Diagnostic criteria for subclinical systolic and diastolic LV function

JRP A3

Tatiana Kuznetsova, Jan A. Staessen University of Leuven, Belgium

Heart failure

Stages of heart failure

Stage A: asymptomatic subjects with normal LV structure and function at high risk for HF, because of hypertension, obesity and/or diabetes; Stage B: asymptomatic patients with structural and/or functional LV abnormalities; Stage C: symptomatic patients with structural and/or functional LV abnormalities; Stage D : patients with refractory symptoms of heart failure.

ACC/AHA Guidelines, Circulation 2005; 112: 1825-52

Heart failure

Background and objectives

Above age 65, the incidence of overt HF is currently ~10/1000 person-years. Because of the ageing of populations, the prevalence of HF will rise by 50% over the next 10-15 years, increasing health care costs. 50% of HF patients die within 4 years. The diagnosis of asymptomatic LV dysfunction (imaging + biomarkers) is key in the prevention and treatment of HF. Objectives:



To explore (using TDI) the prevalence of asymptomatic systolic and diastolic LV dysfunction in a general population;



To identify (cross-sectionally and prospectively) risk factors and biomarkers for LV dysfunction.

IGHC

Outline of presentation

Methods:

 

Epidemiological approach; Echocardiography for cardiac phenotyping; Results:



Systolic LV dysfunction;



Diastolic LV dysfunction; Conclusions.

Methods

Epidemiological approach – echocardiography

EPOGH

Epidemiological methods Randomly recruited nuclear and complex (Belgium) families; Standardised and validated questionnaires in 8 languages; BP at baseline: 2 x 5 conventional BP readings at home, 5 BP readings at examination centre, and 24-h ABPM; Large number of intermediate phenotypes: blood and 24-h urine samples (biobank); Technical examinations: ECG, vascular and cardiac phenotypes; Longitudinal FU (median 15 y in Belgium and 5 years in other centres).

EPOGH

Standardised echocardiographic protocol Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO); A single observer is performing all echocardiographic examinations by means of Vivid 7 ultrasound scanner (GE Vingmed, Horten, Norway) according to a standardised protocol; All echocardiographic examinations are stored in digital format on a local network for off-line reading (EchoPac, GE and SPEQLE, University of Leuven); Leuven is the core centre for cardiac and arterial phenotyping, management of samples, database construction, and statistical analysis.

Subclinical LV dysfunction

Systolic

SysLVF

Background

Conventional echocardiography enables the assessment of global LV systolic function: FS or EF; Colour tissue Doppler imaging makes it possible to specifically evaluate the longitudinal and radial components of regional LV systolic function.

Strain

Echocardiographic characteristics

Conventional LV mass index (g/m 2 ) RWT EF (%) TDI Strain longitudinal (%) SR longitudinal (1/s) Strain radial (%) SR radial (1/s) * p



0.05; ** p



0.01; † p



0.001

Women (n=243) Men (n=237) 83 (17) 0.37 (0.071) 69.6 (7.3) 98 (20) † 0.37 (0.072) 67.8 (7.2)** 23.0 (3.7) 1.31 (0.26) 60.7 (12.5) 3.44 (0.86) 22.7 (3.6) 1.31 (0.23) 57.6 (12.9)* 3.34 (0.82) Kuznetsova T et al, Eur Heart J 2008; 29: 2014-23

Strain

Longitudinal and radial S and SR by age

70 65 60 55 50 25 24 23 22 21 20 n=48 43 113 104 60 N=52 48 123 123 32 86 48 4.0

3.5

3.0

2.5

1.5

1.4

1.3

1.2

1.1

Age group (years) p-values for trends



0.001

Kuznetsova T et al, Eur Heart J 2008; 29: 2014-23

Strain

Longitudinal strain vs WT, WHR and BW p-values



0.00

1 Longitudinal 40 35 30 25 20 15 10 40 35 30 25 20 15 10 0.2

0.3

0.4

RWT 0.5

0.6

0.7

0.6

0.7

0.8

0.9

WHR 1.0

1.1

1.2

100 80 60 40 20 0.2

100 80 60 40 20 45 0.3

0.4

RWT 0.5

0.6

0.7

60 Radial 75 90 Weight (kg) 105 120 Kuznetsova T et al, Eur Heart J 2008; 29: 2014-23

Strain

Summary of stepwise selection*

Variable Age (+10 years) RWT (+0.1) WHR (+0.1) Age (+10 years) RWT (+0.1) BW (+1 kg) Age (+10 years) RWT (+0.1) * p<0.10 – significance level for entry into the model Par Est (SE) R 2 (%) Strain longitudinal (%) - 0.35 (0.14) - 0.74 (0.26) + 1.59 (0.26) + 1.67 (0.49) 8.4

8.4

- 0.59 (0.28) 1.5

- 1.08 (0.48) - 2.57 (1.02) - 0.15 (0.05) Strain radial (%) 8.4

2.0

5.7

Ejection fraction (%) 16.1

2.2

p-value .007 .001 .010

.027 .010 .0004 < .0001 .001 Kuznetsova T et al, Eur Heart J 2008; 29: 2014-23

Strain

Proposal for reference values* for S and SR

Strain (%) Longitudinal Radial SR (1/s) Longitudinal Radial Healthy reference group (n=239) > 18.5

> 44.5 > 1.00

> 2.45

*Upwards rounded the 5 th percentiles

Strain

Annexin A5

Annexins are Ca 2+ and phospholipid binding proteins; Annexin A5 participates in the regulation of ion (Ca 2+ ) currents across the cardiomyocyte membrane; Ravassa et al. showed that the upregulation of myocardial Annexin A5 is associated with impairment of LV systolic function (EF) in patients with HF (Eur Heart J 2007; 28: 2785-91).

