IS LEFT ATRIAL DYSFUNCTION A KEY

TARGET IN HFPEF?

Κώστας Παπαδόπουλος,

Επιμελητής Α΄ Καρδιολογίας,

Νοσοκομείο ΄΄Ερυθρός Σταυρός΄΄

Heart failure with preserved ejection fraction (HFpEF):Role of imaging

LEFT ATRIUM

Complex anatomy

Connected to the LV and pulmonary circulation

It modulates LV filling to maintain LV preload

and cardiac output without untoward increase in

pressure.

Ho SY, et al. Circ Arrhythm Electrophysiol 2012;5:220–8.

Veinot JP, et al.. Circulation 1997;96:3112–5.

PHASES DETERMINANTS

RESERVOIR: LV systole, IVRT LA properties (relaxation and stiffness), LV contraction, RVSP

CONDUIT-PASSIVE EMPTYING: LV early diastole (V-loop) LV relaxation, LV early diastolic pressure

PUMP-ACTIVE EMPTYING: LV end-diastole (A-loop) LA contractility, LV compliance, LV end-diastolic pressure

K Boudoulas, I.A Paraskevaidis,H.Boudoulas , F.Triposkiadis. Cardiology 2014;129:1–17

LEFT ATRIUM - FUNCTION

Flachskampf F, et al. JACC Cardiovascular Imaging 2015:1071 – 93

HFpEF

The primary pathology in HFpEF is diastolic dysfunction

Impaired LV relaxation

Reduced early diastolic suction

(reduced restoring forces)

Increased diastolic Stiffness

Increased LV filling pressures

(mean left atrial pressure)

Senni M, et al. International Journal of Cardiology 173 (2014) 163–169

The role of left atrial dysfunction in the

pathophysiology of HFpEF

Obokata M, et al. European Journal of Heart Failure (2019)

Left Atrium

Key role in preserving diastolic phase and

preventing the onset of HF symptoms

The pathophysiological mechanism that leads from

asymptomatic diastolic dysfunction to HFpEF

LA dysfunction can be a potential subphenotype of

HFpEF

LA volume has been defined as the glycosylated

hemoglobin of diastolic dysfunction

Obokata M, et al. Heart Fail Clin. 2019 Apr;15(2):241-256 European Journal of Heart Failure (2014) 16, 1047–1048

LEFT ATRIUM - DIMENSIONS

-Lang R, et al. J Am Soc Echocardiogr 2015;28:1-39

-Sugimoto T, et al. EACVI NORRE study. EHJ- CV Imaging 2018;19:630-8

-Παπαδόπουλος Κ, Παρασκευαίδης Ι. ‘Καρδιαγγειακή Απεικόνιση’. Έκδοση 2019

LEFT ATRIUM - FUNCTION

LEFT ATRIUM - FUNCTION

2D VOLUMES

3D VOLUMES

Blume, Tsang et al. European Journal of

Echocardiography 2011;12,:421–430

LEFT ATRIUM

2D STRAIN

-Sugimoto T, et al. EACVI NORRE study. EHJ- CV Imaging 2018;19:630-8

-Παπαδόπουλος Κ, Παρασκευαίδης Ι. ‘Καρδιαγγειακή Απεικόνιση’. Έκδοση 2019

MVD

Paraskevaidis I, Panou F, Papadopoulos C et al. Heart 2009;95:483-9

LIMITATIONS

Atrial wall significantly thinner than the LV

Located in the far field of the ultrasound beam

More difficult to trace and track accurately

Image resolution frequently worse than the ventricle

Strain imaging requires significant expertise, training

Moderate interobserver and intraobserver variability

No validated cut off values for atrial fibrosis

Tan, Koutsogeorgis, Grapsa, Papadopoulos, Katsivas, Nihoyannopoulos. Eur J Clin Invest 2014;44:872–82

CARDIAC CT and MRI

Accurate quantification of atrial

dimensions, volume and wall

thickness

Delayed enhancement MRI (DE-

MRI): Useful in localizing and

quantifying diffuse global and

regional atrial fibrosis

Ling, et al. Heart Rhythm. 2015;12:857–864

Oakes RS, et al. Circulation. 2009;119:1758–1767.

McGann CJ, et al. J Am Coll Cardiol. 2008; 52:1263–1271.

Peters DC, et al.Radiology. 2007; 243:690–695.

Atrial dimensions / function:

In HFpEF Diagnosis

In D/D between HFpEF and NCD

As an indicator of pulmonary vascular disease and right HF

As a predictor of:

- Abnormal exercise haemodynamics and clinical symptoms

- Atrial fibrillation

- Hospitalization and mortality, in HFpEF patients

- 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

- Nagueh S, et al.J Am Soc Echocardiogr 2016;29:277-314.

