Leaflet remodelling in functional mitral valve regurgitation: characteristics, determinants, and relation to regurgitation severity.

BACKGROUND: Recently, it has been hypothesized that mitral leaflet remodelling may play a role in the pathophysiology of functional mitral regurgitation (FMR). We investigated the characteristics, determinants, and relation of mitral leaflet remodelling to FMR severity. METHODS AND RESULTS: Three-dimensional transoesophageal echocardiographic data of the mitral valve (MV) were studied in 30 patients with FMR ≥ grade 3 (≥3), 24 patients with FMR < grade 3 (<3), and 22 controls with normal MV. FMR <3 and ≥3 patients showed leaflet remodelling compared with control subjects with larger overall MV leaflet areas (11.47 ± 3.16 and 9.58 ± 1.99 vs. 7.30 ± 1.57 cm(2)/m(2), respectively; all P < 0.01). Tenting volume (r(2) = 0.55), left ventricular (LV) ejection fraction (r(2) = 0.20), annulus area (r(2) = 0.87), and LV sphericity index (r(2) = 0.25) were correlated with overall MV leaflet area (all P < 0.001). Although these correlates were similar between FMR <3 and ≥3 patients (all P > 0.05), the overall MV leaflet area was smaller in FMR ≥3 compared with FMR <3 patients (P = 0.01), indicating less remodelling despite similar tethering degree. Particularly, coaptation/overall MV leaflet area ratio ≤0.24, reflecting insufficient leaflet remodelling, was associated with FMR ≥3 [area under receiver operating characteristic (ROC) curve = 0.93, sensitivity 90%, and specificity 91%]. This ratio was independently associated with FMR ≥3 (odds ratio 70.0, 95% confidence interval 11.7-419.9, P < 0.001) and showed significant correlation with effective regurgitant orifice area (r(2) = 0.38, P < 0.001). CONCLUSION: MV leaflet remodelling in FMR is common and relates to LV function, LV sphericity, MV tenting volume, and annulus dilatation. Insufficient leaflet remodelling relative to the mitral annular and LV changes is independently associated with FMR severity.

Subclinical left ventricular dysfunction by echocardiographic speckle-tracking strain analysis relates to outcome in sarcoidosis.

AIMS: Limited data exist on the risk of developing cardiac sarcoidosis (CS) and/or adverse events in sarcoidosis patients. Using LV global longitudinal strain (GLS), an emerging sensitive parameter of LV function, we evaluated the prevalence of subclinical cardiac dysfunction in sarcoidosis and investigated whether LVGLS predicts adverse outcomes in this population. METHODS AND RESULTS: A total of 130 patients with proven sarcoidosis undergoing echocardiography at our referral centre were identified. Following exclusion of those with evidence of CS (n = 14) or other pre-existing structural heart disease (n = 16), 100 patients (55 ± 13 years, 48% male, 90% pulmonary involvement) and 100 age- and gender-matched controls were included. LVGLS was measured by speckle-tracking analysis. The primary endpoint was a composite of all-cause mortality, heart failure hospitalization, device implantation, new arrhythmias, or future development of CS on advanced cardiac imaging modalities. LVGLS was significantly impaired in sarcoidosis patients compared with controls (-17.3 ± 2.5 vs. -20.0 ± 1.6%, P < 0.001). Overall, 27 patients (27%) reached the endpoint during a median follow-up of 35 months. On Cox proportional hazards model analysis, abnormal 24-h Holter, larger LV end-diastolic diameters, and more impaired LVGLS were significantly associated with the endpoint; however, only LVGLS remained independently associated on multivariate analysis [hazard ratio (HR) 1.4, 95% confidence interval (CI) 1.1-1.7, P = 0.006]. Patients with LVGLS less than -17.3% were significantly more likely to be free of the primary endpoint (log-rank P = 0.01). CONCLUSION: LVGLS is impaired in sarcoidosis patients, suggesting subclinical cardiac dysfunction despite the absence of conventional evidence of cardiac disease, and is independently associated with occurrence of cardiac events and/or development of CS.

Clinical and prognostic value of stress echocardiography appropriateness criteria for evaluation of coronary artery disease in a tertiary referral centre.

