kronisk koronarsyndrom
TRANSCRIPT
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KRONISK KORONARSYNDROM
Svein SolheimOverlege, PhD
Hjertemedisinsk avdeling og Senter for klinisk hjerteforskning,
Oslo universitetssykehus, Ullevål
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KRONISK KORONARSYNDROM
• epidemiologi
• anatomi/fysiologi
• aterosklerotisk prosess
• angina pectoris
• akutt koronar syndrom med komplikasjoner
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• Cirka 40 000 behandles årlig i spesialisthelsetjenesten for angina og hjerteinfarkt, 16 000 for hjertesvikt og 11 000 for hjerneslag
• 1 av 5 lever i dag med etablert hjerte- og karsykdom eller har høy risiko for slik sykdom. Om lag 1,1 million nordmenn bruker legemidler for å forebygge eller behandle hjerte- og karsykdom
• Årlig antall førstegangsinfarkt per 100 000 innbyggere går ned. Av de som rammes er det færre som får et alvorlig infarkt.
Folkehelseinstituttet 2020
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• Nedgang i røyking og bedre behandling forklarer en stor del av nedgangen i antallet førstegangsinfarkter.
• I grupper med lav utdanning er det en høyere andel som rammes av hjerteinfarkt
• Dødsfall som følge av hjerte- og karsykdom er skjøvet opp i høyere aldersgrupper. 50% av dødsfallene blant menn skjer etter 83 års alder, og for kvinner etter 89 år.
• Antall personer med hjerte- og karsykdom vil øke i årene framover.
Folkehelseinstituttet 2020
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Nabel EG, Braunwald E. N Engl J Med 2012;366:54-63.
Decline in Deaths from Cardiovascular Disease in Relation to Scientific Advances.
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CVD Mortality Trends For Males And Females United States: 1979–2015
AHA Councils (EJ Benjamin et. al.) Circulation. 2018;137:e67
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ATEROSKLEROSE
(ÅREFORKALKNING)
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A coronary artery has been opened longitudinally. The coronary extends from left to right across the middle of the picture and is surrounded by epicardial fat. Increased epicardial fat correlates with increasing total body fat. There is a lot of fat here, suggesting one risk factor for atherosclerosis. This coronary shows only mild atherosclerosis, with only an occasional yellow-tan lipid plaque and no narrowing.
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SMC
IEL
EC
Advanced Lesion
Ca CaCa Ca
Ca Ca
Ca
CaCaCaCaCaCaCaCa
Ca
CaCa
PlaqueRupture
Thrombus
Ref: Berliner JA et al., Circulation 1995;91:2488-96
PLAQUERUPTUR MED TROMBEDANNELSE
aterosklerose
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This is the left coronary artery from the aortic root on the left. Extending across the middle of the picture to the right is the anterior descending branch. This coronary shows severe atherosclerosis with extensive calcification. At the far right, there is an area of significant narrowing.
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inflammasjon
aterotrombose
LDL kolesterol-akkumulering
blodplateaktivering
aktivering avkoagulasjonssystemet
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Kliniske manifestasjoner avaterosklerose
• koronar hjertesykdom– angina pectoris, hjerteinfarkt, hjertesvikt,
hjerterytmeforstyrrelser, plutselig hjertedød• cerebrovaskulær sykdom
– Transient ischaemic attacks TIA, hjerneslag• perifer vaskulær sykdom
– claudicatio intermittens, gangren
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Iskemisk hjertesykdom/koronar hjertesykdom (CHD)
• symptomer, tegn eller komplikasjoner som skyldes nedsatt blodforsyning til myocard
• skyldes vanligvis innsnevringer i koronararteriene på grunn av koronar arteriesykdom (CAD), oftest aterosklerose
• stor variasjon i graden av innsnevringer, utbredelse og symptomer
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Myokard-iskemi
oksygenbehov
oksygentilførsel
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ANGINA PECTORIS
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KORONAR ISKEMI
• angina pectoris
• stille ischemi
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Symptomer
ESC Guidelines 2013
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Sannsynlighet for koronarsykdom
ESC 2019
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ANGINA PECTORIS -DIAGNOSTIKK
• sykehistorie
• risikofaktorer
• slektsbelastning
• non-invasiv undersøkelse
• invasiv undersøkelse
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Risikofaktorer for aterosklerotiskhjertesykdom
• Modifiserbare
– røyking
– dyslipidemi• LDL kolesterol é• HDL kolesterol ê• triglycerider é
– hypertensjon
– diabetes mellitus
– overvekt
– ugunstig kosthold
– fysisk aktivitetê
• Ikke modifiserbare
