The Prognostic Value of Right Atrial Strain Imaging in Patients with Precapillary Pulmonary Hypertension.

BACKGROUND: Right ventricular (RV) failure in patients with pulmonary hypertension (PH) is associated with unfavorable clinical events and a poor prognosis. Elevation of right atrial (RA) pressure is established as a marker for RV failure. However, the additive prognostic value of RA mechanical function is unclear. METHODS: The authors tested the hypothesis that RA function by strain echocardiography has prognostic usefulness by studying 165 consecutive patients with precapillary PH defined invasively: mean pulmonary artery pressure ≥ 25 mm Hg and pulmonary capillary wedge pressure < 15 mm Hg. Speckle-tracking strain analyses of the right atrium and right ventricle were performed, along with routine measures. Peak RA strain values from six segments using generic speckle-tracking software were averaged to RA peak longitudinal strain, representing RA global reservoir function. The primary end point was all-cause mortality during 5 years of follow-up. RA strain was similarly analyzed in a control group of 16 normal subjects for comparison. RESULTS: There were 151 patients with PH (mean age, 55 ± 16 years; 73% women; mean World Health Organization functional class, 2.6 ± 0.6), after 14 exclusions (three with atrial septal defects and 11 with left ventricular ejection fractions < 50%). RA strain measurement was feasible in 93% of patients and RV strain measurement in 88%. RA peak longitudinal strain was significantly reduced in patients with PH compared with control subjects, as expected (P < .001). During 5-year follow-up, 73 patients (48%) died. Patients with RA peak strain in the lowest quartile (<25%) had a significant risk for death (P = .006), even after correcting for confounding variables. RA strain was independently associated with survival in multivariate analysis (P = .039) and had additive prognostic value to RV strain (log-rank P = .01) in subgroup analysis. CONCLUSIONS: RA peak longitudinal strain had additive prognostic usefulness to other clinical measures, including RV strain, RA area, and RA pressure, in patients with PH. RA mechanical function by strain imaging has potential for clinical applications in patients with PH.

Left ventricular dispersion as a parameter for augmented left ventricular stroke volume in patients with atrial septal defect following transcatheter closure.

OBJECTIVES: The closure of atrial septal defect (ASD) results in normalized left ventricular (LV) and right ventricular (RV) geometry, and can increase LV stroke volume (LVSV), but the parameters associated with this increase after the closure of ASD remain uncertain. METHODS: Seventy ASD patients, who underwent transcatheter closure, were studied. Their mean age was 57.80 ± 16.88 years, 42 (60%) were female, and LV ejection fraction (LVEF) was 66.76% ± 7.91% (all ≥55%). Transthoracic echocardiography was performed before and 3 months after the procedure. Global longitudinal strain (GLS) was determined as the average peak speckle tracking strain of 18 segments from the 3 standard apical views, LV dispersion was defined as standard deviation of time-to-peak strain from the same views, and RV systolic function was calculated by averaging the 3-regional peak speckle tracking longitudinal strains from the RV free wall. A significant relative increase in LVSV between before and 3 months after the closure was defined as ∆LVSV ≥15%. Twenty age-, gender-, and LVEF-matched controls served as the control group. RESULTS: Global longitudinal strain (GLS) and RV free wall strain were similar for ASD patients and controls, but LV dispersion in ASD patients was significantly larger. Global longitudinal strain (GLS) remained unchanged after transcatheter closure, whereas RV free wall strain and LV dispersion decreased significantly. An important finding of the multivariate logistic regression analysis showed that ∆LV dispersion was the only independent determinant of increased LVSV after the closure (OR 1.023; 95% CI 1.001-1.046; P < .01). CONCLUSIONS: The assessment of LV dispersion may well have clinical implications for better management of ASD patients after transcatheter closure.

Risk Stratification of Future Left Ventricular Dysfunction for Patients with Indications for Right Ventricular Pacing due to Bradycardia.

