Impact of Dapagliflozin on the Left Ventricular Diastolic Function in Diabetic Patients with Heart Failure Complicating Cardiovascular Risk Factors.

Objective Our aim was to investigate the impact of the sodium glucose cotransporter type 2 (SGLT2) inhibitor on the left ventricular (LV) diastolic function in type 2 diabetes mellitus (T2DM) patients with chronic heart failure (HF) complicating cardiovascular risk factors. Methods We analyzed data from our previous prospective multicenter study, in which we investigated the effect of dapagliflozin on the LV diastolic function of T2DM patients with stable HF at five institutions in Japan. Patients who had been taking at least 1 antidiabetic drug other than SGLT2 inhibitors started treatment with dapagliflozin. Echocardiography was performed at baseline and six months after the administration of dapagliflozin. Cardiovascular risk factors other than T2DM were age, gender, hypertension, dyslipidemia, history of cardiovascular events and overweight. Results The LV diastolic function, defined as the ratio of the mitral inflow E to the mitral e' annular velocities (E/e'), significantly decreased from 9.3 to 8.5 by six months after the administration of dapagliflozin (p=0.020) as previously reported. A multivariate logistic regression analysis showed that dyslipidemia was the only independent determinant of improvement in the E/e' after the administration of dapagliflozin among cardiovascular risk factors. Furthermore, the relative change in the E/e' from baseline to six months after the administration of dapagliflozin for HF patients with preserved ejection fraction (HFpEF) and dyslipidemia was significantly larger than that for HFpEF patients without dyslipidemia (-15.2% vs. 29.6%, p=0.014), but no such finding was observed in non-HFpEF patients. Conclusion SGLT2 inhibitors may exert a more beneficial effect on the LV diastolic function for T2DM patients with stable HF, especially those with complicating dyslipidemia, than existing treatments.

Association of type 2 diabetes mellitus with the development of new-onset atrial fibrillation in patients with non-ischemic dilated cardiomyopathy: impact of SGLT2 inhibitors.

The aim of this study was to investigate the association of type 2 diabetes mellitus (T2DM) with the development of new-onset atrial fibrillation (AF) for non-ischemic dilated cardiomyopathy (DCM) patients. We also tested the hypothesis that sodium glucose cotransporter type 2 (SGLT2) inhibitors reduce the risk of development of new-onset AF for non-ischemic DCM patients. We retrospectively studied 210 patients with non-ischemic DCM and sinus rhythm, mean age of 59.0 ± 16.7 years and left ventricular ejection fraction of 31.0 ± 8.2% (all < 45%). T2DM was identified in 60 patients (28.6%), and the remaining 150 patients (71.4%) were classified as non-T2DM patients. New-onset AF occurred in 21 patients (10.0%) over a median follow-up of 6.1 years. Kaplan-Meier curve analysis showed that non-ischemic DCM patients without T2DM experienced fewer occurrences of the development of new-onset AF compared with those with T2DM (log-rank p = 0.0003). Furthermore, global longitudinal strain in patients who showed development of new-onset AF was significantly lower than that in those whose sinus rhythm was preserved (6.4 ± 1.4% vs. 7.7 ± 2.2%, p = 0.01). Of the 60 non-ischemic DCM patients with T2DM, those treated with SGLT2 inhibitors experienced fewer occurrences of the development of new-onset AF than did those not treated with SGLT2 inhibitors (log-rank p = 0.040). T2DM is associated with the development of new-onset AF in non-ischemic DCM patients, and treatment with SGLT2 inhibitors can significantly reduce the development of new-onset AF. Our findings may thus offer a new insight into the management of non-ischemic DCM patients with T2DM.

Impact of diabetes mellitus on left ventricular longitudinal function of patients with non-ischemic dilated cardiomyopathy.

