Additive Prognostic Value of Echocardiographic Global Longitudinal and Global Circumferential Strain to Electrocardiographic Criteria in Patients With Heart Failure Undergoing Cardiac Resynchronization Therapy.

BACKGROUND: Response to cardiac resynchronization therapy is most favorable in patients with heart failure with QRS duration ≥150 ms and left bundle branch block and less predictable in those with QRS width 120 to 149 ms or non-left bundle branch block. METHODS AND RESULTS: We studied 205 patients with heart failure referred for cardiac resynchronization therapy with QRS ≥120 ms and ejection fraction ≤35%. We tested the hypothesis that contractile function using speckle-tracking echocardiographic global circumferential strain (GCS) from 2 short-axis views and global longitudinal strain (GLS) from 3 apical views add prognostic value to electrocardiographic criteria. There were 112 patients (55%) with GLS >-9% and 136 patients (66%) with GCS >-9%. During 4 years, 81 patients reached the combined primary end point (death, circulatory support, or transplant) and 120 reached the secondary end point (heart failure hospitalization or death). Both GLS >-9% and GCS >-9% were associated with increased risk of unfavorable events as follows: for the primary end point (hazard ratio=2.91; 95% confidence interval, 1.88-4.49; P<0.001) and (hazard ratio=3.73; 95% confidence interval, 2.39-5.82; P<0.001) for the secondary end point (hazard ratio=2.10; 95% confidence interval, 1.45-3.05; P<0.001) and (hazard ratio=3.25; 95% confidence interval, 2.23-4.75; P<0.001). In a prespecified subgroup of 120 patients with QRS 120 to 149 ms or non-left bundle branch block, significant associations of baseline GLS and GCS and outcomes remained: P=0.014 and P=0.002 for the primary end point and P=0.049 and P=0.001 for the secondary end point. Global strain measures had additive prognostic value to routine clinical or electrocardiographic parameters (P<0.001). CONCLUSIONS: Baseline GCS and GLS were significantly associated with long-term outcome after cardiac resynchronization therapy and had additive prognostic value to routine clinical and electrocardiographic selection criteria for cardiac resynchronization therapy.

Right Ventricular Function in Peripartum Cardiomyopathy at Presentation Is Associated With Subsequent Left Ventricular Recovery and Clinical Outcomes.

BACKGROUND: Peripartum cardiomyopathy has variable disease progression and left ventricular (LV) recovery. We hypothesized that baseline right ventricular (RV) size and function are associated with LV recovery and outcome. METHODS AND RESULTS: Investigations of Pregnancy-Associated Cardiomyopathy was a prospective 30-center study of 100 peripartum cardiomyopathy women with LV ejection fraction (LVEF) <45% within 13 weeks after delivery. Baseline RV function was assessed by echocardiographic end-diastolic area, end-systolic area, fractional area change, tricuspid annular plane excursion, and RV speckle-tracking longitudinal strain. LV recovery was defined as LVEF of ≥50% at 1 year, persistent severe LV dysfunction as LVEF of ≤35%, and major events as death, transplant, or LV assist device implantation. RV measurements were feasible for 90 of the 96 patients (94%) with echocardiograms available. Mean baseline LVEF was 36±9%. RV fractional area change was <35% in 38% of patients. Of 84 patients with 1-year follow-up data, 63 (75%) had LV recovery and 11 (13%) had LVEF of ≤35% or a major event (4 LV assist devices and 2 deaths). Tricuspid annular plane excursion and RV strain did not predict outcome. Baseline RV fractional area change by multivariable analysis was independently associated with subsequent LV recovery and clinical outcome. CONCLUSIONS: Peripartum cardiomyopathy patients had a high incidence of LV recovery, but a significant minority had persistent LV dysfunction or a major clinical event by 1 year. RV function per echocardiographic fractional area change at presentation was associated with subsequent LV recovery and clinical outcomes and thus is prognostically important.

The Prognostic Utility of a Simplified Biventricular Echocardiographic Index of Cardiac Remodeling in Patients with Pulmonary Hypertension.

