Aucun titre de diapositive · Collagen production and secretion AF AF . Potential elements of a clinically relevant classification of atrial cardiomyopathies ... New pathophysiological

Stanley Nattel, MD

Montreal Heart Institute

Atrial Cardiomyopathy:

is it an evolving clinical reality?

Stanley Nattel, MD

Montreal Heart Institute

Atrial Cardiomyopathy:

is it an evolving clinical reality?

YES!

Review of main aspects of atrial cardiomyopathy

Significance for stroke risk:

— Risk prediction

— Therapeutic decision making

New pathophysiological concepts

Outline



— Risk prediction



Outline

Consensus document 2016

Published simultaneously in Europace, Heart Rhythm and Journal of Arrhythmia

Cardiac disease Risk factors

Systemic conditions Gene variants

Autonomic imbalance

Fibroblasts

Basic mechanisms leading to atrial

cardiomyopathy

AF

Angiotensin-dependent Angiotensin-independent

Cardiac disease Risk factors

Systemic conditions Gene variants

Autonomic imbalance

AF

Ion channel abnormities

Ca2+ handling abnormities

Fibrosis

Myofibroblasts

Collagen production

and secretion

AF

AF

Potential elements of a clinically relevant classification

of atrial cardiomyopathies

Atrial electrical dysfunction, AF

Atrial mechanical dysfunction

Procoagulant state

Atrial fibrosis

ATRIAL CARDIOMYOPATHY

Gene variants Risk factors Ventricular dysfunction Infiltrative disorders

Drug toxicity Valvular heart disease Endocrine abnormalities

1) Causal factors

c) LGE-MRI (fibrosis)

b) ECG indices

(PR; AF rate, amplitude)

a) Echo indices (LA size, contractility)

d) Biomarkers (VWF, coagulation markers)

Cardiac dysfunction

Stroke

Impaired QOL Testing for validity:

Quantifiable outcomes

2) Objective+

quantifiable

classification

measures

Therapeutic decision making



— Risk prediction



Outline

Atrial Cardiomyopathy-

Useful concept or just another term to be forgotten?

To be of value, the term should add something to our practical

understanding and clinical management of AF cases: Evidence of value?

We predict stroke risk and decide on

anticoagulation not based on AF

characteristics, but based on factors

associated with atrial cardiomyopathy.

What is new in this area since my

last presentation here in 2017?

A LOT!

Stroke Risk Determination in AF patients: The ABC

(Age, Biomarkers, Clinical History) Score

Hijazi Z et al, EHJ 2016

Looked at wide range of clinical and biomarker

factors as predictors of stroke in ARISTOTLE

database ( 14,701 pts) and validated the

predictors in STABILITY database (1,400 pts).








Factors included CHA2DS2-VaSc criteria, other

clinical features and a variety of biomarkers.








Factors included CHA2DS2-VaSc criteria, other

clinical features and a variety of biomarkers.

Two biomarkers proved quite significant, both

potentially cardiomyopathic indicators: NT-

proBNP and Troponin.




Each risk factor is assigned points based on

value.

Points are totaled up for each factors.

Total number of points predicts stroke risk.

For example take 64 y.o. man.

With no prior stroke/TIA, an NT-BNP of 1480

and TnT of 4.2.

Risk points would be 0 (no stroke/TIA)





value.





and TnT of 4.2.

Risk points would be 0 (no stroke/TIA) + 1.2

(age 64)





value.





and TnI of 4.2.

Risk points would be 0 (no stroke/TIA) + 1.2

(age 64) +1.4 (Troponin I of 4.2)





value.





and TnI of 4.2.

Risk points would be 0 (no stroke/TIA) +

1.25 (age 64) +1.5 (Troponin I of 4.2) + 7.5

(NT-BNP of 1480)





value.





and TnI of 4.2.


1.25 (age 64) +1.5 (Troponin I of 4.2) + 7.5

(NT-BNP of 1480)=10.25 total risk points





value.





and TnI of 4.2.