Although right ventricular (RV) pacing is the only effective treatment for patients with symptomatic bradycardia, it creates left ventricular (LV) dyssynchrony, which can induce LV dysfunction and heart failure. The current criterion for consideration of cardiac resynchronization therapy (CRT) is LV ejection fraction (LVEF) ≤ 35%, but indication for CRT in patients required for RV pacing with LVEF > 35% remains unclear.We studied 40 patients, all LVEF ≥ 35%, who had undergone implantable cardioverter-defibrillator implantation with RV pacing < 5%. Echocardiography was performed at baseline and during RV pacing. LV dyssynchrony was defined as anteroseptal-to-posterior wall delay from the mid-LV short-axis view using two-dimensional speckle-tracking radial strain (significant: ≥ 130 ms). Patients were divided into two groups based on baseline LVEF: normal LVEF ( ≥ 50%; n = 20) and mildly reduced LVEF (35-50%; n = 20).LVEF and LV dyssynchrony in patients with mildly reduced LVEF deteriorated significantly during RV pacing compared to those in patients with normal LVEF. Moreover, changes in LV dyssynchrony during RV pacing significantly correlated with changes in LVEF (r = -0.44, P < 0.01). Multivariate logistic regression analysis showed that baseline LVEF was the only independent predictor and baseline LVEF < 48% predictive of significant LV dyssynchrony during RV pacing.The extent of RV pacing-induced LV dysfunction may be associated with baseline LV function. These adverse effects on patients with mildly reduced LVEF of 35-50% and indications for RV pacing due to bradycardia can thus be prevented by CRT.

Significant Prognostic Value of Acute Preload Stress Echocardiography Using Leg-Positive Pressure Maneuver for Patients With Symptomatic Severe Aortic Stenosis Awaiting Aortic Valve Intervention.

BACKGROUND: Although aortic valve intervention is recommended for virtually all symptomatic patients with aortic stenosis (AS), how urgently the intervention should be performed remains controversial. The aim of this study was thus to determine whether the preload reserve in response to leg-positive pressure (LPP) maneuver could serve for decision-making for AS patients awaiting aortic valve intervention.Methods and Results:Sixty-eight patients with symptomatic AS, who were referred for aortic valve intervention, were recruited. Stroke volume (SV) was assessed by means of pulsed-wave Doppler, and the ratio between transmitral E wave and mitral annular velocity (e') was calculated to estimate ventricular filling pressure. While waiting for intervention, 11 patients experienced preoperative cardiac events. During acute preload stress, forward SV for patients without cardiac events increased significantly (from 43±9 to 49±10 mL/m2, P<0.01) along with a minimal change in filling pressure (E/e': from 20±8 to 21±9, NS). For patients with cardiac events, the Frank-Starling mechanism was significantly impaired (SVi: from 40±9 to 38±7 mL/m2, NS), while filling pressure increased to the critical level (E/e': from 24±8 to 31±8, P<0.001). Both the patients without flow reserve (∆SVi <4.5 mL/m2) and those without diastolic reserve (∆E/e' ≥2.9) exhibited significantly worse event-free survival than the others (P<0.05, respectively). CONCLUSIONS: Assessment of preload reserve during LPP stress could facilitate risk stratification of patients with severe AS waiting for aortic valve intervention.

Impact of left ventricular longitudinal functional mechanics on the progression of diastolic function in diabetes mellitus.