BACKGROUND: Right ventricular (RV) remodeling has been associated with outcomes in patients with pulmonary hypertension (PH). However, the additive prognostic significance of RV remodeling and left ventricular (LV) morphology in PH is unclear. The objective of this study was to test the hypothesis that the ratio of RV end-diastolic area to LV end-diastolic area is a biventricular index predictive of outcome in patients with PH. METHODS: In total, 139 patients with precapillary PH (mean age, 55 ± 15 years; 75% women) and 22 control subjects (mean age, 40 ± 17 years; 73% women) were studied. The apical four-chamber view was used to measure the RV-to-LV end-diastolic area ratio as an index of biventricular cardiac remodeling. RV free wall and global strain were measured using speckle-tracking echocardiography. The study design was prospective, with all-cause mortality over 5 years predefined as the outcome event. RESULTS: Patients with PH had significantly larger RV to LV end-diastolic area ratios than normal subjects, as expected (1.06 vs 0.67, P < .0001). There were 72 deaths over 5 years. Using a cutoff value of 0.93, patients with RV-to-LV ratios ≥ 0.93 had significantly higher all-cause mortality (hazard ratio,1.84; 95% CI, 1.14-2.96; P = .019). RV global strain was also significantly associated with survival using a cutoff of ≥-15% (hazard ratio, 1.66; 95% CI, 1.03-2.67; P = .044). In a multivariate analysis, only age and biventricular index were independent predictors of survival among other clinical and echocardiographic features. CONCLUSIONS: The RV-to-LV end-diastolic area ratio is a simplified biventricular echocardiographic index of cardiac remodeling that is predictive of long-term survival in patients with PH.

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.

Comparative long-term outcomes after cardiac resynchronization therapy in right ventricular paced patients versus native wide left bundle branch block patients.

BACKGROUND: The current guidelines do not clearly state when we should upgrade a patient with right ventricular pacing (RVP) to cardiac resynchronization therapy (CRT), although the deleterious effect of chronic RVP has been established with recent trials. OBJECTIVES: The aims of this study were to compare the long-term survival after CRT in patients upgraded from RVP with that in patients with left bundle branch block (LBBB) with QRS duration ≥ 150 ms and to compare the mechanical properties associated with CRT response in these groups. METHODS: Overall, 135 patients with implanted CRT from a single center (85 (63%) with native wide LBBB and 50 (37%) with RVP) were studied prospectively. Baseline left ventricular typical contraction pattern was determined using speckle tracking echocardiography in the apical 4-chamber view. The predefined end point was death, heart transplantation, or left ventricular assist device implantation over a period of 4 years. RESULTS: Patients with RVP had a significantly favorable long-term outcomes with adjusted hazard ratio of 0.36 (95% confidence interval 0.14-0.96; P = .04). Both groups had ~70% of patients with typical contraction pattern. The absence of typical contraction pattern was associated with a higher risk of an end point with adjusted hazard ratio of 5.43 (95% confidence interval 2.31-12.72; P < .001). In patients with typical contraction pattern, activation of the apical septal segment occurred more frequently in the RVP group and of the base or mid septal segments in the LBBB group. CONCLUSION: Patients with HF upgraded from RVP have more favorable long-term outcomes after CRT than do native LBBB patients with QRS duration ≥ 150 ms. Contraction pattern assessment can be used to identify potential responders in the RVP group.

Left ventricular dyssynergy and dispersion as determinant factors of fatal ventricular arrhythmias in patients with mildly reduced ejection fraction.

AIMS: Current guidelines recommend implantation of prophylactic implantable cardioverter-defibrillators (ICD) in patients with left ventricular (LV) ejection fraction (EF) <35%. We explored the prognostic factors of fatal ventricular arrhythmias for heart failure (HF) patients with LVEF ≥35%. METHODS AND RESULTS: We retrospectively studied 72 patients with LVEF of 52 ± 12% (all ≥35%) who had undergone ICD implantation. Heterogeneity of LV regional myocardial contraction was defined as standard deviation of peak strain (dyssynergy index) and time-to-peak strain (dispersion index) from 18 LV segments determined by speckle tracking. Fatal ventricular arrhythmias with appropriate ICD therapy occurred in 34 patients (47%) during a median follow-up of 17 months. Receiver operating characteristic curve analysis identified dispersion index ≥101 ms and dyssynergy index ≥6.1% as predictors of fatal ventricular arrhythmias (P = 0.004 and P = 0.0001, respectively). In addition, the combination of dispersion index ≥101 ms and dyssynergy index ≥6.1% was the most predictive of fatal ventricular arrhythmias with a sensitivity of 77%, specificity of 79%, and area under the curve of 0.795 (P < 0.0001). A sequential Cox model based on clinical and conventional echocardiographic variables including age, gender, HF aetiology, and LVEF (χ(2) = 4.8) was improved, but not statistically significant (χ(2) = 4.9; P = 0.82), by addition of global longitudinal strain, whereas improvement by the addition of the dispersion index (χ(2) = 8.9; P = 0.04) and further improvement by the addition of the dyssynergy index (χ(2) = 20.2; P < 0.005). CONCLUSION: Combined assessment of LV dyssynergy and dispersion can enhance predictive capability for fatal ventricular arrhythmias in patients with LVEF ≥35% and may have potential for better management of such patients.

