 김민석울산대학교의과대학서울아산병원 ( 간사 ) 심장내과김응주고려대학교의과대학구로병원순환기내과박대균한림대학교의과대학강동성심병원순환기내과박성지성균관대학교의과대학삼성서울병원순환기내과박진주서울대학교의과대학분당서울대학교병원순환기내과서석민가톨릭대학교의과대학인천성모병원심장혈관내과신미승가천대학교의과대학가천대길병원심장내과유병수연세대학교원주의과대학원주세브란스기독병원심장내과윤종찬한림대학교의과대학동탄성심병원순환기내과 이상언서울대학교의과대학서울대학교병원순환기내과이주희충북대학교의과대학충북대학교병원심장내과임상현가톨릭대학교의과대학부천성모병원순환기내과조상호한림대학교의과대학성심병원순환기내과조재영전남대학교의과대학전남대학교병원순환기내과조현재서울대학교의과대학서울대학교병원순환기내과최진오성균관대학교의과대학삼성서울병원순환기내과한성우한림대학교의과대학동탄성심병원순환기내과황경국충북대학교의과대학충북대학교병원심장내과 vi 만성심부전진료지침

8 추진위원회 위원장 채성철경북대학교의과대학경북대학교병원순환기내과 위원 강석민연세대학교의과대학세브란스병원심장내과김재중울산대학교의과대학서울아산병원심장내과백상홍가톨릭대학교의과대학서울성모병원순환기내과 전은석성균관대학교의과대학삼성서울병원순환기내과조명찬충북대학교의과대학충북대학교병원심장내과최동주서울대학교의과대학분당서울대학교병원순환기내과 신동구영남대학교의과대학영남대학교병원 순환기내과 집필진 vii

9 집필진 강현재서울대학교의과대학서울대학교병원순환기내과김계훈전남대학교의과대학전남대학교병원순환기내과김미나고려대학교의과대학안암병원순환기내과김민석울산대학교의과대학서울아산병원심장내과김용진서울대학교의과대학서울대학교병원순환기내과김응주고려대학교의과대학구로병원순환기내과김준성서울대학교의과대학분당서울대학교병원흉부외과김형섭계명대학교의과대학동산의료원심장내과류동열강원대학교의과대학강원대학교병원심장내과박대균한림대학교의과대학강동성심병원순환기내과박성지성균관대학교의과대학삼성서울병원순환기내과박진주서울대학교의과대학분당서울대학교병원순환기내과 서석민가톨릭대학교의과대학인천성모병원심장혈관내과서혜선순천향대학교의과대학부천병원심장내과손일석경희대학교의과대학강동경희대학교병원심장혈관내과신미승가천대학교의과대학가천대길병원심장내과심지영연세대학교의과대학세브란스병원심장내과양동헌경북대학교의과대학경북대학교병원순환기내과오일영서울대학교의과대학분당서울대학교병원순환기내과유병수연세대학교원주의과대학원주세브란스기독병원심장내과유승기을지대학교의과대학을지병원심장내과윤종찬한림대학교의과대학동탄성심병원순환기내과이가연성균관대학교의과대학삼성서울병원순환기내과이상언서울대학교의과대학서울대학교병원순환기내과 viii 만성심부전진료지침

10 이주희충북대학교의과대학충북대학교병원심장내과이해영서울대학교의과대학서울대학교병원순환기내과임남규국립보건연구원심혈관희귀질환과임상현가톨릭대학교의과대학부천성모병원순환기내과정보영연세대학교의과대학세브란스병원심장내과정욱진가천대학교의과대학가천대길병원심장내과조경임고신대학교의과대학고신대학교복음병원심장내과조상호한림대학교의과대학성심병원순환기내과조은주가톨릭대학교의과대학성바오로병원순환기내과 조재영전남대학교의과대학전남대학교병원순환기내과조현재서울대학교의과대학서울대학교병원순환기내과차태준고신대학교의과대학고신대학교복음병원심장내과최성훈한림대학교의과대학강남성심병원순환기내과최의영연세대학교의과대학강남세브란스병원심장내과최정현부산대학교의과대학부산대학교병원순환기내과최진오성균관대학교의과대학삼성서울병원순환기내과한성우한림대학교의과대학동탄성심병원순환기내과황경국충북대학교의과대학충북대학교병원심장내과 집필진 ix

11 약어목록 약어 풀어쓰기 A-HeFT AIRE Aldo-DHF ANP ARNI ATLAS AV BAMI BMI BNP CANPAP CAPRICORN CARE-HF CBC CHARM CIBIS-II CNP COMPANION CONSENSUS COPERNICUS CORONA CRT CYP3A4 DOSE ECG EMPHASIS-HF EPHESUS ExTraMATCH African-American Heart Failure Trial Acute Infarction Ramipril Efficacy Aldosterone receptor blockade in diastolic heart failure Atrial natriuretic peptide Angiotensin receptor neprilysin inhibition Assessment of Treatment with Lisinopril and Survival Aortic valve The Effect of Intracoronary Reinfusion of Bone Marrow-derived Mononuclear Cells (BM-MNC) on All Cause Mortality in Acute Myocardial Infarction Body mass index B-type natriuretic peptide Continuous Positive Airway Pressure for Central Sleep Apnea and Heart Failure Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction Cardiac Resynchronization in Heart Failure Study Complete blood cell count Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity Cardiac Insufficiency Bisoprolol Study II C-type natriuretic peptide Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure Cooperative North Scandinavian Enalapril Survival Study Carvedilol Prospective Randomized Cumulative Survival Controlled Rosuvastatin Multinational Trial in Heart Failure Cardiac resynchronization therapy Cytochrome P450 3A4 Diuretic Optimization Strategies Evaluation Electrocardiogram Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Exercise training meta-analysis of trials in patients with chronic heart failure x 만성심부전진료지침

12 FAIR-HF GISSI HAS-BLED HEAAL HERA HF HFpEF HFrEF HYDZ ICD INR I-PRESERVE ISDN LV MADIT MADIT-CRT MERIT-HF MIRACLE NOAC NSAID NT-proBNP NYHA OPTIMAAL PARADIGM-HF PEP-CHF PPARγ RAAM-PEF RED-HF REMATCH ROC SAVE SCD-HeFT Ferinject R Assessment in Patients with IRon Deficiency and Chronic Heart Failure Gruppo Italiano per lo Studio della Sopravvivenza nell Insuffi cienza cardiaca Hypertension, Abnormal renal/liver function (1 point each), Stroke, Bleeding history or predisposition, Labile INR, Elderly (.65), Drugs/alcohol concomitantly (1 point each) Heart failure Endpoint evaluation of Angiotensin II Antagonist Losartan HERceptin Adjuvant trial Heart failure Heart failure with preserved ejection fraction Heart failure with reduced ejection fraction Hydralazine Implantable cardioverter defibrillator International Normalized Ratio Irbesartan in heart failure with preserved systolic function Isosorbide dinitrate Left ventricle Multicenter Automatic Defibrillator Implantation Trial Multicenter Automatic Defibrillator Implantation Trial Cardiac Resynchronization Therapy Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure Multicenter InSync Randomized Clinical Evaluation New oral anticoagulant Non-steroidal anti-inflammatory drug N-terminal pro B-type Natriuretic Peptide New York Heart Assoication Optimal Therapy in Myocardial infarction with the Angiotensin II Antagonist Losartan Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial Perindopril for Elderly People with Chronic Heart failure Peroxisome proliferator-activated receptor gamma Randomized Aldosterone Antagonism in Heart Failure with Preserved Ejection Fraction Reduction of Events with Darbepoetin Alfa in Heart Failure Trial Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure Receiver operating characteristic Survival and Ventricular Enlargement Sudden Cardiac Death in Heart Failure Trial 약어목록 xi

13 SENIORS SHIFT SIADH SOLVD STAMINA-HeFT STICH TAPSE TRACE TOPCAT Val-HeFT VALIANT V-HeFT Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure Systolic Heart failure treatment with the If inhibitor ivabradine Trial Syndrome of inappropriate antidiuretic hormone secretion Studies of Left Ventricular Dysfunction Study of Anemia in Heart Failure Trial Surgical Treatment for Ischemic Heart Failure Tricuspid annular plane systolic excursion TRAndolapril Cardiac Evaluation Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist CHA 2 DS 2 -VASc Cardiac failure, Hypertension, Age 75 (Doubled), Diabetes, Stroke (Doubled)-Vascular disease, Age and Sex category (Female) Valsartan Heart Failure Trial Valsartan In Acute myocardial infarction Veterans Administration Cooperative Vasodilator-Heart Failure Trial 5- 플루오로우라실 5-fluorouracil 5 형포스포디에스테라제길항제 Phosphodiesterase-5 Inhibitor 강심제글루카곤유사펩티드-1 나이트레이트네파조돈네프릴리신넬피나비어다베포에틴다비가트란도부타민도페틸라이드디곡신디펩티딜펩티다제-4 라미프릴레닌-앤지오텐신 -알도스테론계통차단제로자탄리바록사반리시노프릴 Inotropics Glucagon like Peptide-1 Nitrate Nefazodone Neprilysin Nelfinavir Darbepoetin Alfa Dabigatran Dobutamine Dofetilide Digoxin Dipeptidyl peptidase-4 Inhibitor Ramipril Renin-angiotensin-adosterone-system Blocker, RAAS Blocker Losartan Rivaroxaban Lisinopril xii 만성심부전진료지침

14 리토나비어마이토마이신-C 마크롤라이드계항생제지속형메토프롤롤메톨라존밀리논바소프레신길항제발사르탄베타차단제부메타니드비소프롤롤비스테로이드항염증제사이클로스포린사쿠비트릴선택적세로토닌재흡수억제제스타틴스피로놀락톤시스플라틴시클로포스파미드실데나필아미오다론아밀로라이드아스피린아픽사반안트라사이클린알로푸리놀암로디핀앤지오텐신수용체길항제앤지오텐신전환효소억제제에플레레논염류코르티코이드길항제와파린이바브라딘이트라코나졸 Ritonavir Mitomycin-C Macrolide Antibiotics Metoprolol succinate extended release (Metoprolol CR/XL) Metolazone Milrinone Vasopressin Antagonist Valsartan Beta Blocker Bumetanide Bisoprolol NSAIDs Cyclosporine Sacubitril Selective Serotonin Reuptake Inhibitors Statin Spironolactone Cisplatin Cyclophosphamide Sildenafil Amiodarone Amiloride Aspirin Apixaban Anthracycline Allopurinol Amlodipine Angiotension II Receptor Blocker Angiotensin Converting Enzyme Inhibitor, ACE Inhibitor Eplerenone Mineralocorticoid antagonist Warfarin Ivabradine Itraconzole 약어목록 xiii

15 인다파미드인터페론적혈구생성자극제중성엔도펩티다제카르베딜롤카테콜라민칸데사르탄칼슘통로차단제캅토프릴케토코나졸콜히친퀴나프릴퀴니딘클라리트로마이신클로르탈리돈탁소이드텔리트로마이신토르세미드톨밥탄트라스투주맙트란돌라프릴트리메토프림-설파메톡사졸트리암테렌티아졸리딘다이온티아지드페린도프릴펠로디핀포스포디에스테라제길항제푸로세미드하이드랄라진하이드로클로로티아지드 Indapamide Interferon Erythropoiesis-stimulating Agents Neutral Endopeptidase Carvedilol Catecholamine Candesartan Calcium Channel Blockers Captopril Ketoconazole Colchicine Quinapril Quinidine Clarithromycin Chlorthalidone Tazoids Telithromycin Torsemide Tolvaptan Trastuzumab Trandopril Trimethoprim-sulfamethoxazole Triamterene Thiazolidinedione Thiazide Perindopril Felodipine Phosphodiesterase Inhibitor Furosemide Hydralzine Hydrochlorothiazide xiv 만성심부전진료지침

16 목차 서문 iii 집필진 vi 약어목록 x 만성심부전진료지침소개 xix I 심부전의정의 1.1. 정의및용어 심부전의정의 심부전용어의변천 박출률감소심부전, 박출률보존심부전의정의 역학 4 목차 xv

17 II 진단 2.1. 증상과징후 심부전이의심되는환자의초기검사 진단의단계적접근 증상과징후에근거한접근 진단알고리즘 진단후확인사항 진단에유용한바이오마커 진단혹은감별진단을위한혈중 BNP 혹은 NT-proBNP 측정 중증도및예후를예측하기위한혈중 BNP 혹은 NT-proBNP 측정 영상학적진단 심초음파 좌심실수축기능의평가 좌심실이완기능의평가 심장컴퓨터단층촬영 / 자기공명영상 24 III 약물치료 3.1. 생존율개선을위한약물 레닌-앤지오텐신계차단제 ( 레닌-앤지오텐신-알도스테론계통차단제 ) 앤지오텐신전환효소억제제 앤지오텐신수용체길항제 앤지오텐신전환효소억제제와앤지오텐신수용체길항제복합투여 베타차단제 염류코르티코이드길항제 하이드랄라진과질산이소소르비드 41 xvi 만성심부전진료지침

18 3.2. 증상개선을위한약물 이뇨제 이뇨제사용의일반적원칙 이뇨제의선택 이뇨제의용량 이뇨제사용과관련된주의사항 이뇨효과가불충분한환자의치료 디곡신 주사용강심제 기타약물치료 항응고약물 스타틴 이바브라딘 바소프레신길항제 ARNI: LCZ 좌심실기능이보존된심부전환자의약물치료 57 IV 비약물치료 4.1. 전인적관리및다학제적접근 일반적관리 식사, 영양, 체중조절 흡연과음주 예방접종과심내막염의예방 타약제의사용 직업과활동범위 심장재활및운동치료 67 목차 xvii

19 4.4. 교육및상담 교육및치료순응도를높이기위한지지요법 동반질환의관리 심방세동 허혈성심장질환 고혈압 당뇨병 만성신질환 만성폐쇄성폐질환 빈혈 우울증 수면무호흡증 악성종양 임신 83 V 기구치료및수술요법 5.1. 심율동전환제세동기 심장재동기화치료 좌심실의기계적보조장치 수술적치료 심장이식 세포치료 97 참고문헌 99 xviii 만성심부전진료지침

20 소개 만성심부전진료지침의목적은만성심부전의진단적접근과치료에관한실제임상에적용할수있는실질적방향을제공하는데있다. 본지침서는한국최초의심부전진료지침으로향후심부전치료의진단과치료가발전함에따라본지침서는주기적으로개정될것이다. 진료지침의권고안들은실제임상은물론, 역학적, 설문조사, 관찰연구및임상연구들중연관성이확연한것들을기반으로제정되었다. 권고안들은명료함과간편성을갖추고, 실제임상에접목이용이하도록하였다. 만성심부전진료지침은심부전환자를진료하는의사는물론전문의료진이실제환자를치료하는것에대한방향제시뿐아니라, 교육이나의뢰에대한부분도제시하고있다. 본진료지침의범위는모든원인에의한박출률저하 / 보존만성심부전의정의, 진단, 치료를포함하고있다. 급성심부전에대해서는이후별도의진료지침에서정리할예정이다. 본진료지침을제정한제정위원회는심부전연구회회원 10명으로구성되었다. 위원들은진료지침의제정형식, 주제선정, 집필위원구성등에대하여결정하였다. 2014년 8월 15명으로제정위원회가확대되었다. 2013년 6월주제선정및집필위원구성이완료된이후 PICO 질문형식의진료지침제정이시작되었다. PICO 질문은각주제와관련된추상적인질문에서부터도출된 Patient, Intervention, Comparison, Outcome의형식을갖춘핵심질문으로, 주제별로어떤내용들이포함될것인가에대한추상적인내용들을좀더구체화하는작업이진행되었다. PICO 질문은실제진료지침에들어가지는않았지만, 내용을보다타당한것으로구성하고추후개정을용이하게하기위해별도로기록되었다. PICO에근거하여집필한집필위원들의주제별원고를제정위원회가수합하여근거중심의척도로정리하였다. 이후 10명의만성심부전진료지침제정고문들로부터검토를받고대한심장학회, 대한고혈압학회, 대한심혈관중재학회, 한국심초음파학회, 한국지질동맥경화학회의배서를받은뒤최종적으로제정을완료하게되었다. 만성심부전진료지침소개 xix

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22 KSHF guideline for the management of CHRONIC HEART FAILURE 2016 심부전의정의 I 1. 정의및용어 2. 역학

23 1 장 정의및용어 심부전의정의 심부전의일반적정의는심장의구조적혹은기능적이상으로말초기관에필요한만큼의산소를전달하지못하는상태를말한다. 심장의기능적혹은구조적이상으로심실의혈액충만혹은심실의혈액박출에이상이발생하여울혈혹은피로등으로발현하는임상증후군이다. 1 일반적으로는숨찬증세, 다리부종, 피로등의증상과폐음의수포음, 경정맥의경정맥압상승등의신체징후로발현되며한가지질환이아니라여러원인질환에의해발생하는임상증후군이다. 과거에는심부전환자의증상과징후를통해진단을하는프레밍햄기준을이용하기도하였으나현재는이를수치화하여진단하지는않고전형적인증상과징후를갖고심초음파에서좌심실의박출률, BNP (B-type natriuretic peptide) 등이진단에도입되면서진단기준에도변화가왔다. 심부전은심장의여러부위심외막, 심근, 심내막, 판막, 우심실, 좌심실다양한부위이외에대혈관 그리고리듬과전도장애등에서발생하나일반적으로는좌심실심근의기능이상이대표적인장애의원인이다. 원인질환의확인은진단뿐만아니라치료적인측면에서매우중요하다 심부전용어의변천 일정기간심부전의증상과징후를보일때 만성심부전 이라부른다. 적어도한달이상증상과징후가잘조절될때안정형이라는용어를사용한다. 만성안정형심부전이악화되는경우비대상성으로부르고, 갑자기발생하여입원등이발생할경우급성이라정의한다. 심근경색, 심근염등의이유로처음심부전증상이발생한경우새로진단된 (de novo) 심부전이라부른다. 일정기간증상이없거나호전된경우대상성심부전으로부른다. 울혈성심부전은특히미국권에서많이사용되는데, 소금이나수분저류의증거가있는급만성심부전을일컫는다. 2 만성심부전진료지침

24 박출률감소심부전, 박출률보존심부전의정의 좌심실박출률은수학적으로일회박출량을확 장기말용적으로나눈값이다. 수축기능즉, 수 축력이떨어지면일회박출량을늘리기위해 확장기말용적을늘려보상할수있다. 하지만 일회박출량이유지되더라도수축기능이떨어 질수록박출률은더욱감소하고심장의크기는 커지게된다. 과거에심부전은수축기능이저하된수축 기심부전 (systolic heart failure), 수축기능 은정상이고확장기능의장애가원인인확장 기심부전 (diastolic heart failure) 으로구분 하였다. 박출률은좌심실의수축기능을측정하 는지표로사용되어일반적으로좌심실박출률 이떨어진경우를수축기심부전으로분류하였 다. 하지만박출률이떨어진경우라도확장기 장애가동반되는경우가많고박출률만으로수 축기장애를모두표현할수없기때문에현재 는수축기 / 확장기심부전이라는용어대신에 박출률감소 / 보존심부전이라는용어를사용하 고있다. 물론임상적편의성과접근성때문에 이렇게구분하는측면도있지만이런분류방법 을따르는것은치료적측면도있다. 대개의전 향적무작위연구에서좌심실박출률이감소된심부전환자에서는약물에의한생존기간연장효과가잘입증된반면박출률이보존된심부전에서는생존기간을연장시킨약물이아직없기때문이다. 미국이나유럽심부전진료지침에서박출률감소심부전 (Heart failure with reduced Ejection fraction, HFrEF) 은좌심실박출률이 35-40% 이하로박출률보존심부전 (Heart Failure with preserved EF, HFpEF) 은 50% 이상으로정의하고그사이박출률인경우박출률감소심부전의아류로경계형 ( 박출률 41-49%) 과개선형 ( 박출률 > 40%) 심부전으로정의하고있다. 2, 3 경계형은보통예후가박출률보존형과비슷하지만, 개선형은조금다를것으로예상하고있다. 4 좌심실박출률은심초음파로가장쉽게측정하지만, 심초음파로측정한좌심실박출률이정상이더라도심장자기공명영상등과같은다른검사기법으로측정시좌심실박출률이떨어져있음을확인할수있으므로해석에주의를요한다. 개선형심부전은박출률감소 / 보존심부전보다예후가좋은것으로보고되었으나바이오마커이상소견이동반되어여전히심부전위험이높은것으로알려져있다. I 심부전의정의1 장정의및용어 3

25 2 장 역학 심부전의유병률은전세계적으로빠르게증가하고있으며, 중대한동반질환및사망과도밀접한연관이있다. 5 특히 65세이상의노인인구에서입원과사망의주요원인중하나이다. 6 미국의경우, 2007년부터 2010년까지국민건강영양조사의결과에의하면 20세이상의인구에서 510만명이상이심부전을갖고있는것으로추정하고있으며, 년에는약 46% 가증가하여 18세이상에서약 800만명을넘어설것으로예상되고있다. 8 아시아권의경우, 중국에서는 2010년의연구결과약 400만명이심부전을갖고있고, 남자보다는여자에서유병률이더높은것으로보고되었다. 9 일본의경우에도 2005년도에심부전환자의유병률이약 100만명으로추정되었고 2035년에는 30% 정도가증가하여 130만명에달할것으로추정하고있다. 10 반면우리나라에서는심부전의유병률이나동반질환및원인질환에대한통계자료가거의없어대부분외국의연구결과에의존하고있다. 최근에공개된건강보험공단의표본코호트데이터베이스를이용한심부전유병률의분 석결과, 2013년도에유병률이 1.5% 로나타나통계청의 2013년도추계인구로환산시, 약 75 만명정도가심부전을갖고있는것으로추정된다. 또한 2002년과 2013년의심부전유병률을살펴보면각각남자는 0.54% 에서 1.24% 로, 여자 0.96% 에서 1.72% 로점차증가하는추세를보이고있다. 심부전의유병률은나이에따라서급격히증가하는경향을보이는데 60세미만에서 1.0% 정도인유병률이 60세이상에서 5.5%, 80세이상에서 12.6% 이상으로급격하게증가한다. 특히 80세이상연령에서의유병률이전체유병률의약 8배이상높아나이가심부전의가장중요한위험요인임을알수있다. 또한심부전위험률의성별에따른차이는낮은연령군에서는남녀간에차이가없거나남자가높은유병률을보이는반면에고연령군에서는여자에서높은유병률을보이고있다. 프레밍햄연구의결과에따르면 65세이상의고령인구에서심부전발생이 1,000명당 10 명에달하고심부전환자의 75% 가이미고혈압을가지고있는것으로보고되었다 만성심부전진료지침

26 년도의건강보험공단자료를이용한우리나라심부전동반질환을분석한결과허혈성심장질환과고혈압이각각 45.4% 와 43.6% 로가장높았고심장판막증이 5.6%, 심근증이 3.1% 로그뒤를이었다. 만성심부전의원인질환과관련하여 2005년도에보고된바가있다. 1998년도부터 2003년까지국내 9개대학병원에서조사한결과, 허혈성심장질환이원인질환인환자가 32.3% 로가장많았고심근증이 22.7%, 고혈압성심장질환이 16.5%, 심장판막증이 13.5% 순이었다. 선천성심장질환, 심내막염, 심근염등의기타원인과원인질환이불 분명한경우가 15.0% 를차지하였다 년부터 2009년까지입원한심부전환자를대상으로조사한바에의하면허혈성심장질환이 52.3%, 고혈압성심장질환이 36.7%, 심근증 26.5%, 심장판막증이 12.7% 를차지하였다. 13 우리나라에서도최근에진행되고있는식습관의서구화, 신체활동시간의부족등으로인한심혈관질환위험요인의증가와급속도로진행되는고령인구의증가로인하여심부전의유병률은앞으로크게증가할것으로예상되며, 심부전에대한국가통계자료생산을위한대규모의조사사업이필요하다. I 심부전의정의2 장역학 5

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28 KSHF guideline for the management of CHRONIC HEART FAILURE 2016 진단 II 1. 증상과징후 2. 심부전이의심되는환자의초기검사 3. 진단의단계적접근 4. 진단에유용한바이오마커 5. 영상학적진단

29 1 장 증상과징후 1. 심부전이의심되는환자의진단을위하여병력청취와신체검진을시행해야한다. (Class I, Level of Evidence C) 2. 심부전발생의위험인자를가진환자에서심부전의유무를확인하기위한기본적인병력청취와신체검진을시행해야한다. (Class I, Level of Evidence C) 3. 심부전의중증도및예후의확인을위하여기좌호흡의유무등을포함한병력의청취와연속적인활력징후, 몸무게및경정맥압, 제3심음, 부종, 신체검진을시행해야한다. (Class I, Level of Evidence B) 환자의증상과징후에대한주의깊은병력의청취와신체검진은심부전환자의평가에가장기본적이며중요한단계이다. 심부전환자는많은증상 ( 표 2.1) 을호소할수있는데, 그중호흡곤란은심부전의가장흔한증상으로활동시에심해지나, 심폐질환이외에도기도, 호흡근육, 흉벽의이상에서도나타나며, 정상인에서도운동시호흡곤란을호소할수있어심부전에비특이적이다. 14 심부전의대상부전이점차심해지면앉아있는자세가누운자세보다더편한좌위호흡을호소하며, 발작성야간호 흡곤란이발생한다. 좌위호흡과발작성야간호흡곤란증의경우심부전의조금더특이적인증상이나빈도가적어경한증상을보이는환자에있어민감하지못하다 또한심박출량의감소는심한피로감을야기하며부정맥이있는환자는심계항진을호소한다. 우심실기능장애가동반되면식욕부진, 소화불량및복부팽만감을호소한다. 또한착란, 어지러움, 우울증등의신경계증상이나타날수있으나일반적으로심부전에비특이적으로다른질환과의감별에도움이되지못한다. 8 만성심부전진료지침