1.25 (age 64) +1.5 (Troponin I of 4.2) + 7.5

(NT-BNP of 1480)=10.25 10.25 total risk

points

This gives a 1-year stroke/systemic

embolism risk of just over 1% and a 3-year

risk of 2.5%

Note that in this calculation, troponin and especially NT-BNP

have great weight, more than age and prior stroke/TIA




Thus, with only 2 clinical (age, prior stroke/TIA) and 2 biomarker criteria,

ABC score is at least as predictive as CHA2DS2-VaSC

The biomarkers used (proNT-BNP and troponin) are atrial cardiomyopathic indices

The biomarkers have very strong weight in the model, supporting the importance of

atrial cardiomyopathy in stroke risk



— Risk prediction



Outline

Atrial Cardiomyopathy- Stroke Risk Time of stroke

AF episodes

Martin DT et al, EHJ 2015

No clear relationship between timing of AF and stroke

6 months pre-stroke

No AF episodes pre-stroke

Could AF-associated stroke risk be a function of associated

atrial cardiomyopathy and not AF itself?

Atrial Cardiomyopathy and Stroke Prevention: ARCADIA Trial

Int J Stroke 2019

This study should tell us whether atrial cardiomyopathy can be a

significant factor in stroke even in patients with sinus rhythm



— Risk prediction



Outline

AF risk in CAD patients:

Biomarker evidence of inflammatory signaling

Nortamo S et al, Int J Cardiol 2017

In ARTEMIS, a prospective Japanese study of 1946 CAD patients, 143 (8.4%) developed new-onset AF .

The authors performed multivariate analysis to define AF predictors among clinical and biomarker indices.

Significant predictors were age (p=.004), weight (p=.045), LAD (p=.001), asthma/COPD meds (p=0.001), lack of

cholesterol meds (p=.008), soluble ST2 (sST2) blood level (p=.006) and CRP

CRP is a well-known inflammatory marker

sST2 binds to the anti-inflammatory interleukin IL-33 and reduces its anti-

inflammatory action; sST2 promotes inflammation and apoptosis

Thus, biomarkers support the idea of an inflammatory atrial cardiomyopathy

as a precursor to AF

Role of cardiomyocyte inflammatory signaling in

AF pathophysiology

Yao C et al, Circulation 2018

The NLRP3 inflammasome is a well known inflammatory protein signaling complex in macrophages

NLRP3 acts via a downstream protein ASC to release active caspase-1, which releases the

inflammatory mediator IL-1β from pro-IL-1β.

This study looked at CARDIOMYOCYTE NLRP3 changes in AF patients and animal models

The NLRP3 inflammasome is activated in

atrial cardiomyocytes from subjects with

clinical and experimental AF

CM-specific overexpression of NLRP3 in

mice causes spontaneous and inducible AF

CM NLRP3 O/E mice

Role of cardiomyocyte inflammatory signaling in

AF pathophysiology

Yao C et al, Circulation 2018

NLRP3 cardiomyocyte overexpression

causes atrial structural remodeling

NLRP3 activation causes chronic cardiomyocyte

inflammatory signaling in AF patients that may

be central to AF pathophysiology

Conclusions

Atrial cardiomyopathy is an evolving concept

Conclusions


There is evidence that consideration of atrial cardiomyopathy may add value to risk estimation

Conclusions


There is evidence that consideration of atrial cardiomyopathy may add value to risk estimation

Atrial inflammatory signaling may play an important role in leading to atrial cardiomyopathy and AF

Conclusions


There is evidence that consideration of atrial cardiomyopathy may add value to patient management

Atrial inflammatory signaling may play an important role in leading to atrial cardiomyopathy and AF

Consideration of the concept of atrial cardiomyopathy may lead to improved risk prediction, therapeutic guidance, pathophysiological understanding and therapeutic innovation

Thank you!..Grazie!

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Aucun titre de diapositive · Collagen production and secretion AF AF . Potential elements of a clinically relevant classification of atrial cardiomyopathies ... New pathophysiological