OBJECTIVE: Appropriateness criteria for stress echocardiography (SE) have been published to reduce the rate of inappropriate testing. We sought to investigate the clinical impact and prognostic value of these criteria. METHODS: 250 consecutive patients undergoing SE for evaluation of coronary artery disease were classified into appropriate, uncertain and inappropriate categories according to appropriateness criteria. A positive SE was defined as the development of new wall motion abnormalities or a biphasic response. The primary end point was the composite of myocardial infarction and death. RESULTS: Of the 250 SE, 120 (48%) were dobutamine studies and 130 (52%) were exercise studies. 156 (62.4%), 71 (28.4%) and 23 (9.2%) were classified as appropriate, inappropriate and uncertain, respectively. A significantly greater proportion of studies classified as appropriate 71 (45.5%) demonstrated inducible ischaemia compared with inappropriate studies 9 (12.7%) or uncertain studies 4 (17.4%), p<0.0001. During a median follow-up of 12.4 months, events occurred in 18 (11.5%), 2 (2.8%) and 0 patients classified as appropriate, inappropriate and uncertain, respectively. Event-free survival was significantly reduced in patients with a SE demonstrating ischaemia compared with patients without inducible ischaemia, p<0.0001. Kaplan-Meier curves demonstrated reduced event-free survival in patients with whose studies were classified as appropriate compared to inappropriate (p=0.01) or uncertain (p=0.05). CONCLUSIONS: Appropriateness criteria differentiate between patients at high risk of ischaemia, subsequent revascularisation/cardiac events (appropriate group) and those at low risk of events (inappropriate group). A large proportion of SE is currently performed in inappropriate patients. Implementation of the criteria in clinical practice would reduce unnecessary testing.

Determinants of functional mitral regurgitation severity in patients with ischemic cardiomyopathy versus nonischemic dilated cardiomyopathy.

AIMS: Functional mitral regurgitation (MR) is prevalent among patients with left ventricular (LV) dysfunction and is associated with a poorer prognosis. Our aim was to assess the primary determinants of MR severity in patients with ischemic cardiomyopathy (ICM) and nonischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: Patients with functional MR secondary to ICM (n = 55) and DCM (n = 48) were prospectively enrolled. Effective regurgitant orifice (ERO) area, global LV remodeling, regional wall-motion abnormalities, and mitral apparatus deformity indices were assessed utilizing conventional and tissue Doppler echocardiography. ICM patients had more severe MR compared with DCM patients despite similar ejection fraction and functional status (ERO = 0.16 ± 0.08 cm(2) vs. ERO = 0.12 ± 0.70 cm(2) , respectively, P = 0.002). Regional myocardial systolic velocities in mid-inferior and mid-lateral wall were negatively correlated with ERO in ICM and DCM patients, respectively. Multivariate analysis identified coaptation height as the only independent determinant of ERO in both groups. In a subset of ICM patients (n = 9) with relatively high ERO despite low coaptation height, a higher prevalence of left bundle branch block was detected (88.9% vs. 46.7%, P = 0.02). CONCLUSIONS: Functional MR severity was chiefly determined by the extent of mitral apparatus deformity, and coaptation height can provide a rapid estimation of MR severity in heart failure patients. Additional contributory mechanisms in ICM patients include depressed myocardial systolic velocities in posteromedial papillary muscle attaching site and evidence of global LV dyssynchrony.

Clinical utility and prognostic value of appropriateness criteria in stress echocardiography for the evaluation of valvular heart disease.

We examined the prognostic value of stress echocardiography appropriateness criteria for evaluation of valvular heart disease in 100 consecutive patients. Of the studies, 49%, 36%, and 15% were classified as appropriate, uncertain, and inappropriate, respectively. Over a median of 12.6 months, 24 events (12 deaths and 12 heart failure admissions) occurred. The 12-month event-free survival was significantly reduced in patients with appropriate or uncertain studies compared with patients with inappropriate studies (p = 0.04 and p = 0.005, respectively). There was no survival difference between patients with an appropriate or uncertain indication (p = 0.1). The only independent predictors of events were a positive stress echocardiogram (hazard ratio: 15.5, p < 0.0001) and left ventricular ejection fraction (hazard ratio: 0.95, p = 0.02). The appropriateness criteria for evaluation of valvular heart disease provide the ability to differentiate between patients at high- (appropriate group) and low- (inappropriate group) risk of cardiac events. Reclassification of the uncertain group may improve the differential value of these criteria.