Utility of Isovolumic Contraction Peak Velocity for Evaluation of Adult Patient Status after Transcatheter Closure of Atrial Septal Defect.

BACKGROUND: Transcatheter closure is a well-established treatment for patients with atrial septal defect (ASD), but long-term outcome prognostic factors for adults have not been fully identified yet. METHODS: Forty-nine consecutive patients (age 57 ± 17 years, 59% female), who underwent transcatheter closure of ASD, were the subjects of this study. Transthoracic echocardiography was performed before and midterm after the procedure (6 ± 1 months). Isovolumic contraction peak velocity (IVV) was measured at the lateral site of the tricuspid annulus using spectral tissue Doppler imaging, and ΔIVV was determined as the absolute change at midterm follow-up. Long-term unfavorable outcome events, tracked for 19 ± 9 months, were prespecified as primary end points comprising newly developed atrial fibrillation, cerebral infarction, and heart failure. RESULTS: Symptomatic improvement, defined as an improvement in New York Heart Association functional class by one grade or more at midterm after the procedure, was observed in 24 patients (49%), and the remaining 25 (51%) were classified as not symptomatically improved. ΔIVV was significantly larger for patients with symptomatic improvement than for those without (from 11.5 ± 4.3 cm/s to 14.2 ± 3.7 cm/s vs. from 11.8 ± 4.1 cm/s to 12.5 ± 2.9 cm/s; P = 0.045). An important finding of the multivariate Cox proportional-hazards analysis was that only ΔIVV was independently associated with cardiovascular events (HR: 0.701; 95% CI 0.537-0.916; P = 0.01). Kaplan-Meier analysis showed that more patients with enhanced ΔIVV presented with favorable long-term outcome than those with diminished ΔIVV (log-rank P = 0.0001). CONCLUSIONS: IVV, which is a less volume-sensitive parameter, can be useful for comprehensive evaluation of ASD patients referred for transcatheter closure.

Mechanical Dyssynchrony by Tissue Doppler Cross-Correlation is Associated with Risk for Complex Ventricular Arrhythmias after Cardiac Resynchronization Therapy.

BACKGROUND: Tissue Doppler cross-correlation analysis has been shown to be associated with long-term survival after cardiac resynchronization defibrillator therapy (CRT-D). Its association with ventricular arrhythmia (VA) is unknown. METHODS: From two centers 151 CRT-D patients (New York Heart Association functional classes II-IV, ejection fraction ≤ 35%, and QRS duration ≥ 120 msec) were prospectively included. Tissue Doppler cross-correlation analysis of myocardial acceleration curves from the basal segments in the apical views both at baseline and 6 months after CRT-D implantation was performed. Patients were divided into four subgroups on the basis of dyssynchrony at baseline and follow-up after CRT-D. Outcome events were predefined as appropriate antitachycardia pacing, shock, or death over 2 years. RESULTS: Mechanical dyssynchrony was present in 97 patients (64%) at baseline. At follow-up, 42 of these 97 patients (43%) had persistent dyssynchrony. Furthermore, among 54 patients with no dyssynchrony at baseline, 15 (28%) had onset of new dyssynchrony after CRT-D. In comparison with the group with reduced dyssynchrony, patients with persistent dyssynchrony after CRT-D were associated with a substantially increased risk for VA (hazard ratio [HR], 4.4; 95% CI, 1.2-16.3; P = .03) and VA or death (HR, 4.0; 95% CI, 1.7-9.6; P = .002) after adjusting for other covariates. Similarly, patients with new dyssynchrony had increased risk for VA (HR, 10.6; 95% CI, 2.8-40.4; P = .001) and VA or death (HR, 5.0; 95% CI, 1.8-13.5; P = .002). CONCLUSIONS: Persistent and new mechanical dyssynchrony after CRT-D was associated with subsequent complex VA. Dyssynchrony after CRT-D is a marker of poor prognosis.

