ATRIAL FIBRILLATION AND LEFT ATRIUM: STRUCTURAL REMODELING AND EVOLUTION OF ARRHYTHMIA PATTERN

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1 Atrial Fibrillation and Heart Failure: the ugly and the nasty 13 International Meeting February th 2019, Bologna ATRIAL FIBRILLATION AND LEFT ATRIUM: STRUCTURAL REMODELING AND EVOLUTION OF ARRHYTHMIA PATTERN Marco Vitolo, Alessandra Reggi, Elisa Fantecchi, Anna Chiara Valenti, Vincenzo Livio Malavasi, Giuseppe Boriani Cardiology Division, Department of Diagnostics, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Policlinico di Modena, Modena, Italy

2 BACKGROUND AND AIM OF THE STUDY Why the study? There are few evidences on the correlation between AF patterns and atrial structural remodeling, especially concerning its evolution throughout time Previous adoption of linear measurement for the LA Aim of the study Analyze the time-course of LA enlargement, Why the study? categorized by LA volume indexed by body surface area (LAVi) according to the classification published in the ASE 2015 Guidelines and AF pattern's evolution. Relationship between LA enlargement and clinical variables LA enlargement progression and patients outcome.

3 THE CONCEPT OF REMODELING A time-dependent, complex and still not completely understood response of atrial cardiac myocytes to varying stressors, which is defined as a persistent change in LA size or function 1 The entity of such phenomenon can be extremely various, depending on type, severity and duration of exposure to stressors Structural remodeling: LA dilation Functional remodeling: Reservoir function, Conduit function, Booster pump function TO KEEP IN MIND Atrial remodeling and enlargement is a complex phenomenon LA may expand throughout any spatial plane and not uniformly Precise quantification may be difficult 1 Thomas, Liza, and Walter P. Abhayaratna. JACC: Cardiovascular Imaging 10.1 (2017): 65-77

4 LA CHAMBER QUANTIFICATION Volumetric measurements more reliable, stronger association with outcomes Cutoffs refer to ASE 2015 Guidelines Document on Cardiac Chamber Quantification The biplane disk summation technique, which incorporates fewer geometric assumptions, should be the preferred method Linear measures no more recommended for inaccuracy Left atrial volume cutoffs

5 MATERIALS AND METHODS Prospective study, from February 1 st 2016 to June 30 th 2017 A full baseline transthoracic echocardiographic evaluation (TTE) was mandatory for the inclusion. TTE was repeated 1 year ± 1 month after the enrollment Logistic regression analysis was performed to evaluate variables independently associated to LAVi dilation. Cox regression analysis was performed to calculate the hazard ratios (HR) and 95% confidence interval for a pre-specified composite endpoint (death, admissions for heart failure or AF, thromboembolism, NYHA class worsening).

6 STUDY SELECTION CRITERIA 201 PATIENTS REQUIREMENTS FOR INCLUSION 12-lead ECG or 24-h Holter confirming AF diagnosis Occurrence of the qualifying arrhythmic episode within one year from the date of screening AF as a primary or second diagnosis for the admission/outpatient evaluation Presence of echocardiographic examination at baseline Evaluation at AF service executed 1y ±month before EXCLUSION CRITERIA Absence of an ECG/Holter documentation of AF Presumptive diagnosis made by implantable devices (AHRE) Documentation of atrial flutter and not of AF A timeframe longer than 1 year since the occurrence of the qualyfing episode Age < 18 years

7 BASELINE POPULATION CHARACTERISTICS Prevalence Age BMI (kg/m2) EF (%) LAVI (ml/mq) GFR with CKD-EPI (ml/min) CHA 2 DS 2 -VASc Mean value SD 73,32 9,06 26,73 5,25 53,94% 10,68 40,38 14,72 74,28 16,91 3,28 1,53 Female sex N=79 (39,3%) Hypertension N=152 (75,6%) Diabetes N=24 (12%) Cancer N=42 (21%) CKD according to CKD-EPI N=39 (19,4%) CAD N=38 (19%) CHA 2 DS 2 -VASc 2 (F) N=192 (95,5%) CHA 2 DS 2 -VASc 1 (M) Previous stroke N=9 (4,5%) Prevalence HF at basal NO N= 158 (78,6%) NYHA I N=9 (4,5%) NYHA II N=27 (13,4%) NYHA III N=6 (3%) NYHA IV N=1 (0,5%) Previous TIA N=14 (7%) Prevalence Cardiomyopathy N=29 (14,4%) EF <40% at basal N=25 (12,4%) Moderate and severe MR N=33 (16,4%) Moderate and severe AS N=5 (2,5%) Prosthetic valve N=3 (1,5%)