BACKGROUND: Left ventricular (LV) longitudinal dysfunction has been identified in type 2 diabetes mellitus (T2DM) patients with preserved LV ejection fraction (LVEF). However, the impact of T2DM on LV longitudinal function or the association of LV longitudinal function with outcome for dilated cardiomyopathy (DCM) remains unclear. METHODS: We retrospectively studied 206 patients with non-ischemic DCM, mean age of 59 ± 17 years and LVEF of 31 ± 8% (all < 45%). All patients underwent a standard echocardiographic examination, and LV longitudinal function was assessed in terms of global longitudinal strain (GLS). Long-term outcomes were assessed, with a median follow-up period of 6.2 years, as primary endpoints of death from or hospitalization for deteriorating heart failure. RESULTS: GLS of DCM patients with T2DM (n = 55) was significantly lower than that in DCM patients without T2DM (n = 151) in spite of similar conventional LV function (7.0 ± 2.0% vs. 7.8 ± 2.2%, p = 0.03). Kaplan-Meier curves indicated that long-term outcomes for DCM patients without T2DM were better than for those with T2DM (log-rank p = 0.001). Subdividing the two groups into four with by using the median value of GLS (7.9%) showed long-term outcome was worst for DCM patients with T2DM and low GLS. Cox proportional hazards analyses demonstrated an independent association of T2DM, GLS and left atrial volume index with long-term outcome. Moreover, multiple regression analysis for the association of GLS showed that T2DM was the independent determinant parameter for GLS as well as for LVEF and left atrial volume index. CONCLUSION: Management of DCM patients with T2DM may be improved by using GLS guidance.

Cardiac resynchronization therapy improves left atrial reservoir function through resynchronization of the left atrium in patients with heart failure with reduced ejection fraction.

This study aimed to test the hypothesis that left ventricular dyssynchrony may negatively affect left atrial (LA) dyssynchrony and reservoir function, and cardiac resynchronization therapy (CRT) may improve LA function. It also assessed, whether residual LA dyssynchrony affects the prognosis in patients with heart failure with reduced ejection fraction (HFrEF). Ninety subjects were included: 40 HFrEF patients with a wide-QRS complex (≧130 ms), 28 HFrEF patients with a narrow-QRS, and 22 normal controls. LA global longitudinal strain (LA-GLS) and LA dyssynchrony were quantified by speckle-tracking strain analysis. LA dyssynchrony was defined as the maximal difference of time-to-peak strain (LA time-diff). All patients with a wide-QRS underwent CRT, and event-free survival was tracked for 24 months. At baseline, LA dyssynchrony was significantly more pronounced in patients with a wide-QRS HFrEF (342 ± 126 ms) than that in patients with a narrow-QRS (236 ± 127 ms, P < 0.001) and controls (186 ± 78 ms, P < 0.001). Six months after CRT, LA-GLS significantly improved from 11.9 ± 4.7 to 19.6 ± 10.1% (P < 0.05) and LA time-diff was reduced from 338 ± 123 to 245 ± 141 ms (P < 0.05) in responders only. Patients with an LA time-diff < 202 ms and those with an LA-GLS ≧14.6% six months after CRT showed significantly better outcomes than the others (P < 0.05, respectively). Among the responders, those with an LA time-diff < 202 ms after CRT showed a better prognosis than others (P < 0.05). CRT improved LA dyssynchrony and reservoir function through the improved left ventricular coordination. Reduced LA dyssynchrony and improved LA reservoir function after CRT lead to better outcomes.

Positive effect of dapagliflozin on left ventricular longitudinal function for type 2 diabetic mellitus patients with chronic heart failure.

BACKGROUND: The effect of sodium glucose cotransporter type 2 (SGLT2) inhibitor on left ventricular (LV) longitudinal myocardial function in type 2 diabetes mellitus (T2DM) patients with heart failure (HF) has remained unclear. METHODS: We analyzed data from our previous prospective multicenter study, in which we investigated the effect of the SGLT2 inhibitor dapagliflozin on LV diastolic functional parameters of T2DM patients with stable HF at five institutions in Japan. Echocardiography was performed at baseline and 6 months after administration of dapagliflozin. LV diastolic function was defined as the ratio of mitral inflow E to mitral e' annular velocities (E/e'). LV longitudinal myocardial function was assessed as global longitudinal strain (GLS), which in turn was determined as the averaged peak longitudinal strain from standard LV apical views. RESULTS: E/e' significantly decreased from 9.3 to 8.5 cm/s 6 months after administration of dapagliflozin (p = 0.020) as previously described, while GLS showed significant improvement from 15.5 ± 3.5% to 16.9 ± 4.1% (p < 0.01) 6 months after administration of dapagliflozin. Furthermore, improvement of GLS in HF with preserved ejection fraction patients was more significant from 17.0 ± 1.9% to 18.7 ± 2.0% (p < 0.001), compared to that in HF with mid-range ejection fraction and HF with reduced ejection fraction patients from 14.4 ± 2.4% to 15.5 ± 1.8% (p = 0.06) and from 8.1 ± 1.5% to 7.8 ± 2.1% (p = 0.44), respectively. It was noteworthy that multiple regression analysis showed that the change in GLS after administration of dapagliflozin was the only independent determinant parameters for the change in E/e' after administration of dapagliflozin. CONCLUSION: Dapagliflozin was found to be associated with improvement of LV longitudinal myocardial function, which led to further improvement of LV diastolic function of T2DM patients with stable HF. GLS-guided management may thus lead to improved management of T2DM patients with stable HF.