Left ventricular (LV) diastolic dysfunction and longitudinal systolic dysfunction were identified in patients with diabetes mellitus (DM). This study's aim was to investigate the impact of LV longitudinal systolic function on LV diastolic function in DM patients with preserved LV ejection fraction (LVEF). We studied 177 DM patients with preserved LVEF (all ≥50%), and 82 age-, gender- and LVEF-matched healthy volunteers as control. Global longitudinal strain (GLS) was defined as the average peak strain of 18 segments from standard apical views, GLS <18% as subclinical LV systolic dysfunction (LVSD), and LV dispersion as the standard deviation of time-to-peak strain from the same views. For DM patients with LVSD (n = 74), E/A and E' were lower, and E/E' and isovolumic relaxation time (IVRT) were greater than for DM patients without LVSD (n = 103) and normal controls (n = 82). Moreover, these parameters were lower for DM patients without LVSD than for normal controls. Multivariate analysis revealed that GLS was a strong determinative factor for E' and E/E' (ß = 0.30, p < 0.001 and ß = -0.25, p < 0.001, respectively), as was LV dispersion for E-wave deceleration time and IVRT (ß = 0.21, p = 0.002 and ß = 0.30, p < 0.001, respectively) independently of age. For normal subjects, however, only age was associated with all LV diastolic parameters. In conclusions, in contrast to age-related LV diastolic dysfunction in normal subjects, in DM patients with preserved LVEF, LV diastolic function was associated with LV longitudinal systolic function and LV dispersion independently of age. Our findings have obvious clinical implications for the management of DM patients.

Effects of a changeover from other angiotensin II receptor blockers to olmesartan on left ventricular hypertrophy in heart failure patients.

Left ventricular (LV) hypertrophy (LVH) is an independent cardiovascular risk factor for heart failure (HF) patients. The renin-angiotensin system plays a key role in LVH, and since olmesartan increases plasma angiotensin-(1-7) through an increase in angiotensin-converting enzyme-related carboxypeptidase (ACE2) expression, it was hypothesized to reduce LVH, unlike other angiotensin II receptor blockers (ARBs). The objective of this study was therefore to investigate the effects of a changeover from other ARBs to olmesartan on LVH in HF patients. Participants enrolled in this prospective trial were 64 outpatients with stable HF who had received ARBs other than olmesartan for more than 1 year (age: 59 ± 13 years). Transthoracic echocardiography and laboratory tests were performed before and 6 months after administration of olmesartan. Other drugs were not changed during follow-up. The primary end point was defined as a change in LV mass index (LVMI) from baseline up to 6 months after administration of olmesartan. No significant changes were observed in blood pressures and heart rate after administration of olmesartan. LVMI showed a significant decrease from 119 ± 38 to 110 ± 24 g/m2 (p = 0.007) 6 months after administration of olmesartan, and further decreased from 110 ± 24 to 103 ± 35 g/m2 (p = 0.0003) after 12 months. Moreover, this reduction tended to be more prominent in patients with LVH. In conclusions, LVH in HF patients was reduced by the changeover to olmesartan. This finding may well have clinical implications for better management of HF patients.

Right ventricular relative wall thickness as a predictor of outcomes and of right ventricular reverse remodeling for patients with pulmonary hypertension.

Mid-term right ventricular (RV) reverse remodeling after treatment in patients with pulmonary hypertension (PH) is associated with long-term outcome as well as baseline RV remodeling. However, baseline factors influencing mid-term RV reverse remodeling after treatment and its prognostic capability remain unclear. We studied 54 PH patients. Mid-term RV remodeling was assessed in terms of the RV area, which was traced planimetrically at the end-systole (RVESA). RV reverse remodeling was defined as a relative decrease in the RVESA of at least 15% at 10.2 ± 9.4 months after treatment. Long-term follow-up was 5 years. Adverse events occurred in ten patients (19%) and mid-term RV reverse remodeling after treatment was observed in 37 (69%). Patients with mid-term RV reverse remodeling had more favorable long-term outcomes than those without (log-rank: p = 0.01). Multivariate logistic regression analysis showed that RV relative wall thickness (RV-RWT), as calculated as RV free-wall thickness/RV basal linear dimension at end-diastole, was an independent predictor of mid-term RV reverse remodeling (OR 1.334; 95% CI, 1.039-1.713; p = 0.03). Moreover, patients with RV-RWT ≥0.21 showed better long-term outcomes than did those without (log-rank p = 0.03), while those with RV-RWT ≥0.21 and mid-term RV reverse remodeling had the best long-term outcomes. Patients with RV-RWT <0.21 and without mid-term RV reverse remodeling, on the other hand, had worse long-term outcomes than other sub-groups. In conclusions, RV-RWT could predict mid-term RV reverse remodeling after treatment in PH patients, and was associated with long-term outcomes. Our finding may have clinical implications for better management of PH patients.