30 표 2.1. 심부전의증상과징후 증상 징후 전형적비전형적특이적비특이적 호흡곤란 좌위호흡 발작성야간호흡곤란 운동능력 피로감, 운동후회복지연 발목부종 호흡곤란과같은심부전의증상은발현에 필요한활동의정도에따라중증도를나누게 되는데 ( 표 2.2), 심부전의질병경과나치료에 대한반응을추적하는데도움이되나심장기 21, 22 능의이상정도와비례하지는않는다. 심부전환자의병력청취에있어과거병력 또한중요한데, 심부전은과거병력이없는사 람에서는드물며, 특정질환특히과거심근경 색이있었던경우심부전의가능성은크게증 14-18, 23 가한다 ( 표 2.3). 야간기침 천명 체중증가 (> 2 kg/ 주 ) 체중감소 포만감 식욕저하 착란 우울 두근거림 실신 객관적으로심부전의유무를판단하고임 경정맥압상승 간경정맥확장 제 3 심음 심첨박동전위 심잡음 표 2.2. NYHA (New York Heart Assoication) 기능등급 I II III IV 신체활동에제한이없음. 일상활동에서증상이없음 말초부종 폐비빔소리 (Pulmonary crepitations) 폐기저부타진시둔탁음 빈맥 불규칙한맥박, 빈호흡 (> 16 회 / 분 ) 빈호흡 (> 16 회 / 분 ) 간비대 복수 카켁시아 신체활동에약간의제한이있음. 안정시에는증상이없으나, 일상활동에는증상이있음 신체활동에심한제한이있음. 안정시에는증상이없으나, 일상활동보다낮은활동시에도증상이있음 안정시에도증상이있으며, 신체활동으로증상이심해짐 상경과를알기위하여자세한신체검진이시행 되어야한다. 심부전징후는다양한데 ( 표 2.1), 이는저하된심박출량에적응하고심박출량을 정상화시키려는여러병태생리학적기전에의 해발생하며, 대부분은체액의저류로인한것 으로비특이적이다. 부종의경우흔히발견되 나다른질환에의해서도발생할수있으며, 이 뇨제와같은약제의사용에의해많이영향을 받는다. 경정맥압의상승, 제 3 심음, 심첨부박 동의전위는심부전에높은예측도를보이나 자주나타나지않으며, 14, 15, 17, 19, 20, 특히비 1 장증상과징후 9 진단II

31 표 2.3. 심부전의임상양상의평가를요하는적응증과거병력또는상태고혈압당뇨병비만관상동맥질환 ( 특히, 심근경색 ) 말초동맥질환또는뇌혈관질환판막질환직계존속의심근병가족력심장독소에대한폭로의과거력수면무호흡증검사소견지속적인부정맥심전도이상소견 ( 좌심실비대, 좌각차단, Q파 ) 흉부방사선상심장비대 만, 만성폐쇄성폐질환, 고령에서는증상및 23, 29, 30 징후의발견이더욱어렵다. 이러한 임 상적인징후는각각발견될때는낮은예측도 를보이는것으로나타났다. 15, 20, 31 즉, 여러개 의징후와증상이나타날때진단은좀더확실 하게이루어질수있다. 그러나다른질환에서 도심부전과유사한증상과징후는나타날수 있으므로 ( 표 2.4), 심부전을진단하기에는추 가적인검사가필요하다. 일단심부전진단이된경우, 심부전의원 인의확인과질병의경과와치료에대한반응 을확인하는데있어증상과징후는중요하다. 호흡곤란의경우뉴욕심장학회의분류에따라 증상의변화를평가하며좌위호흡의유무등 표 2.4. 심부전증상과징후의감별진단심근허혈폐질환 ( 폐렴, 천식, 만성폐쇄성폐질환, 폐색전, 원발성폐동맥고혈압 ) 수면무호흡증비만상태악화영양실조빈혈간부전만성신질환저알부민혈증정맥울혈우울증불안과과호흡증후군갑상선기능항진증또는저하증 을확인한다. 환자의신체검진상소견으로몸 무게의측정, 활력징후의측정, 경정맥압의측 정, 폐야의수포음, 부종의유무를관찰하여체 액의저류정도를판단하며, 제 3 심음과심잡음 의변화를관찰한다. 특히진행된수축기능부 전을동반한환자에서경정맥압의상승은좌심 실충만압의상승을잘반영하는것으로알려 19, 24, 25 져있다. 또한이러한증상과징후는질환의중증도 와환자의예후에대한정보를제공하는데, 당 뇨, 빈혈, 신기능부전과같은질환이동반될경 우, 좌위호흡과제 3 심음의존재및경정맥압의 상승이있을경우예후가좋지못한것으로알 24, 려져있다. 10 만성심부전진료지침

32 2 장 심부전이의심되는환자의초기검사 1. 심전도 (Class I, Level of Evidence B) 2. 심초음파 (Class I, Level of Evidence A) 3. 일반혈액검사 (CBC, 전체혈구계산 ), 혈청전해질및신장기능, 간기능검사를포함하는일반화학검사, 갑상선기능검사, 요검사 (Class I, Level of Evidence C) 4. 흉부방사선촬영 (Chest X-ray) (Class IIa, Level of Evidence C) 5. 혈중 BNP 또는 NT-proBNP 측정 (Class I, Level of Evidence A) 심전도서안정시심전도가정상으로나오는경우는심전도는심부전이의심되는환자의초기검사드물어배제진단으로의가치도있다. 하지만로써꼭시행하여야한다. 진단에도움이될뿐안정적인상태의만성심부전환자에서심전도아니라심부전의원인질환을가늠할수있으가정상으로나오는경우가 10-15% 가량되므며, 치료계획수립에도도움이된다 ( 예 : Q 파로음성예측도는높지않다 가있는경우허혈성심장질환에의한심부전일가능성, 동성빈맥이있는경우치료방침으심초음파로맥박수조절, 과도한동성서맥이있는경우심초음파는좌심실의수축기능과이완기능뿐약제용량조절, QRS 간격이큰좌각차단이있아니라, 심실벽의두께, 판막의모양과기능는경우치료방침으로심장재동기화치료고려등여러가지중요정보를제공하며, 향후추가등 ). 급성증상과징후를가지는심부전환자에적인검사와치료방향에결정적인역할을하 2 장심부전이의심되는환자의초기검사 11 진단II

33 게된다. 예를들어대동맥판협착증이심부전 의원인인경우수술을통해적절한치료를할 수있고, 확장성심근병이의심되는소견이있 으면적극적으로베타차단제와레닌 - 앤지오텐 신 - 알도스테론계통차단제를고려하게된다. 국소벽운동장애가있을경우관상동맥질환에 대한추가적인검사가필요하고, 좌심실수축 기능은정상이나심실벽의두께가증가되어있 으면서이완기능장애가심한경우침윤성심근 38, 39 병을의심하여심근조직검사를고려한다. 일반혈액검사 (CBC, 전체혈구계산 ), 혈청전해질및신장기능, 간기능검사를 포함하는일반화학검사 심전도와더불어심부전이의심되는환자의초 기검사로써꼭시행하여야한다. 심부전의원 인에대한진단적가치뿐아니라, 치료방침수 립에도중요하며, 예후예측에도도움이된다 ( 예 : 혈중크레아티닌과칼륨상승시레닌 - 앤 지오텐신 - 알도스테론계통차단제사용에주 의필요, 저나트륨혈증이있는경우예후불 량등 ). 또한심부전의증상과징후를발현하게 할수있는빈혈과갑상선기능항진 / 저하여부 에대한검사가심부전진단초기에는필요하 다 흉부방사선촬영 (Chest X-ray) 일반적인흉부방사선촬영이심부전의진단적 가치를가지는것은아니지만, 폐부종의여부, 동반된폐질환의유무, 심장비대여부에대한 확인을위해초기검사로는시행되어야한다. 45 BNP 또는 NT-proBNP 측정심부전이의심되는환자에서혈중 BNP 또는 NT-proBNP 측정은여러가지중요한의미를가지고있으며많은임상자료와근거가축적되어있어강력히권고되고있다. 심부전이의심되어경흉부심초음파를시행하였으나별다른이상을발견하지못한경우또는심초음파를당장시행할수없는경우혈중 BNP 또는 NT-proBNP 검사를시행하여심부전여부를판단할수있다. 또한심부전의 배제진단 이가능하다는장점이있다. 즉혈중 BNP 또는 NT-proBNP 수치가정상일경우환자가호소하는증상과신체검진에서관찰된징후는심부전에의한것이아닐가능성이높아다른원인을찾아보아야한다. 실제현장에서사용하는검사에서배제하기위한기준점 (cut-off 수치 ) 은심부전이강력하게의심되는비교적특이적증상과징후를보이는급성기환자와다소모호한증상과징후를보이며, 만성적으로천천히진행하는증상을호소하는환자에서는다르게적용되어야한다. 즉심부전이의심되는증상과징후를보이는경우에는가음성을줄이기위하여배제하기위한기준점중낮은수치를사용하는것이추천되고, 반대의경우에는배제하기위한기준점중높은수치를사용하는것을고려한다 (* 주의 : BNP와 NT-proBNP는측정시약과방법에따라배제하기위한기준점이다를수있음 ). BNP 또는 NT-proBNP는일반적으로좌심실의부하에의해분비가항진되므로좌심 12 만성심부전진료지침

34 실이완기말압력을잘반영한다. 하지만우심실과심방의부하증가가있을때도증가하므로해석에주의가필요할수있다 ( 예 : 심방세동, 폐동맥색전증 ). 또한 NT-proBNP의경우 나이에따라보정이필요하다는점과심부전이아니지만상승하는예외적인경우에대해서는추후자세히다룬다 ( 참고 : 2.4. 진단에유용한바이오마커 ) 장심부전이의심되는환자의초기검사 13 진단II

35 3 장 진단의단계적접근 심부전은단일질환이아니고복합적임상증후 군으로, 여러가지원인의심장질환이진행함 에따라최종적으로심장의수축기능또는이 완기능이저하되어말초장기의산소요구량에 맞는혈액량을절대적으로또는상대적으로공 급할수없는상태와함께체액저류에의한폐 부종과전신울혈을초래하여일상생활에장애 를일으키는상태를말한다 이와같이다 소추상적인정의로인해실제환자가심부전 상태인지아닌지에대한진단은임상의에게항 19, 59 상어려운일이다 증상과징후에근거한접근 대체로심부전에특이적인증상은호흡곤란이 좌위호흡형태인경우, 발작성야간호흡곤란 이있는경우, 발목부종등이있으며징후로는 경정맥압상승, 간경정맥역류, 제 3 심음, 심첨 부의좌하향편위등이있다. 하지만, 심부전을 시사하는증상과징후는비특이적인경우가많 고심부전초기에는없는경우도많아민감도 와특이도가모두높지않다. 특히비만한환 자, 고령의환자, 만성폐질환이동반된환자 에서는증상과징후가무엇때문인지를정확히 19, 감별하기매우어렵다. 하지만병력청취를통한증상과신체검진 을통한징후의파악은심부전의진단뿐아니라 심부전의원인질환을가늠할수있는중요한부 분이다. 또한심부전으로진단후치료하는과 정에서환자가호소하는증상과징후의개선이 더딜경우추가치료를적극적으로고려해보아 야하며, 증상과징후가악화될경우입원등의 적극적인치료방법을고려해야한다. 17 심부전의진단적어려움을극복하고자심 전도와더불어심장의구조적그리고기능적 이상이있는지를살펴보는심초음파와심실의 부하에의해분비가항진되는혈중 BNP 또는 NT-proBNP 농도측정이실제심부전여부에 대한판단에있어도움이된다. 즉객관적 ( 또는 원인이될수있는 ) 지표의측정과심장의기질 적혹은기능적이상유무를신속히밝히는심 초음파가중요하다 만성심부전진료지침

36 진단알고리즘 경흉부심초음파를먼저시행할것인지혈중 BNP 또는 NT-proBNP 검사를먼저시행할것인지를선택하는것이중요하다. 응급실또는예정되지않은외래로내원한급성증상이있는환자와예정된외래로방문한다소모호한심부전증상을호소하는환자는진단적접근방법이다를수있다 심부전이의심되는비교적특이적증상과징후를보이는급성기환자는경흉부심초음파를빨리시행하여심장에어떠한기질적이상이있는지를알아본후이상의정도를조기에확인하여적절한치료를시작하는것이추천된다. 또한환자의병력상심부전이있을가능성이높은경우 ( 예 : 조절되지않은고혈압과심근경색증의병력등이있는경우등 ) 조기에경흉부심초음파를시행하는것이추천된다. 심초 비교적특이적증상과징후를보이는환자, 증상과징후의진행이급성인환자, 과거병력상기저심장질환을가지고있는환자 ECG: 정상그리고 BNP < 100 NT-proBNP < 300 pg/ml 심부전가능성이떨어져 심초음파검사를생략하고, 환자의증상과징후를일으킬 만한다른원인에대한검사 ECG Chest X-ray 심부전의심증상과신체검진소견 심초음파검사가즉시 이루어질수없는경우 ECG/Chest X-ray: 비정상또는 BNP 100 NT-proBNP 300 pg/ml 경흉부심초음파 그림 2.1. 심부전진단의알고리즘 모호한증상과징후를보이며, 만성적으로천천히진행하는 증상을호소하는환자 ECG 가능하면 Chest X-ray 일반혈액검사 (CBC, 전체혈구계산 ) 혈청전해질및신장기능검사, 간기능검사일반화학검사, 갑상선기능검사, 요검사 심부전의원인질환과악화인자에대한탐색 적절한치료시작 ECG/Chest X-ray: 비정상 또는 BNP 35 NT-proBNP 125 pg/ml * 주의 : BNP 와 NT-proBNP 는측정시약과방법에따라 cut-off value 가다를수있음 ECG: 정상그리고 BNP < 35 NT-proBNP < 125 pg/ml 심부전가능성이떨어져 심초음파검사를생략하고, 환자의증상과징후를일으킬만한 다른원인에대한검사 3 장진단의단계적접근 15 진단II

37 음파를빠른시간내에시행할수없을경우에는심전도와흉부방사선촬영후혈중 BNP ( 또는 NT-proBNP) 검사를먼저시행하는것을차선책으로고려할수있으며, 이러한경우가음성을줄이기위하여배제하기위한기준점중낮은수치를사용하는것이추천된다 (BNP <100, NT-proBNP<300 pg/ml일경우심부전이아닐가능성이높아짐 ). 심전도와흉부방사선촬영에서이상소견이없고, 혈중 BNP 또는 NT-proBNP 수치가낮다면심부전의가능성이매우떨어져심초음파를생략하고, 환자의증상과징후를일으킬만한다른원인에대한검사를고려한다. 반대로 BNP 100 또는 NT-proBNP 300 pg/ml일경우에는심부전을배제할수없어심초음파를반드시시행해야한다. 다소모호한증상과징후를보이며, 만성적으로천천히진행하는증상을호소하는환자에서는심부전이아닐가능성을먼저알아보기위하여심전도와흉부방사선촬영을한후혈중 BNP ( 또는 NT-proBNP) 검사를먼저시행한후심초음파시행여부를결정하는것이추천된 다. 심전도가정상이고혈중 BNP ( 또는 NTproBNP) 수치가충분히낮을경우 ( 가양성을줄이기위하여배제하기위한기준점중높은수치를사용함 : BNP<35, NT-proBNP<125 pg/ml) 심부전이아닐가능성이높아심초음파가필요하지않으며, 반대로심전도와흉부방사선촬영이비정상적이거나혈중 BNP ( 또는 NT-proBNP) 수치가높을경우에는심부전의가능성을배제할수없어심초음파를고려해야한다 진단후확인사항 심부전으로진단된경우심부전의원인질환이무엇인지그리고악화인자가무엇인지를밝혀내는것이향후치료에매우중요한다음단계라하겠다. 예를들어관상동맥질환이심부전의원인으로의심되는경우관상동맥조영술또는운동부하검사를고려하고, 재관류치료의대상이되는지평가를진행한다 ( 참고 : 허혈성심장질환 ). 16 만성심부전진료지침

38 4 장 진단에유용한바이오마커 심부전을진단하는임상기준의적용은예민도와특이도가높지않으며많은감별진단을요한다. 심초음파는심부전을진단하는명확한기준 (gold standard) 이되는가장유용한검사이고진단및치료의지침이되는유용한검사이나, 검사의활용이제한되고가격이비싸며호흡곤란을주소로하는만성폐질환이나비만을동반한일부환자에서는효과적이지않을수있다. 그러므로올바른심부전의진단을위해심부전의유무및정도를명확히판단하고이를쉽게진단하며예후를예측할수있는생화학적지표는임상적으로유용하다. 나트륨이뇨펩티드에는 ANP, BNP, CNP가있으며 ANP는주로심방에서 BNP는주로심실에서합성되는심장호르몬이며, 혈중순환하고있다. BNP의분비는심실용적증가및압력과부하등혈역학적자극에반응하여 probnp 가생물적작용이있는 C-terminal (BNP) 과생물학적작용이없는 N-terminal ( 이하 NT-proBNP) 로분절되어순환계에유입된 다. BNP 와 NT-proBNP 는 probnp 에서동시 에분리되는물질로현재이두가지를측정하 는다양한검사방법이여러회사에서개발되 었다. 또한생물학적특징및화학적특징이달 라각각의장단점이있어검사시행시이를고 려해야하나두가지모두진단, 예후인자로 유용하고차이가없어어느것한가지를사용 해도된다. 하지만상호간의기준값혹은범 위가틀려해석시교차혹은치환될수없으 며각기기준을확인해서해석하는것이필요 하다. 일부환자에서는환자의임상적상황과 배치되는검사결과가나오는경우가있다. 또 한 BNP 값이나이나성별, 동반된질환이나약 물에따라서그수치가변할수있다는사실을 항상기억해야하며따라서단독검사로진단을 하는오류를조심해야한다 ( 표 2.5). 결국 BNP 검사는단독 (stand-alone) 진단도구가아닌 심부전의보조진단법으로환자의임상적상황 47, 60, 61 을고려하여판단하는것이중요하다. 4 장진단에유용한바이오마커 17 진단II

39 표 2.5. 심부전진단에서부정확한 BNP 혹은 NT-proBNP 결과를보이는경우높은 BNP 수치를보이지만심부전이없는경우 1. 고령 2. 빈혈 3. 신부전 4. 급성관동맥증후군 5. 일부호흡기질환 ( 수면무호흡증, 심한폐렴, 폐고혈압 ) 6. 세균성패혈증 7. 심한화상심부전환자에서낮은 BNP 수치를보이는경우 1. 비만 (BMI > 30 kg/m 2 ) 2. 급격히진행된폐부종 (1-2시간이내 ) 3. 좌심실상방의원인으로인한심부전 ( 급성승모판폐쇄부전, 승모판협착증 ) 4. 안정되고증상이없는심부전 으로할때정확도가 90% 정도이고특히음성예측도가약 90% 정도로높다. 국내환자를대상으로검사의예민도및특이도를산출하였고 BNP 검사의정확도는 ROC 곡선에서 108 pg/ ml에서 98.0% 로가장높았고, 이때예민도, 특이도가각각 92.5%, 88.9% 로외국과동일한검사법으로시행한검사에서비슷한결과를보였다 급성호흡시감별진단뿐아니라만성환자에도유용하며 Cowie 등이심부전클리닉을방문한심부전환자를대상으로한연구에의하면 BNP 76.4 pg/ml 이상인군에서 97% 의민감도와 84% 의특이도를가졌으며흥미로운사실은 BNP가흉부방사선촬영보다도더정확하게심부전을진단했다. 하지만최 근 Tang 등은외래에내원한만성안정형심부 전환자에서 BNP 는약 21% 정도에서정상수 진단혹은감별진단을위한혈중 BNP 혹은 NT-proBNP 측정 BNP 와 NT-proBNP 는최근심부전진단에필 수검사로이용되고있으며이미많은연구에 서급성호흡곤란의감별진단, 심부전의진단 치를보여외래환자의경우비교적안정적인 심부전환자의경우에는그수치판단에주의 를요한다. 또한일반인을대상으로좌심실비 대나심장기능의이상을선별하는생체표지자 로 BNP 측정이유용하나비용효과측면에서 50, 고려해야한다. 및예후판정등에필수적인임상검사로증명 되었다. 응급실혹은진료실에서호흡곤란을 주소로내원한환자의진단은정확해야하며또한빠른시간내에이루어지는것이중요하다. 특히검사의유용성중에음성예측도가중요하며이는급성호흡곤란의배제진단수단으로써의중요한의의가있으며응급실에서심부전환자의감별진단에많은도움이될수있다. 일반적으로 BNP값 100 pg/ml 혹은 NTproBNP 162 pmol/l을배제하기위한기준점 중증도및예후를예측하기위한혈중 BNP 혹은 NT-proBNP 측정 BNP 농도는심부전여부뿐만아니라환자의 심부전의중증도와도밀접한관계가있어실 제 NYHA 기능등급분류정도가심할수록수 치가증가되며이는환자상태를예측하고치 18 만성심부전진료지침

40 료하는데큰도움이될수있다. 이러한관점에서 BNP는심부전뿐만아니라심근경색후에유병률과사망률을예측할수있는독립인자로도입증이되었다. 중증만성심부전환자를대상으로앤지오텐신수용체길항제유용성을검토한 Val-HeFT 연구의분석에서 BNP가높은환자군에서심장사고의발생이통계적으로높은것으로나타났고 BNP값이 10 pg/ml 상승할때마다사망률이 1.2% 상승하는것으로보고하였다. 그러므로심부전환자의중증도및예후를예측하기위한 BNP 농도 (NTproBNP도포함 ) 측정은임상적으로유용하다. 66, 또한심부전의경과및증상을완화시키는여러약제의개발이이루어지면서약물 치료에대한반응을관찰하여임상적호전의지표로 BNP 측정을한다. Bayes-Genis 등의 NT-proBNP 연구에서지속적인비대상성심부전상태로유지되는환자는 21% 감소가되었고 57% 정도의환자가안정형심부전으로완전회복되었음을보고하였다. 이와같은임상호전여부를반영하는 BNP를이용하여진료지침에근거한약물치료의향상을통해예후를개선시키고자하는다기관전향적임상연구가다수진행되었으나그결과는일정하지않다. 또한추적검사에서실제로치료방침을결정하고약물의용량을판단하는기준에대해서진아직모호하여추후연구가필요하다 장진단에유용한바이오마커 19 단II

41 5 장 영상학적진단 심초음파 1. 심부전의초기평가시심초음파를시행해야한다. (Class I, Level of Evidence B) 2. 심부전환자에서사망률, 이환율, 심부전에의한입원율을낮추기위해심초음파추적관찰은 도움이될수있다. (Class IIa, Level of Evidence B) 호흡곤란환자에서심부전이의심되는경우, 심부전진단을위해가장유용한영상검사법은심초음파다. 91 심초음파를통하여심장의용적, 질량등해부학적구조에대한평가와심실의구조와벽운동, 판막의기능, 혈역학적정보등기능에대한평가를할수있다. 또한심초음파는무증상심부전을진단하고후발사건의위험도를예측할수있으며, 심부전이의심되는환자에서정확한진단과적절한치료방향결정에중요한역할을한다. 97 좌심실수축기능이저하된경우, 좌심실구조가이상한경우나다른구조적이상이동반된경우는정밀한심초음파가필요하며좌심실박출률, 좌심실크기, 벽두께, 좌심실용적등 이정량적으로평가되어야한다. 좌심실박출률은심부전에서의료의질에대한임상성과측정지표로사용된다. 98 좌심실뿐아니라우심실크기와기능, 우심방크기도측정해야하며, 모든판막의형태적이상과기능적이상여부를평가하고심부전의이차변화로고려될수있는승모판기능부전과삼첨판기능부전의중증도를정확히평가해야한다. 이때비침습적인혈역학적데이터가중요한정보를제공한다. 승모판유입패턴, 폐정맥유입패턴, 승모판륜속도는좌심실충만압과좌심방압력에관한부가적인정보를제공한다. 삼첨판역류압력과하대정맥직경과호흡에따른하대정맥직경의변화를종합하여수축기폐동맥압력과 20 만성심부전진료지침

42 표 2.6. 심부전환자에서흔한심초음파이상소견 99 측정치 이상소견 임상적유용성 수축기능과연관된측정변수들 좌심실박출률 저하 (<50%) LV global systolic dysfunction 좌심실구획단축률 (fractional shortening) 저하 (<25%) LV radial systolic dysfunction 좌심실국소기능 Hypokinesis, akinesis, dyskinesis 심근경색 / 허혈 심근병, 심근염 좌심실이완기말크기증가 (diameter 55 mm, > 34 mm/m 2, volume > 81 ml/m 2 ) 용적과부하심부전가능성높음 좌심실수축기말크기 증가 (diameter > 36 mm, > 22 mm/m 2, 용적과부하심부전가능성높음 volume > 33 ml/m 2 ) 좌심실유출로속도시간적분 저하 (< 15 cm) LV stroke volume 저하 이완기능과연관된측정변수들좌심실이완기능부전변수 Mitral inflow, e 또는 E/e ratio 이상 좌심실이완기능부전단계와좌심실충만압정도시사 좌심실질량지수 증가 : 여자 - 96 g/m 2, 남자 g/m 2 고혈압, 대동맥판협착, 비후성심근병 판막기능과연관된측정변수 판막형태와기능판막 협착또는폐쇄부전 ( 특히대동맥판협착또는승모판역류 ) 다른변수들 심부전의원인또는복잡변수또는심부전의결과 ( 이차성승모판역류 ) 기능부전의중증도와혈역학적 상태의평가수술고려 우심실기능 ( 예 : TAPSE) 감소 (TAPSE < 16 mm) 우심실기능부전 TR peak velocity 증가 (>3.4 m/s) 우심실수축기압증가 수축기폐동맥압 증가 (>50 mmhg) 폐고혈압가능성높음 하부대정맥 호흡에의한직경감소없이확장 우심방압상승우심실기능부전, 용적과부하폐고혈압가능성있음 심막 삼출, 심막혈종, 석회화 심낭압전, 악성종양, 전신질환, 급만성심막염, 수축성심막염고려 LV, left ventricular; HF, heart failure; TAPSE, tricuspid annular plane systolic excursion; TR, tricuspid regurgitation 5 장영상학적진단 21 진단II