Impact of dapagliflozin on left ventricular diastolic function of patients with type 2 diabetic mellitus with chronic heart failure.

BACKGROUND: The objective of this study was to investigate the impact of sodium glucose cotransporter type 2 (SGLT2) inhibitors on left ventricular (LV) diastolic function of type 2 diabetes mellitus (T2DM) patients with heart failure (HF). METHODS: This trial was a prospective multicenter study of 58 T2DM patients with stable HF at five institutions in Japan. Patients who had been taking at least one antidiabetic drugs other than SGLT2 inhibitors started the administration of 5 mg/day of dapagliflozin. The physical examinations, blood tests, and echocardiography were performed at baseline and 6 months after administration of dapagliflozin. The primary endpoint was defined as a change in mitral inflow E and mitral e' annular velocities (E/e') between baseline and 6 months after the administration of dapagliflozin. The secondary end points consisted of a change in brain natriuretic peptide (BNP), LV mass index (LVMI) and left atrial volume index (LAVI). RESULTS: E/e' significantly decreased from 9.3 to 8.5 cm/s (p = 0.020) 6 months after administration of dapagliflozin. LAVI and LVMI significantly decreased from 31 to 26 mL/m2 (p = 0.001), and from 75.0 to 67.0 g/m2 (p < 0.001), respectively, 6 months after administration of dapagliflozin. No significant change was observed in BNP (from 27.9 to 28.9 pg/mL; p = 0.132) 6 months after administration of dapagliflozin, except for a significant decrease from 168.8 to 114.3 pg/mL (p = 0.012) in patients with BNP ≥ 100 pg/mL. CONCLUSION: This prospective multicenter trial showed the beneficial effect of SGLT2 inhibitors on LV diastolic functional parameters for T2DM patients with HF. Our findings may thus offer a new insight into the management of T2DM patients. Trial registration UMIN000019789, Registered 28 September 2014, Date of registration: 11/14/2015, Date of enrolment of the first participant to the trial: 6/15/2016, Date of enrolment of the last participant to the trial: 12/9/2017.

Noninvasive Assessment of Preload Reserve Enhances Risk Stratification of Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: The leg-positive pressure maneuver can safely and noninvasively apply preload stress without increase in total body fluid volume. The purpose of this study was to determine whether preload stress could be useful for risk stratification of patients with heart failure with reduced ejection fraction. METHODS AND RESULTS: For this study, 120 consecutive patients with heart failure with reduced ejection fraction were prospectively recruited. The stroke work index was estimated as product of stroke volume index and mean blood pressure, and the E/e' ratio was calculated to estimate ventricular filling pressure. The echocardiographic parameters were obtained both at rest and during leg-positive pressure stress. During the median follow-up period of 20 months, 30 patients developed adverse cardiovascular events. During preload stress, stroke work index increased significantly (from 3280±1371 to 3857±1581 mm Hg·mL/m2; P<0.001) along with minimal changes in ventricular filling pressure (E/e', from 16±10 to 17±9; P<0.05) in patients without cardiovascular events. However, patients with cardiovascular events showed impairment of Frank-Starling mechanism (stroke work index, from 2863±969 to 2903±1084 mm Hg·mL/m2; P=0.70) and a serious increase in E/e' ratio (from 19±11 to 25±14; P<0.001). Both the patients without contractile reserve and those without diastolic reserve exhibited worse event-free survival than the others (P<0.001). In a Cox proportional-hazards analysis, the changes in stroke work index (hazard ratio: 0.44 per 500 mm Hg·mL/m2 increase; P=0.001) and in E/e' (hazard ratio: 2.58 per 5-U increase; P<0.001) were predictors of cardiovascular events. CONCLUSION: Contractile reserve and diastolic reserve during leg-positive pressure stress are important determinants of cardiovascular outcomes for patients with heart failure with reduced ejection fraction.