Impaired Mechanics of Left Ventriculo-Atrial Coupling in Patients With Diabetic Nephropathy.

BACKGROUND: Diabetic nephropathy is independently associated with longitudinal systolic dysfunction of the left ventricle (LV) in asymptomatic diabetes mellitus (DM) patients with preserved LV ejection fraction (LVEF). However, the effect of diabetic nephropathy on left atrial (LA) function remains unknown. METHODS AND RESULTS: We studied 198 asymptomatic DM patients (LVEF ≥50%). Diabetic nephropathy was defined as a protein level higher than for micro-albuminuria. LV global longitudinal strain (GLS) and LA strain were analyzed by 2D speckle-tracking; 69 age-, sex-, and LVEF-matched controls were also studied. GLS and LA strain in systole (LAS-s) decreased significantly from normal controls to DM patients without (n=137) and with nephropathy (n=61), in that order. Furthermore, GLS, LAS-s, and LA strain in late diastole (LAS-a) were significantly lower in DM patients with macro-albuminuria (n=19) than in those with micro-albuminuria (n=42). Although 1 multivariate regression analysis identified albuminuria as an independent determinative factor of LAS-s among other relevant clinical background factors (ß=-0.16, P=0.002), another multivariate regression model for LAS-s+GLS (ß=0.40, P<0.001) showed that albuminuria was not a significant factor (ß=-0.02, P=0.68). Similarly, another multivariate regression model including GLS (ß=0.32, P<0.001) demonstrated that clinical features relevant for LAS-a, except for age, were not independent determinants of LAS-a. CONCLUSIONS: The cross-linked association of LA strain with GLS and albuminuria may be important for better understanding the development of diabetic cardiomyopathy. (Circ J 2016; 80: 1957-1964).

Comprehensive Functional Assessment of Right-Sided Heart Using Speckle Tracking Strain for Patients with Pulmonary Hypertension.

BACKGROUND: Right ventricular (RV) systolic function is one of the most important determinants of outcome for pulmonary hypertension (PH) patients, but the factors influencing prognosis vary widely. Elevated right atrial (RA) pressure is reported to be one of these prognostic factors, but its functional importance has scarcely been assessed. METHODS: Eighty-two PH patients, all of whom underwent echocardiography and right heart catheterization, were recruited. RV function was assessed by two-dimensional speckle tracking longitudinal strain from RV-focused apical four-chamber view and calculated by averaging the three regional peak strains from the RV free wall (RV-free). RA function was determined as the sum of three peak strain values comprising reservoir, conduit, and contractile function (sum of RA strain). RESULTS: Sum of RA strain correlated significantly with hemodynamic parameters such as mean right atrial pressure (r = -0.35, P = 0.002) and end-diastolic RV pressure (r = -0.29, P = 0.008). Patients with sum of RA strain ≥30.2% experienced more favorable outcomes than those with sum of RA strain <30.2% (log-rank P = 0.001). Furthermore, patients with impaired RV systolic function (RV-free <20%) and RA function (sum of RA strain <30.2%) showed the worst outcome (P = 0.001). A sequential Cox model based on clinical variables (χ(2) = 5.8) was improved by addition of RV-free (χ(2) = 8.7; P < 0.05) and further improved by addition of sum of RA strain (χ(2) = 12.0; P < 0.01). CONCLUSION: Right atrial strain appears to be a valuable additive factor for predicting outcomes for PH patients, and comprehensive functional assessment of right-sided heart using speckle tracking strain may have potential clinical implications for better management of PH patients.