43 중심정맥압을추정할수있다. 심부전환자에서흔한심초음파이상소견을표 2.6에정리하였다 좌심실수축기능의평가좌심실박출률은심장수축기능의지표로흔히생각하는데좌심실박출률은용적, 전부하, 후부하, 심박수, 판막기능등에영향을받기때문에심장수축기능의지표라할수없다. 또한, 좌심실박출률은일회박출량과도동일한용어가아니다. 심부전에서좌심실이확장된경우일회박출량은유지되고좌심실박출률보존심부전에서동심좌심실비대가동반된경우는감소한다. 또한유의한승모판역폐쇄부전환자의경우좌심실박출률은유지되나박출양은감소한다. 따라서좌심실박출률은숫자만으로평가해서는안되며임상적상황을고려하여평가하여야만한다. 심초음파에서좌심실박출률측정시권고하는방법은 Simpson법이다. 38, 39, 100 그러나이방법을사용하기위해서는심내막경계가적어도 80% 이상잘보이는영상에서만정확하게측정할수있다는단점이있다. 101 좌심실박출률을측정하는다른방법중직경으로계산하는 Teichholz, Quinones 법의경우국소벽운동장애가동반된경우부정확하며, 좌심실수축기능을평가하는방법인구획단축률의경우도동일한단점이있다. 따라서 Teichholz, Quinones법, 구획단축률, 직관적평가 (eye-balling) 방법은권고하지않는다 차원심초음파는좌심실용적과좌심실박출률을더정확하게평가한다. 102 좌심실수축기능을평가하는다른방법으로는 AV plane systolic excursion, systolic tissue Doppler velocities, deformation imaging (strain, strain rate) 등이있다. Deformation imaging 은좌심실수축기능의미미한변화도측정 가능하여좌심실박출률보다더민감한지표이 나재현성과표준화문제때문에아직까지임 상에서일반적으로사용되고있지는않다. 일 회박출량과심박출량은좌심실유출로의 Time velocity integral 로계산가능하다 좌심실이완기능의평가 좌심실이완기능은좌심실박출률보존심부전 을진단하는데필수적이다. 100 좌심실이완기 능지수는나이, 심박수, 신체크기에영향을 받는다. 103, 104 중요한점은단일심초음파지표 로좌심실이완기능을진단할수없다는점이 다. 따라서좌심실이완기능을평가하는여러 가지심초음파지표들을모두측정하여종합적 103, 104 으로평가할것을권고하고있다. 승모판륜에서측정하는 Tissue Doppler imaging-derived early diastolic myocardial velocities (e ) 는심근완화 (myocardial relaxation) 를평가하는지표로사용된다. 심 부전환자에서정상 e (septal e > 8 cm/s, lateral e > 10 cm/s, 또는평균 > 9 cm/s) 를보인다면이는매우드문경우이다. E/e 103, 104 ratio는좌심실충만압과관련이있다 년유럽심장학회의심부전진료지침 에언급된심부전환자에서흔한좌심실이완 기능지표의이상소견과그임상적의미를표 3.7 에정리하였다. 22 만성심부전진료지침

44 표 2.7. 심부전환자에서흔한좌심실이완기능지표의이상소견과임상적의미 측정치이상임상적유용성 e Low (<8 cm/s septal, <10 cm/s lateral, or <9 cm/s average) Delayed LV relaxation E/e ratio High (> 15) High LV filling pressure Low (<8) Intermediate (8-15) Normal LV filling pressure Gray zone (additional parameters necessary) Mitral inflow E/A ratio Restrictive (> 2) High LV filling pressure Volume overload Impaired relaxation (<1) Delayed LV relaxation Normal LV filling pressure Normal (1-2) Inconclusive (may be pseudonormal ) Mitral inflow during Valsalva maneuver Change of the pseudonormal to the impaired relaxation pattern High LV filling pressure (unmasked through Valsalva) (with a decrease in E/A ratio 0.5) (A pulm A mitral) duration > 30 ms High LV filling pressure LV, left ventricular 심부전이의심되는환자에서심초음파를반복기능에유의한영향을미칠수있는치료를받적으로측정하면서추적관찰하는것이심초음은경우, 기구치료의대상자인경우반복적인파를시행하지않고추적관찰하는경우에비심초음파를시행하는것은타당하다. 그러나해사망률, 이환율, 심부전에의한입원율을낮환자상태에의미있는변화가없거나, 특별한춘다 하지만심부전환자경과관찰시심치료가행해지지않은경우에좌심실기능의초음파를자주시행하여야하는지에대해서명반복적인평가는이득이없다. 확한해답을제시하는연구나진료지침은없는실정이다. 임상적상태의의미있는변화가관찰된경우, 임상사건을경험하거나회복된경우, 진료지침에따른약물치료를포함한심장 5 장영상학적진단 23 진단II

45 심장컴퓨터단층촬영 / 자기공명영상 1. 심부전이의심되는환자에서심장의크기, 폐울혈여부를확인하기위해흉부방사선촬영을시행해야한다. (Class I, Level of Evidence C) 2. 심초음파가불충분한경우, Radionuclide ventriculography나심장자기공명영상을좌심실박출률과용적을평가하기위해시행하는것은타당하다. (Class IIa, Level of Evidence C) 3. 심부전환자에서탈륨-201 혹은테크네튬-99m을이용한단일광자방출단층촬영, 심장컴퓨터단층촬영혹은심장자기공명영상을이용하여허혈성심장질환을진단하는것이타당하다. (Class IIa, Level of Evidence C) 좌심실기능저하및심부전으로내원한환자치료의기본은근본원인을파악하는것으로가장큰분류는허혈성원인과비허혈성원인을감별하는것이다. 이는관동맥재관류치료가심부전의중요한치료이기때문이다. 전통적인접근법은심전도, 심초음파, 핵의학검사를통하여과거심근경색의유무, 관류장애를평가하는것이다. 그러나심장자기공명영상기법을통하여지연조영증강영상 (late gadolinium enhancement), 부하관류검사, 관동맥영상을얻는다면, 과거의경색유무, 심근관류상태, 동맥의협착여부를동시에관찰할수있어허혈성심부전감별에도움이된다 또한만성신질환이없어조영제사용이가능한환자에서는관동맥전산화단층영상을통한관동맥협착을진단하는것도도움이된다 ( 참고 : 허혈성심장질환 ). 109 비허혈성심근병의원인으로확장성심근병, 비후성심근병, 침윤성심근병, 제한성심근병, 부정맥유발우심실심근병등이있다. 자 기공명영상기법중지연조영증강영상, T2 강조영상, T1, T2 지도영상을통하여각각의양상에따른기저원인을파악해볼수있다 모든비허혈성심근병의말기단계에서는전심근의침윤및섬유화가진행되는양상으로감별이어려운경우도있다. 허혈성심부전환자의예후개선에가장주요한인자는성공적인재관류치료이다. 그러나모든환자에서재관류치료의효과를볼수있는것이아니라, 생존심근에서시행할때심근의수축력회복을통한호전을기대해볼수있다. 심장자기공명영상의지연조영증강영상을이용한통벽성측정과도부타민부하심장자기공명영상을통하여이를예측할수있으며, 이를통한재관류치료여부를결정하는것이예후및증세호전에도움이된다 확장성심근병환자에서볼수있는심근중간층의선형지연조영증강은향후자연회복여부예측및심실부정맥혹은심부전의악화로인한재입원을예측하는데도움이되는것으로 24 만성심부전진료지침

46 124, 125 보고되고있으며, 비후성 심근병에서발 견되는지연조영증강및범위는향후심실빈맥 발생과관련하여사망률과관련된다는보고가 있어, 이를통한심율동전환제세동기삽입의 126, 127 또하나의위험인자로간주되기도한다. 그러나소규모연구간의성적에차이가있어, 정확한지침으로지정되기위해서는좀더많 은수의대상자를포함하고, 장기간의추적관 찰이된연구결과가나와야할것이다. 다양한 치료후좌심실, 우심실의박출률, 좌심실용 적및질량을측정하여치료효과를확인하는 데이용하고있으며, 심장자기공명영상은심 초음파를통한측정에비해좀더정확하고재 현성이높아측정간차이가적어이들측정의 명확한기준으로알려져있다 특히이들 의높은재현성으로인해기존의심초음파혹 은핵의학검사로시행했던연구보다적은수 를대상으로결과를알아볼수있는장점이있 어점점더많은연구가심장자기공명영상을 사용하고있다 선천성심장질환은소아기의수술및치료 성적의향상으로소아청소년기의생존율은좋 아졌으나성인에서는향후심부전이병발될가 능성이높아성인심부전의중요원인이되고 있다. 특히우심실과관련된대혈관을침범하 는선천성심장질환, 과거수술후교정된선천 성심장질환의폐동맥혈류, 혈관간의연관성, 좌우심실의기능및조직학적변화를정확히 측정하는데심장자기공명영상이중요한진단 적정보를제공해준다 이식된심장의거부반응중동종이식맥관 장애는만성거부반응에서발견되어재이식까 지진행하게되는치명적인합병증이다. 이를 조기에찾기위해침습적관동맥조영술을시 행하고있으나, 컴퓨터전산촬영기법의발전과 해상도의향상으로관동맥협착을효율적으로 141, 142 찾아낼수있다는연구가보고되고있다. 5 장영상학적진단 25 진단II

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48 KSHF guideline for the management of CHRONIC HEART FAILURE 2016 약물치료 III 1. 생존율개선을위한약물 2. 증상개선을위한약물 3. 기타약물치료 4. 좌심실기능이보존된심부전환자의약물치료

49 1 장 생존율개선을위한약물 레닌 - 앤지오텐신계차단제 ( 레닌 - 앤지오텐신 - 알도스테론계통차단제 ) 1. 이전에증상이있었거나현재증상이있는좌심실박츌률저하심부전환자에서금기증이없다면, 심부전이환율및사망률감소를위해앤지오텐신전환효소억제제를사용해야한다. (Class I, Level of Evidence A). 2. 이전에증상이있었거나현재증상이있는경우와좌심실박출률저하심부전환자에서앤지오텐신전환효소억제제에내약성이없는경우금기증이없다면심부전이환율및사망률감소를위해앤지오텐신수용체길항제를사용해야한다. (Class I, Level of Evidence A) 3. 좌심실박출률저하심부전환자에서앤지오텐신전환효소억제제대신이미앤지오텐신수용체길항제를다른이유로사용하고있는경우앤지오텐신수용체길항제를사용하는것은타당하다. (Class IIa, Level of Evidence A) 4. 좌심실박출률저하심부전환자에서앤지오텐신전환효소억제제와베타차단제를이미투여하고있으며염류코르티코이드억제제를투여할수없는경우앤지오텐신수용체길항제를추가하여사용하는것을고려할수있다. (Class IIb, Level of Evidence A) 앤지오텐신전환효소억제제앤지오텐신전환효소억제제는좌심실수축기능저하심부전환자의증상을호전시키며, 사망률과재입원율을낮춘다. 이러한효과는이전에심부전증상이있었거나, 현재증상이있는 경우, 증상의중증도및관상동맥질환동반여부와상관없이모두확인되었다. 1987년에날라프릴이 NYHA 기능등급 IV 의심한좌심실수축기능저하심부전환자에서총사망률을 27% 감소시키는것이처음으로 28 만성심부전진료지침

50 확인되었고 (CONSENSUS trial), 143 NYHA 기능등급 II-III가 90% 를차지하는좌심실수축기능저하심부전환자에서도 16% 감소시키는것이재확인되었다 (SOLVD trial). 144 리시노프릴의용량, 즉저용량과고용량에따른효과를 NYHA 기능등급 II-IV의좌심실수축기능저하심부전환자에서관찰한연구에서는고용량을사용한군에서비해사망률과재입원율이 15% 감소하였다 (ATLAS trial). 145 그외에도무증상의좌심실수축기능저하환자에게서는심부전으로인한사망률및재입원율이 20% (SOLVD trial), 146 급성심근경색이후심부전환자의메타분석에서는 27% 감소하였다. 147 이후다양한앤지오텐신전환효소억제제 ( 캅토프릴, 리시노프릴, 페린도프릴, 라미프릴, 퀴나프릴, 트란돌라프릴 ) 에서그효과가증명되었고, 현재까지는약제의종류에따른차이는없는것으로여겨지고있다. 148 이전에투약중심한혈관부종이발생한적이있었거나임신을하였을경우에는절대투여하지말아야하며, 수축기혈압이 80 mmhg 이하 로매우낮거나크레아티닌이 3 mg/dl 이상, 양측신동맥협착혹은혈청칼륨이 5 meq/l 이상인경우에는투약을매우조심스럽게결정해야한다. 초기에는저용량부터시작하여서서히증량해야하며, 투약 1-2주이내에는혈청칼륨을포함한신기능검사를해야한다. 약과관련된부작용은대부분앤지오텐신전환효소억제에따른앤지오텐신억제와키닌분해억제와관련이있다. 기침이가장흔하고, 투약환자의 20% 까지나타날수있으며, 일부에서는심한혈관부종이발생할수있지만대부분의심부전환자들이투약에내약성을보인다. 한국인에서는기침이더많은것으로알려져있다. 무작위연구에서생존율향상이관찰되는용량은심부전의증상호전이보이는용량에의해결정되는것이아니라초기에제시된목표용량까지충분히올렸을때효과가있다. 따라서이전에증상이있었거나현재증상이있는좌심실박출률저하심부전환자에서금기증이없다면앤지오텐신전환효소억제제를사용해야하고, 심혈관사건을줄인것으로보 III 약물치료표 3.1. 앤지오텐신전환효소억제제의시작과목표용량 앤지오텐신전환효소억제제 시작용량 (mg) 목표용량 (mg) 캅토프릴 6.25 mg 1일 3회 50 mg 1일 3회 에날라프릴 2.5 mg 1일 2회 mg 1일 2회 포시노프릴 5-10 mg 1일 1회 40 mg 1일 1회 리시노프릴 mg 1일 1회 mg 1일 1회 페린도프릴 2 mg 1일 1회 8-16mg 1일 1회 라미프릴 mg 1일 1회 10 mg 1일 1회 트란돌라프릴 0.5 mg 1일 1회 4 mg 1일 1회 1 장생존율개선을위한약물 29

51 고되었던목표용량 ( 캅토프릴 50 mg 1일 3회, 에날라프릴 mg 1일 2회, 리시노프릴 mg 1일 1회, 라미프릴 5 mg 1일 2회 ) 까지가능하면올려야한다. 최근증가하고있는좌심실박출률보존심부전환자에서임상증상호전이외에사망률개선효과가확인된약물은아직까지없다. 다만페린도프릴이 70세이상 ( 평균 76세 ) 의좌심실수축기능유지심부전환자에서 1년사망률 / 재입원율을모두포함하는심혈관사건율을 31% 감소시키는경향을보였으며, 재입원율을 37% 감소시켰다 (PEP-CHF trial). 149 사망률 / 재입원율의심혈관사건율은통계적의미를가지지는못하였지만, 70세이상의고령에서장기적효과가능성을확인시켜주었으며, 추가연구필요성도제기되었다. 따라서앤지오텐신전환효소억제제는좌심실박출률보존심부전환자에서사용하는것을고려할수있겠다 앤지오텐신수용체길항제앤지오텐신수용체길항제는앤지오텐신전환효소억제제의제한점, 즉앤지오텐신전환효소억제제가레닌-앤지오텐신계를차단하더라도다른시스템 ( 비전환효소계 ) 을통해앤지오텐신 II가지속적으로생성되며, 키닌분해를억제하여기침과혈관부종의부작용을발생시키는두가지제한점을이론적으로극복할수있는레닌-앤지오텐신계차단제이다. 2001년발사르탄은 NYHA 기능등급 II-IV 의좌심실수축기능저하심부전환자에서, 총사망률에는영향이없었지만, 복합종말점인사망률또는재입원율을 13% 감소시켰다 (Val-HeFT trial). 150 특히이전에앤지오텐신전환효소억제제를사용하지않았던군에서가장효과가있었고, 앤지오텐신전환효소억제제나베타차단제두가지중한가지를사용하고있는군에서도효과가있었지만, 두가지를모두사용하고있는군에서는효과가없었으며, 부작용이더많았다. 칸데사르탄도좌심실박출률저하심부전환자에서앤지오텐신전환효소억제제를사용하고있거나혹은사용하고있지않더라도전체적으로연구종말점의감소효과가확인되었고 (CHARM-overall program trial), 151 특히부작용으로앤지오텐신전환효소억제제를사용하지못하였던군에서는대신사용하였을경우복합종말점인심혈관사망률또는재입원율을 30% 나감소시켰다 (CHARM-Alternative). 152 로자탄의용량, 즉저용량과고용량에따른효과를 NYHA 기능등급 II-IV의좌심실박출률저하심부전환자에서관찰한연구에서는고용량을사용한군에서저용량군에비해복합종말점인사망률또는재입원율이 10% 감소하였다 (HEAAL trial). 153 앤지오텐신수용체길항제역시앤지오텐신전환효소억제제와같이임신을하였을경우에는절대투여하지말아야하며, 수축기혈압이 80 mmhg 이하로매우낮거나크레아티닌이 3 mg/dl 이상, 양측신동맥협착혹은혈청칼륨이 5 meq/l 이상인경우에는투약을매우조심스럽게결정해야한다. 앤지오텐신전환효소억제제투여중발생한혈관부종혹은기침으로투여가어려울경우대체약물로사용할수있으나일부에서는혈관부종혹은기침이나타날수있다. 무작위연구에서생존율향 30 만성심부전진료지침

52 표 3.2. 앤지오텐신수용체길항제의시작과목표용량 앤지오텐신수용체길항제 시작용량 (mg) 목표용량 (mg) 칸데사르탄 4-8 mg 1일 1회 32 mg 1일 1회 발사르탄 40 mg 1일 2회 160 mg 1일 2회 로자탄 50 mg 1일 1회 150 mg 1일 1회 상이관찰되는용량역시목표용량 ( 칸데사르탄 32 mg 1일 1회, 발사르탄 160 mg 1일 2회, 로자탄 150 mg 1일 1회 ) 까지충분히올렸을때효과가있는것으로알려져있다. 따라서이전에증상이있었거나현재증상이있는좌심실박출률저하심부전환자에서특히앤지오텐신전환효소억제제에내약성이없는경우, 금기증이없다면앤지오텐신수용체길항제를사용해야한다. 좌심실박출률보존심부전환자에서앤지오텐신수용체길항제의사망률개선효과가확인된연구는아직없다. 칸데사르탄의경우좌심실박출률보존심부전환자에서사망률을줄이지는못하였으나, 총심부전입원율을 16% 감소시켰으며 (CHARM-preserved), 154 이르베사르탄은사망률, 입원율을모두감소시키지못하였다 (I-PRESERVE). 155 앤지오텐신수용체길항제를좌심실박출률보존이유지된심부전환자에게사용하기에는추가적연구가필요한상황이다. 현재까지좌심실박출률저하심부전환자에서앤지오텐신전환효소억제제대신에앤지오텐신수용체길항제를우선적으로사용할수있다는근거는아직부족하다. 많은소규모연구에서앤지오텐신수용체길항제우선투여 가심부전증상뿐아니라혈역학적인자와신경체액물질변화에서좋은효과가증명되었지만, 앤지오텐신전환효소억제제대신에앤지오텐신수용체길항제의우선사용을고려하였던대규모연구는전술한발사르탄연구가유일하며 (Val-HeFT), 150 대부분은앤지오텐신전환효소억제제를부작용으로사용하지못하였던환자에서대신사용하여효과가증명되었다. 급성심근경색이후발사르탄이캅토프릴에비해사망률감소에서열등하지않음이확인되었고 (VALIANT trial), 156 이는로자탄에서도재확인되었다 (OPTIMAAL trial). 157 따라서다른이유로앤지오텐신수용체길항제를이미사용하고있는경우라면앤지오텐신수용체길항제를사용하는것은타당하다 앤지오텐신전환효소억제제와앤지오텐신수용체길항제복합투여앤지오텐신전환효소억제제를이미사용하고있는좌심실박출률저하심부전환자에서칸데사르탄추가투여가앤지오텐신전환효소억제제단독투여보다복합종말점인심혈관사망률또는재입원율을 15% 감소시켰다 (CHARM-Added trial). 158 이연구에서는환자의 55% 에서베타차단제를, 17% 에서스피 III 약물치료1 장생존율개선을위한약물 31

53 로놀락톤을이미사용하고있었다. 위에서기 술한바와같이발사르탄은 NYHA 기능등급 사르탄을추가투여한연구에서는사망률과입 원율을낮추지못하였다 (substuty from Val II-IV 의좌심실박출률저하심부전환자에서 HeFT trial). 159 급성심근경색이후발사르탄 사망률또는입원율을 13% 감소시켰는데, 특히이전에앤지오텐신전환효소억제제를사용하지않았던군에서가장효과가있었고, 앤지오텐신전환효소억제제나베타차단제두가지중한가지를사용하고있는군에서도효과가있었지만, 두가지를모두사용하고있는군에서는효과가없었으며부작용이더많았다 (Val-HeFT trial). 베타차단제사용없이앤지오텐신전환효소억제제만사용하고있는좌심 투여, 캅토프릴투여, 발사르탄과캅토프릴복합투여군을비교한연구에서는복합투여군이각각의단독투여군보다사망률과입원율의차이는없었다 (VALIANT trial). 156 따라서좌심실박출률저하심부전환자에서앤지오텐신전환효소억제제와베타차단제를이미투여하고있는경우앤지오텐신수용체길항제를추가하여사용하는것을고려할수있다. 실수축기능저하심부전환자를대상으로발 표 3.3. 좌심실박출률저하심부전환자에서앤지오텐신전환효소억제제 ( 또는앤지오텐신수용체길항제 ) 의처방가이드목적증상완화, 심부전으로인한입원감소, 생존율증가대상및처방시기 1) 적응증모든좌심실박출률저하심부전환자 ( 박출률 40%) 베타 차단제, 염류코르티코이드길항제와함께 NYHA 기능등급 II-IV 심부전환자의일차치료제 ( 질병의경과중가급적일찍사용해야함 ) 앤지오텐신전환효소억제제는무증상박출률저하심부전환자 (NYHA 기능등급 I) 에서도도움이됨 2) 주의점고칼륨혈증 ( 칼륨 > 5.0 mmol/l) 신부전 ( 크레아티닌 > 2.5 mg/dl 혹은사구체여과율예측치 <30 ml/min/1.73 m 2 ) 증상이있거나증상이없어도심한저혈압 ( 수축기 < 90 mmhg ) 3) 약물상호작용칼륨보충제 / 칼륨보존이뇨제 ( 아밀로라이드, 트리암테렌 ) 염류코르티코이드길항제 / 레닌억제제비스테로이드항염증제트리메토프림 / 트리메토프림-설파메톡사졸고농도칼륨성분을포함한대체저염 4) 금기증혈관부종병력양측신동맥협착증임신 / 임신가능성 ( 계속 ) 32 만성심부전진료지침

54 처방법 신기능과전해질 ( 칼륨 ) 확인 저용량부터시작 적어도 2주이상간격을두고용량증가 ( 입원환자나모니터링이잘되는일부환자에서는더빨리증량 ) 목표용량까지증량, 실패할경우최대한고용량 모든앤지오텐신수용체길항제가도움이되는것은아님 약제시작후또는용량증량시 1-2주후일반화학검사 ( 요소, 크레아티닌, 칼륨 ) 확인 이후 4개월마다일반화학검사확인 심부전전문간호사가환자교육및추적관찰, 검사결과확인, 그리고용량증량등을도울수도있음환자교육 약제사용시기대되는효과를설명 증상완화, 심부전으로인한입원율및사망률호전을목적으로치료 약제처방수주에서수개월이내에증상호전이보임 부작용발생을의사에게알릴것 ( 어지럼증 / 증상이있는저혈압, 기침등 ) 의사처방없이임의적인비스테로이드항염증제사용을피할것문제해결 증상이없는저혈압 대부분치료의변화를주지않음증상이있는저혈압 어지럼증, 몽롱함이흔하고시간이지나면서호전되는경우가많으므로환자를안심시킴 나이트레이트, 칼슘통로차단제, 다른혈관확장제를재고하고, 가능한줄이거나중단 울혈증상이나징후가없으면이뇨제용량을감량 이러한방법으로호전되지않을경우전문가와상의기침 심부전환자에서흔하고, 많은경우흡연에의한폐질환과연관 폐부종의증상일수있으므로새로기침이발생할경우이를고려해야함 앤지오텐신전환효소억제제에의한기침이더라도반드시약제를중단할필요는없음 수면을방해할정도로심한기침이고, 앤지오텐신전환효소억제제에의한것으로판단될경우앤지오텐신수용체길항제로약제를변경신기능의악화및고칼륨혈증 앤지오텐신전환효소억제제처방후요소, 크레아티닌, 칼륨수치가다소올라갈수있음 ; 상승폭이적고증상이없을경우더이상의조치가필요없음 크레아티닌이기준치의 50% 이하또는 3 mg/dl 혹은사구체여과율예측치 25 ml/min/1.73 m 2 이하일경우허용 칼륨상승이 5.5 mmol/l 이하일경우허용 요소, 크레아티닌, 칼륨이과도하게상승할경우신독성약제 ( 비스테로이드항염증제등 ), 다른칼륨보충제또는칼륨보존이뇨제 ( 아밀로라이드, 트리암테렌 ) 를중단하고울혈증상이없을경우이뇨제를감량 약제조정이후에도칼륨, 크레아티닌이지속적으로증가할경우앤지오텐신전환효소억제제 ( 또는앤지오텐신수용체길항제 ) 를절반으로감량하고 1-2주이내다시혈액검사를확인 ; 반응이여전히불만족스러울경우전문가와상의 칼륨상승이 5.5 mmol/l 이상이거나크레아티닌이기준치의 100% 이상또는 3.5 mg/dl 이상혹은사구체여과율예측치 20 ml/min/1.73 m 2 이하일경우앤지오텐신전환효소억제제 ( 또는앤지오텐신수용체길항제 ) 중단및전문가와상의 칼륨상승이 5.5 mmol/l 이하일경우허용 일반화학검사는칼륨과크레아티닌이안정될때까지지속적으로빈번히확인해야함 III 약물치료1 장생존율개선을위한약물 33