Predictors and Clinical Outcomes of Transient Responders to Cardiac Resynchronization Therapy.

BACKGROUND: Left ventricular end-systolic volume (LVESV) changes at 6 months and clinical status are useful for assessing responses to cardiac resynchronization therapy (CRT). Regression of the LVESV following CRT has not been described beyond 6 months. This study aimed to assess the proportion, predictors, and clinical outcomes of responders whose LVESVs had regressed. METHODS: We retrospectively analyzed 104 consecutive CRT patients. A responder was defined as a patient with a relative reduction in the LVESV ≥15% at 6 months after CRT. Fifty-six responders participated in this study. A transient responder was defined as a responder without a relative reduction in the LVESV ≥15% at 2 years after CRT or who died of cardiac events during the 24-month follow-up period. RESULTS: Of the 56 responders, 16 (29%) were transient responders. Multivariable logistic regression analysis showed that chronic atrial fibrillation (odds ratio [OR] = 19.2, 95% confidence interval [CI] [1.93, 190], P = 0.012) and amiodarone usage (OR = 60.9, 95% CI [4.18, 886], P = 0.003) were independent predictors of transient responses. Hospitalizations for heart failure were significantly higher among the transient responders than among the lasting responders during a mean follow-up period of 7.6 years (log-rank P < 0.001), and all-cause mortality tended to be higher among the transient responders (log-rank P = 0.093). CONCLUSIONS: One-third of the responders were transient responders at 2 years after CRT, and their long-term prognoses were poor. Careful attention should be paid to maintain the reduction in LVESV especially in patients with chronic AF.

Slit-Like Deformation of the Coronary Sinus Orifice due to Compression of the Inferior Pyramidal Space by the Severely Dilated Left Ventricle.

The coronary sinus is located within the inferior pyramidal space, which is the part of the epicardial visceral fibroadipose tissue wedging between the four cardiac chambers from the bottom of the heart. Therefore, this region is susceptible to the morphological changes of the cardiac chambers. We present a case of slit-like deformation of the coronary sinus orifice due to compression of the inferior pyramidal space by the severely dilated left ventricle, which has not been previously described.

Association of Apical Longitudinal Rotation with Right Ventricular Performance in Patients with Pulmonary Hypertension: Insights into Overestimation of Tricuspid Annular Plane Systolic Excursion.

BACKGROUND: Current guidelines recommend the routine use of tricuspid annular plane systolic excursion (TAPSE) as a simple method for estimating right ventricular (RV) function. However, when ventricular apical longitudinal rotation (apical-LR) occurs in pulmonary hypertension (PH) patients, it may result in overestimated TAPSE. METHODS: We studied 105 patients with PH defined as mean pulmonary artery pressure >25 mmHg at rest measured by right heart cardiac catheterization. TAPSE was defined as the maximum displacement during systole in the RV-focused apical four-chamber view. RV free-wall longitudinal speckle tracking strain (RV-free) was calculated by averaging 3 regional peak systolic strains. The apical-LR was measured at the peak rotation in the apical region including both left and right ventricle. The eccentricity index (EI) was defined as the ratio of the length of 2 perpendicular minor-axis diameters, one of which bisected and was perpendicular to the interventricular septum, and was obtained at end-systole (EI-sys) and end-diastole (EI-dia). Twenty age-, gender-, and left ventricular ejection fraction-matched normal controls were studied for comparison. RESULTS: The apical-LR in PH patients was significantly lower than that in normal controls (-3.4 ± 2.7° vs. -1.3 ± 1.9°, P = 0.001). Simple linear regression analysis showed that gender, TAPSE, EI-sys, and EI-dia/EI-sys were associated with apical-LR, but RV-free was not. Multiple regression analysis demonstrated that gender, EI-dia/EI-sys, and TAPSE were independent determinants of apical-LR. CONCLUSIONS: TAPSE may be overestimated in PH patients with clockwise rotation resulting from left ventricular compression. TAPSE should thus be evaluated carefully in PH patients with marked apical rotation.

Significant prognostic impact of improvement in ventriculo-arterial coupling induced by dobutamine stress on cardiovascular outcome for patients with dilated cardiomyopathy.

