Left atrial strain in acute heart failure: clinical and prognostic insights.

AIMS: In acute heart failure (AHF), the consequences of impaired left atrial (LA) mechanics are not well understood. We aimed to define the clinical trajectory of LA mechanics by left atrial strain (LAS) analysis. METHODS AND RESULTS: Eighty-five consecutive AHF patients with reduced, mildly reduced, and preserved left ventricular ejection fraction (LVEF) were enrolled in the LAS-AHF trial and underwent LA mechanics analysis by speckle tracking echocardiography. Seventy-seven patients were followed-up (FU) at 6 and 12 months. At hospital admission, discharge, 6 and 12 months post-discharge, LA reservoir function (LAS), LA pump strain, LAVi, LA stiffness, indicators of right ventricular (RV) and left ventricular (LV) function, congestion indexes (B lines, inferior vena cava, X-ray congestion score index), and biomarkers (NT-pro-BNP) were measured. The primary outcome was time to first event of re-hospitalization, worsening HF, or cardiovascular death. From admission to discharge, RV function significantly improved after decongestion, whereas no significant differences were observed in LA dynamics and LV function. In sinus rhythm patients with mild or no mitral regurgitation, decongestion was associated with a significant improvement of LAS and LA pump strain rate during hospitalization. At 12 months, 24 CV events occurred and lack of LAS improvement at 12 months FU emerged as the most powerful predictor followed by NT-pro-BNP. Kaplan-Meier curves showed a better survival for LAS >16%, improvement of LAS > 5%, and an LAS/LAVi ratio >0.25%/mL/m2 compared with lower cut-off values [log-rank: heart rate (HR) 3.5, 95% confidence interval (CI) 1.8-7.3, P = 0.004; log-rank: HR 3.6, 95% CI 2-7.9, P < 0.01; log-rank: HR 3.27, 95% CI 1.4-7.7, P = 0.007]. CONCLUSION: In AHF of any LVEF, LA dynamics is highly predictive of re-hospitalization and cardiovascular outcome and allows to ease risk-stratification, potentially becoming an early reference target for improving long-term outcome.

Revisiting and Implementing the Weber and Ventilatory Functional Classifications in Heart Failure by Cardiopulmonary Imaging Phenotyping.

Background In heart failure, the exercise gas exchange Weber (A to D) and ventilatory classifications (VC-1 to VC-4) historically define disease severity and prognosis. However, their applications in the modern heart failure population of any left ventricular ejection fraction combined with hemodynamics are undefined. We aimed at revisiting and implementing these classifications by cardiopulmonary exercise testing imaging. Methods and Results 269 patients with heart failure with reduced (n=105), mid-range (n=88) and preserved (n=76) ejection fraction underwent cardiopulmonary exercise testing imaging, primarily assessing the cardiac output (CO), mitral regurgitation, and mean pulmonary arterial pressure (mPAP)/CO slope. Within both classes, a progressively lower exercise CO, higher mPAP/CO slopes, and mitral regurgitation (P<0.01 all) were observed. After adjustment for age and sex, Cox proportional hazard regression analyses showed that Weber (hazard ratio [HR], 2.9; 95% CI, 1.8-4.7; P<0.001) and ventilatory classes (HR, 1.4; 95% CI, 1.1-2.0; P=0.017) were independently associated with outcome. The best stratification was observed when combining Weber (A/B or C/D) with severe ventilation inefficiency (VC-4) (HR, 2.7; 95% CI, 1.6-4.8; P<0.001). At multivariable analysis the best hemodynamic determinants of peak oxygen consumption and ventilation to carbon dioxide production slope were CO (ß-coefficient, 0.72±0.16; P<0.001) and mPAP/CO slope (ß-coefficient, 0.72±0.16; P<0.001), respectively. Conclusions In the contemporary heart failure population, the Weber and ventilatory classifications maintain their prognostic ability, especially when combined. Exercise CO and mPAP/CO slope are the best predictors of peak oxygen consumption and ventilation to carbon dioxide production slope classifications representing the main targets of interventions to impact functional class and, likely, event rate.

Left Atrial Dynamics During Exercise in Mitral Regurgitation of Primary and Secondary Origin: Pathophysiological Insights by Exercise Echocardiography Combined With Gas Exchange Analysis.