55 베타차단제 1. 박출률감소심부전환자는생명연장을도모하고질병의진행을늦추기위해서, 비소프롤롤, 지속형메토프롤롤, 카르벨딜롤중한개의베타차단제를지속적으로투여받아야한다. (Class I, Level of Evidence A) 2. 70세이상의환자에서네비볼롤투여는도움이될수있다. (Class IIa, Level of Evidence B) 베타차단제는앤지오텐신전환효소억제제이후여러대규모임상연구에서생명연장및심부전악화방지효과를입증하였다. 현재비소프롤롤 (CIBIS-II), 160 지속형메토프롤롤, 161 카르베딜롤 (COPERNICUS, CAPRICORN), 네비볼롤 (SENIORS) 165 4가지약제만이심부전에서예후개선효과를입증하였으며심부전환자에서사용이가능하다 ( 표 3.4). 앤지오텐신전환효소억제제와달리베타차단제는 클래스효과 가없다. 프로프라놀롤또는아테놀롤같은 1세대베타차단제및단기작용메토프롤롤타르테이트는심부전환자에서예후를개선하지못하였기에사용을피해야한다. 비스프롤롤과지속형메토프롤롤은선택성베타 1- 수용체를차단한다. 그리고카르베딜롤은알파 1-, 베타 1-, 베타 2-수용체를차단한다. 베타차단제를시작하기전앤지오텐신전환효소억제제를먼저사용하는것을추천한다. 하지만앤지오텐신전환효소억제제를투여중인환자에서베타차단제를추가하는최적의시점은알려져있지않다. 베타차단제를사용할때에는반드시고용량의앤지오텐신전환효소억제제나앤지오텐신수용체길항제를사용할 필요가없으며, 저용량의앤지오텐신전환효소억제제를사용하고있다고해도가능한빨리베타차단제를추가하는것이좋다. 166 베타차단제는아주낮은용량으로부터시작하고, 조금씩증량하여수주에서수개월후목표용량에도달하게한다. 베타차단제를증량하는동안울혈이발생하는지확인해야하며, 울혈이발생하는경우우선이뇨제를추가하거나이미이뇨제를사용하는경우는이뇨제를증량해야한다. 만약베타차단제복용중심부전이악화되는경우급성비대상성심부전에도가능하면베타차단제를유지하고먼저이뇨제를추가또는증량한다. 하지만낮은심박출량이심부전악화의원인인경우에는베타차단제를감량하거나일시적으로중단하고, 포스포디에스테라제억제제 (milrinone) 같은강심제를투여한다. 환자가안정되면퇴원전베타차단제를재개하는것을고려한다. 34 만성심부전진료지침

56 표 3.4. 베타차단제의시작과유지용량 약품명 초기용량 최대용량 기존연구에서사용된평균용량 비소프롤롤 1.25 mg 1일 1회 10 mg 1일 1회 8.6 mg 1일 1회 카르베딜롤 mg 1일 2회 50 mg 1일 2회 37 mg 1일 1회 지속형메토프롤롤 mg 1일 1회 200 mg 1일 1회 159 mg 1일 1회 네비볼롤 1.25 mg 1일 1회 10 mg 1일 1회 7.7 mg 1일 1회 표 3.5. 좌심실박출률저하심부전환자에서차단제베타차단제의처방가이드목적증상완화, 심부전으로인한입원감소, 생존율증가대상및처방시기 1) 적응증모든좌심실박출률저하심부전환자 ; 심한좌심실기능저하가있을경우주의깊게사용앤지오텐신전환효소억제제와염류코르티코이드길항제와함께안정된심부전환자의일차치료제 ; 질병의경과중가급적일찍사용해야함 2) 주의점 NYHA 기능등급 IV의심부전최근의심부전악화 ( 최근 4주이내 ), 방실차단, 서맥 (<60회/ 분 ) 지속적인울혈징후, 저혈압 ( 수축기<90 mmhg), 경정맥압상승, 복수, 심한말초부종 울혈을개선시켜정상체액상태에서약물시작 3) 약물상호작용베라파밀, 딜티아젬 ( 중단고려 ) 디곡신, 아미오다론, 이바브라딘 4) 금기증천식 ( 만성페쇄성폐질환은금기아님 ) 2도또는 3도방실차단 ( 인공심박동기가없는경우 ) III 약물치료1 장생존율개선을위한약물 35

57 처방법 저용량부터시작 적어도 2주이상간격을두고용량증가 ( 일부환자에서는더천천히증량 ) 목표용량까지증량, 실패할경우최대한고용량 모든베타차단제가도움이되는것은아님 맥박, 혈압, 임상상태 ( 증상, 징후 특히울혈징후, 체중 ) 확인 심부전전담전문간호사가환자교육및추적관찰, 그리고용량증량등을도울수도있음환자교육 약제사용시기대되는효과를설명 증상완화, 심부전으로인한입원율및사망률호전을목적으로치료 약제처방후서서히, 때로는 3-6개월이상걸쳐증상호전이보임 약물시작, 또는용량증량이후일시적으로증상악화가발생할수있으나장기적으로는환자의회복을도움 의사의상담없이임의대로약물중단하지않을것. 또한상태악화시의사에게알릴것 상태악화를알기위해매일체중을재고 ( 기상후소변본직후, 식전 ), 체중증가시이뇨제용량을증량할것 ( 이틀이상, kg 증가시 ) 문제해결증상또는징후악화 ( 호흡곤란, 피로, 부종, 체중증가등 ) 울혈이증가할경우, 이뇨제용량을늘리거나베타차단제용량을절반으로줄임 ( 이뇨제를증량해도효과없을경우 ) 피로감증가시 ( 혹은서맥 ), 베타차단제용량을절반으로줄인다 ; 1-2주환자를관찰 ; 호전되지않으면전문가와상의 상태악화가심할경우, 베타차단제용량을절반으로줄이거나중단 ; 전문가와상의서맥 맥박이 50회 / 분이하이고증상이악화될경우베타차단제용량을절반으로줄이거나중단 다른서맥을유발하는약제사용을재고 ( 디곡신, 아미오다론, 딜티아젬, 베라파밀 ) 방실차단을확인하기위해심전도를시행 전문가와상의증상이없는저혈압 대부분치료의변화를주지않음증상이있는저혈압 어지럼증, 몽롱함, 또는착란이있고, 저혈압인경우, 나이트레이트, 칼슘통로차단제, 다른혈관확장제를재고하고, 가능한줄이거나중단 울혈증상이나징후가없으면이뇨제용량을감량 이러한방법으로호전되지않을경우전문가와상의 36 만성심부전진료지침

58 염류코르티코이드길항제 1. NYHA 기능등급 II-IV의좌심실박출률감소심부전 ( 35%) 환자에서사망률및이환율개선을위해서, 금기증이없는한앤지오텐신전환효소억제제 ( 또는앤지오텐신수용체길항제 ), 베타차단제등의약물치료에부가적으로염류코르티코이드길항제를사용하여야한다. (Class I, Level of Evidence A) 2. 좌심실박출률이 40% 이하이고심부전증상또는당뇨병을동반한급성심근경색후환자에서, 금기증이없는한앤지오텐신전환효소억제제 ( 또는앤지오텐신수용체길항제 ), 베타차단제등의약물치료에부가적으로염류코르티코이드길항제를사용하여야한다. (Class I, Level of Evidence B) 현재널리알려진염류코르티코이드길항제는 스피로놀락톤과에플레레논이있으나, 우리나라 에서에플레레논은사용하기어려운약제이다. 심부전병태생리에있어서알도스테론은자 율신경계의균형을저해시키며콜라겐합성을 증가시켜심혈관계의재형성에관여하는중요 한역할을담당하는데, 이는레닌 - 앤지오텐신 계통의차단만으로는억제가부족하다. 167 따라 서심부전치료시기존의앤지오텐신전환효소 억제제 / 수용체차단제와베타차단제를사용하 고있는환자에게염류코르티코이드길항제를 부가적으로사용해야한다. 심부전치료관련의 RALES 연구에서는심 박출률이 35% 미만이며 NYHA 기능등급 III 이상호흡곤란이있는환자에서스피로놀락톤 mg 을기존약물치료에부가적으로사 용하여 30% 의사망률감소, 35% 의입원율감 소효과와함께, 혈역학적소견과증상개선효 168, 169 과를보여주었다. 박출률이 30% 이하 (QRS 간격이 130 ms를넘을경우 35% 이하 ) 인 NYHA 기능등급 II 이상의호흡곤란환자를대상으로한 EMPHA- SIS-HF 연구에서는앤지오텐신전환효소억제제 / 수용체차단제와베타차단제를사용하고있는환자에게에플레레논을부가적으로사용하여심혈관사망률과심부전으로인한입원율을 37% 감소시켰다. 170 그리고 35% 이하의심박출률을지닌 65세이상의고령의환자에서도심부전으로인한입원율을감소시켜주었다. 171 따라서심부전으로입원한경우에, 퇴원전염류코르티코이드길항제의사용은사망률및이환율을감소시키는데도움이된다. 급성심근경색관련 EPHESUS 연구에서는심박출률이 40% 이하인급성심근경색 3-14 일이내의환자중당뇨병이나심부전이동반된환자들을대상으로기존약물치료에에플레레논 mg을사용하여심혈관계사망률을 15% 감소시키고심혈관계사망및입원 III 약물치료1 장생존율개선을위한약물 37

59 율은 13% 감소시킴으로써급성심근경색이후심부전에좋은효과를보여주었다. 172 좌심실박출률감소심부전환자에서임상적소견외에, 혈역학적개선효과가있을수있는데, 에플레레논은좌심실재형성에관한많은자료가없는상태이나스피로놀락톤은심부전및심근경색이후심실재형성을억제하고그에따른검사실소견을호전시키고, 심박출률을상승시킬수있다. 현재까지좌심실박출률보존심부전에서의염류코르티코이드길항제에대한연구결과는많지않은상태이다. 소규모연구에서에플레레논은혈역학적소견및검사실소견등의호전을보여주었으며, 스피로놀락톤을 65세이상의고령환자들에게사용하였을경우에삶의질이향상됨을보여주었다. 따라서임상적효과를확인하고자몇가지대규모연구가최근진행되었는데, RAAM-PEF 연구에서는심박출률이 40% 이상인 65세이상이완기심부전환자에서에플레레논의사용은사망률이나입원율을감소시키지못하였고, 173 심박출률이 50% 이상인 NYHA 기능등급 II-III의환자를대상으로한 Aldo-DHF 연구에서도스피로놀락톤은호흡곤란과연관된삶의질을개선시키지는못하였다. 174 심박출률 45% 이상인증상이있는심부전환자를대상으로한 TOPCAT 연구에서도스피로놀락톤의사용은심혈관계사망, 심정지, 심부전으로인한입원의총합을유의하게감소시키지는못하였고, 심부전으로인한입원율만을 17% 감소시켰다. 175 스피로놀락톤은하루 mg의용량으로시작하고에플레레논은하루 25 mg 으로시작하여 50 mg까지증량할수있다 ( 표 3.6) , 176 주된부작용으로고칼륨혈증이발생할수있으므로주의를기울여야한다. 혈중칼륨농도는 mmol/l 이하로유지하여야하며, 신기능평가가약물투여전후로이루어져야한다. 약제를안전하게사용할수있는신기능은혈중크레아티닌<2.0 mg/dl ( 남자 ), < 2.5 mg/dl ( 여자 ), 혹은사구체여과율예측 > 30 ml/min/1.73 m 2 이며 ( 표 3.7), 57 앤지오텐신전환효소억제제, 앤지오텐신수용체길항제, 그리고염류코르티코이드길항제 3 가지를같이사용해서는안된다. 또한, 신기능감소와함께심박출률이감소된 (< 35%) 심방세동환자에서는오히려부정맥으로인한사망률이현저히높을수있음을보고하였다. 그외에주의할부작용으로스피로놀락톤사용시여성형유방이나통증등이나타날수있으나, 이는유방암과의연관성을보여주지않았다. 38 만성심부전진료지침

60 표 3.6. 신기능에따른염류코르티코이드길항제의처방용량 176 약제사구체여과율예측치 > 50 ml/min/1.73 m 2 사구체여과율예측치 <30-49 ml/min/1.73 m 2 초기용량유지용량초기용량유지용량 스피로놀락톤 mg 25 mg 12.5 mg mg 1 일 1 회 1 일 1 회, 혹은 2 회 1 일혹은 2 일 1 회 1 일 1 회 에플레레논 25 mg 1 일 1 회 50 mg 1 일 1 회 25 mg 2 일 1 회 25 mg 1 일 1 회 * 칼륨 > 6.0 meq/l 혹은신기능악화가있을경우에칼륨 < 5.0 meq/l 가될때까지약제중단을하고최소 3 일간고칼륨혈증 및신부전의호전을확인하고약제용량을줄여적정용량을결정한다. 표 3.7. 좌심실박출률저하심부전환자에서염류코르티코이드의처방가이드 57 목적증상완화, 심부전으로인한입원감소, 생존율증가대상및처방시기 1) 적응증베타차단제와앤지오텐신전환효소억제제 ( 또는앤지오텐신수용체길항제 ) 의사용에도불구하고 NYHA 기능등급 II-IV 정도의지속되는증상과 35% 미만의심박출률을보이는모든환자 2) 주의점고칼륨혈증 ( 칼륨 > 5.0 mmol/l) 신부전 ( 크레아티닌 > 2.5 mg/dl 혹은사구체여과율예측치<30 ml/min/1.73 m 2 ) 3) 약물상호작용칼륨보충제 / 칼륨보존이뇨제 ( 아밀로라이드, 트리암테렌 ) 앤지오텐신전환효소억제제 / 앤지오텐신수용체길항제 / 레닌억제제비스테로이드항염증제트리메토프림 / 트리메토프림-설파메톡사졸고농도칼륨성분을포함한대체저염 4) 금기증에플레레논 ; CYP3A4 억제제 ( 케토코나졸, 이트라코나졸, 네파조돈, 텔리트로마이신, 클라리트로마이신, 리토나비어, 넬피나비어 ) III 약물치료처방법 신기능과전해질 ( 칼륨 ) 확인 저용량부터시작 4-8주이후용량증가고려 약제사용및용량조절후 1, 4주째혈액검사확인, 이후 2, 3, 6, 9, 12개월째, 그리고 1년후부터는 4개월마다혈액검사확인 칼륨 > 5.5 mmol/l, 크레아티닌 > 2.5 mg/dl, 혹은사구체여과율예측치<30 ml/min/1.73 m 2 인경우에 1/2 용량감량및혈액검사확인 칼륨 > 6.0 mmol/l, 크레아티닌 > 3.5 mg/dl, 혹은사구체여과율예측치<20 ml/min/1.73 m 2 인경우약제중단후전문의와상의 심부전전문간호사가환자교육및추적관찰, 그리고혈액검사확인등을할수도있음 1 장생존율개선을위한약물 39

61 환자교육 약제사용시기대되는효과를설명 증상완화, 심부전으로인한입원율및사망률호전을목적으로치료 약제처방수주에서수개월이내에증상호전이보임 의사처방없이임의적인비스테로이드항염증제사용을피할것 설사및구토등이생기면약제를중단하고의료진을찾을것문제해결신기능의악화및고칼륨혈증 약제사용법확인 고칼륨혈증 (> 6.0 mmol/l) 의유무확인 디곡신을복용중인심부전환자에서는칼륨수치가높은정상 (high-normal) 이도움될수있음 칼륨보존이뇨제와신독성약제 ( 비스테로이드항염증제 ) 를피하는것이중요 앤지오텐신전환효소억제제혹은앤지오텐신수용체길항제의단일약제에병용하는것보다두가지약제를포함한세가지약제병용요법에서부작용위험이높아지므로세가지약제병용은권장하지않음 스피로놀락톤은남성에게여성유방증및유방통증을야기시킬수있음 ( 에플레레논으로대치할것 ) 40 만성심부전진료지침

62 하이드랄라진과질산이소소르비드 1. 하이드랄라진과질산이소소르비드의병용요법은금기가없다면앤지오텐신전환효소억제제와베타차단제로적정치료를받는 NYHA 기능등급 III-IV인좌심실박출률저하심부전을가진흑인환자에게사망률과이환율감소를위해권고된다. (Class I, Level of Evidence B) 2. 하이드랄라진과질산이소소르비드의병용요법은금기가없다면앤지오텐신전환효소억제제나앤지오텐신수용체길항제를복용할수없는경우 ( 약에불내성이있거나, 저혈압또는신기능부전등의이유로 ) 좌심실박출률저하심부전환자에게치명률과이환율감소에도움이될수있다. (Class IIa, Level of Evidence B) 하이드랄라진과질산이소소르비드와같은혈관이완제의사용이심부전의혈역학및증상과운동내성개선에유용하다는연구결과에따라 1980년 V-HeFT I 무작위임상연구가시작되었다. 당시심부전표준치료이던이뇨제및디곡신 ( 베타차단제나앤지오텐신전환효소억제제는사용되지않음 ) 에추가적인하이드랄라진-질산이소소르비드병용요법은 642명의남성 HFrEF 환자에서전기간에걸쳐 ( 평균 2.3년추적 ) 유의하게위약대비전체원인에의한사망의감소 ( 상대위험도감소 28%) 를보였고, 운동능력과좌심실박츌률을향상시켰다. 177 하지만앤지오텐신전환효소억제제 ( 에날라프릴 ) 와하이드랄라진-질산이소소르비드병용요법의좌심실박출률저하심부전에대한효과를비교한 V-HeFT II 연구에서는앤지오텐신전환효소억제제사용군의사망률이유의하게낮았다. 178 한편, V-HeFT I과 II 두연구의사후분석은매우흥미로운결과를제시하였다. 179 즉두연구에참여하였던환자들을인종별로나눠분석하였는데, V-HeFT-I에서흑 인들은하이드랄라진-질산이소소르비드병용요법에치사율이유의하게감소된반면, 백인들은위약군대비유의한차이가없었다. 179 반면 V-HeFT-II에서는백인에서만유의하게앤지오텐신전환효소억제제 ( 에날라프릴 ) 사용시사망률이감소하고, 흑인에서는앤지오텐신전환효소억제제사용군과하이드랄라진과질산이소소르비드의병용요법사용군간에사망률에차이가없었다. 179 결국앤지오텐신전환효소억제제는특히백인에서효과적이며하이드랄라진과질산이소소르비드의병용요법은유사하게흑인에서효과적임을알수있다. 이러한배경에서, 하이드랄라진-질산이소소르비드병용요법의좌심실박출률저하심부전에대한효과를흑인만을대상으로검증한연구가 A-HeFT이다 ,050명의흑인박출률저하심부전환자에서표준적정심부전약물치료 ( 베타차단제, 앤지오텐신전환효소억제제또는앤지오텐신수용체길항제, 알도스테론길항제포함 ) 에하이드랄라진-질산이소소르비드를추가한군의사망률이유의하게낮았다 III 약물치료1 장생존율개선을위한약물 41

63 (6.2% 대 10.2%, 상대위험도 0.57). 두군간의사망률은 6개월째부터차이가나지속되었고심부전에의한입원율도유의한차이를보여 (16.4% 대 22.4%) 연구는조기종료 ( 평균 10개월추적 ) 되었다. 180 용법은하이드랄라진 37.5 mg, 질산이소소르비드 20 mg을하루세번복용하는것으 로시작해서용량을 2배까지증량할수있다. 복용해야할알약의수가많고, 자주복용해야하며, 부작용빈도가높다는것이사용의제한점이다. 흔한부작용은두통, 현기증과소화기계불편감등이다. 하지만천천히증량하면서내약성을기른다면하이드랄라진-질산이소소르비드사용에따른이득을기대할수있다. 42 만성심부전진료지침

64 2 장 증상개선을위한약물 이뇨제 이뇨제는체액저류에의한증상 ( 좌위호흡, 호흡곤란, 부종등 ) 이나징후 ( 경정맥압상승, 부종, 간종대, 폐수포음등 ) 가있는환자에서적정체액량을유지하기위해사용해야한다. (Class I, Level of Evidence B) 체액량을평가하고적절한체액균형을유지 하는것은수축기능부전의동반여부와상관 없이심부전환자의치료에있어필수적인요 소이다. 하지만레닌 - 안지오텐신 - 알도스테론 차단제나베타차단제와달리, 이뇨제가심부전 환자의예후를개선시킬수있는가에대해서는 무작위연구가많지않아제시할수있는증거 가제한적이다. 적은수의환자를대상으로한연구에서이 뇨제는위약군과비교하여사망률을줄이고, 증상의악화에의한입원의위험을낮출수있 181, 182 었다. 그러나 일련의관찰연구에서많은 용량의이뇨제를사용하는것은사망률의증가 와관련된예후인자였으며칼륨보존이뇨제가 아닌경우는부정맥에의한사망위험을증가시 켰다. 183 그렇지만관찰연구의결과인만큼고용 량의이뇨제를사용해야할임상적조건이사 망률의증가와관련되었을가능성이있다 이뇨제사용의일반적원칙 심부전환자의초기치료는수분및염분섭취 의제한과더불어이뇨제를사용하며, 고리작 용이뇨제를사용하는것이일반적이다. 우리 나라에서사용가능한고리작용이뇨제는푸 로세미드, 토르세미드가있으며토르세미드는 작용시간이오래유지되는서방형제제가있 다. 184 체액량과다시사하는대표적소견은폐 울혈, 말초부종, 경정맥압의상승이며위와같 III 약물치료2 장증상개선을위한약물 43

65 은소견을보이는급성심부전환자의경우고리작용이뇨제를정맥주사한다. 고리작용이뇨제의정맥주사시용량 ( 고용량또는저용량 ) 과주사방법 ( 지속적주입또는분할주사 ) 에관해서는급성심부전진료지침에서다룰내용이지만최근의 DOSE연구의결과에의하면어떠한방법이더우월하다는증거는없다. 185 체액량의조절과증상의완화를위해서는고리작용이뇨제를사용하는것이일반적이지만고리작용이뇨제는저칼륨혈증, 저마그네슘혈증등의전해질불균형을유발할수있고이는부정맥에의한사망의증가와관련이있을수있다. 알도스테론길항제는레닌-앤지오텐신-알도스테론길항작용으로좌심실박출률저하심부전환자의생존율을개선하는효과가있지만고리작용이뇨제와같이사용함으로써저칼륨혈증의발생을억제하는효과를기대할수도있다 이뇨제의선택심부전환자에서과도한체내수분을제거하기위해서는고리작용이뇨제를선택하는것이일반적이다. 티아지드계열이뇨제에의한염분배설효과는이론적으로는 1주일이내에사라지게되며이후에는혈관저항감소에의한혈압조절효과가나타나게된다. 따라서체액량조절목적으로는고리작용이뇨제를사용하는것이적절하다. 하지만티아지드계열이뇨제를고리작용이뇨제와병합하여사용할경우원위세뇨관에서염분재흡수를억제함으로써 (sequential blocking) 고리작용이뇨제만으로는이뇨효과가불충분한환자에서보다효과 184, 186 적인이뇨효과를얻을수있다. 어떤고리작용이뇨제가더효과적인가를 비교한연구는매우드물다. 일반적으로푸로 세미드가가장많이쓰이는고리작용이뇨제이 지만푸로세미드의체내이용률은 50% 정도이 며환자개인별차이와환자의상태에따른차 이가매우심해부종이있는경우체내이용률 이 10% 에미치지못하는경우도있다. 따라서 투여한용량과나타나는효과의상관관계가일 정하지않아반응이예상에미치지못하는경 우용량을증량하거나정맥주사로전환하는방 법을고려해야한다. 184 반면에토르세미드는푸로세미드에비해높 고안정적인체내이용률을보이며작용시간이 길다. 187 만성심부전환자 234 명을대상으로 한비맹검무작위연구에의하면푸로세미드 투여군 ( 평균투여량 136 mg) 에비해토르세미 드투여군 ( 평균투여량 72 mg) 에서일차종말 점인심부전에의한재입원율이유의하게낮았 다. 188 또한 1,377 명의심부전환자를대상으로 한관찰연구에서토르세미드 10 mg 투여군이 푸로세미드 40 mg 투여군에비해유의하게낮 은사망률을보였다 (2.2% 대 4.4%). 189 따라서 토르세미드가푸로세미드에비해가격이비싸 기는하지만재입원을줄일수있다면좀더경 제적인치료법이될수도있다 이뇨제의용량 고리작용이뇨제는사구체에서신세뇨관으로 배설이되어신세뇨관의내강안에존재하여야 효과를나타내는데, 일정수준의역치를넘어 서야비로소이뇨작용을나타내며역치에미치 44 만성심부전진료지침

66 지못하는낮은용량에서는효과가전혀없다. 따라서초기용량에반응을보이지않는경우체내이용률이 50% 정도임을감안하여두배의용량을투여하는것이두번투여하는것보다효과적이다. 또한, 일정수준까지는용량을증량하였을때이뇨효과가더증가하는용량의존적효과를보이지만최대이뇨효과를보이는농도에도달한이후에는이뇨효과가더이상증가하지않는다. 190 푸로세미드의경우초기용량은 mg 을하루 1-2회투여하며 ( 토르세미드는 mg 하루한번 ) 통상적인용량은 240 mg을넘지않는다. 신장기능저하로인해소변이배출되지않는경우최대 600 mg까지도사용할수는있지만대개티아지드계열이뇨제와병용요법을하거나한외여과를시행하는것이일반적이다 이뇨제사용과관련된주의사항이뇨제를사용하면서가장주의를기울여야할문제는환자의체액균형상태를잘평가하는것이다. 울혈상태를개선하는것도중요하지만지나친이뇨효과로인해체액부족상태가되는경우저박출상태를초래할수있으며, 저혈압, 신장기능악화와같은문제가나타날수있다. 이뇨제의사용과관련하여좀더흔히나타나는문제는저칼륨혈증, 저마그네슘증, 저나트륨혈증과같은전해질불균형이며저칼륨혈증이가장흔히나타난다. 따라서이뇨제를사용하기전부터칼륨 3.5 meq/l의저칼륨혈증을보이는환자에서는주의해서사용해야 하며칼륨보존이뇨제를같이사용하거나칼륨보충을같이시행한다. 또한혈중크레아티닌 > 2.5 mg 또는사구체여과율예측치 < 30 ml/min/1.73 m 2 의환자에서는신장기능이더나빠질수있으므로주의를기울여야한다. 특히알도스테론길항제의경우신장기능이저하된환자에서는고칼륨혈증을유발할위험이높으므로가급적사용하지않는것이좋다 이뇨효과가불충분한환자의치료고용량의경구이뇨제를투여하여도폐울혈이나부종이개선되지않는경우가드물지않게있다. 이러한환자들은우선, 염분과수분의섭취량을정확하게파악하여염분섭취를철저하게제한하는것이필요하며, 비스테로이드항염증제 (NSAID) 와같은약물을다른곳에서처방받아복용하거나통증치료목적으로효과가오래유지되는부신피질호르몬제제를투여받은경우가있을수있으므로병력을자세히확인하는것이중요하다. 부종이심한환자의경우푸로세미드는장에서의흡수가불충분할수있으므로단기간정맥주사로투여하거나토르세미드로교체하는것을고려할수있다. 앞서언급한바와같이고리작용이뇨제에대한저항성을보이는기전가운데원위세뇨관에서의염분재흡수기능이항진되는것이포함되어있으며티아지드계열이뇨제를병합하는것이효과적인치료가될수있다. 191 위와같은방법으로조절이되지않는경우한외여과와같은물리적인방법을사용할수있다. III 약물치료2 장증상개선을위한약물 45