– etablert
– arv
– alder
– kjønn
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Non-invasive hjerteundersøkelser
• Arbeidsbelastnings EKG (sykkel eller tredemølle)
• CT koronararterier
• Stress SPECT (isotop)
• Stress ekkokardiografi
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ANGINA PECTORIS - DIAGNOSTIKK
• Arbeids EKG (AKG)
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KORONAR ANGIOGRAFI
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Venstre koronar-arterie
Høyre koronar-arterie
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Homod. 2008
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< 50% stenose av lumendiameter
• blodflow i koronararterien opprettholdes
• ingen revaskularisering
• optimal sekundærprofylakse
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> 50% stenose av lumendiameter (signifikant)
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Invasiv koronar angiografiFractional Flow Reserve (FFR)
• Trykksensor på tuppen av kateteret
• FFR = Pd/Pa ( Pd = trykk distalt for stenosen, Pa = trykkproksimalt for stenosen)
• Identifiserer hemodynamiske eller funksjonelt signifikante stenoser
• FFR<0,75-0,80 indikerer signifikant koronar stenose som kan affisere blodforsyningen til deler av myokard
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Invasiv koronar angiografi
• bekrefte eller eksludere signifikant epikardiellkoronarsykdom
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Invasiv koronar angiografi
• bekrefte eller eksludere signifikant epikardiellkoronarsykdom
• risikostratifisering (i tillegg til kliniske faktorer, venstre ventrikkelfunksjon, respons påstresstesting)
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Invasiv koronar angiografi
• bekrefte eller eksludere signifikant epikardiellkoronarsykdom
• risikostratifisering (i tillegg til kliniske faktorer, venstre ventrikkelfunksjon, respons påstresstesting)
• selektere ut pasienter som kan ha nytte av(symptombedring og/eller overlevelse) avrevaskularisering (PCI eller ACB)
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INTRAKORONAR ULTRALYD(IVUS)
A1=14,8 mm 2
A2= 5,0 mm 2
%sten=66,3%diam=42
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Koronar angiografi
Høyre
koronararterie
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Koronarangiografi - patologiOkklusjon
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BEHANDLING AV KRONISK KORONARSYNDROM
Mål:• bedre livskvalitet• symptomlindring• redusere sykelighet• livsforlengende
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Behandling av kroniskkoronarsyndrom
Optimal medisinsk
terapi
ACBPCI
PCI; percutaneous coronary intervention ACB; aorto coronar bypass
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OPTIMAL MEDISINSK BEHANDLING VED KRONISK
KORONARSYNDROM
• røyekutt• optimalt kosthold (”middelhavsdiett”)• regelmessig fysisk aktivitet• vektreduksjon ved overvekt
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OPTIMAL MEDISINSK BEHANDLING VED KRONISK
KORONARSYNDROM
Antitrombotisk:• acetylsalicylsyre (aspirin 75 mg), evt.
clopidogrel 75 mg (ASA intoleranse)
Antithrombotic Trialists Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death,myocardial infarction, and stroke in high risk patients. BMJ 2002
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OPTIMAL MEDISINSK BEHANDLING VED KRONISK
KORONARSYNDROM
Mål for lipidsenkende behandling:
• LDL < 1,4 mmol/l (<1,0) og/eller >50% reduksjon
ESC 2019
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HYPERTENSJON
ESC 2019
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OPTIMAL MEDISINSK BEHANDLING
Diabetes:
• HbA1C < 7% (53 mmol/mol)
ESC 2016
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ANTI-ISKEMISK BEHANDLING VED KRONISK KORONARSYNDROM
• hurtigvirkende nitroglycerin
• betablokker
• calciumblokker
• langtidsvirkende nitroglycerin
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PERKUTAN KORONAR INTERVENSJON (PCI)
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PERKUTAN KORONAR INTERVENSJON
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PCI MED STENTMetallstent – ”bare metal stent” (BMS)
•reduksjon av restenose sml. med POBA
• fremdeles 10-20% har behov for ny revaskularisering p.g.aintimahyperplasi
Cutlip et al. J Am Coll Cardiology 2002;40:2082
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PCI med medikamentavgivende stentdrug eluting stent (DES)
DES sammenlignet med BMS: •reduserer intimahyperplasi og angiografisk restenose•reduserer behovet for ny target lesion revaskularisering•ingen effekt på mortalitet
BVS (Bioabsorbable Vascular Scaffold)
DEB (Drug-Eluting Balloon)
Roiron et al. Drug eluting stents: an updated meta-analysis of randomised controlled trials. Heart 2006; 92:641.
