Higher Ventricular-Arterial Coupling Derived from Three-Dimensional Echocardiography Is Associated with a Worse Clinical Outcome in Systemic Sclerosis

Abstract

Primary myocardial involvement is common in systemic sclerosis (SSc). Ventricular-arterial coupling (VAC) reflecting the interplay between ventricular performance and arterial load, is a key determinant of cardiovascular (CV) performance. We aimed to investigate VAC, VAC-derived indices, and the potential association between altered VAC and survival free from death/hospitalization for major adverse CV events (MACE) in scleroderma. Only SSc patients without any anamnestic and echocardiographic evidence of primary myocardial involvement who underwent three-dimensional echocardiography (3DE) were included in this cross-sectional study and compared with healthy matched controls. 3DE was used for noninvasive measurements of end-systolic elastance (Ees), arterial elastance (Ea), VAC (Ea/Ees) and end-diastolic elastance (Eed); the occurrence of death/hospitalization for MACE was recorded during follow-up. Sixty-five SSc patients (54 female; aged 56 ± 14 years) were included. Ees (p = 0.04), Ea (p = 0.04) and Eed (p = 0.01) were higher in patients vs. controls. Thus, VAC was similar in both groups. Ees was lower and VAC was higher in patients with diffuse cutaneous form (dcSSc) vs. patients with limited form (lcSSc) (p = 0.001 and p = 0.02, respectively). Over a median follow-up of 4 years, four patients died for heart failure and 34 were hospitalized for CV events. In patients with VAC > 0.63 the risk of MACE was higher (HR 2.5; 95% CI 1.13–5.7; p = 0.01) and survival free from death/hospitalization was lower (p = 0.005) than in those with VAC < 0.63. Our study suggests that VAC may be impaired in SSc patients without signs and symptoms of primary myocardial involvement. Moreover, VAC appears to have a prognostic role in SSc.

Sclerodermic Cardiomyopathy—A State-of-the-Art Review

“…SSc patients need annual 2DTTE for assessing LV systolic and diastolic function and sPAP [51]. LV systolic function: 5.4% prevalence of LV systolic dysfunction [52]; reduced strain rate values in the IVS and antero-lateral wall [12]; myocardial electromechanical proprieties-diffuse deterioration of LV segments [3].…”

“…LV diastolic function: 4-5 times more frequent than systolic dysfunction (17-30% of cases) [22,53]; Risk factors for low e'velocities: duration of the disease, age, CAD, HTN [53]; e'-baseline value predicts mortality risk and every decrease in standard deviation elevates mortality risk 3.2 times [53]. VAC: Higher in dcSSc compared to lcSSc [51]; VAC might predict MACE in SSc population [51].…”

“…Even though the end-diastolic LV diameter, fractional shortening and LVEF are routinely used parameters for the 2D echocardiographic evaluation of SSc patients, they are load-dependent and do not systematically reflect the myocardial contractile status [51]. VAC is a novel measurement that is based on the complex interplay between the cardiac function and arterial system and is a major determinant of global cardiovascular performance [78].…”

“…VAC is a novel measurement that is based on the complex interplay between the cardiac function and arterial system and is a major determinant of global cardiovascular performance [78]. It is defined by the ratio between arterial elastance (Ea) and end-systolic LV elastance (Ees) [51]. Therefore, VAC uncoupling may be able to predict morbi-mortality in different pathogenic entities, including SSc, because regulating processes from the extracellular matrix and cytoskeleton are complex biochemical pathways that simultaneously damage both the structure and function of the heart and arteries by means of fibrosis deposits [51,78].…”

“…It is defined by the ratio between arterial elastance (Ea) and end-systolic LV elastance (Ees) [51]. Therefore, VAC uncoupling may be able to predict morbi-mortality in different pathogenic entities, including SSc, because regulating processes from the extracellular matrix and cytoskeleton are complex biochemical pathways that simultaneously damage both the structure and function of the heart and arteries by means of fibrosis deposits [51,78]. Tona et al are the first to have conducted a study that evaluated the relationship between LV pressure-volume status and VAC by three-dimensional TTE (3DTTE) in SSc [51].…”