67 표 3.8. 심부전환자에서사용하는경구이뇨제 이뇨제 초기용량 통상적유지용량 최대용량 작용시간 고리작용이뇨제푸로세미드 mg 1-2회 mg 600 mg 6-8시간 토르세미드 mg 1회 mg 200 mg 12-16시간 부메타니드 * mg 1-2회 1-5 mg 10 mg 4-5시간 티아지드계이뇨제하이드로클로로티아지드 25 mg 1-2회 mg 200 mg 6-12시간 클로르탈리돈 mg 1회 mg 100 mg 24-72시간 인다파미드 2.5 mg 1회 mg 5 mg 36시간 메톨라존 2.5 mg 1회 mg 20 mg 12-24시간 칼륨보존이뇨제 ** 스피로놀락톤 mg 1회 mg 50 mg 1-3시간 아밀로라이드 5 mg 1회 5-10 mg 20 mg 24시간 트리암테렌 * mg 2회 100 mg 200 mg 7-9시간 병합요법 ( 고리작용이뇨제에추가 ) 메톨라존 하이드로클로로티아지드 mg 1 회 mg 1-2 회 * 국내에서는사용되지않는다. ** 혈중칼륨농도의관찰이필요하다. 46 만성심부전진료지침

68 표 3.9. 심부전환자에서이뇨제의처방가이드 목적 울혈증상이나징후가동반된환자에서호흡곤란과부종을개선 대상및처방시기 1) 적응증좌심실박출률과상관없이, 울혈증상이나징후가동반된모든환자좌심실박출률저하심부전에서앤지오텐신전환효소억제제 ( 앤지오텐신수용체길항제 ), 베타차단제, 염류코르티코이드길항제와함께사용해야함용량은환자의체액정도에따라증감 ; 환자는필요에따라이뇨제용량을조정하도록교육받고훈련될수있음 2) 주의점심한저칼륨혈증 ( 칼륨 3.5 mmol/l) 이뇨제에의해악화가능신부전 ( 크레아티닌 > 2.5 mg/dl 혹은사구체여과율예측치<30 ml/min/1.73 m 2 ) 이뇨제에의해악화가능또는이뇨제반응감소 ( 특히, 티아지드이뇨제 ) 증상이있거나증상이없지만심한저혈압 ( 수축기<90 mmhg) 이뇨제에의한체액부족으로악화가능 3) 약물상호작용앤지오텐신전환효소억제제, 앤지오텐신수용체길항제또는레닌억제제와병용 저혈압의위험 ( 일반적으로문제되지않음 ) 다른이뇨제끼리병용 ( 고리작용계 + 티아지드 ) 체액부족, 저혈압, 저칼륨혈증, 신부전의위험비스테로이드항염증제 이뇨제반응을감소 4) 금기증울혈의증상, 징후가없을경우알레르기반응 / 약제별부작용처방법 신장기능, 전해질확인 저용량부터시작 울혈의증상, 징후, 혈압, 신장기능에따라용량조절 약제시작후또는용량증량시 1-2주후일반화학검사 ( 요소, 크레아티닌, 칼륨 ) 확인 심부전전문간호사가환자교육및추적관찰, 검사결과확인, 그리고용량증량등을도울수도있음 III 약물치료환자교육 약제사용시기대되는효과를설명 약제처방후수일이내에증상호전이보임 갈증이있을경우과도한저장성수액섭취를피하도록설명, 어지럼증 / 증상이있는저혈압의발생을알리도록설명 비스테로이드항염증제를복용하지말도록조언 이뇨제저항성과신부전발생가능 증상, 징후, 체중변화에따라용량조절을하도록훈련받을수있음 체액부족인경우 ( 설사 / 구토, 과도한발한 ) 용량을줄일필요가있음 ( 계속 ) 2 장증상개선을위한약물 47

69 문제해결증상이없는저혈압 울혈이없다면이뇨제용량을줄일수있음증상이있는저혈압 울혈이없다면이뇨제용량을줄임 칼슘통로차단제, 나이트레이트, 다른혈관확장제의중단을고려저칼륨혈증 앤지오텐신전환효소억제제의용량을늘림 알도스테론길항제를추가 칼륨, 마그네슘보충저나트륨혈증 티아지드를사용하고있다면고리작용계이뇨제로변경 울혈의소견이심하지않으면이뇨제를감량하거나중단 울혈의소견이뚜렷하다면수분섭취제한 바소프레신길항제사용을고려고요산혈증 티아지드계열이뇨제는중단 증상을동반한통풍발생시콜히친, 진통제사용 예방적알로푸리놀사용고려이뇨효과가불충분한경우 복약여부, 수분 ( 염분 ) 섭취량을확인 푸로세미드를토르세미드로교체 염류코르티코이드길항제를추가하거나증량 티아지드나메톨라존을병합 이뇨제복용횟수를늘리거나정맥주사신장기능의악화 체액부족상태인지확인 신장독성을가진약물을사용중인지확인 ( 비스테로이드항염증제 ) 염류코르티코이드길항제중단 앤지오텐신전환효소억제제감량고려 48 만성심부전진료지침

70 디곡신 좌심실박출률저하심부전환자에서재입원율감소를위해디곡신을사용하는것은도움이 될수있다. (Class IIa, Level of Evidence B) 좌심실수축기능이저하된환자에서디곡신은이뇨제와더불어매우오래전부터고전적인치료제로사용되어왔다. 그러나심부전의병태생리에대한이해가깊어지고특히레닌-앤지오텐신-알도스테론계통차단제가보편적으로사용되면서부터디곡신의임상적효용성에대한많은논란이있었으나이에대한임상연구는충분히진행되지못하였다. 디곡신을 1-3개월동안투여한소규모무작위연구결과들을종합해보면환자의삶의질이나증상개선, 운동능력의호전이일관되게확인되었지만 이는레닌-앤지오텐신-알도스테론계통차단제와베타차단제, 염류코르티코이드길항제를포함하는현재와같은표준적인진료지침이전에진행된연구이어서임상적인적용에제한이따른다. 디곡신에대한비교적최근에시행한대규모임상연구로는 DIG 연구가대표적인데, EF 45%, NYHA 기능등급 II-IV 심부전환자 6,800명을디곡신투여군과대조군으로나누어평균 3년정도추적관찰하였을때생존율에서는차이가없었으나재입원율, 특히심부전악화에따른재입원율에서유의한개선효과를입증하였다. 197 다른소규모무작위연구에대한메타분석을하였을때에도비슷한결론을얻을수있었다. 198 좌심실박출률저하심부전환자에서디곡신을고용량으로투여하거나높은혈중농도를유지하는경우, 디곡신을저용량으로투여하거나낮은혈중농도를유지하는경우에비하여추가적인임상적이득없이부작용만더증가하는것으로알려져있으므로 디곡신투여시에는저용량이나 2일 1회로시작하여 mg 1일 1회나 0.25 mg 1일 1회로유지하는것이일반적이며독성에의한부작용발생에주의를기울여야한다. 디곡신독성의대표적인증상으로는소화기계증상 ( 식욕부진, 오심, 구토 ) 과신경계증상 ( 시각장애, 지남력장애, 착란 ) 을들수있으며치명적인부정맥도발생할수있고이러한디곡신독성은특히고령 (> 70세 ) 이나, 신부전이동반된경우, 체중이작거나전해질이상이동반된경우, 디곡신대사에영향을줄수있는약제 ( 마크롤라이드계항생제, 이트라코나졸, 사이클로스포린, 아미오다론, 퀴니딘등 ) 를함께복용하는경우에잘발생하는것으로알려져있다. 디곡신혈중농도를측정하여독성발현을예측하거나배제할수없으므로 202, 203 디곡신혈중농도를측정하기보다는저용량으로투여하며독성이발생하지않는지임상적으로경과관찰하는것이중요하다. III 약물치료2 장증상개선을위한약물 49

71 주사용강심제 1. 심인성쇼크를동반한심부전환자에서전신관류를유지하고다른장기의기능을보존하기위해서일시적으로주사용강심제를사용해야한다. (Class I, Level of Evidence C) 2. 심장이식이나기계적순환보조를기다리는말기심부전환자에서지속적인주사용강심제를사용하는것은타당하다. (Class IIa, Level of Evidence B) 3. 심한수축기능저하, 낮은혈압, 조직관류저하등의소견이없는심부전환자의치료에주사용강심제를사용하면해가된다. (Class III, Level of Evidence A) 불응성말기심부전환자는급성악화요인에의해심인성쇼크가발생하여전신조직관류가저하되는위험한상태에이를수있다. 이러한상태에서는주사용강심제를일시적으로사용하여불안정한혈역학적상태를개선함으로써급성악화요인을해결하고관상동맥재관류, 기계적순환보조, 심장이식등최종치료를시행할때까지환자의혈액순환을유지하여야한다 하지만강심제는일시적으로환자의혈역학적인상태는개선시키지만전반적인임상경과를호전시키지는못하였다. 다양한작용기전을가진경구용강심제가개발되었지만대부분부정맥발생률을증가시켜장기적으로사용할경우심부전환자의사망률이증가하였다 따라서강심제는심한수축기능저하, 낮은혈압, 조직관류저하등의소견이있는심부전환자에서일시적으로사용하거 나심장이식이나기계적순환보조를기다리는 불응성말기심부전환자에서가교치료의목 적으로사용하는경우를제외하고는심부전환 자의사망률을증가시킬수있으므로사용하 지말아야한다. 주로사용되는주사용강심제 로는카테콜라민계통인도부타민과포스포디 에스테라제길항제인밀리논이있다. 밀리논은 도부타민보다강력한혈관확장효과가있어 폐동맥압력이나전신혈관저항의감소를유발 할수있으며맥박수와심근산소소비량의증 가가적은장점이있으나저혈압의발생빈도 가높다. 주사용강심제의사용이필요한심부 전환자에서강심제개별약제에따른임상경 과의유의한차이는없었다. 따라서약제의선 택은환자의상태에따라담당의사가결정할 205, 217 수있다. 50 만성심부전진료지침

72 3 장 기타약물치료 항응고약물 1. 심방세동을동반한심부전환자에서추가적인혈전의위험인자들이있는경우항응고약물을투여해야한다. (Class I, 와파린, Level of Evidence A / 다비가트란, 리바록사반, 또는아픽사반, Level of Evidence B) 2. 심방세동을동반한심부전환자에서항응고제 ( 와파린, 다비가트란, 아픽사반, 또는리바록사반 ) 의선택은위험인자, 비용, 수용성, 선호도, 약물상호작용가능성과다른임상특징들을고려해결정해야한다. (Class I, Level of Evidence C) III 약물치료3. 심방세동을동반한심부전환자에서추가적인혈전의위험인자가없는경우라도항응고약물을투여하는것이타당하다. (Class IIa, 와파린, Level of Evidence A / 다비가트란, 리바록사반, 또는아픽사반, Level of Evidence B) 4. 심부전환자에서심방세동이나, 혈전-색전사건의병력이나심장내혈전이없는경우에는항응고약물투여가추천되지않는다. (Class III, Level of Evidence B) 심방세동은대표적인혈전-색전사건의위험인자로서심부전환자에서혈전-색전사건의유병률은 13-27% 에이른다. 218 심방세동관련최근진료지침에서는뇌졸중을포함한혈전- 색전사건의위험도를동반위험인자의개수에따라 CHA 2 DS 2 -VASc 공식으로점수화하고 219, 220 있다. 즉 심부전, 고혈압, 연령 75 세이 상, 당뇨병, 과거뇌졸중 / 일과성허혈성발작, 혈관질환 ( 심근경색병력, 말초혈관질환, 대동 맥의동맥경화반 ), 연령 세, 여성 과같 은위험인자중 연령 75 세이상 과 과거뇌졸 중 / 일과성허혈성발작 에는 2 점, 나머지위험 3 장기타약물치료 51

73 인자들에는각 1점을부여해합계 2점이상인경우항응고치료를해야하며, 219, 220 1점인경우역시항응고치료가타당하다고언급하고있다. 219 심부전은그자체가 CHA 2 DS 2 -VASc 점수 1점에해당한다. 따라서심방세동을동반한심부전환자로서기타혈전의위험인자 ( 고혈압, 연령 65세이상, 당뇨병, 뇌졸중또는일과성허혈성발작, 혈관질환, 여성 ) 를하나이상가지고있다면 CHA 2 DS 2 -VASc 점수는 2 점이상이고, 심부전외기타위험인자가전혀없다면그대로 1점이다. 직접적인트롬빈길항제인다비가트란과응고인자 Xa 길항제인리바록사반, 아픽사반등은기존의비타민 K 길항제인경구항응고제와파린과구별하여 NOAC (new oral anticoagulant) 으로분류한다. NOAC은효능과안전성측면에서조금씩다른면이있지만, 대체로와파린에비해우수하거나열등하지않은결과를보였다 이에 2012년유럽심방세동진료지침에서는 NOAC을와파린과똑같이 CHA 2 DS 2 -VASc 2점이상일때 Class I (Level of Evidence A), 1점일때 Class IIa (Level of Evidence A) 로권고하면서최선은 NOAC이고차선이와파린이라고명시하였다. 219 하지만, NOAC마다효능과안전성면에서차이가있으므로획일적으로하나의계열로간주하는것은부적절하다. 226, 년미국심방세동진료지침에서는 CHA 2 DS 2 -VASc 2점이상일때 Class I (Level of Evidence B) 으로항응고제투여를권고하지만최선혹은차선의선택과같은표현을사용하지는않 았다. 220 또한 1점일때는 Class IIb (Level of Evidence C) 로항응고치료를하지않거나혹은아스피린이나경구항응고제의사용을고려할수있는것으로기술하였다. 심방세동을동반한심부전환자에서다른혈전발생의위험인자가없는경우 (CHA 2 DS 2 - VASc=1), 항응고치료를권할것인지, 권한다면아스피린, 와파린혹은새로운경구항응고제중어떤약제를권할것인지에대해서는아직충분한연구가이루어지지않았다. 그러나, 심방세동환자에게아스피린보다와파린이뇌졸중예방에우수하며, NOAC이와파린에열등하지않은뇌졸중예방효과를보이면서도주요출혈위험측면에서우수하였던결과 들을고려할때심방세동을동반한심부전환자에서다른혈전발생의위험인자가없는경우라도와파린이나 NOAC의사용은타당할것이다. 한편, 심방세동이없는동율동의심부전환자들의경우아스피린, 와파린, 클로피도그렐로치료한군간에임상경과에유의한차이가없었고오히려출혈과같은부작용만와파린군에서더높은것으로나타났다 임상적으로안정적인심부전환자들에서혈전-색전의발생률은낮았으며 (1-3%/ 년 ), 좌심실박출률이매우저하되어있거나심초음파에서심장내혈전이관찰되는경우라도혈전-색전의발생률은높지않았다 따라서특정한적응증이없다면출혈의위험성을고려할때, 수축기심부전환자에게와파린이나아스피린을통상적으로투여하는것은적절하지않다. 52 만성심부전진료지침

74 스타틴 다른적응증이없는심부전환자에서심부전의예후개선을목적으로한스타틴사용은추천 되지않는다. (Class III, Level of Evidence A) 동맥경화증을가진환자에서심혈관위험을줄이고고지혈증치료를위한목적으로스타틴투약이권고된다 하지만심부전의예후를개선시킬목적으로스타틴을투약하는것은추천되지않는다. 일부연구에서는스타틴이심부전환자에게도움이되는것으로보고하였지만이는대부분관찰연구이거나후향적연구결과였다. 227, 만성심부전환자를대상으 로한대규모무작위연구 (CORONA, GISSI- HF) 에서는스타틴이심부전환자의장기예후를개선시키지못하였다. 246, 247 또한심부전환자에서혈중콜레스테롤이낮은경우사망률이증가한다는보고도있다. 248, 249 따라서다른특별한적응증없이심부전의예후개선을목적으로스타틴을처방하는것은부적절하다 이바브라딘 III 약물치료1. 좌심실박출률이 35% 이하이고, 맥박수가분당 70회이상인동율동의심부전환자에서, 베타차단제및앤지오텐신전환효소억제제를사용함에도불구하고심부전증상이 (NYHA 기능등급 II-IV) 지속될경우이바브라딘을사용하는것은타당하다. (Class IIa, Level of Evidence B) 2. 좌심실박출률이 35% 이하이고, 맥박수분당 70회이상인동율동의심부전환자에서, 베타차단제를사용할수없는경우이바브라딘치료를고려할수있다. (Class IIb, Level of Evidence C) 심부전환자에서맥박수가중요한예후인자 라는것은잘알려져있다 이바브라딘은 동결절의 I f channel 을억제하여동율동인환 자에서맥박수를낮추는작용을한다. 이바브 라딘은심혈관계다른채널에는작용하지않아 박출률저하심부전환자에서심근수축력이 3 장기타약물치료 53

75 나심장내전도에영향을미치지않고맥박수만을특이적으로감소시킨다. 박출률저하심부전환자를대상으로이바브라딘의효과를평가한 SHIFT 연구에서베타차단제를포함한기본적인약물치료에이바브라딘을추가하는것이심부전환자의예후를개선시켰다. 253 사후분석에서예후개선효과는맥박수감소와유의한상관관계가있었다. 254 따라서좌심실박출률 35% 이하, 맥박수분당 70회이상, 표준심부전약물치료에도지속되는 NYHA 기능등급 II-IV인심부전환자에서이바브라딘사용을고려할수있다. 한편, 베타차단제를사용 할수없는환자에서이바브라딘이베타차단제를대체할수있는가에대한무작위연구결과는아직없지만 SHIFT 연구에서베타차단제를사용할수없었던약 10% 의환자를분석한결과에서는이바브라딘이위약에비해심혈관계사망혹은심부전으로인한재입원을유의하게감소시켰다. 250 따라서좌심실박출률 35% 이하, 맥박수분당 70회이상, 표준심부전약물치료에도증상이지속되는 NYHA 기능등급 II-IV인심부전환자에서베타차단제를사용할수없는경우에도이바브라딘사용을고려할수있다 바소프레신길항제 다른치료에불응하는저나트률혈증을동반한심부전환자에서바소프레신길항제사용을고 려할수있다. (Class IIb, Level of Evidence B) 저나트륨혈증은인지장애를일으켜주의력을감소시켜쉽게넘어지게할수있으며심한경우의식소실을유발할수있다. 251 용적과부하에동반된저나트륨혈증에서 2형바소프레신수용체길항제는인지기능을유의하게향상시키는것으로보고되었다. 252 저나트륨혈증에서는항이뇨호르몬분비이상증후군 (SIADH) 이나갑상선기능저하증, 저알도스테론증과같은다른원인이없는지확인하는것이중요하며, 그렇지않은경우수분섭취를제한하거나앤지 오텐신II를억제하는약물을사용할수있다. 바소프레신길항제는용적과부하가동반된저나트륨혈증에서혈중나트륨농도를증가시킬수있으나, 252, 253 심부전환자에서장기사용이생존율을개선시키지는못하였다. 254 현재국내에는톨밥탄이라는바소프레신길항제가있으며심부전환자에서저나트륨혈증에의한인지장애가있는경우사용을고려할수있다. 하지만, 장기적인효과나안전성은아직확립되어있지않다. 한편, 바소프레신길항제는기존이 54 만성심부전진료지침

76 뇨제와는전혀다른작용기전을갖기때문에 이뇨제저항성심부전환자에서그유용성을 기대할수있으며일본에서는심인성부종에서 적응증을갖고있다 ARNI (Angiotensin Recep tor Neprilysin Inhibitor): LCZ696 LCZ696 는최초의앤지오텐신수용체길항 제와네프릴리신의이중저해제 (dual inhibitor) 이며, 네프릴리신억제제사쿠비트릴 (AHU377) 과앤지오텐신수용체길항제인발 사르탄의작용기를가지고있는 Angiotensin Receptor Neprilysin Inhibition (ARNI) 계 열약제로심각한혈관부종의위험을최소화 하도록설계되었다. 이중네프릴리신이라불 리는중성엔도펩티다제는나트륨이뇨펩티드, 브라디키닌등여러내인성혈관활성펩티드 를비활성화시킨다. 네프릴리신의억제는내 인성혈관활성펩티드의비활성화를저해하 여체내농도를증가시키게되며이는결국혈 관확장, 나트륨배설항진, 세포자멸감소, 섬 유화예방등의효과가기대되며불리한작용 을하는신경호르몬의과도한활성화를막는 256, 257 다. PARADIGM-HF 연구는좌심실박 출률 40% 이하인 NYHA 기능등급 II-IV 의심 부전환자총 8,442 명을대상으로앤지오텐신 전환효소억제제에날라프릴 1 일 2 회 10 mg 군 과 LCZ696 1 일 2 회 200 mg 을비교한무작위 연구로에날라프릴군대비 LCZ696 군이심혈 관원인사망위험도 20%, 심부전입원율 21%, 전체원인으로인한사망위험도 16% 를감소시켰으며전체연구는 27개월시점에조기종료됐다. 258 위임상시험의중요한점중하나는기존의심부전치료의표준치료로이미사망률과입원율감소가입증된에날라프릴투여군과비교한것으로이를대조위약군과비교한 SOLVD-T, CHARM-Alternative 연구처럼위약과 LCZ696을비교한추가추정분석에서는 LCZ696이 SOLVD-T를적용하였을때위약사용군보다심혈관사망률 34%, 심부전재입원율 49% 감소효과가추정되었고 CHARM-Alternative를적용하였을때각각 32%, 46% 감소효과가예측되었다. 259, 명의한국인이포함된연구에서는좌심실박출률감소심부전에서사망률감소를입증한연구로비교적대규모로진행되었고명확한임상결과로조기종료된점을고려하면향후박출률감소심부전치료패라다임의변화가있을것으로예상된다. 최근에미국과유럽에서도진료지침이개정되지않았으나캐나다진료지침에는좌심실박출률감소의경도혹은중등도심부전환자중 BNP 상승소견이있거나과거 12개월내심부전으로입원한병력이있으며혈중칼륨 <5.2 mmol/l, 사구체여과율예측치 30인경우앤지오텐신전환효소억제제나앤지오텐신수용체길항제를대신하여사용하는것을권고하고있으며그수준은양질의증거 (high quality evidence) 를가지나아직제품화되지않아일시적권유 (conditional recommendation) 상태로정의하였다. 261 추후혈압및전해질변화를확인하는임상적관찰 III 약물치료3 장기타약물치료 55

77 이필요하며장기적인사용을통한안전성또 한확보되어야할것이다. 하지만중요진료지 침의권고사항으로포함될것으로생각되어 1 차치료제혹은효과적인앤지오텐신전환효소 억제제혹은앤지오텐신수용체길항제를대체 할수있는약으로대두될가능성이있다. 56 만성심부전진료지침

78 4 장 좌심실기능이보존된심부전환자의약물치료 1. 동반된고혈압은합병증의발생을줄이기위해고혈압진료지침에따라치료해야한다. (Class I, Level of Evidence B) 2. 수분저류에의한증상은이뇨제를사용해치료해야한다. (Class I, Level of Evidence C) 3. 표준약물치료에도불구하고심부전증상이지속되고협심증혹은심근허혈이이를악화시킬것으로판단되는경우관상동맥중재술을시행하는것은타당하다. (Class IIa, Level of Evidence C) 4. 박출률보존심부전환자에서심부전증상의호전을위하여심방세동을진료지침 ( 참고 : 심방세동 ) 에따라치료하는것은타당하다. (Class IIa, Level of Evidence C) III 약물치료5. 고혈압의조절을위해앤지오텐신전환효소억제제, 앤지오텐신수용체길항제및베타차단제등을사용하는것은타당하다. (Class IIa, Level of Evidence C) 6. 심부전증상의호전을위해앤지오텐신수용체길항제나알도스테론길항제를사용하는것을고려할수있다. (Class IIb, Level of Evidence B) 좌심실박출률의정상범위는정의에따라다 를수있지만, 심부전환자의 40-50% 는좌심 262, 263 실박출률이보존된것으로알려져있다. 여러연구에서사용한정상좌심실박출률의 기준은 40%, 45% 혹은 50% 이상으로조금씩 다르며실제로좌심실박출률이 40-50% 정도 의경계선상에있는환자들을박출률보존심 56, 154, 155, 175, 262, 264, 265 부전에포함하기도한다. 좌심실박출률이좌심실의수축능력을대표하 는지표로인식되어왔기때문에좌심실수축 기능이정상인심부전혹은이완기심부전이라 는용어가사용되기도하였다. 하지만이완기 4 장좌심실기능이보존된심부전환자의약물치료 57

79 능장애에의해심부전이발생하였다하더라도 이완기능장애를명확하게진단하기어려운경 우가많아, 최근에는박출률보존심부전이라 는용어가선호되고있다. 박출률보존심부전 은일반적으로고령이나여성에많고, 고혈압, 당뇨병, 허혈성심장질환, 비만, 고지혈증혹은 심방세동등이주된원인이나위험인자로알려 져있다. 263, 266, 267 박출률보존심부전환자들의 생존율은박출률저하심부전환자들과비교할 때거의비슷하거나약간좋은것으로알려져 있으나, 심부전에의한입원율이나운동능력 등에는차이가없는것으로알려져있다. 262 박출률보존심부전환자들의약물치료에 대한여러대규모연구들이시행되었지만, 아 155, 175, 직까지효과가확실히증명된약은없다. 267, 268 따라서현재로써는증상에대한치료와 심부전을진행시킬수있는동반질환혹은위 험인자를교정하는것이주된치료로알려져 있다. 즉수분저류에의한울혈증상이있으 면이뇨제를사용하여증상을호전시킬수있 고, 동반된고혈압은심부전을악화시킬수있 으므로충분히조절해야한다. 269, 270 어떤약제 를선택해야하는가에대해서는동반된질환 에따라앤지오텐신전환효소억제제, 앤지오텐 신수용체길항제, 베타차단제, 칼슘통로차단 제등의고혈압치료제를선택할수있다. 목 표혈압은특별히정해진것은없으나일반적인고혈압치료와다르지않다. 최근알도스테론길항제를사용한연구에서심부전에의한사망률을감소시키지는못하였으나, 심부전악화에의한입원율을줄일수있는것으로보고되었다. 하지만고칼륨혈증과혈중크레아티닌수치가증가될수있어이에대한주의가필요하다. 175 박출률보존심부전환자에서허혈성심장질환이동반된경우가많으나중재시술이나수술적치료등의적극적치료가예후를호전시킨다는직접적인연구결과는아직없다. 따라서허혈성심장질환환자의일반적인치료방침에따라치료하여야한다. 즉, 동반된관상동맥협착이심부전을악화시킬것으로생각되는경우에는중재시술이나수술적치료를적극적으로고려하여야한다. 심실반응이증가되어심박수가높아진심방세동의경우에는칼슘통로차단제나베타차단제를사용하여심박수를낮추어이완기충만시간을증가시킬수있다. 271, 272 박출률저하심부전환자에서사용하지말아야하는약제들은일반적으로박출률보존심부전환자에서도사용해서는안되지만, 칼슘통로차단제를고혈압의조절이나심방세동에서의심박수조절을위해사용하는경우는예외적으로사용할수있다. 58 만성심부전진료지침