Characterization of right ventricular remodeling in pulmonary hypertension associated with patient outcomes by 3-dimensional wall motion tracking echocardiography.

BACKGROUND: Adverse right ventricular (RV) remodeling has significant prognostic and therapeutic implications to patients with pulmonary hypertension (PH). However, differentiating RV adaption from adverse remodeling associated with poor outcomes is difficult. We hypothesized that novel 3-dimensional (3D) wall motion tracking echocardiography can differentiate morphological features of RV adaption from adverse remodeling heralding an unfavorable short-term prognosis in patients with PH. METHODS AND RESULTS: We studied 112 subjects: 92 patients with PH and 20 normal controls with 3D wall motion tracking for RV end-systolic volume index (ESVi), RV ejection fraction (EF), and RV global area strain. Patients with PH also had invasive hemodynamic measurements. Pressure-volume relations classified patients with PH into 3 groups, such as RV adapted, RV adapted-remodeled, and RV adverse-remodeled. The predefined combined end point was PH-related hospitalization, death, or lung surgery (lung transplantation or pulmonary endarterectomy) during 6 months. The 92 patients with PH had significantly larger RV volumes, lower RVEF and global area strain than normal controls as expected. Patients with PH classified as RV adapted (ESVi, ≤72 mL/m(2)) had a more favorable clinical outcome than those classified as RV adapted-remodeled (ESVi, 73-113 mL/m(2)) or RV adverse-remodeled (ESVi, ≥114 mL/m(2)): hazard ratio, 0.15; 95% confidence intervals, 0.07 to 0.39; P<0.0001. RV adverse-remodeled patients (ESVi, ≥114 mL/m(2)) had worse short-term outcome than the RV adapted-remodeled patients: hazard ratio, 2.2; 95% confidence interval, 0.91 to 5.39; P=0.04. CONCLUSIONS: Quantitative 3D echocardiography in patients with PH demonstrated morphological subsets of RV adaption and remodeling associated with clinical outcomes.

Association of peripheral nerve conduction in diabetic neuropathy with subclinical left ventricular systolic dysfunction.

BACKGROUND: Subclinical left ventricular (LV) longitudinal myocardial systolic dysfunction occurs in patients with diabetes mellitus (DM) and preserved LV ejection fraction (LVEF), and is closely related to DM-related complications. However, the association of diabetic neuropathy (DN) with subclinical LV systolic longitudinal dysfunction in such patients has not been fully clarified. METHODS: The subjects of this study were 112 consecutive DM patients with preserved LVEF (all ≥50%) without coronary artery disease and overt heart failure (aged 59 ± 14 years; 60 women, 52 men). Global longitudinal strain (GLS) was determined as the average peak strain of 18 segments from the three standard apical views, and was expressed as an absolute value. DN was diagnosed by experienced diabetologists. Median, ulnar, and sural nerves were subjected to motor and sensory nerve conduction studies. F-wave latency was defined as the minimum F-wave latency after a total of 16 stimulations of the tibial nerve. RESULTS: Forty-one (37%) patients were clinically diagnosed with DN. LV functions of DM patients with and without DN were similar except for GLS being significantly smaller in patients with than in patients without DN (18 ± 2% vs. 20 ± 2%, p < 0.001). It was noteworthy that, of the parameters for the nerve conduction study, only F-wave latency correlated with GLS (r = -0.34, p < 0.001), and also was identified as an independent determinative value of GLS in a multivariate linear regression model (ß = -0.25, p = 0.001) even after adjustment for other closely related GLS factors. CONCLUSIONS: Monitoring of F-wave latency may aid early detection of not only DN but also subclinical LV dysfunction. Joint planning of assessment by diabetologists and cardiologists is therefore advisable for better management of DM patients.