AIMS: The purpose of this study was to investigate the prognostic impact of the changes in ventriculo-arterial (VA) coupling during dobutamine stress on the cardiovascular events for patients with dilated cardiomyopathy (DCM). METHODS AND RESULTS: For this study, 89 DCM patients with ejection fractions of 32 ± 10% and 30 normal controls were recruited. Ees was estimated with the non-invasive single-beat method using three-dimensional echocardiography at rest and during dobutamine stress (20 µg/kg/min). Effective arterial elastance (Ea) was calculated as left ventricular (LV) end-systolic pressure divided by stroke volume, and VA coupling was calculated as Ea/Ees. Event-free survival was then tracked for 32 months. At baseline, VA coupling was far from optimal in patients with DCM compared with controls (Ea/Ees: 2.49 ± 1.02 vs. 1.04 ± 0.21, P < 0.001). During the follow-up period, 22 patients developed adverse cardiovascular events. During dobutamine stress, VA coupling was significantly improved in patients without cardiovascular events (from 2.47 ± 1.09 to 1.59 ± 0.68, P < 0.001), but remained unchanged in those with cardiovascular events. A multivariate Cox proportional-hazards analysis revealed that age, NYHA functional class (>II), and the change in VA coupling during dobutamine stress were the independent determinants of cardiovascular events (P < 0.05, <0.01, and <0.001, respectively). When patients were divided into two subgroups based on the finding of receiver operating characteristic curve analysis, patients with good VA coupling reserve (cut-off: change in VA coupling> 0.29) showed significantly favourable event-free survival than those with poor VA coupling reserve (P < 0.001). CONCLUSIONS: Improvement in VA coupling during dobutamine stress is an important determinant of cardiovascular outcome for patients with DCM.

Bi-ventricular contractile reserve offers an incremental prognostic value for patients with dilated cardiomyopathy.

AIMS: Right ventricular (RV) as well as left ventricular (LV) function has been recognized as an important prognostic factor for heart failure patients. Our objective was thus to investigate the prognostic significance of combined assessment of bi-ventricular functional reserve for patients with dilated cardiomyopathy (DCM). METHODS AND RESULTS: We studied 104 DCM patients with ejection fractions (EF) of 32 ± 9%, and speckle-tracking echocardiography was used to assess both RV and LV contractile reserve under dobutamine stress (20 µg/kg/min). RV contractile function was measured as peak global longitudinal strain (GLS) from the RV free wall (RV-free), and LV function as global circumferential strain (GCS) and GLS, respectively. Event-free survival was then tracked for 17 months. Twenty-one patients (20%) developed cardiovascular events. A multivariate Cox proportional-hazards analysis revealed that the baseline EF, E/A, and the relative change in EF (ΔEF), in GCS (ΔGCS), and in RV-free (ΔRV-free) during dobutamine stress were the independent predictors of cardiovascular events (P < 0.001, <0.05, <0.01, <0.05, and <0.01, respectively). A Cox model based on baseline clinical and echocardiographic variables (χ(2) = 23.6) was improved by the addition of LV contractile reserve parameters (plus ΔGCS and ΔEF) (χ(2) = 49.1; P < 0.001) and further improved by adding RV contractile reserve (plus ΔRV-free) (χ(2) = 60.3, P < 0.001). CONCLUSION: Assessment of RV contractile reserve during dobutamine stress offers a significantly better prognostic value for patients with DCM. Bi-ventricular contractile reserve may be required for a favourable outcome, so that estimation of RV contractile reserve should be considered part of a comprehensive functional assessment of these patients.

Association of left atrial booster-pump function with heart failure symptoms in patients with severe aortic stenosis and preserved left ventricular ejection fraction.