80 KSHF guideline for the management of CHRONIC HEART FAILURE 2016 비약물치료 IV 1. 전인적관리및다학제적접근 2. 일반적관리 3. 심장재활및운동치료 4. 교육및상담 5. 동반질환의관리

81 1 장 전인적관리및다학제적접근 1. 심부전환자에서심장기능및삶의질개선을위해팀관리및다학제적접근을해야한다. (Class I, Level of Evidence A) 2. 심부전환자에서사망률, 이환율및심부전으로인한재입원율을감소시키기위해팀관리및다학제적접근을해야한다. (Class I, Level of Evidence A) 심부전치료가지속적으로발전하고있으나심부전환자의전반적인예후는여전히좋지않아, 의학적, 정신사회적, 행동학적요인에대한다각적인접근이필요하다. 팀관리와다학제적접근을통한환자교육, 적절한의학적치료, 심장재활, 정신심리학적인지지및보건관리체계에대한접근성의개선등을통해임상결과를호전시킬수있다. 여기에는심부전치료전문가 ( 심장전문의, 심부전전문간호사 ) 와타보건전문가 ( 일차진료의, 약사, 영양사, 운동처방사, 물리치료사, 정신심리학자및사회사업가 ) 의유기적연결과협력이필요하며, 각지역및국가의사회, 문화, 경제적인여건에따라적절한조정이필수적이다. 다학제적접 근의구체적인구성요소에는적절한약물및기구치료, 심부전에대한적절한환자교육, 근거중심치료전략에대한환자의순응도개선, 자기관리에대한교육, 증상에대한자기감시및유연한이뇨제사용, 퇴원후정기적인추적관찰 ( 외래및가정방문또는전화추적및원격관리프로그램 ), 보건관리체계에대한접근성개선, 심부전의급성악화시보건의료시스템의빠른접근, 설명하지못하는갑작스러운체중증가에대한평가, 영양상태및삶의질그리고검사결과에대한평가, 최신치료전략에대한교육및환자와가족에대한정신심리적지지등이포함된다. 이와관련된주요과제는심부전의정의와병인에대한교육, 증상감 60 만성심부전진료지침

82 시및자기관리, 약물치료의효과와부작용에대한교육, 약물순응도, 식사관련교육, 음주관련교육, 금연교육, 운동, 여행과여가생활, 성생활을포함하는활동범위, 직업의선택, 백신접종, 수면과호흡이상그리고정신심리적인측면을포함한다. 특히고위험군의환자가포괄적인심부전관리의대상이되며, 고위험군은다음과같다. 신기능장애, 저심박출량상태, 당뇨병, 만성폐쇄성폐질환, 지속적인 NYHA 기능등급 III- IV의증상들, 잦은입원, 여러가지동반질환이있는경우, 우울증의과거력, 인지장애, 사회적지지가부적절한경우, 건강지식의부족, 치료계획을지속적으로준수하지않는경우등이다. 또한, 구조적인심장의변화및증상이있는심부전환자와심부전악화로입 퇴원병력이있는환자들은사망및이환율의고위험군이어서자기관리에대한교육이필요하다 이러한교육내용은증상의변화, 체중의변동, 염분섭취제한, 처방대로약물복용하기및신체활동의지속등을포함한다. 환자와가족및간병인등에대한교육및상담, 환자자기관리에대한교육, 추적관찰, 수분저류증상및징후에대한빠른대처법교육, 일차의료기관과의연계가필요하다. 다학제적팀접근이심부전환자의입원율 및사망률을낮출수있으며, 자기관리를중심 으로하는교육을통하여지시순응도의향상, 자기감시및약물순응도, 입원까지의시간, 재원일수의향상을보였다. 273 만성심부전환 자를대상으로하는다학제적접근은재입원율 도감소시키며, 추적관찰기의환자에대한다 학제적접근역시재입원율과사망률을감소시 278, 279 킨다고보고되었다. 또한 다학제적인접 근은예기치않은입원을최소화하는것으로 알려져있다. 280 다학제적접근에대한연구들 을종합하여분석해보면특화된다학제적접 근팀을구성한경우사망률을줄이고심부전 입원을줄였다. 281 따라서고위험환자군에서 다학제적심부전관리프로그램의시행을권고 해야한다 수술적치료또는기계적순환 보조를할때환자선정, 치료및추적관찰모 두에서이러한접근이필요하며, 내과, 외과, 마취과, 기타여러과와의다학제적접근이필 요하다. 56, 58 특히심장이식의경우, 환자선정 에있어서이식전문심장내과의사, 흉부외과 의사, 간호사, 사회사업가및완화치료전문가 와의다학제적접근이필요하다. 56 IV 비약물치료1 장전인적관리및다학제적접근 61

83 2 장 일반적관리 식사, 영양, 체중조절 증상이있는심부전환자에서울혈증상을줄이기위해염분을제한 (sodium restriction) 하는 것이타당하다. (Class IIa, Level of Evidence C) 심부전환자를위한식사및영양에대한근거는아직충분하지않은상황이다. NYHA 기능등급 II-III의심부전환자를대상으로한소규모무작위연구에서식사조절을통해염분섭취량및체중을줄이고, 주 3-5회단계적운동을시행한결과운동능력이향상되고심리적으로보다안정된것으로보고되었다. 284 만성심부전환자의식사조절에서염분제한이중요한데, 2013년미국심부전진료지침에서는울혈증상을줄이기위해증상이있는환자에서염분을제한하는것이타당하다고권고하고있다. 56 반면에과도하게염분을제한하면신경호르몬계를활성시킬우려가있으며무작위연구에서는과도한염분제한이박출률저하심 부전환자의임상경과를악화시킨다는보고가 285, 286 있었다. 한국인은기본적으로높은염분섭취를보 이며이에대한교정이매우어렵다. 우리와비 교적비슷한식생활을보이는일본의만성심 부전진료지침에서도서양의기준대로염분섭 취를권고하는것이일본인의식생활에서는부 적절하다고기술하고있으며, 식사지도를통 해빵이나가락국수등의가공식품에도상당한 양의염분이함유되어있음을교육하도록권고 하고있다. 국내연구결과에의하면 232 명의 NYHA 기능등급 III-IV, 좌심실박출률 30% 이하인심부전환자에서하루소변나트륨배 출량이 3 g 이상인경우, 증상도심하고심혈 62 만성심부전진료지침

84 관사건도더많이발생하는것으로확인되었다. 287 따라서아직까지이견이있기는하나통상적으로중등도이상의심부전환자의경우하루 2 g ( 소금으로는 7-8 g) 이하의나트륨을섭취하는것을권고하고있다. 비만은고혈압, 수면무호흡증과같은심부전의위험인자와관련이있고좌심실비후, 이완기능장애와도연관이있으므로심부전의발생을예방하기위해서는체중을조절하는것이도움이된다. 288, 289 그러나이미심부전진단을받은환자에서는과체중인경우뿐만아니라체중이지나치게낮은경우에도오히려예후가더좋지않은것으로알려져있다. 체질량지수가 kg/m 2 인심부전환자가정상체질량지수를가진환자에비해오히려사망률이나입원율이낮다고일관되게보고되었으며, 심인성카켁시아는불량한예후인자로서, 체질량지수가 18.5 kg/m 2 미만인경우예후가매우나쁘다 증상이심한심부전환자는과다한체액저류여부를확인하기위해매일일정한시간에체중을측정하는것이바람직하다. 하루에체중이 2 kg 이상증가하는경우, 급성악화의발생가능성이높으므로스스로활동을줄이고염분섭취를엄격하게제한하면서담당의료진을가급적신속히만나야한다 흡연과음주 흡연은심혈관질환에서예방가능한중요한위험인자중하나이다. 295 흡연은심부전의발생 에도중요한영향을미치며, 고령의심부 전환자에서흔히동반되는폐질환이나악성종 양의중요위험인자로, 삶의질저하에큰영향 을미친다. 299 또한심부전환자에서흡연을중 지하면심부전증상이호전되고사망률이감소 300, 301 하므로적극적으로 금연을권고해야한 다. 그러나실제진료현장에서는금연교육이 잘이루어지지않고있어, 302 의료진은심부전 환자에게지속적으로금연의위험성을알리고 금연을유지하도록교육해야한다. 58 과다한알코올섭취는심부전발생의중요 한위험인자이다. 296, 303, 304 심부전발생을초래 하는알코올의용량과성별에따른차이는확 실하지않지만과다한알코올섭취가심부전의 발생과진행에위험인자인것은분명하다. 따 라서심부전환자에서알코올을과도하게섭취 하지않도록지속적으로교육하는것이바람직 하며특히알코올성심근병이의심되는경우에 는엄격한금주가필요하다 예방접종과심내막염의예방 독감은전세계적으로주요한입원및사망원 인이다. 심혈관질환이있거나, 당뇨병이있는 경우특히 65 세이상고령환자의경우독감에 의한입원, 사망등의합병증이발생하는경우 가많다. 305 아직까지심부전환자에서예방접 종의효과를확인한무작위연구결과는없지 만, 급성관상동맥증후군환자에서독감예방 접종이 1 년심혈관사망률을감소시키는것으 로보고되었으며, 306 고령의심부전환자에서 IV 비약물치료2 장일반적관리 63

85 입원감소효과가확인되었다. 307 반면예방접종에의한심혈관사건의증가는특별히보고된바없다. 308 젊은심혈관질환환자에서는예방접종의효과가뚜렷하지않았지만, 309 만성심장질환이있는 65세이상인구대상의관찰연구에서예방접종을통해심혈관질환발생감소효과가확인되었다. 310 따라서금기증이없는한 65세이상고령의심부전환자는폐렴구균예방접종과매년독감예방접종을시행해야한다. 58 판막증등다른적응증이없는경우심부전진단만으로심내막염예방치료를하는것은필요하지않다. 311 심부전환자에서심내막염예방이필요한동반질환은다음과같다 : 인공판막, 심내막염의과거력, 인공조직을이용해수술한선천성심장기형 ( 특히시술 / 수술후 6 개월이내 ), 심장판막질환으로심장이식대기중인경우 타약제의사용 심부전환자들은식사량감소와이뇨제등의사용으로비타민이나기타영양성분이부족할수있다. 이에대하여몇가지영양보조요법 과호르몬요법 이부가적인치료로제안되었으나아직심부전환자의생존율을증가시켰다는임상연구결과는없다. 오메가-3 지방산의경우에는일부무작위연구에서사망률과이환율, 특히재입원율을감소시키는것으로보고되었으며, 319, 320 소규모무작위연구에서좌심실박출률을 10% 이상증가시켰다. 321 심방및심실부정맥이심부전의이환율과사망률을증가시키기때문에이를조절하기위하여다양한종류의항부정맥약제들에대하여임상연구가진행되었으나대부분의약제가심부전환자들의사망률을증가시키는것으로확인되었고, 아미오다론과도페틸라이드만이사망률에중립적인효과를가지는것으로밝혀져있다 이전에는칼슘통로차단제가말초혈관수축및좌심실후부하를감소시킴으로써만성심부전환자에게도움이될수있을것으로여겨졌으나대부분심근활성도를저하시켜오히려심부전증상을악화시키는것으로확인되었다. 271, 328, 329 암로디핀만이유일하게대규모연구에서심부전의이환율과사망률에중립적인효과를가지고있어심부전환자에서추가적인혈압조절을위해사용을고려할수있다. 330 일반적으로박출률저하심부전환자에서칼슘통로차단제는권고되지않는다. 비스테로이드항염증제는신장에서프로스타글란딘합성을저해하므로신장에서의혈관확장을억제하고헨레고리상행각및집합관에서나트륨재흡수를억제하지못하므로결국나트륨과수분이저류되고이뇨제의효과를감소시킨다. 여러관찰연구에서비스테로이드항염증제는심부전환자의이환율과사망률을증가시켰다 티아졸리딘다이온은세포핵의 PPARγ를활성화시킴으로써인슐린감수성을증가시키는데신장의집합관에도 PPARγ가발현되어있어나트륨재흡수와관련되어있다. 이약제는기존의심부전환자뿐만아니라심부전으로진단된적이없는환자에서도심부 64 만성심부전진료지침

86 전에의한입원이나악화의빈도를증가시켰다 직업과활동범위 만성심부전환자를대상으로직업선택을제한하는것이자유로운직업선택에비하여사망률과재입원율을감소시키는지를확인한연구는없다. 하지만직업수행에필요한운동능력을고려하여직업을선택하는것은타당하다. 만성심부전환자가최근증상악화를경험하는경우, 일정기간임상적인안정후근무의가능성을재검토해야하며, 이때기능적운동능력을평가하는것이도움이된다. 운동능력에대한평가후에는결과에따라일시적으로작업시간또는작업량을조절하더라도기존의직업을유지하는것이바람직하다. 만성심부전환자에서일상적인생활 ( 걷기, 계단오르기, 가벼운가정활동 ) 이가능하다면성생활에도큰제한이없지만이는개인마다차이가있을수있다. 340 일반적으로심부전환자의약 60-85% 에서성생활욕구및활동의감소, 또는중단등의성생활문제가있으나, 심부전환자에서성행위로인한사망률은잘알려져있지않다. 그러나역학연구에서일반적인성행위와관련된급사는약 0.6% 로보고된바있고, 344 심근경색증후의고위험환자와일반인을비교한연구에서성행위와연관된사망률은 1.1% 대 1.0% 로차이를보이지않았다. 345 따라서직접적인코호트연구는없으나성생활자체가심부전으로인한사망 을증가시킨다는근거는없다. 성행위의위험성과관련된요인은좌심실의수축기능보다는임상증상 (NYHA 기능등급또는 6분보행검사 ) 과관련되어있다. 342 NYHA 기능등급 I의경우, 성행위로인한사망또는심부전악화의가능성은낮은것으로알려져있다. 또한적절한심부전약물치료를받고있는환자는안전하고만족스러운성생활을유지할수있다. 346 NYHA 기능등급 II는중간위험도를가지며운동능력에대한평가가도움이된다. 운동부하검사상 5 METs 이상이고, 심초음파상중증의좌심실수축기능저하소견이없다면성생활은비교적안전하다고할수있다. 그러나 NYHA 기능등급 III-IV의경우는고위험군으로성생활을시작하기전심부전전문가에의한정밀한평가와상담이필요하다. 발기부전의경우실데나필과같은 5형포스포디에스테라제길항제의사용은안정상태의심부전환자에서비교적안전하며일부연구에서는심장기능특히운동능력개선면에서효과가있다고알려져있다. 347 그러나질산염제제를사용하는환자에서는동시에투여해서는안된다. 만성심부전환자에서여행과여가생활은삶의질과관련된중요한문제이다. 적절한약물요법중인 NYHA 기능등급 I-II의경우에 7 시간이내의비행기여행은특별히제한되지않는다 그러나일상생활에서심부전의증세가있는 NYHA 기능등급 III-IV의경우비행시간이길거나고온다습하고고도가높은곳으로의여행은제한할필요가있다. 비행기여행과고온환경에노출되는경우수분손실양이증가하므로적절한체액균형에대한 IV 비약물치료2 장일반적관리 65

87 확인이필요하며심부전을포함한병력과현재 투약에대한서면기록을소지하는것이바람 직하다. 또한현재복용중인약과추가적인여 분의약제를반드시가지고있어야한다. 66 만성심부전진료지침

88 3 장 심장재활및운동치료 1. 심부전환자에서운동치료 ( 또는규칙적인신체활동 ) 는기능상태를개선하기위한안전하고효과적인방법으로써, 참여가가능한환자들에게시행되어야한다. (Class I, Level of Evidence A) 2. 임상적으로안정된심부전환자에서활동능력, 운동지속시간, 삶의질과사망률개선을위해심장재활을시행하는것은타당하다. (Class IIa, Level of Evidence B) 심부전환자의치료에있어운동처방의역할은 2001년캐나다심장학회심부전진료지침에서새로이논의가시작되었다 년대후반까지만해도심부전환자들에게증상을최소화하고손상된심장을보호하기위해신체운동을피할것을권고하였다. 하지만현재는운동능력저하자체가심부전을악화시키는것으로알려져있고, 이는다양한기전으로설명되고있다. 실제심장내충만압의증가나좌심실의수축기능뿐아니라말초동맥이나움직임등도운동능력을결정하는중요한인자이며, 운동훈련프로그램은말초이상과운동능력을함께개선시켜, 적절한운동처방은심부전악 화를줄일수있다. 또한운동은혈관내피세포의기능을향상시키고, 카테콜아민의과잉반응을억제하여안정화시키며, 말초에서산소의방출을증가시키는등의좋은효과들로인하여심부전에의한재입원을막을수있는장점이있다 일부연구들은규칙적으로유산소운동 ( 예 : 자전거혹은달리기운동 ) 과근력강화운동을안전하게병행함으로써 NYHA 기능등급 II- III 환자에서증상개선과운동능력이 15-25% 정도향상될수있음을보여주었으나, 358, 359 규모가작고주로병태생리학적결과만을보았다는제한점이있었기때문에만성심부전환자 IV 비약물치료3 장심장재활및운동치료 67

89 들에서의운동훈련의역할에대한메타분석 이이루어졌다 (ExTraMATCH Trial) 년부터시행된연구들에서 800 여명의심부전 환자들을메타분석한결과, 운동처방이심부전 환자의사망률을 32% 줄이고종말점 ( 사망이나 354, 361, 362 재입원율 ) 을 23% 감소시켰다. 다른대규모연구에서는심부전환자 2,331 명을대상으로 3 개월동안운동을시킨군과 대조군을비교하였는데, 다른요소들을보정 한후에도운동군에서사망률이 11% 가낮았고, 심혈관계연관사망률혹은재입원율도의미있 게낮았다. 355 또다른메타분석에서도최대산소 요구량의증가와사망률감소가확인되었다. 363 따라서운동처방 ( 혹은규칙적인신체운동 ) 은 신체기능상태를안전하고효과적으로개선시 킬수있고, 심장재활은신체기능상태, 운동능력, 좌심실의수축기능과삶의질을개선시키고사망률을줄이기때문에, 심부전환자에서시행되어야한다. 심부전환자에게도움이되는운동량은준비운동과정리운동을포함한중등도강도의운동을 1주일에 3-5일간약 30-45분간으로하되, 운동프로그램을시작하기전점진적으로운동강도를높여가며신체기능상태, 협심증증세등과가장적절한목표맥박수를파악하여야한다. 훈련은유산소운동과근력강화운동을병합하여중등도강도로, 잘훈련된운동지도자와함께시작하는것이좋으며, 가능하면제세동기를곁에두고하도록한다. 68 만성심부전진료지침

90 4 장 교육및상담 교육및치료순응도를높이기위한지지요법 심부전환자는심부전에대한자기관리능력을향상시킬수있는특이적인교육을받아야한다. (Class I, Level of Evidence B) 심부전환자교육에대한여러연구에서, 심부전교육은이해증진, 자기관찰, 투약에대한순응도향상, 재입원율및입원기간감소등의좋은효과가있었다. 273 퇴원전교육을받은사람은퇴원시와퇴원 1년후심부전에대한이해도가훨씬높았다. 364 어떤형태의교육이든환자에대한병원내교육은퇴원 6개월이내의사망률감소에좋은성과를보였다 , 365, 366 퇴원시혹은외래치료중환자와가족에대한교육은식사와수액제한및체중관찰, 심부전악화에따른증상과신체검진상소견의인지, 위험도산정과예후, 삶의질산정, 완화치료등더발전된치료계획, 가족들에대한심폐소생술교육및사회적지원등이포함 된다. 퇴원후심부전환자의가정중심자가치료에대해서는 1990년후반과 2000년대초반에집중적으로연구된결과들이있는데, 환자에대한포괄적이고통합적인치료를위해서는가정중심의환자자신과가족에대한치료뿐만아니라, 이를지원하기위한시스템이구성되어야한다. 약물요법의적절성, 환자와가족교육과상담, 추적관찰, 용적과부하로인한증상과신체검진상소견의조기발견, 질관리및의료기관접근도등다각적인접근이필요하다. 최근체내삽입형기구 ( 흉부임피던스, 폐동맥압력등이용 ), 전화를통한원격관찰등에대한일부긍정적인연구가있으나객관적인증거가부족하여이에대한후속연 IV 비약물치료4 장교육및상담 69

91 379, 380 구들이필요하다. 결론적으로 심부전환 자및가족의교육과이를통한치료순응도향 상은사망률과재입원율을낮출수있으며삶 의질측면에서중요하므로적극적인고려가 필요하다. 70 만성심부전진료지침

92 5 장 동반질환의관리 심방세동 1. 심방세동이동반된심부전환자에서박동수조절을위해서는베타차단제를가장먼저사용해야한다. (Class I, Level of Evidence A) 2. 심방세동이동반된심부전환자에서뇌졸중예방을위한치료결정을위해 CHA 2 DS 2 -VASc 점수법을사용해야한다. (Class I, Level of Evidence B) 3. 심방세동이동반된심부전환자에서심박동기가필요하거나심장재동기화의치료기준을만족하는경우방실결절절제후 CRT는타당하다. (Class IIa, Level of Evidence B) 4. 심방세동이동반된심부전환자에서박동수조절에추가로율동조절을고려할수있다. (Class IIb, Level of Evidence A) 5. 심방세동이동반된심부전환자에서율동조절고려시전극도자를이용한폐정맥고립술을고려할수있다. (Class IIb, Level of Evidence B) IV 비약물치료심방세동은가장흔한지속성부정맥으로만성심부전에동반될경우전신색전증, 특히뇌졸중의위험을증가시키고증상의악화를유발할수있다. 우리나라의급성심부전등록연구에서심부전환자의 27% 에서심방세동이동반된것으로나타나, 381 심부전환자의상당수는심 방세동의치료도병행해야한다. 심부전환자에서심방세동의치료는뇌졸중의위험평가, 박동수조절, 율동조절의측면에서시행되어야한다. 심방세동이동반된심부전환자의심박동수조절을위해서는베타차단제를가장우선으 5 장동반질환의관리 71

93 로사용해야한다. 디곡신은안정시에만제한 적인박동수조절을하기때문에베타차단제가 선호된다. 382 추가로베타차단제는심부전환자 의사망률과이환율을감소시키는효과를갖고 , 383 있다. 심방세동이동반된심부전환자에서박동수 조절에추가로율동조절을하는것은사망률이 나이환율을감소시키지못했다. 384 하지만심 기능의감소가빈맥에의해발생한경우혹은 의심이될때에는적극적인율동조절은도움이 될수있다. 385, 386 좌심실수축기능저하가있는 환자에서는아미오다론이유일한항부정맥제이 다. 387, 388 최근많이시행되고있는전극도자를 이용한폐정맥고립술을통한율동조절이증상 과심기능을개선시키는효과를보여주고있어 서특히약물사용에도증상이있는환자들에서 는고려할수있는치료법이다 심방세동이동반된심부전환자에서뇌졸 중및색전증의예방을위해서는 CHA 2 DS 2 - VASc 점수법 ( 표 4.1) 이추천된다. 392 CHA 2 DS 2 -VASc 점수법은이전의 CHADS 2 점수법에 혈관질환, 세의나이, 여성이추가되 어심방세동에서뇌졸중의위험도를더세분 화하여평가하는방법으로, 최근미국, 유럽 393, 394 의진료지침에서추천되고있다. 국내에 서는 modified CHADS 2 점수법 395 을발표하였 는데, CHA 2 DS 2 -VASc 점수법과유사하게여 성, 관상동맥질환, 세의나이가포함되 고추가로만성신부전이포함된다. 심부전환 자에서심방세동이동반된대부분의환자는 CHA 2 DS 2 -VASc 점수가 2 점이상이기때문 에항응고제치료가추천된다. 하지만이때환 자별출혈의위험도를고려하여치료를결정해 야한다. 환자의출혈위험도는고혈압, 신장 / 간기능이상, 뇌졸중, 출혈의과거력, 불안정 한 INR (International Normalized Ratio), 65 세이상의나이, 약물 / 알코올병용에점수를 부여하는 HAS-BLED 점수법 ( 표 4.2) 사용을 추천하며 3 점이상에서는출혈의고위험군이 므로항응고제사용에주의를요한다. 396 ( 참고 : 항응고약물 ) 72 만성심부전진료지침

94 표 4.1. CHA 2 DS 2 -VASc 점수법 위험요소 점수 심부전 (Congestive heart failure) 또는좌심실수축기능저하 (EF 40% 이하 ) 1 고혈압 (Hypertension) 1 75세이상 (Age 75) 2 당뇨병 (Diabetes mellitus) 1 뇌졸중 / 일과성허혈성발작 / 전신색전증 (Stroke/TIA/Thrombo-embolism) 2 혈관질환 *(Vascular disease) 세의나이 (Age 65-74) 1 여성 (Sex category, i.e. female sex) 1 총합 9 * 과거심근경색증, 말초혈관질환, 대동맥동맥경화증 표 4.2. HAS-BLED 점수법 위험요소 점수 고혈압 (Hypertension) 1 신장, 간기능이상 (Abnormal renal and Liver function), 각 1 점 1 혹은 2 뇌졸중 (Stroke) 1 출혈 (Bleeding) 1 불안정한 INR (Labile INRs) 1 65세이상의고령 (Elderly) 1 약물혹은알코올병용 (Drugs or Alcohol), 각 1점 1 혹은 2 IV 비약물치료총합 9 * 고혈압은수축기 160 mmhg 이상, 신기능장애는투석, 신이식, 크레아티닌 2.3 mg/dl 이상, 간기능장애는간경화혹은빌리루빈정상의 2배이상상승혹은간효소수치정상의 3배이상상승, 출혈은과거출혈력혹은출혈성경향혹은빈혈, 불안정한 INR은지나치게높은 INR 혹은치료범위 60% 이내로잘조절안되는 INR, 약물및음주는항혈소판제, 비스테로이드항염증제의사용혹은알코올중독으로정의한다. 5 장동반질환의관리 73