OBJECTIVES: The aim of this study was to identify the pattern of exercise left atrial (LA) dynamics, its gas exchange correlates, and prognosis in mitral regurgitation (MR) of primary and secondary origin. BACKGROUND: The adaptive response and clinical significance of LA function during exercise in MR is undefined. METHODS: A total of 196 patients with MR (81 with primary MR, 115 with secondary MR) and 54 control subjects underwent exercise stress echocardiography and cardiopulmonary exercise testing with LA function assessment. Patients with MR were divided into 4 groups according to etiology and severity using a cutoff of 3+. RESULTS: LA dynamics was studied using speckle-tracking echocardiography. Compared with control subjects, patients with MR had a lower LA strain and strain rate at rest. Exercise LA strain and LA strain rate progressively worsened from primary MR <3+ through secondary MR ≥3+. In primary MR, some reserve in exercise LA strain and LA strain rate was observed, but not in secondary MR. In secondary MR, LA strain at rest and during exercise (18.1 ± 5.7 s-1, 18.3 ± 6.9 s-1, 18.6 ± 5.5 s-1, 13.9 ± 3.8 s-1) and peak oxygen consumption (11.7 ± 3 ml/min/kg) were decreased compared with the other groups. In secondary MR ≥3+, the slope of ventilation versus carbon dioxide was higher compared with the other groups: 35.1 (interquartile range [IQR]: 29.0 to 44.2) compared with control subjects: 26.5 (IQR: 24.4 to 29.0); patients with primary MR <3+ (26.9; IQR: 24.0 to 31.9); those with primary MR >3+ (25.5; IQR: 23.4 to 29.0); and those with secondary MR <3+ (29.5; IQR: 26.5 to 33.7) (p < 0.05 for all). A progressive impairment in exercise LA mechanics combined with limited cardiac output increase and right ventricular-to-pulmonary circulation uncoupling was observed from primary to secondary MR. LAS during exercise was predictive of all-cause mortality and hospitalization for heart failure. CONCLUSIONS: In MR of any origin, exercise LA reservoir and pump function are impaired. For similar MR extent, secondary MR exhibits worse atrial function, resulting in the lowest exercise performance, limited cardiac output increase, impaired right ventricular-to-pulmonary circulation coupling, and the highest event rate.

Correlation of Left Atrial Strain and Doppler Measurements with Invasive Measurement of Left Ventricular End-Diastolic Pressure in Patients Stratified for Different Values of Ejection Fraction.

BACKGROUND: This study aimed at exploring the correlation of left atrial longitudinal function by speckle tracking echocardiography (left atrial strain) and Doppler measurements (E/E' ratio) with direct measurements of left ventricular (LV) end-diastolic pressure (LVEDP) in patients stratified for different values of ejection fraction. METHODS: The study population was 80 stable patients with sinus rhythm undergoing cardiac catheterization. This population was selected in order to have four groups of 20 patients each with different LV ejection fraction (>55%, 45-54%, 30-44%, and <30%). LVEDP was obtained during cardiac catheterization; peak atrial longitudinal strain (PALS) and mean E/E' ratio were measured in all subjects. RESULTS: Similar correlations with LVEDP of global PALS and E/E' ratio were recorded in patients with preserved (r = -0.79 vs. r = 0.72, respectively; P < 0.0001 for both) or mildly reduced ejection fraction (r = -0.75 vs. r = 0.73, respectively; P < 0.0001 for both). A closer correlation of global PALS compared to E/E' ratio was evident in patients with moderate (r = -0.78 P < 0.0001; vs. r = 0.47 P = 0.01, respectively) and severe reduction (r = -0.74 P < 0.0001; vs. r = 0.19 ns, respectively) of LV ejection fraction. In multivariate analysis of all measurements, global PALS emerged as a determinant of the LVEDP, independent on other confounding factors and, with the cutoff value of 18.0% presented the best diagnostic accuracy to predict a LVDP above 12 mmHg (AUC 0.87). CONCLUSIONS: In patients with preserved or mildly reduced LV ejection fraction, global PALS and mean E/E' ratio presented good correlations with LVEDP. In patients with moderate or severe reduction of ejection fraction, E/E' ratio correlated poorly with invasively obtained LV filling pressures. Global PALS provided an overall better estimation of LV filling pressures.