Strain

Radial strain vs annexin A5

100 90 80 70 60 50 40 30 20 n = 265 r = –0.13

adjusted p = 0.006

0.56

1 1.78

3.16

Annexin A5, ng/mL 5.62

Strain

Conclusions of this section

LV strain and strain rate, as measured by 1-dimensional colour Doppler imaging in a general population, decreased with age, body weight, central obesity, and RWT.

LV strain and strain rate are sensitive tools for the detection of subclinical systolic dysfunction associated with abdominal obesity and LV remodelling.

The clinical applicability of strain and strain rate in the stratification and/or in the administration of treatment remains to be established.

This cross-sectional study shows that LV radial strain decreased with plasma Annexin A5.

Subclinical LV dysfunction

Diastolic

DiaHF

Transmitral and pulmonary vein blood flows, and pulsed TDI

A

DiaHF

Age-specific percentiles of E/A and E/Ea in 392 “healthy” subjects 2.75

2.50

2.25

2.00

1.75

1.50

1.25

1.00

0.75

0.50

97.5% 75% 50% 25% 2.5% 6 5 4 3 10 9 8 7 97.5% 75% 50% 25% 2.5% Age group (years) Kuznetsova T et al, Circulation Heart Failure 2009; 2:105-112

DiaHF

Classification of LV diastolic dysfunction

1 group - impaired relaxation (n=53; 9.8%; NT-proBNP 269 pmol/l*):



E/A: abnormally low age-specific values



E/Ea: normal range (< 8.5) 2 group – elevated E/Ea (end-diastolic LV filling pressure?) (n=76; 14.1%; NT-proBNP 302 pmol/l*):



E/A: normal age-specific range;



E/Ea: > 8.5



(Adur < ARdur) + 10



3 group – elevated E/Ea ratio and an abnormally low age-specific E/A (n=18; 3.4%; NT-proBNP 245 pmol/l*) * p ≤0.05 vs normal: 214 pmol/l Kuznetsova T et al, Circulation Heart Failure 2009; 2:105-112

DiaHF

Diastolic dysfunction stages*

E Normal LV Press DIASTOLIC HEART FAILURE Impaired Relaxation Pseudonormal Restrictive LA Press E A E A E A A Mitral Doppler Velocity Pulmonary Vein Velocity PV s PV d PV a PV s PV d S m PV a S PV s PV d m PV s PV d PV a S m Doppler Tissue Imaging S m E m A m E m A m E m A m PV a E m A m Zile MR et al, Circulation 2002; 105:1387-93

DiaHF

Correlates of LV diastolic dysfunction Age (+10 years) Women BMI (+5 kg/m 2 ) Heart rate (+10 bpm) SBP (+10 mm Hg) Use of β-blockers Insulin (



2 µU/ml) Serum creatinine (+10 µmol/l) NT-pro BNP (



2 pmol/ml) 0.5

1.0

1.5

2.0

Odds ratio 2.5

3.0

3.5

4.0

OR 2.71

1.63

2.07

1.55

1.27

1.94

1.43

1.33

2.20

95% CI 2.02-3.61

0.86-3.09

1.42-3.04

1.16-2.10

1.07-1.69

0.98-3.84

1.03-1.93

1.05-1.69

1.47-3.31

p-value <0.0001

0.13

0.0002

0.0035

0.0052

0.056

0.032

0.018

0.0001

Kuznetsova T et al, Circulation Heart Failure 2009; 2:105-112

DiaHF

Conclusions

LV diastolic dysfunction in a random population sample, as estimated from echocardiographic measurements, is common (27.3%). Our findings are clinically relevant, because patients with subclinical diastolic dysfunction often progress to overt HF.

TDI is a sensitive method for the detection of early diastolic (and systolic) LV dysfunction in a general population, particularly in subjects with LV remodelling and normal EF.

EPOGH

Team work Katholieke Universiteit Leuven, B Jagiellonian University Cracow, PL Universitá degli Studi di Padova, I Institute of Internal Medicine, RU University of Gdánsk, PL JA Staessen, T Kuznetsova, Y Jin, L Thijs, T Richart K Kawecka-Jaszcz, K Stolarz E Casiglia, V Tikhonof Y Nikitin, S Malyutina, G Simonova K Narkiewicz, W Sakiewicz, A Rojch

EPOGH

Team work (2) Charles University Pilzen, CZ Universidad de Navarra, E Universitá di Milano, I Universität Münster, D Universiteit Maastricht, NL University of Lausanne, CH University of Leicester, UK J Filipovsky, J Kucerová J Diez, S Ravassa , A González B López G Bianchi, P Manunta, C Lanzani, L Tizzoni E Brand, SM Herrmann, Hasenkamp S H Struijker-Boudier, S Heymans M Burnier, M Bochud, M Maillard N Samani, V Codd