95 허혈성심장질환 1. 모든심부전환자에서관상동맥질환의동반여부를평가하고, 협심증이의심되거나심부전의원인및악화요인이불분명한경우비침습적인검사나관상동맥조영술을시행해야한다. (Class I, Level of Evidence C) 2. 심부전환자에서는탈륨-201 혹은테크네튬-99m을이용한단일광자방출단층활영, 심장컴퓨터단층촬영혹은심장자기공명영상을이용하여허혈성심장질환을진단하는것이타당하다. (Class IIa, Level of Evidence C) 3. 허혈성심부전환자에서는생존심근여부를확인하고생존심근이있는경우관상동맥우회술이나관상동맥중재술을통해재관류를시켜주는것이타당하다. (Class IIa, Level of Evidence B) 4. 좌심실박출률 35% 이하의심부전환자에서는관상동맥질환에대해관상동맥우회술을시행하는것이타당하다. (Class IIa, Level of Evidence B) 국내심부전환자에서허혈성심부전이차지하는비율은약 38% 로보고되었으며 381 관상동맥질환이동반된심부전환자의예후가더불량한것으로알려져있다 허혈성심부전환자나관상동맥질환이동반된심부전환자의경우급사하여부검을하면급사의원인으로심근경색이나급성관상동맥증후군이발견되는빈도가높았으나, 관상동맥질환이동반되지않은심부전환자에서는그렇지않아허혈성심부전환자와비허혈성심부전환자의사망기전이다름을알수있다. 404 따라서심부전환자에서관상동맥질환의동반여부를평가하고필요시아스피린과스타틴과같이급성관상동맥증후군의발생을줄일수있는약제를사용해야한다. 하지만어떤환자에서관상동맥질 환동반여부를확인하기위해추가적인검사를시행해야하며이를위해어떤검사를하는것이효율적인지, 동반된관상동맥질환이있다면재관류치료를하는것이심부전환자의예후를호전시키는지에대해서는논란이있다. 모든환자에서관상동맥질환을배제하기위해관상동맥조영술을시행해야하는지아니면특정위험요인이나증상이있는환자에서만검사를시행해야하는지에대한연구는아직없다. 방사성핵종심근관류영상의민감도와음성예측도가높아허혈성심부전환자의선별검사로이용할수있다는보고가있다 한편, 양전자방출단층촬영이허혈성심부전과비허혈성심부전을감별진단할수있는지에대해서는 11C-팔미테이트의심근내축적정도와양상에 74 만성심부전진료지침

96 차이가난다고보고한연구외에는연구가부 족한상황이다 열다검출기컴퓨터단층촬 영를이용한연구에서는 92-97% 의민감도와 90-98% 의특이도를보였으며, 412, 413 심장자기 공명영상은고해상도로국소심실수축기능을 평가하고후기가돌리늄조영증강양상의차이 를분석하여허혈성심근증과비허혈성심근증 110, 을감별하는데도움이된다. 관상동맥질환에의한심부전의중요한기전으 로동면이관여하는것으로알려져있다 동 면심근을진단하는방법으로저용량도부타민 부하심초음파검사로수축능력의회복여부를평 가하는방법, 탈륨 -201 혹은테크네튬 -99m 을 이용한단일광자방출단층활영을이용하여세포 막의투과성을평가하는방법, 그리고양전자방 출단층촬영을이용하여대사활동능력을평가하 는방법이있으며 420, 421 앞에서언급한심장자 기공명영상을이용하는방법도있다. 118 이러한 동면심근이있는경우재관류치료를시행하는것이심부전환자의생존율을높인다고보고되었다. 420 하지만이를예측하는능력에있어앞에서언급된검사들사이에차이가있다는보고는없다. 한편, 최근발표된 STICH 하위연구에서는방사성핵종부하검사나도부타민스트레스심초음파상유발되는허혈의유무는환자의생존에영향을미치지않았다. 422 좌심실박출률 35% 이하의심부전환자에서관상동맥질환에대해관상동맥우회술을시행하는것이환자의생존율을증가시키는지평가한 STICH 연구에서는일차종말점인전체사망률에서는통계적으로유의한차이를보이지는못했으나, 사망률이감소하는경향을보였으며, 모든원인에의한사망과심혈관질환에의한재입원율로구성한총종말점와심혈관질환에의한사망률에있어서는유의한차이를보였다. 423 IV 비약물치료5 장동반질환의관리 75

97 고혈압 1. 앤지오텐신전환효소억제제또는앤지오텐신수용체길항제, 베타차단제, 알도스테론길항제를각각 1차, 2차, 3차치료제로사용해야한다. (Class I, Level of Evidence A) 2. 만약앤지오텐신전환효소억제제 ( 혹은앤지오텐신수용체길항제 ), 베타차단제, 알도스테론길항제병용요법에도혈압이조절되지않는다면티아지드이뇨제를병합해야한다 ( 혹은만약티아지드이뇨제를투약받고있었던환자는루프이뇨제로바꾼다.) (Class I, Level of Evidence C) 3. 앤지오텐신전환효소억제제 ( 혹은앤지오텐신수용체길항제 ), 베타차단제, 알도스테론길항제, 이뇨제의병합에도혈압이조절되지않는다면암로디핀이나하이드랄라진을추가해야한다. (Class I, Level of Evidence A) 4. 앤지오텐신전환효소억제제 ( 혹은앤지오텐신수용체길항제 ), 베타차단제, 알도스테론길항제, 이뇨제의병합에도혈압이조절되지않는다면, 펠로디핀을투약하는것은타당하다. (Class IIa, Level of Evidence B) 5. 알파차단제는신경호르몬계활성화, 수분저류, 심부전의악화를야기할수있어투약해서는안된다. (Class III, Level of Evidence A) 혈압의상승은좌심실의압력부하를증가시켜수축기및확장기장애를일으키고좌심실재형성을촉진시킨다. 또한, 좌심실벽스트레스증가에의한산소소비량의증가및미세순환장애와관상동맥내피세포기능장애로인한심근허혈을유발함으로써심근장애를악화시킨다. 심부전환자에서혈압의상승은기능이저하된심장에혈역학적부하를증가시키게된다. 고혈압은전연령에서심부전발생과악화의중요한위험인자며, 424 국내대규모등록연구에서도이와같은내용이발표되었다. 381 수축기와이완기혈압의적절한관리는심부전 발생의위험을약 50% 정도낮출수있는것으로알려져있으며, 425, 426 적절한혈압의관리로심근수축능이회복되는것이보고되었다. 427 진행한심부전환자에서는혈압이저하된경우가많지만, 혈압이상승되어있다면심부전에대한일반적인치료외에도고혈압의치료가중요하다. 약제선택은혈압의강하를도모하면서심부전을치료하는것을원칙으로한다. 앤지오텐신전환효소억제제와앤지오텐신수용체길항제 ( 앤지오텐신전환효소억제제에부작용이있는경우 ) 는심부전의 1차치료약제이고, 심부전환자에투약하였을때증상을 76 만성심부전진료지침

98 개선하고, 심기능악화를둔화하며, 심혈관계 144, 148 사망률을감소시킨다. 앤지오텐신전환효 소억제제와앤지오텐신수용체길항제는심비 대를동반한고혈압환자에서심비대를퇴행시 키며, 이효과는베타차단제보다크다고알려 져있다. 428, 429 따라서고혈압을동반한심부전 환자에서앤지오텐신전환효소억제제와앤지오 텐신수용체길항제는 1 차치료제로사용되어 야한다. 430 일반적으로심부전환자에서칼슘통로차단 제의사용은권고되지않으나, 암로디핀의경 우대규모무작위연구에서심부전환자에있 어이환율과사망률을더높이지않았고, 부작 용이크지않았기때문에, 고혈압이나관상동 맥질환을동반한심부전환자에서는투약을고 려할수있다. 고혈압을동반한심부전환자의혈압강하 목표는환자에따라다르지만, 여러진료지침 58, 431, 432 에서수축기혈압을 130 mmhg 이하 로낮추는것을권고하고있으며, 고혈압이합 병된수축기능이보존된심부전환자, 심비대 를동반한환자에서는 130/80 mmhg 이하로 낮추는것을권고하고있다 당뇨병 당뇨병뿐아니라인슐린저항성도심부전발생 의중요한위험인자이다. 이상당혈증과당뇨병 은심부전환자에서매우흔하며, 381 당뇨병은 심부전환자에서기능상태악화, 입원율과사 망률의증가와연관이있다. 당뇨병을동반한심부전환자를대상으로 적절한혈당조절목표에대한전향적무작위 연구는시행된적이없어명확한혈당조절목 표수치를제시하는것은어렵다. 그러나한관 찰연구에따르면, 당뇨병을동반한심부전에 있어당화혈색소와사망률의관계는 U 자형으 로나타나는데, 당화혈색소를 7.1% 에서 7.8% 정도로조절했던경우가사망률이가장낮았으 며, 당화혈색소가극단적으로높거나낮은경 우사망률이급격히증가하였다. 433 일반적으로 당뇨병환자의혈당을당화혈색소 7.0% 미만 으로조절할것을권고하고있지만, 동반질환 이위중할경우에는혈당조절을덜엄격하게 하는것 ( 당화혈색소 < 8.0%) 을권고하고있 다. 434 따라서당뇨병을동반한중증의심부전 환자의경우당화혈색소를 8.0% 미만으로조 절할수있겠다. 435 앤지오텐신전환효소억제제나앤지오텐신수 용체길항제는당뇨병의기본적인치료로신장 기능저하와같은심부전의다른위험인자의 발생을예방함으로써심부전의발생을낮출수 있다. 당뇨병을동반한심부전환자를대상으 로한연구에서, 앤지오텐신전환효소억제제나 앤지오텐신수용체길항제는생존율을향상시 키고입원율을감소시켰다 베타차단제 의경우도그종류에따라혈당에미치는영향 이다르지만당뇨병을동반한심부전환자에서 금기가아니며, 당뇨병을동반하지않은심부 전환자에서와같이예후를향상시킨다 또한알도스테론길항제의생존율에대한이득 도당뇨병을동반하지않은환자에서와다르지 170, 442 않았다. 그러나 알도스테론길항제를사 IV 비약물치료5 장동반질환의관리 77

99 용할경우고칼륨혈증과신기능악화에주의해야한다. 심부전환자에서당뇨병약제들의안정성및유효성은아직확실하게정립되지않았다. 그러나메트포민을투약한경우, 설폰요소제나인슐린에비하여입원과사망, 심혈관사건발생이낮았다 티아졸리딘다이온계열의약물은수분저류를유발할수있어서, 446, 447 NYHA 기능등급 II 이상의심부전환자에서는투약하지말아야한다. 글루카곤유사펩티드-1이나디펩티딜펩티다제-4는심부전환자에서그효과가입증되지않았다 만성신질환 심부전환자의 40% 이상이만성신질환을가지고있다. 448 과도한이뇨제사용, 구토및설사에의한나트륨과수분부족, 저혈압, 체액과잉, 우심부전, 신장정맥울혈등이신장기능을저하시키는원인으로알려져있다. 2 특히신장기능이심하게떨어진경우, 이자체가심부전의예후에큰영향을미치게된다. 449 일반적으로심장-신장증후군은심부전과신기능저하가서로상호작용하면서악화되는고리를일컬으며, 심부전으로인해신장으로의혈류가감소하는것외에도중심정맥울혈, 신경- 호르몬의변화, 빈혈, 신장교감신경의활성화등다양한기전이관여한다. 450 신장기능저하가동반된심부전환자에서주의할약제사용의 원칙은앞에기술되었다 ( 참고 : 레닌-앤지오텐신계차단제, 염류코르티코이드길항제 ). 급성비대상성심부전환자에서모든이뇨제를사용해도반응하지않는경우, 초미세여과를고려할수있다. 초미세여과는수분과저중량또는중간중량의용질을반투막을통해여과시켜서체액과잉을해결한다. 이뇨제는소변을저장성으로만들지만, 초미세여과는등장성소변을만들기때문에상대적으로더많은나트륨이소변으로제거된다. 2007년급성비대상성심부전환자 200명을대상으로한무작위연구에서초미세여과군은대조군에비해 18시간시점에서체중감소가더많았으며, 90일입원율역시더낮았다. 451 그러나심장-신장증후군이동반된급성비대상성심부전환자 188명을대상으로한다른무작위연구에서는초미세여과의유의한이득이나타나지않아상반된결과를보여주었다. 452 이연구에서는 96시간시점의양군간체중감소정도에유의한차이가없었으며, 60일째입원율과사망률도차이를보이지않았다. 오히려, 초미세여과군에서 60일째더많은합병증이발생하였다. 초미세여과치료는저혈압, 출혈, 용혈, 카테터관련합병증, 알레르기반응, 공기색전증과같은부작용을나타낼수있다. 453 따라서초미세여과에대한충분한경험이없는심장내과의사는초미세여과치료를시행하기전에신장내과의자문을구하는것이바람직하겠다. 448 만성심부전환자에서앤지오텐신전환효소억제제또는앤지오텐신수용체길항제의효과 78 만성심부전진료지침

100 는익히알려져있다. 그러나높은심혈관계사 건을보이는만성신기능저하가동반된경우, 그효과에대한증거는부족하다. 대부분의임 상시험에서혈청크레아티닌이 mg/ dl 이상인환자가제외되거나, 만성신기능저 하환자들에대한하위분석이이루어지지않 144, 150, 156, 았기때문이다. 다만, 에날라프 릴의생존율개선효과를보여준 CONSEN- SUS 연구는혈청크레아티닌 3.4 mg/dl 까 지많은신기능저하환자를포함하였으며, 143 비록혈청크레아티닌 2.5 mg/dl 이하인환 자를대상으로하였지만사구체여과율예측치 60 ml/min/1.73 m 2 을기준으로하위분석을 하였을때신기능저하가동반된환자들에서도 에날라프릴의생존율개선효과는유지되었음 을보여준연구 457 도있어, 투석을하지않는신 기능저하환자들에서앤지오텐신전환효소억 제제의효과를기대해볼수있다. 또한, 심부전 환자를대상으로한연구는아니지만, 혈액투 석환자를대상으로한소규모무작위연구에 서앤지오텐신수용체길항제의사용이심혈관 계사건의발생을감소시켰음을보여준연구가 있어투석을하는심부전환자에서앤지오텐 신수용체길항제사용의간접적인근거가된 458, 459 다. 베타차단제의 경우, 투석을하지않 는신기능저하를동반한심부전환자에서그 이득이보다분명하다. 메토프롤롤, 카르베딜 롤, 비소프롤롤을이용한무작위연구및하위 분석에서신기능저하정도와관계없이베타차 단제의생존율개선효과가유지되었다 뿐만아니라카르베딜롤의경우, 투석환자 114 명을대상으로한위약대조무작위연구에서, 2 년째심혈관계사망률이카르베딜롤군에서 29.3% 로, 위약군의 67.9% 와비교하여현저하 게낮았다 만성폐쇄성폐질환 만성폐쇄성폐질환은심부전의진단을어렵 게하고, 환자의기능상태및예후악화와연관 464, 465 이있다. 심부전에서 예후를향상시키는 베타차단제는기관지연축을악화시킬수있어 투약에제한이있다. 그러나베타차단제의경 우천식을동반한환자에서는금기이지만, 만 성폐쇄성폐질환을동반한심부전환자에서 는금기가아니다. 베타차단제를소량으로시 작하여, 점차적으로용량을올리는것이추천 된다. 선택성베타 1- 차단제 ( 예 : 비소프롤롤, 메토프롤롤, 네비볼롤 ) 는안전하게사용할수 있다 만성폐쇄성폐질환에서기관지확장제로 사용되는베타 2- 작용제는경구복용의경우 심부전의발생을증가시킬뿐아니라 469 전환자에서사망률을증가시켰다. 470 심부 흡입베 타 2- 작용제의경우전신영향이적고, 심부전 환자에서폐기능이향상되었다는보고가있으 나, 471 심부전으로인한입원율증가와연관이 있어 472 사용에주의가필요하다. 스테로이드의경우경구용은염분과수분의 저류를야기하고심부전을악화시킬가능성이 있다고알려져있으나, 흡입용은심부전악화 와의연관성이보고되지않았다. IV 비약물치료5 장동반질환의관리 79

101 빈혈 1. 철결핍성빈혈이동반된심부전환자에서철분제를정맥투여하는것은타당하다. (Class IIa, Level of Evidence A) 2. 특별한원인이없는빈혈이동반된만성심부전환자에서적혈구생성자극제를사용하는것은해가될수있다. (Class III, Level of Evidence B) 빈혈은만성심부전환자에서흔히동반된다. 연구마다빈혈의정의에차이가있어정확한유 병률을제시하기는어렵지만대략 25-40% 의 심부전환자에서빈혈이발견되며심부전의중 증도가높을수록빈혈의유병률도증가하는것 으로알려져있다. 또한빈혈은여자에서보다 흔하며박출률저하심부전환자와박출률보 존심부전환자모두에서발견된다. 40, 심 부전환자에서빈혈은사망률증가와상관관 계가있으며운동능력의감소, 높은재입원율, 40, 76, 473, 478, 그리고삶의질저하와관련이있다. 479 하지만, 빈혈을교정했을때심부전증상이 나운동능력이개선되고삶의질이높아지며 궁극적으로는심부전에의한재입원과사망을 줄일수있는지에대해서는논란이있다. 심부 전환자에서빈혈교정과관련된중요한논점 은첫째, 심부전과동반된철결핍성빈혈을교 정하는것이환자의증상을개선하고예후를 호전시키는지에대한것과둘째, 특별한원인 이없는빈혈에서적혈구생성자극제를사용하 여빈혈을교정하는것의효능에대한것으로 나눌수있다. 소규모연구들에서적혈구생성자극제는빈 혈을교정하고환자의운동능력을개선시키는 효과를보였다 이후이루어진비교적대 규모의무작위연구에서는, 165 명의환자를대 상으로다베포에틴의효능을평가하였는데, 운 동능력, 좌심실박출률의호전은없었지만일 부삶의질지표의개선을보였다. 그러나, 대 조군 55 명에서는사망환자가없었는데비해 다베포에틴을투여받은 110 명의환자중 6 명 이치료와무관하게사망하여적혈구생성자극 제의안전성문제가대두되었다. 485 또한 319 명 의환자를대상으로한 STAMINA-HeFT 연 구에서는안전성문제는제기되지는않았으나 치료효능을증명하는데실패했다. 486 한편, 적 혈구생성자극제의효능에대한두개의메타 487, 488 분석에서도서로상반된결론이나왔다. 이러한논란을바탕으로 1,142 명의대규모환 자군에서다베포에틴의효능과안전성을평가 한 RED-HF 무작위연구가진행되었는데, 다 베포에틴을투여한환자군에서증상이나예후 는유의하게호전되지않은반면혈전색전증의 빈도가유의하게상승하였다. 489 따라서특별한 80 만성심부전진료지침

102 원인이없는빈혈이동반된만성심부전환자 에서적혈구생성자극제를사용하는것은권고 되지않는다. 철결핍성빈혈에서의철분제정맥투여대해 서는 Bolger 등이 16 명의철결핍성빈혈을동반 한심부전환자에서정맥으로철분을투여하여 증상과운동능력이호전됨을보여준 490 이후여 러소규모연구에서철분제정맥투여가환자의 운동능력과삶의질, 그리고증상을개선시킴을 증명하였다 특히일부연구에서는재입원 491, 494 이나사망도줄일수있다고보고하였다. 한편, 빈혈없이철결핍만있는경우에도도움 이될수있다는결과도있다. 492, 495 철분제정 맥투여와관련된최대규모다기관무작위연구 로는 FAIR-HF 연구가있다. 혈색소 g/dl 의철결핍이동반된수축기심부전환자 459 명을대상으로철분제와생리식염수정맥 투여를비교하였다. 그결과 6 개월치료후철 분제투여군에서증상과운동능력그리고삶의 질지표가호전되었다. 495 따라서철결핍성빈혈 이동반된심부전환자에서철분제를정맥투여 하는것은타당하다고할수있다 우울증 우울증은말기심부전에서매우높은유병률 을보이지만잘인지되지못하고있는실정이 다. 이는심부전자체가우울증을유발할수있 고심부전의신체증상과우울증의신체증상 을구분하기어렵기때문이다. 심부전환자의 우울증이적절하게치료되지못하면생존기간 이감소되고, 삶의질이떨어지게되므로우울증에대한적극적인치료가필요하다. 우울증이심부전과관련이있는원인으로자율신경계의변화, 염증, 부정맥, 혈소판기능변화등이제시되고있지만, 그정확한기전은알려져있지않다. 496 우울증이있는심부전환자들은삶의질이저하되어있고자기관리를못하며임상경과가불량하다 또한우울증이있으면약물순응도가떨어지고사회적고립이유발된다. 심부전환자에서의우울증은입원시대부분나타나지만 500 입원후 3개월이지나더라도 63% 정도의환자가우울증을호소한다는보고도있다. 501 심부전환자에서우울증의진단은여러신체증상, 식욕및성욕의감소, 에너지의저하, 불면등을토대로이루어진다. 그러나신체질환에의한식욕감소, 피로, 조절되지못한통증에의한불면등은우울증진단에혼란을줄수있다. 따라서신체질환환자의우울증진단은신체적증상보다는인지적, 정서적증상에초점을두고이루어져야한다. 심부전환자에서우울증의치료는지지적정신치료, 인지-행동치료와항우울제치료를복합하여이루어질수있다. 심리사회적치료는개인, 가족, 집단으로제공되며, 교육, 행동적혹은정신역동적접근을통한대처기술을증진시키는것이전반적인목표가된다. 정신약물치료는중등도에서고도의우울증치료에주로사용되며, 항우울제치료가안전하고효과적인치료임이많은연구와임상경험을통해확인되었다. 선택적세로토닌재흡수억제제가비교적안전하다고알려져있고삼환계항 IV 비약물치료5 장동반질환의관리 81

103 우울제는기립성저혈압, 심장전도이상및부정맥등의부작용이있기때문에사용해서는안된다. 502 또한선택적세로토닌재흡수억제제는강한단백질결합력이있기때문에와파린, 디곡신, 시스플라틴의혈중농도를높일수있다. 우울증의치료가예후를향상시키는데도움이된다고는하지만가장효과적인방법은 알려져있지않다. 498, 502 심부전환자와가족들 에대한지지요법은복잡하지만중요하고특 히, 치료전환기에매우중요하다. 이러한지지 요법을이해하지못하고제대로행해지지않는 경우심부전에의한 30 일째재입원율과사망 503, 504 률이증가한다는보고가있다 수면무호흡증 수면무호흡증이있는심부전환자에서좌심실박출률을증가시키고, 환자의기능수준을향상 시키기위해지속기도양압치료를하는것은타당하다. (Class IIa, Level of Evidence B) 많은심부전환자들이종종수면에어려움을겪는다. 이에기여하는요소는다양하다. 폐울혈로인한좌위호흡과발작성야간호흡곤란, 이뇨제치료에따른야간빈뇨등이그요인이다. 또한, 불안과다른정신과적문제등도수면장애에기여한다. 2 뿐만아니라, 심부전환자가주간졸림같은증상호소가드문데도불구하고, 505, 506 높은수면무호흡증빈도 (30-69%) 를보인다는사실이이미보고된바있다. 505, 507, 508 수면무호흡증은수면다원검사로진단하는데, 공기흐름이 10초넘게중단될때를무호흡이라고하고, 공기흐름이완전히중단되지는않지만, 50% 를초과하여감소할때를호흡저하라고한다. 509 이무호흡-호흡저하지표로 수면무호흡증의중증도를평가한다. 수면무호흡증의일차치료는야간지속기도 양압이다. 야간지속기도양압치료는폐쇄성수 면무호흡증에서인두폐쇄자체를호전시킬뿐 아니라, 중심성수면무호흡증의경우에도그 509, 510 정도를완화시킬수있다. 수면무호흡증 이동반된심부전환자에서야간지속기도양 압의효과를보여준가장큰연구는 2005 년에 511, 512 발표된 CANPAP 연구이다. 이 연구에서 는좌심실박출률평균이 24.5±7.7% 인심부 전환자 258 명을대상으로 3 개월간야간지속 기도양압을무작위배정으로시행하였는데, 야 간지속기도양압군에서무호흡 - 호흡저하지표 가감소되고, 좌심실박출률및노르에피네프 82 만성심부전진료지침

104 린수치, 6 분보행검사결과가향상되었다. 또 한, 이연구의사후분석에서 3 개월뒤무호흡 - 호흡저하지표가 15 미만으로감소한야간지 속기도양압치료군은대조군에비해생존율이 높았다. 511 이외에도, 규모는작지만여러연구 에서폐쇄성수면무호흡증이동반된심부전환 자에서야간지속기도양압치료가심장기능, 교 감신경의활성화, 삶의질을호전시켰다는보 506, 513, 514 고가있었다 악성종양 특정항암제는심부전을일으키거나악화시킬 수있다. 대표적인약제는안트라사이클린과 515, 516 트라스투주맙이다. 이 외에도고용량시 클로포스파미드, 탁소이드, 마이토마이신 -C, 5- 플루오로우라실, 인터페론등이심장 독성을가지는대표적인약제이다. 448 안트라 사이클린이포함된항암치료를할때덱스라족 산은심장보호역할을한다는것이메타분석 을통해알려진바있다. 525 트라스투주맙으로 인한심기능의저하는, 약제를중단하면대부 분회복되는것으로보고되었다. 트라스투주맙 사용이후심부전이발생한 38 명의환자를대 상으로한관찰연구에서트라스투주맙을중단 한 37 명의환자들모두평균 1.5 개월이후좌 심실박출률을회복하였고, 520 3,386 명의환자 를무작위배정한 HERA 연구에서트라스투주 맙군에서증상을동반한심부전이 2.15% 로위 약군 (0.12%) 에비해유의하게많이발생하였 지만, 약물중단후 6 개월이내에대부분심장 기능을회복하였다. 516 따라서현재트라스투주 맙에관련된심부전의발생및악화를예방하 는데가장중요한전략은, 적절한관찰을통해 필요한시점에트라스투주맙투여를중단하는 것이다. 526 여러해외진료지침에서는트라스투 주맙 4-8 주기또는치료시작 3 개월마다심초 음파를통해좌심실박출률을확인하여좌심실 박출률 45% 이하가되거나, 비록좌심실박출 률이정상범주라도초기시점과비교하여 10-15% 이상감소하는경우트라스투주맙을중단 하고좌심실박출률을재평가할것을권고하고 522, 526 있다. 하지만 아직국제적으로항암치료 중심기능의악화를관찰하는구체적인방법이 나, 항암제의심장독성을예방할수있는방법 에대한근거자료는충분하지않다. 현재권고 안에서는심장독성이있는항암약제를시작할 때심부전발생의위험요인이될수있는심혈 관계질환, 즉관상동맥질환또는고혈압과같 은동반질환을확인하고함께조절해줄것을 2, 515, 526, 527 권고하고있다 임신 만성심부전이있는임산부는사망률이높으 며, 정상적인임신, 분만이곤란한경우가있 다. 혈역학적으로불안정한급성심부전증상 이있는임산부는임신의고위험군이며, 조기 분만이필요할수있다. 경증의만성심부전에 서도임신이심부전을악화시킬위험성이있기 때문에이에대해충분히설명해야하고, 임신 희망시의사와의상담이필수적이다. 심근수 IV 비약물치료5 장동반질환의관리 83

