coronary microvascular dysfunction

Coronary Microvascular Dysfunction – An Update

Magdy El-MasryProf. of Cardiology

Tanta University,Egypt

?Coronary microcirculationCoronary microvascular

dysfunction

Angina with normal coronary arteries, a continuous dilemma

* Cardiac syndrome X : 1973* Microvascular angina : 1985

Can we open the “black

box” ?Finding the missing piece to the puzzle

• Coronary Microcirculation

• Classification of CMVD

• Pathophysiologic mechanisms

• Clinical presentation• Assessment • Management

Coronary microvascular dysfunction(CMVD) Much discussed but little

understood

What we can see is only 5% of the total coronary tree.

Coronary blood flow is driven by the pressure difference between the aorta and the capillary bed and modulated further by various physical and neural factors, which affect the microcirculation. Moreover, the different compartments of the microcirculation are influenced by one main physiological mechanism to control their vascular tone with cardiac metabolism as the final determining factor.

Impaired CFR

Microvascular Angina

• Coronary Microcirculation• Classification of CMVD• Pathophysiologic mechanisms• Clinical presentation• Assessment • Management

Coronary microvascular dysfunction(CMVD) Much discussed but little

understood

Clinical settingRisk factorsMicrovascular angina

Type 1 : in the absence of myocardial diseases and obstructive CAD

Hypertrophic cardiomyopathyDilated cardiomyopathyAnderson-Fabry’s diseaseAmyloidosisMyocarditisAortic stenosis

Type 2 : in myocardial diseases

Stable anginaAcute coronary syndrome

Type 3 : in obstructive CAD

PCICABG

Type 4 : iatrogenic

Classification of coronary microvascular dysfunctionS

econ

dary

C

MV

D

• Coronary Microcirculation• Classification of CMVD• Pathophysiologic mechanisms• Clinical presentation• Assessment • Management

Coronary microvascular dysfunction(CMVD) Much discussed but little

understood

Main pathogenetic mechanisms

Endothelial dysfunctionSMC dysfunctionVascular remodelling

Type 1 : in the absence of myocardial diseases and obstructive CAD

Vascular remodellingSMC dysfunctionExtramural compressionLuminal obstruction

Type 2 : in myocardial diseases

Endothelial dysfunctionSMC dysfunctionLuminal obstruction

Type 3 : in obstructive CAD

Luminal obstructionAutonomic dysfunction

Type 4 : iatrogenic

Pathophysiologic mechanisms of coronary microvascular dysfunction

• Coronary Microcirculation• Classification of CMVD• Pathophysiologic mechanisms• Clinical presentation• Assessment • Management

Coronary microvascular dysfunction(CMVD) Much discussed but little

understood

Coronary microvascular dysfunction(CMVD) ‘microvascular angina’ (MVA)

Primary

*CMVD in the absence of myocardial diseases and obstructive CAD

Secondary

*CMVD in myocardial diseases

*CMVD in obstructive CAD

* Iatrogenic CMVD

Primary ‘microvascular angina’

Stable

Predominant effort angina

Unstable

Acute rest angina

Largely investigated formPoorly investigated form

Primary ‘Microvascular angina’

Typical Angina Evidence of stress-induced Myocardial ischemia

Normal coronary angiogram

ST-segment depression

Perfusion defects in antero-lateral wall of the LV at peak exercise.

Myocardial perfusion scintigraphy in a patient with typical effort angina and normal coronary arteries

Evidence of stress-induced myocardial ischemia

* IC acetylcholine (ACH) constriction* IC nitroglycerin (NTG) dilation

Spasm of epicardial coronaries on acetylcholine provocation should be

excluded.

• Coronary Microcirculation• Classification of CMVD• Pathophysiologic mechanisms• Clinical presentation• Assessment • Management

Coronary microvascular dysfunction(CMVD) Much discussed but little

understood

The classical ischemic cascade, triggered by coronary vasospasm and/or epicardial stenosis.

The alternative ischemic cascade, triggered by coronary microvasculature dysfunction(CMVD).

Diagnostic challengeEpicardial

CAD

CMVD

Assessment of CMVD is primarily functional and not anatomic.

RWMAs(Stress echo)

+ VE

- VE

CFR

Distribution of myocardial ischemia - Diffuse- Patchy

FFR and CFR: What Do They Investigate?