BACKGROUND: Identification of heart failure (HF) symptoms in patients with severe aortic stenosis (AS) and preserved left ventricular (LV) ejection fraction (EF) is clinically important, but assessment of HF symptoms is challenging. It was recently reported that resting left atrium (LA) functions are related to exercise performance and are also important prognostic markers for patients with HF. The aim of this study was to assess the association of the HF symptoms with LA function in patients with severe AS and preserved LVEF. METHODS: We retrospectively studied 40 patients with severe AS and preserved LVEF (all ≥50%) who were referred for aortic valve replacement (AVR). LA reservoir (SR-LAs), conduit (SR-LAe), and booster-pump (SR-LAa) functions were determined as the averaged global LA speckle tracking longitudinal strain rate from apical four- and two-chamber views. Twenty patients were symptomatic and 20 asymptomatic. RESULTS: Aortic stenosis severity was similar for the 2 groups. Symptomatic status was associated with age, LV mass index, hemoglobin, B-type natriuretic peptide, LV end-systolic volume index, LVEF, LA volume index, SR-LAs, SR-LAe, and SR-LAa. Importantly, multivariate logistic regression analysis revealed that SR-LAa was the only independent determinant of symptomatic status (OR = 0.242, P = 0.002). Furthermore, significant improvement of SR-LAa was observed along with the reduction in LA volume index and LV mass index after AVR. CONCLUSIONS: SR-LAa was found to be associated with the HF symptoms. Characterization of LA booster-pump function may be useful for the assessment of the symptomatic status in patients with severe AS patients and limited physical activity.

Easy-to-use comprehensive speckle-tracking approach for cardiac resynchronization therapy.

BACKGROUND: Left ventricular (LV) dyssynchrony has emerged as an important mechanism contributing to the patient's response to cardiac resynchronization therapy (CRT), but other potential factors, especially LV myocardial viability, are also influential. METHODS AND RESULTS: We studied 132 patients undergoing CRT. LV dyssynchrony was determined by anteroseptal-to-posterior wall delay on the mid-LV short-axis view using 2-dimensional speckle-tracking radial strain (≥130 ms as significant). Global circumferential strain (GCS), considered as a parameter of LV intrinsic myocardial function, was also determined as the peak GCS from the same view. Long-term follow-up was tracked over 40 months. Kaplan-Meier analysis indicated that patients with GCS >3.9% experienced fewer cardiovascular events overall (log-rank P=0.034). Similarly, patients with GCS >3.9% and ≥6.6% experienced fewer cardiovascular events than those with GCS ≤3.9% and <6.6% among patients with and without LV dyssynchrony (log-rank P=0.025 and P=0.029, respectively). An important finding from multivariate Cox proportional hazards analysis was that LV dyssynchrony and GCS were independently associated with cardiovascular events. Of note, only 2±1 min per patient were needed to analyze both LV dyssynchrony and GCS from the same routine mid-LV short-axis view. CONCLUSIONS: This easy-to-use combined assessment of LV dyssynchrony and myocardial function using speckle-tracking strain from the same mid-LV short-axis view may well have clinical implications for CRT.

Global endocardial area change rate for the assessment of left ventricular relaxation and filling pressure: using 3-dimensional speckle-tracking study.

Early diastolic mitral inflow and annulus velocities ratio (E/e') is the parameter used to estimate left ventricular (LV) filling pressure, but their use for patients with reduced ejection fraction (EF) (<50 %) is controversial. LV endocardial area change rate with 3-dimensional (3-D) speckle-tracking can be used to evaluate the entire LV diastolic function, we tested the hypothesis that the early diastolic area change rate (E-ACR) represents LV relaxation, and E and E-ACR ratio (E/E-ACR) can accurately predict LV filling pressure in patients with reduced and preserved EF (≥50 %). We studied 125 patients with EF of 40 ± 17 %. E-ACR of all patients was measured using the global area change rate, and LV relaxation time constant (τ, n = 53) and pulmonary capillary wedge pressure (PCWP, n = 125) were measured by cardiac catheterization. E-ACR significantly correlated with τ (r = -0.60, p < 0.001). In the retrospective group (n = 101), E/E-ACR correlated with PCWP for patients with reduced EF as well as those with preserved EF (n = 79 and 22, r = 0.62 and 0.81, both p < 0.001). In overall patients, E/E-ACR ≥94 cm was a better predictor of elevated mean PCWP (>12 mmHg) (sensitivity: 69 %, specificity: 87 %, areas under the curves = 0.82; p < 0.001) and was a more accurate predictor than E/e' (p = 0.001) for the retrospective group. For the validation group (n = 24), E/E-ACR ≥94 cm was similarly predictive for elevated mean PCWP (sensitivity: 60 %, specificity: 100 %, positive predictive value: 100 %, negative predictive value: 78 %). In conclusions, global E-ACR by 3-D speckle-tracking proved to be dependent on LV relaxation. Moreover, E/E-ACR was found to be a powerful predictor of LV filling pressure regardless of EF.