105 축력이 40% 이하인환자가임신한경우는고위험군으로상위의료기관에서의집중관찰이필요하며, 심근수축력이 20% 이하인환자가임신한경우에는모성사망률이매우높아임신중단을고려한다. 528 심부전환자가임신하였을경우의치료는, 임신시금기인몇몇약제를제외하고는임신하지않은경우와같이치료한다. 앤지오텐신전환효소억제제나앤지오텐신수용체길항제는태아독성때문에임신시에는금기이다. 하이드랄라진과나이트레이트가후부하감소목적으로앤지오텐신전환효소억제제나앤지오텐신수용체길항제대신사용될수있다. 베타차단제의경우모든심부전환자에서투약되어야하며선택성베타 1-차단제가추천된다. 그러나신생아의저혈당, 서맥, 호흡저하를야기할 수있기때문에아테놀롤은금기이다. 폐울혈이있는경우이뇨제가유일하게사용할수있는약이지만, 태반의혈류를감소시킬수있어주의가필요하다. 푸로세미드와하이드로클로로티아지드가주로사용될수있다. 스피로놀락톤은임신첫세달에는항안드로겐효과가있어금기이고, 에플레레논은아직규명되지않았다. 일반적으로알도스테론길항제는추천되지않는다. 혈역학적으로안정된심부전환자에서는질식분만이선호된다. 이때에는집중혈역학적관찰이필요하며, 경막외마취가추천된다. 그러나혈역학적으로불안정한진행된심부전환자에서는임신주수와상관없이긴급한분만을고려해야하며, 제왕절개가추천된다. 84 만성심부전진료지침

106 KSHF guideline for the management of CHRONIC HEART FAILURE 2016 기구치료및수술요법 V 1. 심율동전환제세동기 2. 심장재동기화치료 3. 좌심실의기계적보조장치 4. 수술적치료 5. 심장이식 6. 세포치료

107 1 장 심율동전환제세동기 (ICD, Implantable Cardioverter Defibrillator) 1. ICD는비허혈성심부전혹은심근경색후 40일이경과된허혈성심부전환자가좌심실박출률이 35% 이하이고, 적절한약물치료에도불구하고 NYHA 기능등급 II-III의증상을가지며, 1년이상생존이가능한경우사망률을감소시키기위하여일차예방목적으로사용해야한다. (Class I, Level of Evidence A) 2. ICD는심근경색후 40일이경과된허혈성심부전환자가좌심실박출률이 30% 이하이고, 적절한약물치료에도불구하고 NYHA 기능등급 I의증상을가지며, 1년이상생존이가능한경우사망률을감소시키기위하여일차예방목적으로사용해야한다. (Class I, Level of Evidence C) 3. 잦은입원, 악성종양, 심한신기능장애등의동반질환이심각하여급사가아닌다른원인에의한사망위험도가높은환자에서 ICD의효과는불분명하다. (Class IIb, Level of Evidence C) 좌심실수축기능이감소되어있는환자들은심실성부정빈맥의위험이증가되고이로인한급성심장사의가능성이높다. 이러한환자들에서일차예방을위한 ICD의이득은여러연구에서입증되었다. 1996년 MADIT 연구에서이전에심근경색을앓았던환자들중좌심실박출률이 35% 이하이고무증상의비지속성심실빈맥이있었거나전기생리학적에서심 실성부정빈맥이유발된환자에서 ICD가기존의약물치료에비해환자의생존율을증가시킴을증명하였다. 529 이후허혈성심근병환자를대상으로한 MADIT II 연구에서부정맥유무에관계없이좌심실박출률이 30% 이하인환자에서 ICD는생존율을향상시켰다. 530 SCD- HeFT 연구에서는허혈과비허혈에의한심근병을포함하여좌심실박출률 35% 이하, 86 만성심부전진료지침

108 NYHA 기능등급 II-III인경우 ICD는생존율을향상시켰다. 531 하지만심근경색이후좌심실박출률이 35-40% 미만의고위험군에서 40일이내에 ICD를삽입하였을경우에는기존의치료와큰차이가없었다. 532, 533 ICD 치료를받은군에서급성심장사는감소하지만다른원인으로인한사망이증가되어 ICD 치료로인한이득을상쇄시켜버렸다. 이러한결과를근거로허혈성심부전환자에서는심근경색이후 40일이지난뒤에재평가를하여 ICD를삽입할것을추천하고있다. 좌심실박출률이감소된심부전환자에서일차예방을위해 ICD 삽입을고려할경우에는반드시적어도 3개월간의적절할약물치료후에결정을해야한다. 3개월간의약물치료이후에재측정한좌심실박출률의의미있는감소가관찰될때 ICD를삽입하여야한다. ICD 삽입의국내건강보험급여인정기준은표와같다 ( 표 5.1). ICD 삽입으로모든치료가끝나는것이아 니며삽입후적절한관리가이루어져야한다. 일차예방목적으로 ICD 가삽입된환자들은 1-3 년이내에전기충격을경험하고, 이중삼 분의일은부적절한전기충격이다. 534 전기충격 의잦은발생은외상후스트레스장애를유발하 고 535 더나아가환자의사망률을증가시킬수 536, 537 있다. 따라서 전기충격의빈도를감소시 키기위하여약물치료를병행하고부적절한전 기충격감소를위한 ICD 의적절한설정을위하 여부정맥전문가와협진이필요하다. 심부전환자에서여러다른질환을갖고있 고심부전으로수차례입원을반복했던고령의 환자들은 ICD 치료의이득을받지못할수있 다. 538 따라서다른동반된질환으로인해기대 여명이 1 년이내인환자들에서는 ICD 를삽입 하지않는것을추천한다. 표 5.1. ICD의국민건강보험급여인정기준돌연사위험이있는환자에서심장돌연사의위험을줄이면서생존을증가시켰다는근거가있는경우에시행함을원칙으로하되, 다음에해당되는경우에는요양급여 ( 일부본인부담 ) 를인정하며, 동기준이외시행한경우시술료및치료재료요양급여비용은전액본인이부담함. - 다음 - 심부전 (1) 심근경색발생후 40일경과한허혈성심부전으로적절한약물치료에도불구하고 NYHA 기능등급 II-III의증상을보이고, 1년이상생존이예상되는환자의경우 ( 가 ) 좌심실박출률 30% ( 나 ) 좌심실박출률 31-35% 로비지속성심실빈맥이있으며, 전기생리학적검사에서지속성심실빈맥이유발되는경우 (2) 비허혈성심부전으로 3개월이상의적절한약물치료에도불구하고 NYHA 기능등급 II-III의증상을보이고, 1년이상생존이예상되는환자의경우 ( 가 ) 좌심실박출률 30% ( 나 ) 좌심실박출률 31-35% 로비지속성심실빈맥이있으며전기생리학적검사에서지속성심실빈맥이유발되는경우 V 기구치료및수술요법1 장심율동전환제세동기 87

109 2 장 심장재동기화치료 (CRT, Cardiac Resynchronization Therapy) 1. CRT는좌심실박출률 35% 이하, 동성리듬, 좌각차단, QRS 간격 150 ms 이상, 적절한약물치료에도불구하고 NYHA 기능등급 II-III 및보행가능한 IV 증상환자에서시행해야한다. (Class I, NYHA 기능등급 III-IV, Level of Evidence A / NYHA 기능등급 II, Level of Evidence B) 2. CRT는좌심실박출률 35% 이하, 동성리듬, 좌각차단, QRS 간격 ms, 적절한약물치료에도불구하고 NYHA 기능등급 II-III 및보행가능한 IV 증상환자에서타당하다. (Class IIa, Level of Evidence A) 3. CRT는좌심실박출률 35% 이하, 동성리듬, 비좌각차단, QRS 간격 150 ms 이상, 적절한약물치료에도불구하고 NYHA 기능등급 III 및보행가능한 IV 증상환자에서타당하다. (Class IIa, Level of Evidence A) 4. CRT는심방세동, 좌심실박출률 35% 이하환자에서심실조율이필요하거나 CRT 적응증에맞는경우, 혹은방실결절절제술이나약물치료를통하여 100% 에가까운심실조율이가능하면타당하다. (Class IIa, Level of Evidence B) 5. CRT는좌심실박출률 35% 이하환자에서새로운혹은박동기 ( 제세동기포함 ) 교체가필요하며 40% 이상의심실조율이예상되는경우타당하다. (Class IIa, Level of Evidence C) 6. CRT는좌심실박출률 30% 이하, 허혈성심부전, 동성리듬, 좌각차단, QRS 간격 150 ms 이상, 적절한약물치료에도불구하고 NYHA 기능등급 I 증상환자에서고려할수있다. (Class IIb, Level of Evidence C) 7. CRT는좌심실박출률 35% 이하, 동성리듬, 비좌각차단, QRS 간격 ms, 적절한약물치료에도불구하고 NYHA 기능등급 III 및보행가능한 IV 증상환자에서고려할수있다. (Class IIb, Level of Evidence B) 8. CRT는좌심실박출률 35% 이하, 동성리듬, 비좌각차단, QRS 간격 150 ms 이상, 적절한약물치료에도불구하고 NYHA 기능등급 II 증상환자에서고려할수있다. (Class IIb, Level of Evidence B) 88 만성심부전진료지침

110 술요법2 장심장재동기화치료 심부전환자의상당수에서심부전이진행하면서 QRS 간격의증가가동반되고이는나쁜예후와관련이있다. CRT는심실의여러부위에서심박조율을하여좌심실수축을개선하고승모판막폐쇄부전을호전시키며심실재형성을되돌릴수있다. 가장먼저 2002 년 MIRACLE 연구에서중등도및중증심부전증상을가지면서좌심실박출률 35% 이하, QRS 간격이 130 ms 이하인환자에서 CRT 가환자의증상을호전시킴을보였다. 539 뒤이어 COMPANION 연구에서허혈성및비허혈성심부전, 좌심실박출률 35% 이하, 적절한약물치료에도불구하고 NYHA 기능등급 III- IV의증상, QRS 간격이 120 ms 이상인환자를대상으로약물치료에비하여 CRT가사망률및입원율을감소시킴을최초로보고하였다 년 CARE-HF 연구도유사한생존율호전의연구결과를보였다. 541 이를근거로국내건강보험급여인정기준 ( 표 5.2) 이정해져현재까지사용되고있다. 하지만기존의기준인 QRS 간격 120 ms, 좌심실박출률 35% 이하만으로는 CRT의효과를예측하는데어려움이있었는데뒤이은연구결과들을통해서좀더세분화된기준을제시할수있게되었다 ( 그림 5.1). 2009년 MADIT- CRT 연구에서 CRT의효과가좌각차단, QRS 간격이 150 ms 이상에서효과가좀더뛰어 남이확인되면서 542 현재의 Class I 적응증 ( 좌 심실박출률 35% 이하, 동성리듬, 좌각차단, QRS 간격 150 ms 이상, 적절한약물치료에도 불구하고 NYHA 기능등급 II-III 및보행가능 한 IV 증상환자 ) 이만들어졌다. 다른조건은 Class I 과동일하면서 QRS 간격이 ms, 비좌각차단등의소견을단독으로보이는 경우에는 CRT 가유용할수있다. 또한정상동율동환자뿐만아니라심방세동 환자에서도 CRT 의효과가증명되었다. 심방세 동환자에서는좌심실박출률이 35% 미만이고, 심박동기가필요하거나 CRT 의기준을만족할 경우방실결절전극도자절제를시행하여 100% 심실조율이가능하게한뒤 CRT 를시행하면 543, 544 유용할수있다. 하지만 이는아직국내 건강보험급여인정기준에는반영이되지않은 실정이어서실제적용시에유의해야한다. CRT 도적어도 3 개월이상의적절한약물치 료이후에도지속되는심부전이관찰될때고 려되어야하며, 삽입이후에도적절할약물치 료는반드시병행해야한다. 또한 CRT 에반응 하지않는환자들에서는 CRT 의적절한설정을 위해서부정맥전문가와심장영상전문가와 함께치료방침을결정해야한다. V 기구치료및수89

111 심근병 (3 개월이상약물치료 ), 심근경색 (40 일이상약물치료 ), 혹은 다른이유로심박조율기및제세동기치료가요구되는경우 좌심실박출률 35% 전신건강상태조사 동반질환등으로 1 년이상생존불가 약물치료 NYHA 기능등급 I Class IIb 좌심실박출률 30% QRS 간격 150 ms 좌각차단 허혈성심근병 NYHA 기능등급 NYHA 기능등급 II-III 및보행가능한기능등급 IV Class I 좌각차단, 동율동, QRS 간격 150 ms Class IIa 좌각차단, QRS 간격 ms 혹은 비좌각차단, QRS 간격 150 ms 혹은 예상좌심실조율 (> 40%) 혹은 심방세동환자가 QRS 간격기준이맞고, 100% 심실조율이가능한경우 Class IIb 비좌각차단, QRS 간격 ms NYHA 기능등급 IV 증상조절안되며, 주사용강심제에의존적임 심장이식, 좌심실보조장치 치료예정인경우를제외하고 적응증이안됨 그림 5.1. CRT 의적응증알고리즘 표 5.2. CRT의국민건강보험급여인정기준 CRT는심실을재동기화함으로써심부전을개선시킬수있는근거가있는경우에시행함을원칙으로하되, 다음에해당하는경우에는요양급여 ( 일부본인부담 ) 를인정하며, 동기준이외에시행한경우시술료및치료재료요양급여비용은전액본인이부담함. - 다음 - 가. CRT-P (CRT-Pacemaker) 3개월이상의적절한약물치료에도불구하고증상이지속되는심부전환자중아래의사항에모두해당되는경우 - 아래 - (1) 심박출률 35% (2) QRS 간격 120ms (3) 동율동 (4) NYHA 기능등급 III 또는보행가능한기능등급 IV 환자 적절한약물치료 ( 앤지오텐신전환효소억제제 / 앤지오텐신수용체길항제 + 이뇨제 ± 베타차단제 ) 나. CRT-D (CRT-Defibrillator) CRT-P와 ICD 기준에모두적합한경우 90 만성심부전진료지침

112 3 장 좌심실의기계적보조장치 1. 약물치료에불응하는심장이식대기환자에서심실보조장치를사용하는것은타당하다. (Class IIa, Level of Evidence B) 2. 약물치료에불응하고주사용강심제를중단할수없지만심장이식의적응증이되지않는환자에서삽입형심실보조장치를사용하는것은타당하다. (Class IIa, Level of Evidence B) 약물치료에불응하는말기심부전환자에게가장근본적인치료는심장이식이다. 하지만말기심부전환자의증가와함께기증자부족현상이발생하여서구에서는기계적심실보조장치가일찍부터개발되었다. 1963년 Dr. Debakey에의해처음사용된이래 1994년 Heartmate가미식품의약국의승인을받으면서관련된연구및임상경험이비약적으로증가하였다. 심실보조장치는기본적으로좌심실 ( 또는우심실 ) 에서혈액을뽑아대동맥 ( 또는폐동맥 ) 으로혈액을보내주어심실의부하를줄임으로써심박출량증가및심실재형성을유도하는기계적장치이다. 심실보조장치는혈류의특성 ( 박동성또는지속성 ), 펌프의기능 ( 축 성또는원심성 ), 거치위치 ( 체내또는체외 ), 접근법 ( 경피또는수술 ), 지지심실 ( 좌, 우, 양심실 ) 등의기준으로분류할수있다. 또한수시간에서수일간사용할수있는비삽입형보조장치와수개월에서수년간사용할수있는삽입형보조장치로도나뉜다. 심실보조장치는크게 3가지목적으로사용된다. 첫째는심장이식을대기하고있는환자들에서기증자를기다리는동안환자를지지해주는가교치료이고, 둘째는심장이식의적응이되지않는환자에서평생심실보조장치를사용하는것이다. 마지막으로현재심장이식의대상이되는지판단하기어려운경우로환자상태를안정시킬목적으로심실보조장치를사용 V 기구치료및수술요법3 장좌심실의기계적보조장치 91

113 하는것이다. 심장이식가교목적으로심실보조장치를사용하는것은가장흔한적응증이었다. 최근 2 세대심실보조장치중하나인 HeartMate II 를사용한다기관전향적연구결과에서 6개월째심장이식을받거나, 심실기능이회복되어기계적보조장치를떼거나, 보조장치를하면서생존한환자가 79% 였다. 545 이후 18개월이상의장기간추적관찰연구에서도비슷한결과를보여서현재기증자장기가부족하고, 대기기간이긴외국에서많이사용되고있다 처음심실보조장치를개발한이유는심장이식의적응증이되지않는말기심부전환자에서평생동안기계장치를사용해서수명을연 장하고자했던것이었다. 이러한최종치료목 적의심실보조장치사용에대한연구는일찍이 시작되었고, 관련된무작위연구는 2001 년보 고되었다. 549 REMATCH 연구에서 2 년까지약 물치료에비해심실보조장치를받은환자의생 존율이높았으나보조장치삽입이후감염, 출 혈, 신경학적이상, 기계장치관련합병증이 더많이발생한것으로보고되었다. 2 세대이 후의심실보조장치를사용한연구들에서도역 시이식적응증이되지않는환자에서심실보 조장치는생존율향상에도움이되는것으로 확인되었고부작용발생도점차줄어서최근 최종치료목적의심실보조장치사용이증가하 550, 551 고있다. 92 만성심부전진료지침

114 4 장 수술적치료 심부전은약물치료가원칙이고외과적치료는 전통적으로일부환자에게만적용되었다. 약물 치료에불응하는말기심부전환자에게는선택 적으로심장이식을시행하는것이원칙이지만, 적절한공여심장이부족하기때문에특정형태 의수술적치료가불가피하다. 최근에발표된 STICH 연구에따르면좌심 실박출률 35% 이하의관상동맥우회술이가능 한환자에서, 관상동맥우회술은약물치료에비 하여사망률은차이가없었으나, 심장관련사 망이나재입원면에서는우위를보였다. 423 연구전에발표된여러후향적연구들에서는 생존심근이확인된경우, 심부전을동반한허 혈성심장질환에서관상동맥우회술은명백히 사망률을감소시키고, 심근의회복을가져왔 420, 552 다. 이 심부전이동반된허혈성심장질환에서관상 동맥우회술과관상동맥중재술은아직확실하 게우열을가릴수는없다. 그러나여러후향적 연구에서관상동맥중재술의결과가관상동맥 우회술에비해열등하였고, 이는관상동맥우회 술에서완전재관류가더많이이루어질수있 었기때문이라고설명하였다 외과적좌심실용적축소술의효용성에대해서는아직이견이많다. 가장중요한연구인 STICH 연구에서좌심실용적축소술은관상동맥우회술만단독으로시행한군에비해장점을보이지못하였고, 556 이전에시행된여러후향적연구에서도비슷한결과를보였다 그러나생존심근이없이반흔조직으로대체되어있는심부전환자에서는좌심실용적축소술이좌심실박출률을상승시키고증상을완화시킨다는보고도있다 비허혈성심부전환자에서좌심실용적축소술은기대되는장점보다수술로인한사망률이높아시행하지않는다. 현재까지의연구결과를토대로좌심실용적축소술은허혈성심장질환에서심한좌심실기능부전이동반되어있고생존심근의범위가많지않은경우선택적으로고려해볼수있겠다. 판막질환은심부전을유발하기도하고악화시키기도한다. 판막수술의적응증이되는경우, 판막수술이후동반된심부전증상의완화를얻을수있다. 심부전의외과적치료에대한연구는많지 V 기구치료및수술요법4 장수술적치료 93

115 않은실정으로, 향후추가연구를토대로새로 운치료방향이제시되어야할것이다. 특히말 기심부전의표준치료인심장이식의대상이되 지않는경우에는기계적보조장치의발전과 함께기존의외과적수술의적절한적용이필 요하겠다. 94 만성심부전진료지침

116 5 장 심장이식 약물치료에불응하는말기심부전환자에서가장근본적인치료는심장이식이다. 심장이식은 1967년 Dr. Barnard에의해처음으로성공적으로시행된이래, 년강력하고안전한면역억제제인사이클로스포린이미식품의약국의사용승인을받으면서예후가크게개선되었다. 현재성인에서심장이식후 1, 3, 5년생존율은각각 87.8%, 78.5%, 71.7% 로보고되고있다. 564 국내한대학병원발표자료에의하면우리나라심장이식환자의 1년생존율은 94% 에달하며 5년생존율도 84% 이상을유지하고있다. 565 그러나말기심부전환자는증가하고있으나기증자는부족하여심장이식을대기하는중에약 20% 의환자가이식전사망하는것으로보고된다. 566 기계적심실보조장치는심장이식을대기하고있는환자들에서기증자를기다리는동안환자를지지해주거나, 최종치료목적의심실보조장치로사용되고있다. HVAD 연구에서심실보조장치를삽입한환자의 2년생존율이 80% 로 549, 567 심장이식환자와비슷하였지만, 563 5년생존율은약 40% 로큰차이를보 였다. 또한기계적심실보조장치는출혈, 감염, 혈전형성과같은합병증발생률이높기에, 568 말기심부전환자에서는근본적인치료로심장이식을우선고려해야한다. 심장이식을받은환자는장기생존율뿐만아니라운동능력및삶의질이향상된다 심장이식 6개월후최대산소섭취량이유의하게증가하고, 환기효율은정상인과비슷한정도로회복된다. 572 또한적극적인심장재활은운동능력을유의하게개선시킬수있다. 573 심장이식의적응이되는환자는심인성쇼크로강심제또는기계적보조치료를요하는말기심부전환자, 관상동맥성형술및관상동맥우회술이불가능하고어떠한치료에도반응하지않는협심증환자, 고주파치료및 ICD에반응하지않는악성심실성부정맥환자등이다. 574 심장이식은말기심부전환자중고위험군환자에서만예후를개선시킨다. Deng 등은심장이식대기자중고위험군환자에서는심장이식후예후가개선되는반면, 중등도및저위험군환자에서는예후개선효과가없는것으로보고하였다. 575 V 기구치료및수술요법5 장심장이식 95

117 운동부하검사는심장이식의적응이되는환자의선별에도움을줄수있다. 최대산소섭취량은최대심박출량과비례하며, 심혈관계최대산소수송기능및말초최대산소이용률을반영한다. 최대산소섭취량이 14 ml/min/kg 이상의말기심부전환자의예후는심장이식을받 은환자의예후와비슷하지만, 최대산소섭취량이 14 ml/min/kg 미만인환자에서 1년생존율은 70% 로심장이식보다나쁘다. 576 그러므로말기심부전환자에서심장이식을고려할때, 심부전중증도및최대산소섭취량등으로환자의예후를평가한후결정해야한다. 96 만성심부전진료지침

118 6 장 세포치료 현재까지심부전환자에서의세포치료는충분히평가되지못한상태이다. 심부전에대한세포치료는주로경도-중등도의좌심실기능부전을동반한허혈성심장질환환자를대상으로연구가이루어져왔다. 그러나대부분소규모임상연구들이어서세포치료의장단기예후그리고심장기능, 심실재형성에대한평가를내리기에근거가충분치않다 세포치료에는세포를얻는개체에따라자가혹은동종세포가, 세포의기원조직에따라골수기원의단핵구, 중간엽줄기세포, 지방조직중간엽줄기세포, 심장줄기세포등다양한세포가이용되고있다. 이중현재까지자가골수기원의단핵구가가장활발히세포치료의임상연구에서평가되어왔다. 허혈성심부전환자에대한골수기원의단핵구세포치료의메타분석결과를살펴보면세포치료군에서유의한좌심실의수축기능개선, 좌심실용적의감소소견이관찰되었다. 580 또한장기추적결과를보고한연구들에서는사망률, 심부전으로인한재입원의유의한감소효과가보고되었다. 그러나이들결과만으로심부전에대한세포치료의효과를평가 하기에는근거가충분치못하다. 따라서개별임상연구들과메타분석에서보고되는세포치료의심장기능, 심장재형성, 그리고임상경과개선에대한효과에도불구하고세포치료를일반적으로심부전환자에게추천할근거는충분하지않다. 세포치료의효능에대한논란에도불구하고장단기경과관찰을통해줄기세포가비교적안전하다는점에대해서는일관된결과들이보고되고있다. 현재로써는심부전환자에대한줄기세포치료를고려하는경우줄기세포에대한생물학적이해와신치료법에대한경험이있는기관을중심으로임상연구차원의접근이고려될수있을것이다. 심부전환자에서세포치료를고려하는경우상대적으로효능이클것으로기대되는경우를기존의연구를통해살펴볼수있다. 우선중등도이상의좌심실수축기능저하가동반된경우가경도의좌심실수축기능저하가있는경우보다는효과가클것으로예상되고있다. 581 그러나심부전환자에서세포치료를고려할때불안정한심부전환자나고도의좌심실수축기능부전을가진환자들은 V 기구치료및수술요법6 장세포치료 97

119 대부분기존의임상연구에서제외되었다는점 을고려할필요가있다. 줄기세포혹은전구세 포의기능 ( 예 : 집락형성능이큰경우 ) 이좋거나 혹은골수단핵구중줄기세포분율이높은경 우에는상대적으로세포치료의효과가큰것으 582, 583 로알려지고있다. 줄기세포의 분율이나 세포의기능성은환자개개인의특성에크게 좌우되어, 임상적고위험군 ( 고령, 신부전, 당뇨 병등 ) 에서상대적으로줄기세포의기능이떨어지고, 줄기세포의분율이낮은것으로알려지고있다. 584 현재심부전을대상으로한세포치료의 3상임상연구는진행되고있지않지만, 급성심근경색증환자에대한사망률감소효과를평가하기위한세포치료 3상연구 (BAMI 연구 ) 가진행중으로그결과를주시할필요가있다. 98 만성심부전진료지침

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153 KSHF guideline for the management of CHRONIC HEART FAILURE 2016 만성심부전진료지침 발행일 2016년 3월 15일발행처 대한심장학회심부전연구회주소 서울특별시마포구독막로 331 마스터즈타워빌딩 805호우 ) 전화 팩스 [email protected] 홈페이지 디자인 ( 주 ) 대한의학서적