Shuchman M. Trading restenosis forthrombosis? New questions aboutdrug-eluting stents. N Engl J Med 2006;355:1949.
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HVEM FÅR UTFØRT PCI I DAG?• Klinisk indikasjon:– Angina pectoris og/eller positivt belastnings-EKG– Stenose som affiserer >10% av myokard– Alvorlige arytmier antatt iskemiutløst– STEMI (primær, etter trombolyse, kardiogent sjokk,
persisterende smerter)– Non-STEMI
• Angiografisk indikasjon:– >50% diameter stenose sentralt i de store karene– FFR<0,75-0,80– Stenosene må være teknisk egnet for PCI
• OBS: Hvis det forventes bedret overlevelse med ACB, anbefales dette
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PCI vs Medical Therapy Alone in Patients With Stable Obstructive CAD and Myocardial Ischemia: Meta-analysis of RCTs
Selected for >50% statin use in both groups and >50% stent useSubset of patients with ischemia documented (4064 of 5286)
Stergiopoulos et al. JAMA Intern Med. 2014;174:232-40.
Death
Unplanned Revascularization
MI (non-fatal)
Angina
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The ischemia trial
Cardiovascular Clinical Research Center
Study Flow
Enrolled (8518)
Screen Failure (3339)Major Reasons:• Insufficient ischemia (N = 1350)• No obstructive CAD (N = 1218)• Unprotected LMD (N =434)
Randomized (5179)Study CCTA in 73% of randomized participants
Randomized to INV (2588)
Median follow-up for survivors 3.3 years (IQR 2.2 to 4.3 years)
Proportion of follow-up completed: 99.4%
Median follow-up for survivors 3.3 years (IQR 2.2 to 4.4 years)
Proportion of follow-up completed: 99.7%
Randomized to CON (2591)
Ischemia, Symptoms + Non-Obstructive CAD
66% Women
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Cardiovascular Clinical Research Center
Baseline Coronary Artery Anatomy by CCTA
# of Vessels with >50 % Stenosis (%)(% of total)
1
87
46
68 70
1
87
47
67 68
0102030405060708090
100
Left Main Left AnteriorDescending
Proximal LAD Left Circumflex Right CoronaryArtery
2429
47
22
34
44
0
10
20
30
40
50
6070
80
90
100
1 2 ≥ 3
Specific Vessels with >50% Stenosis (%)
Hochman JS et al. JAMA Cardiology. 2019 Mar 1;4(3):273-86.
N=2982 N=3739
The ischemia trial
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Enrolled (8518)
Screen Failure (3339)Major Reasons:• Insufficient ischemia (N = 1350)
•No obstructive CAD (N = 1218)
•Unprotected LMD (N =434)
Randomized (5179)Study CCTA in 73% of randomized participants
Randomized to INV (2588)
Median follow-up for survivors 3.3 years (IQR 2.2 to 4.4 years)
Proportion of follow-up completed: 99.7%
Randomized to CON (2591)
Ischemia, Symptoms + Non-Obstructive CAD
66% Women
Cardiovascular Clinical Research Center
Baseline Coronary Artery Anatomy by CCTA
# of Vessels with >50 % Stenosis (%)(% of total)
1
87
46
68 70
1
87
47
67 68
0102030405060708090
100
Left Main Left AnteriorDescending
Proximal LAD Left Circumflex Right CoronaryArtery
2429
47
22
34
44
0
10
20
30
40
50
6070
80
90
100
1 2 ≥ 3
Specific Vessels with >50% Stenosis (%)
Hochman JS et al. JAMA Cardiology. 2019 Mar 1;4(3):273-86.