Utility of combining assessment of right ventricular function and right atrial remodeling as a prognostic factor for patients with pulmonary hypertension.

We tested the hypothesis that the addition of right atrial (RA) remodeling to right ventricular (RV) function enhances the capability of the latter to predict long-term outcome for pulmonary hypertension (PH) patients. We studied 82 PH patients, all of whom underwent echocardiography and right heart catheterization. RV function was calculated by averaging the three regional peak speckle-tracking longitudinal strains from RV free wall (RV-free). RA remodeling was assessed as the RA area traced planimetrically at end-systole. Pre-defined cutoffs for RV dysfunction and RA remodeling were RV-free ≤19.4 % and RA area of >18 cm(2), respectively. Long-term unfavorable outcome events were tracked for 2.0 years. RA area correlated with mean RA pressure (r = 0.62, p < 0.001), as well as with tricuspid E/E' (r = 0.38, p = 0.001). Moreover, RA area in patients with RV restrictive filling was significantly larger than that in patients with others (all p < 0.05). Kaplan-Meier analysis revealed that patients with RV-free ≤19.4 % had worse long-term outcomes than those with RV-free >19.4 % (log-rank p = 0.01), as did patients with RA area >18 cm(2) compared with those with RA area ≤18 cm(2) (log-rank p < 0.05). For sequential Cox models, a model based on hemodynamic parameters of RV performance (χ2 = 3.11) was improved by addition of brain natriuretic peptide, World Health Organization functional class (χ2 = 9.24; p < 0.05), and RV-free (χ2 = 17.11; p = 0.005), and further improved by addition of RA area (χ2 = 21.36, p < 0.05). In conclusion, the combined assessment of RV function and RA area results in more accurate prediction of long-term outcome, and may well have clinical implications for better management of PH patients.

Evaluation of global circumferential strain as prognostic marker after administration of ß-blockers for dilated cardiomyopathy.

The use of ß-blockers has improved the prognosis of dilated cardiomyopathy (DCM) and the appearance of left ventricular (LV) reverse remodeling is generally thought to result in a more favorable prognosis. While there are many prognostic predictors, not all of them are applicable to individual patients. Global circumferential strain (GCS) was identified as a powerful prognostic marker, which appears to be a better parameter than LV global function for patients with depressed left ventricular (LV) ejection fraction. Seventy consecutive patients with newly-diagnosed DCM with LVEF of 28 ± 8 % (all <45 %) were retrospectively recruited. Either carvedilol or bisoprolol was titrated to a dose that was tolerable for each of the patients. GCS was determined as the peak global speckle-tracking circumferential strain from the mid-LV short-axis view. LV reverse remodeling was defined as an absolute increase in LVEF of at least 10 % during 8.1 ± 5.2-month follow-up after initiation of the maintenance dose of ß-blockers. GCS ≥ 5.4 % was identified as the best predictor of LV reverse remodeling with 91 % sensitivity and 82 % specificity, and an area under the curve of 0.896 (p < 0.0001). An important finding of multivariate logistic regression analysis was that GCS was the best independent predictor of LV reverse remodeling (OR 7.692; 95 % CI 2.292-25.82; p = 0.001). It should be noted that only 1.3 ± 0.4 min per patient was needed to analyze GCS. In conclusions, GCS could result in further improvements in predicting LV reverse remodeling after ß-blocker administration, and have clinical implications for better management in daily clinical practice.

Preliminary observations of prognostic value of left atrial functional reserve during dobutamine infusion in patients with dilated cardiomyopathy.