8 AF PATTERN AND LA ENLARGMENT EVOLUTION DURING THE STUDY TIMELAPSE AF PATTERN LA ENLARGEMENT Basal Follow-up Basal Follow-up 47% 38,30% 35,30% 20,40% 24% 25% 27% 28,00% 28,40% 18,40% 21,90% 19,40% 19,90% 23,90% 22,90% 0% First d iagnosed A F Paroxysmal AF Persistent A F Permanent A F Normal LA Mild Enlargement Moderate Enlargement Severe Enlargement Relevant increase in the arrhythmic burden Big raise in the group of permanent AF Same trend for atrial dimensions Severely dilated LA almost doubled

9 STRUCTURAL LA REMODELING DURING THE STUDY Number of patients with different atrial conditions Normal atria at the end of the study LA enlargement Only less than a fifth of the sample terminated the study with a normodimensioned LA chamber LA class dilation switch 40% switched to a further class of dilation 0% 20% 40% 60% 80%

10 MULTIVARIABLE ANALYSIS FOR LA ENLARGEMENT AND FURTHER CLASS LA DILATION Parameters significantly associated to LA enlargement class switch LA enlargement at FUP OR 95%IC P value Age 75y 2,35 (1,07-5,13) 0,032 LAVi at baseline 0,93 (0,90-0,96) <0,001 AF pattern at FUP 1,26 (0,61-2,6) 0,522 Sinus rhythm at FUP 0,26 (0,07-0,95) 0,04 Antiarrhythmic therapy at FUP 0,74 (0,27-1,96) 0,54 Cancer 5,7 (1,72-18,93) 0,004

11 MULTIVARIABLE ANALYSIS FOR THE COMPOSITE ENDPOINT Parameters significantly associated to the occurrence of the composite end-point 451± 233 days 39 pts (19.9%) Composite end-point HR 95%IC P value EF<40% at FUP 1,73 (0,71-4,21) 0,223 First detected AF 3,19 (1,33-7,62) 0,009 Rate/rhythm control 0,59 (0,32-1,10) 0,098 VHD 3,03 (1,30-7,05) 0,010 Coronary artery disease 2,26 (1,09-4,69) 0,028 EHRA lower 2,26 (0,92-5,50) 0,073 LA enlargement at FUP 0,83 (0,58-1,19) 0,327 The composite endpoint: Death Admissions for atrial fibrillation Admissions for new/worsening HF NYHA class worsening Thromboembolism Structural remodeling was not associated to the endpoint Does function matters more than structure? AF first detected is not a so benign entity

12 RELATIONSHIP BETWEEN STRUCTURE AND FUNCTION LAVI and LA EMPTYING FRACTION Relationship between structural and functional remodeling Patients N= 145 R= - 0,619 P <0,001 Structural and functional remodeling were linked by a direct linear negative relationship Functional remodeling occurred in parallel to structural remodelling, with opposite directions LAEF as an indicator of global atrial function, with special reference to reservoir function

13 CONCLUSIONS Arrhythmic burden defined according to AF pattern and LA enlargement experienced a significant parallel increase during the study course AF pattern was not associated to LA structural remodeling, while the presence of sinus rythm at FU exert a protective function Ageing and cancer were strongly related to LA dilation Structural and functional remodeling were linked by a direct linear negative relationship (p<0,001)

14 THANK YOU FOR YOUR ATTENTION AKNOWLEDGMENTS Professor Giuseppe Boriani Alessandra Reggi Elisa Fantecchi Anna Chiara Valenti Vincenzo Livio Malavasi