N=2982 N=3739
Cardiovascular Clinical Research Center
0%
5%
10%
15%
20%
25%
30%
0 1 2 3 4 5
Cum
ulat
ive
Inci
denc
e (%
)
Follow-up (years)
CON
INV
Adjusted Hazard Ratio = 0.93 (0.80, 1.08)P-value = 0.34
Subjects at Risk
CON 2591 2431 1907 1300 733 293INV 2588 2364 1908 1291 730 271
6 months:Δ = 1.9% (0.8%, 3.0%)
4 years:Δ = -2.2% (-4.4%, 0.0%)
Absolute Difference INV vs. CON
Primary Outcome: CV Death, MI, hospitalization for UA, HF or resuscitated cardiac arrest
15.5%
13.3%
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ACB-OPERASJON
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ACB vurderes ved:
• signifikant stenose i venstre koronararteries hovedstamme
• signifikant 3-karsykdom (RCA, CX og LAD), spesielt hos pasienter med nedsatt venstre ventrikkelfunksjon, diabetes, kronisk nyresykdom
• signifikant 2-karsykdom (RCA eller CX) med høygradig proximal LAD-stenose
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1964 1977 1986 2002
ACB POBA BMS DES DEB BVS
ACB; aorto coronar bypassPOBA; plain old balloon angioplasty (ballongutblokking)BMS; bare metal stent (metallstent)DES; drug eluting stent (medikamentavgivende stent)DEB; drug eluting balloon (medikamentballong)BVS: Bioresorbable Vascular Scaffold (absorberbar stent)
Koronar revaskularisering
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KRONISK KORONARSYNDROM–MEDIKAMENTELL BEHANDLING• Acetylsalicylsyre (ALBYL-E 75 mg)• Clopidogrel 75 mg x 1 (evt. nyere platehemmere)
etter PCI (6 mnd.)• Betablokker• Calcium-blokker• Langtidsvirkende nitroglycerin• Statin (LDL<1,4) • Hutrigvirkende nitroglycerin under tungen
(anfallsbehandling/profylakse)
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AKUTT KORONAR SYNDROM (ACS)
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Brystsmerter
HjerteinfarktMyokardittPerikarditt
KardiomyopatiTako-Tsubo
TraumeKlaffefeil
AortadisseksjonAortaaneurismeCerebrovaskulær
sykdom
ØsofagittØsofagusspasme
UlcusPancreatitt
Cholecystitt/cholelitiasis
CostafracturMuskel/skjelettska
decostaochrondritis
LungeembolismeLungeinfarkt
PneumoniPleuritt
Pneumothorax
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Non ST-elevation ST-elevation
Akutt koronarsyndrom
NSTEMIDavies MJ
Heart 83:361, 2000
STEMIUSTABIL ANGINA
Troponin < 99% percentileTroponin > 99% percentile Troponin > 99% percentile
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Myokardskade-markører målt i blodprøve
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Clinical Classification of differentTypes of Myocardial Infarction
Type 1 Spontaneous myocardial infarction related to ischemia due to a primary coronary event such as plaque fissuring or rupture
Type 2 Myocardial infarction secondary to ischemia due to imbalance between oxygen demand and supplies e.g. coronary spasm
Type 3 Sudden cardiac death with symptoms of myocardial ischemia, accompanied by new ST elevation or LBBB, or verified coronary thrombus by angiography, but death occurring before blood samples could be obtained
Type 4 Myocardial infarction associated with PCI
Type 5 Myocardial infarction associated with CABG
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Troponiner uten infarkt
• hjertesvikt, arytmier, myokarditt• takotsubo, aortadisseksjon,
hjertekontusjon• lungeemboli, pulmonal hypertensjon• sepsis, sjokk, toksiner• nyresvikt• hjerneslag
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ESC GUIDELINES 2018
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Behandling avakutt koronarsyndrom uten
ST-elevasjon/nyoppdaget grenblokk
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Non ST-elevation
Akutt koronarsyndrom
NSTEMIDavies MJ
Heart 83:361, 2000
USTABIL ANGINA
Troponin < 99% percentileTroponin > 99% percentile
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Behandling av akutt koronarsyndrom utenST-elevasjon/nyoppdaget grenblokk
• Risikostratifisering (GRACE/TIMI score) avgjør intensitet av antitrombotisk behandling og hastegrad for koronar angiografi
• Anti-iskemisk(nitrateter, betablokker, revaskularisering)
• Anti-trombotisk (platehemmere, antikoagulasjon)
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<2 timer
<24 timer
<72 timer
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Trombedannelsen
Thrombin
AGGREGATION
Fibrin
HemostaticClot
ClottingPlatelet Aggregation
0 min 10 min5 min
SECONDARY
PRIMARY
COAGULATION
Adapted from Ferguson JJ, et al. Antiplatelet Therapy in Clinical Practice. 2000:15-35.
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Figure 2 | Targets of antiplatelet drugs. Platelets have a variety of cell-surface receptors that mediate their activation (green shading), their adhesion to the blood vessel wall (red) and their aggregation with each other (blue). The ligands for various receptors are shown. Antiplatelet drugs and their targets are also indicated; targets include thromboxane A2 (TXA2),protease-activated receptor 1 (PAR1), the ADP receptor P2Y12 and αIIbβ3-integrin.
NATURE|Vol 451|21 February 2008
ADP receporantagonist;clopidogrel,prasugrel,ticagrelor
Thromboxane inhibitors;aspirin
Gp IIb/IIIareceptor blocker; abciximab, eptifitabide,aggrastat
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Figure | Targets of anticoagulant drugs.