FFR: Specific for epicardial disease

CFR : Affected by both epicardial and microcirculatory disease (cannot distinguish between the two)

Pa

Pd

FFR = Pd /Pa (during hyperemia) = 58/79 = 0.730

Pa

Pd

Baseline HyperemiaAdenosine IC

100

80

60

40

20

FFR

FFR threshold for ischemia

FFR

Noischemia

Yes ischemia

1.00 0.8 0.00

FFR < 0.8 inducible ischemia FFR > 0.8 no inducible ischemia

CFR

Coronary flow velocity profile obtained with tranthoracic Doppler of LAD: in diastole the flow velocity is higher than in systole.

LAD:mid & distal

FFR > 0.80 FFR ≤ 0.80DiagnosisNon-flow-limiting stenosisPreserved microvascular function

TreatmentMedical therapy, no PCI

DiagnosisFlow-limiting stenosisPreserved microvascular function

Treatment PCI

CFR >2.0

DiagnosisNon-flow-limiting stenosis

CMVD

TreatmentMedical therapy, no PCI

DiagnosisFlow-limiting stenosis

CMVD

Treatment PCI

CFR <2.0

Diagnosis and Treatment Based on Fractional Flow Reserve and Coronary

Flow Reserve Values

Level Class RecommendationsC IIa Exercise or dobutamine echo should be considered in

order to establish whether RWMAs occur in conjunction with angina and ST-changes.

C IIb Transthoracic doppler echo of the LAD with measurement of diastolic CBF following iv adenosine and at rest may be considered for non invasive measurement of CFR

C IIb IC acetylcholine and adenosine with Doppler measurements may be considered during coronary arteriography, if the arteriogram is visually normal, to assess endothelium dependent and non-endothelium CFR and detect microvascular/epicardial vasospasm.

Investigation in patients with suspected CMVD

2013 ESC guidelines on the management of stable coronary artery disease

• Coronary Microcirculation• Classification of CMVD• Pathophysiologic mechanisms• Clinical presentation• Assessment • Management

Coronary microvascular dysfunction(CMVD) Much discussed but little

understood

Old anti-anginalsDRUG CLASS VASODILATION HEART RATE MYOCARDIAL

CONTRACTILITY

Short acting

nitrate -

sublingual

Beta-blockers

Long-acting

nitrates

Calcium channel

blockers

DHP Amlodipine Non-DHP Diltiazem and Verapamil

Limited effect in coronary microcirculation

Main anti-ischemic effects Drugs

Improvement of left ventricular relaxation and diastolic function during ischemia

Ranolazine

Reduction of heart rate Ivabradine

Vasodilation through ATP/K-channel opening and nitrate-like effects

Nicorandil

Improved cardiac metabolism during ischemia Trimetazidine

Newer anti-anginals

Main anti-ischemic effects DrugsImproved endothelial function; antagonism of angiotensin II

ACE inhibitors

Improvement of endothelial function Statins

Redistribution of coronary blood flow towards ischemia areas

Xanthines

Anti-α vasoconstrictor effects α-antagonists

Improvement of endothelial function Estrogens(Post-menopausal

(women

Additional drugs

Anti-angina effects TherapyInhibition of visceral pain transmission Imipramine

Non-pharmacological Treatments :

Modulation of pain transmission and processing; modulation of ischemic sympathetic effects

Spinal cord stimulation

Improvement of endothelial function; development of coronary microvessels

Enhanced external counterpulsation

Training effect; reduction of sympathetic tone

Rehabilitation programs

Improvement of pain tolerance; reduction of anxiety

Psychologic interventions

Additional alternative therapies proposed for patients with refractory microvascular angina

Spinal cord stimulation

Enhanced external counterpulsation

Level Class RecommendationsB I It is recommended that all patients receive secondary

prevention medications including aspirin and statins.B I ß-blockers are recommended as a first line treatmentB I Calcium antagonists are recommended if ß-blockers

do not achieve sufficient symptomatic benefit or are not tolerated.

B IIb ACE inhibitors or nicorandil may be considered in patients with refractory symptoms

B IIb Xanthine derivatives or nonpharmacological treatments such as neurostimulatory techniques may be considered in patients with symptoms refractory to the above listed drugs.

2013 ESC guidelines on the management of stable coronary artery disease

Treatment in patients with MVA

Key Take-Home Points

Underlying pathophysiology is heterogenous.

This is responsible for nonuniform response to different diagnostic tests and therapeutic approaches.

This appears to be insufficient because ischaemia-related

symptoms frequently recur and these patients incur in relatively

large health-care costs, in addition to the major adverse cardiac

events.

Existing guidelines focus on symptom management and current clinical practice on ‘reassurance’.

Definition and classification of microvascular angina

Stepwise therapeutic approach to patients with microvascular angina.

Thank You