BACKGROUND: The importance of left atrial (LA) functional reserve in patients with depressed left ventricular function remains unclear. Thus, the aim of this study was to test the hypothesis that diminished augmentation of LA function during dobutamine stress might be associated with cardiovascular events in patients with dilated cardiomyopathy. METHODS: Eighty-four patients with dilated cardiomyopathy with a mean ejection fraction of 34 ± 9% were retrospectively recruited, and LA strain was determined as the averaged global speckle-tracking longitudinal strain from apical four-chamber and two-chamber views during dobutamine stress (20 µg/kg/min). The systolic component of LA strain was considered to reflect reservoir function, whereas the passive and active emptying components were considered to reflect passive and active emptying function, respectively. Event-free survival was tracked for 17 months. RESULTS: Multivariate Cox proportional-hazards analysis identified LA volume index (hazard ratio [HR], 1.060; P < .001) and ß-blocker use (HR, 0.048; P < .05) as the independent variables associated with cardiovascular events among the baseline parameters and changes in systolic LA strain (HR, 0.971; P = .02), in passive emptying LA strain (HR, 0.942; P < .001), and in left ventricular early diastolic strain rate (HR, 0.986; P = .03) under dobutamine as the variables among the functional reserve parameters. In sequential Cox models, a model based on clinical variables (χ(2) = 9.3) was improved by conventional echocardiographic parameters (χ(2) = 19.2, P = .012) and LA strain parameters at rest (χ(2) = 40.1, P = .005) and further improved by the addition of changes in LA strain parameters under dobutamine (χ(2) = 61.6, P < .001). CONCLUSIONS: The assessment of LA reservoir and passive emptying function during dobutamine stress provides important incremental prognostic value in patients with dilated cardiomyopathy.

Left atrial booster-pump function as a predictive parameter for new-onset postoperative atrial fibrillation in patients with severe aortic stenosis.

Postoperative atrial fibrillation (POAF) is associated with increased risk of embolic events and heart failure, but its associated factors remains unknown. Left atrial (LA) subclinical mechanical dysfunction caused by the acute stress of surgery may be clinically manifested as POAF. The purpose of our study was therefore to test the hypothesis that preoperative LA subclinical myocardial dysfunction is a potential predictor of development of POAF in patients with aortic stenosis (AS). We studied 27 patients with severe AS undergoing aortic valve replacement (AVR) with left ventricular (LV) ejection fraction of 63 ± 11 %. All patients were in sinus rhythm and had no history of atrial fibrillation (AF). LA reservoir (SR-LAs), conduit (SR-LAe), and booster-pump (SR-LAa) functions were determined as the averaged global LA speckle-tracking longitudinal strain rates from apical four- and two-chamber views. POAF, defined as any episode of AF within 30-day after AVR, was observed in 15 patients (56 %). There were no differences in clinical characteristics, LA and LV volumes, and global LV function between patients with and without POAF. Multivariate logistic regression analysis identified SR-LAa as the only independent predictor of POAF. Furthermore, SR-LAa >0.79 s(-1) predicted POAF with 60 % sensitivity, 92 % specificity, and area under the curve of 0.828 (p < 0.0001). Of the 15 patients with POAF, one developed paroxysmal AF during long-term follow-up. In conclusions, SR-LAa helped to detect subtle LA booster-pump dysfunction and was associated with new-onset POAF in patients with severe AS. These findings may be useful for risk stratification and management of such patients.

Combined baseline strain dyssynchrony index and its acute reduction predicts mid-term left ventricular reverse remodeling and long-term outcome after cardiac resynchronization therapy.

The objective of this study was to test the hypothesis that combining assessment of baseline radial strain dyssynchrony index (SDI), that expressed both left ventricular (LV) dyssynchrony and residual myocardial contractility, and of acute changes in this index can yield more accurate prediction of mid-term responders and long-term outcome after cardiac resynchronization therapy (CRT). Radial SDI for 75 CRT patients was calculated as the average difference between peak and end-systolic speckle tracking strain from 6 segments of the mid-LV short-axis view before and 8 ± 2 days after CRT. Mid-term responder was defined as ≥ 15% decrease in LV end-systolic volume 6 ± 2 months after CRT. Long-term outcome was tracked over 5 years. Baseline radial SDI ≥ 6.5% is considered predictive of responder and favorable outcome, as previously reported. Acute reduction in radial SDI ≥ 1.5% was found to be the best predictor of mid-term responders with CRT. Furthermore, patients with acute reductions in radial SDI ≥1.5% were associated with a significantly more favorable long-term outcome after CRT than those with radial SDI <1.5% (log rank P < 0.001). An important findings were that baseline radial SDI ≥6.5% and acute reductions in radial SDI ≥ 1.5% in 42 patients were associated with the highest event-free survival rate of 92%, whereas, 21 patients corresponding values of <6.5% and <1.5% were associated with low event-free survival rate of 46% (log rank P < 0.001). Combined assessment of baseline radial SDI and its acute reduction after CRT may have clinical implications for predicting responders and thus patients' care.