NATURE|Vol 451|21 February 2008
Targets of anticoagulant drugs
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ST-elevation or new LBBB
Acute Coronary Syndrome
Davies MJ Heart 83:361, 2000
STEMI
TIME IS MUSCLE!
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REDUKSJON I MORTALITET RELATERT TIL TID FRA SMERTEDEBUT TIL
TROMBOLYSE
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Akuttbehandling av ST-elevasjons-hjerteinfarktPCI: perkutan
koronar intervensjon
STEMI/nyoppdaget grenblokk
Akutt koronar angiografi (PCI)acetylsalicylsyre 300 mg, clopidogrel 600 mg eller
prasugrel 60 mg, heparin 70IE/kg i.v.
Trombolyse
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Acute ST-elevation myocardialinfarction (inferior wall)
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Acute ST-elevation myocardial infarction
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Akutt hjerteinfarkt - komplikasjoner
• Iskemiske• Mekaniske• Arytmier• Blødning• Emboliske• Inflammatoriske
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Slag-volum
preload afterload
kontraktilitet
Cardiac Output
hjertefrekvens• Synergisme i kontraksjon• klaffesuffisiens
Venstre ventrikkelfunksjon
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Hypotensjon
• Lavt minuttvolum (= SV x HR)– Redusert preload/diastolisk fylning– Nedsatt kontraksjonsevne og mekaniske endringer– Øket afterload– Ekstrem bradykardi
• Lav systemisk motstand– Patologisk vasodilatasjon– Vasodilaterende medikamenter
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Iskemiske komplikasjoner
• Angina• Reinfarkt• Infarktekspansjon
• EKG, infarktmarkører, ekkokardiografi, koronarangiografi
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Mekaniske komplikasjoner
• Hjertesvikt (venstre/høyre ventrikkel)• Kardiogent sjokk
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Endediastolisk volum - endesystolisk volum Endediastolisk volumEF =
Endediastole Endesystole
Ejeksjonsfraksjon
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ESC 2016
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Klinikk/diureseEkkoCVPSVO2LaktatPICCOSwan-Ganz
ESC 2016
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ESC 2016
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ESC 2016
ARNI: angiotensin receptor/neprilysin inhibitor: sacubitril/valsartan (Entresto™)
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Mekaniske
• Hjertesvikt (venstre/høyre ventrikkel)• Kardiogent sjokk• Mitralklaffe dysfunksjon (papillemuskelruptur)• Hjerteruptur (ventrikkelseptumruptur, ruptur
av fri vegg med tamponade)• Aneurismer
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IABP (Intra-aortic balloon pump)
aortaballongpumpe
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Impella(left ventricular assist device)
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Arytmier
• Atrieflimmer, arieflutter, atrietachycardi• Ventrikkeltakykardi, ventrikkelflimmer• Sinusknutedysfunksjon (S-A blokk)• A-V blokk (grad I, II, III)
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Blødning
• Perforasjon av koronararterie med tamponade• Blødning fra innstikksted (a. femoralis, a.
radialis)• Hjerneblødning• G-I blødning• Blødning fra thorax/abdomen etter HLR
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Emboli
• CNS (hjerneslag)• Perifer embolisering (iskemi i
underextremitet)
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Inflammasjon
• Perikarditt• Infeksjoner (f.eks pneumoni, sepsis)
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”Den dårlige infarktpasient”
• venstre og/eller høyre ventrikkelsvikt på grunn av utbredt myokardinfarkt
• reokklusjon av infarktrelatert koronararterie• mekaniske komplikasjoner
(VSR*, MI**, ruptur av fri vegg, tamponade)• arytmier • blødning • infeksjon
*VSR; ventrikkelseptumruptur**MI; mitalinsuffisiens
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Behandling etter akuttkoronarsyndrom
• Aspirin 75 mg x 1 (livslang) + prasugrel (Efient) 10 mg x 1 eller ticagrelor (Brilique) 90 mg x 2 ellerclopidogrel (Plavix) 75 mg x 1 i 1 år
• betablokker• statin/kolesterolsenkende LDL kolesterol < 1.4 (1,0)
mmol/L• v.v. funksjon êACE-I eller AT II blokker ± aldosteron
antagonist (evt. vurdere Entresto ved EF<35%)• optimal behandling av hypertensjon (BT<120-130 mmHg)
og diabetes mellitus (HbA1C<53 mmol/mol) • Livsstilsintervensjon røykekutt, kosthold, fysisk
aktivitet, vektkontroll
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Takk for oppmerksomheten!