HFpEF DIAGNOSIS

LV filling pressures and grading LV diastolic function in pts with depressed LVEF or with

myocardial disease and normal LVEF after consideration of clinical and other ECHO data

Left atrial reservoir strain may provide enhanced diagnostic accuracy beyond conventional echocardiographic measures to discriminate HFpEF from NCD.

Reddy Y, et al. European Journal of Heart Failure (2019)

Left atrial strain and compliance in the diagnostic evaluation of HFpEF

Incremental Diagnostic Value of LA Strain Over Clinical

Data and Conventional Echocardiographic Values

Obokata M, et al. J Am Coll Cardiol Img 2013;6:749–58

Cameli M, et al. Heart Fail Rev 2016 Algorithm for the diagnosis of HFpEF in patients presenting with suspected

symptoms and/or signs of heart failure

Impaired LA reservoir and pump function are associated with abnormal exercise haemodynamics in HFpEF. These markers provide significant HFpEF diagnostic utility in elderly ambulatory patients with dyspnoea.

Telles F, et al. European Journal of Heart Failure (2019)

Impaired left atrial strain predicts abnormal exercise haemodynamics in HFpEF

-Cut-off left atrial reservoir strain of 32.2% predicted HFpEF diagnosis with 82% sensitivity and 86% specificity-Cut-off of ≤33% showed a net reclassification improvement (NRI) of 12%,

LA diastolic and systolic function were significantly impaired, and inter-atrial dyssynchrony was prolonged in patients with HFpEF. Decreased LA systolic function and prolonged inter-atrial dyssynchrony were possibly associated with deteriorated clinical symptoms

S. Liu et al. / International Journal of Cardiology 257 (2018) 177–181

Impaired left atrial systolic function and inter-atrial dyssynchrony may

contribute to symptoms of HFpEF

LA function is associated with pulmonary vascular disease and right HF in both HF phenotypes

Melenovsky V, et al. Circ Heart Fail. 2015;8:295-303

LA function is associated with pulmonary vascular disease and right HF

In patients with HF, LA dysfunction seems to be a hemodynamic key mediator of RV-to-PC uncoupling and impaired ventilation efficiency during exercise. Monitoring LA-strain during exercise is feasible, and its maladaptive response during physical stress represents a novel

and additional target of interventions to prevent/avoid the negative evolution toward RV-to-PC uncoupling.

Sugimoto T, et al. J Am Coll Cardiol Img 2017;10:1253–64

Left Atrial Function Dynamics During Exercise in Heart Failure

Pathophysiological Implications on the Right Heart and Exercise Ventilation Inefficiency

PROGNOSIS in HFpEF

Prognostic markers of death and/or HF hospitalization in patients with HF (ESC-HF Guidelines 2016)

LA dysfunction in HFpEF is associated with a higher risk of HF hospitalization.

Santos A, et al. Circ Heart Fail. 2016 April ; 9(4):

The Prognostic Relevance of Left Atrial Dysfunction in HFpEF

LA function is associated with outcome more closely in HFpEF, supporting efforts to improve LA function in this cohort

Melenovsky V, et al. Circ Heart Fail. 2015;8:295-303

LA function is associated with pulmonary vascular disease and right HF

Diastolic parameters of left atrial function (A wave changes) possibly are more important markers of AF risk than left atrial dilation in HFpEF.

Oneal W, et al. European Heart Journal - Cardiovascular Imaging (2017) 18, 725–729

Echocardiographic predictors of atrial fibrillation in patients with HFpEF

LA strain: <30%, indicates significant

alteration of LA reservoir function,

which predicts the poor outcome.

Kleemann T, et al. Eur J Echocardiogr 2009;10:383–8.

Impairment of LA longitudinal deformation, as

assessed by the global PALS, correlated strongly

with the extent of LA fibrosis and remodeling

Cameli Μ, et al. Am J Cardiol 2013;111:595e601

How Left atrial dysfunction could be targeted in HFpEF?

Reduction of LV filling pressures (through a variety of means)

Agents that directly target myocardial structure and function in the

left atrium, such as neurohormonal antagonists.

Maintenance of SR or restoration of AF.

-Obokata M, et al. European Journal of Heart Failure (2019)

-Solomon SD, et al.. Lancet 2012;380:1387–1395.

-Lam CS, et al. JACC Heart Fail 2017;5:92–98.

-Marrouche NF, et al.. N Engl J Med 2018;378:417–427

CONCLUSIONS

Left Atrium key role in preserving diastolic phase and preventing the

onset of HF symptoms

LA dysfunction may represent an important target for therapy

Echocardiography allows to accurately and noninvasively evaluate

LA dimensions and function.

This could improve correct diagnosis, therapy and prognostication in

patients with HFpEF.