Clinical features of subclinical left ventricular systolic dysfunction in patients with diabetes mellitus.

BACKGROUND: Left ventricular (LV) longitudinal systolic dysfunction has been identified even in asymptomatic patients with diabetes mellitus (DM) and preserved LV ejection fraction (LVEF). However, its relevant clinical features have not been fully evaluated. METHODS: We studied 144 asymptomatic DM patients without coronary artery disease. Their mean age was 57 ± 15 years, 79 (55%) were female, and mean LVEF was 66 ± 4% (all ≥50%). Global longitudinal strain (GLS) was determined as the average peak strain of 18 segments from the three standard apical views, and was expressed as an absolute value. With the pre-defined cutoff for subclinical LV systolic dysfunction in DM patients with preserved LVEF set at GLS < 18%, this dysfunction was detected in 53 patients (37%). RESULTS: Multivariate logistic regression analysis revealed that type 2 DM, hypertriglyceridemia, overweight/obesity, nephropathy and neuropathy were independently associated with GLS < 18%, with nephropathy being the highest risk factor (OR: 5.26; 95% CI 2.111-13.12, p < 0.001). For sequential logistic regression models, a model based on clinical variables including gender, type 2 DM and DM duration (χ(2) = 24.1) was improved by addition of overweight/obesity and hypertriglyceridemia (χ(2) = 45.6, p < 0.001), and further improved by addition of nephropathy and neuropathy (χ(2) = 70.2, p < 0.001) as variables. Furthermore, albuminuria significantly correlated with GLS (r = -0.51, p < 0.001), and a multivariate regression model showed it to be the factor most closely associated with GLS (ß = -0.33, p < 0.001). CONCLUSIONS: Diabetic complications, hypertriglyceridemia and overweight/obesity were closely associated with early stage of LV systolic longitudinal myocardial dysfunction in asymptomatic DM patients with preserved LVEF. Our findings can be clinically noticeable for the management of DM patients.

Right ventricular function and right-heart echocardiographic response to therapy predict long-term outcome in patients with pulmonary hypertension.

BACKGROUND: Right ventricular (RV) dysfunction in pulmonary hypertension (PH) is linked to adverse outcomes, but this response is considered heterogeneous because it can be associated with multiple factors. METHODS: RV function of 51 PH patients was calculated by averaging peak speckle-tracking longitudinal strain from RV free-wall (RV-free), and the cutoff for RV dysfunction was predefined as RV-free ≤ 19%. Right-sided heart remodelling was assessed in terms of RV end-systolic area (RVESA) and right atrial (RA) area (RA-area). Midterm reverse remodelling was defined as a relative decrease in RVESA (ΔRVESA) and RA-area (ΔRA-area) of at least 15% at 5.7 ± 4.0 months after introduction of pulmonary artery hypertension-specific drugs. Long-term outcome was tracked for 3.0 ± 2.0 years. RESULTS: Patients with midterm RV and RA reverse remodelling showed more favourable long-term outcomes than those without (P = 0.01, P = 0.047, respectively). Sequential Cox models showed that a model based on hemodynamic parameters (χ(2) = 0.3) was improved by the addition of RV-free (χ(2) = 6.4; P = 0.01), and further improved by addition of ΔRVESA and ΔRA-area (χ(2) = 28.2; P < 0.001). Furthermore, preservation of baseline RV function and midterm reverse remodelling in right-sided heart was associated with an optimal outcome: a survival rate of 100%. In contrast, absence of midterm reverse remodelling in the right-sided heart of patients with impaired baseline RV function was associated with significantly worse outcome with a survival rate of 33% (P = 0.01). CONCLUSIONS: RV function and echocardiographic right-heart reverse remodelling with therapy improves the prediction of long-term outcomes for PH patients over standard hemodynamic indices.

Interdependence of right ventricular systolic function and left ventricular filling and its association with outcome for patients with pulmonary hypertension.

Although impaired right ventricular (RV) performance has been associated with adverse outcomes for pulmonary hypertension (PH) patients, the relationship between bi-ventricular interdependence and outcomes is not yet fully understood. We studied 96 PH patients. RV systolic function was assessed by means of RV free-wall longitudinal speckle-tracking strain (RV-free), and left ventricular (LV) filling as early diastolic transmitral flow velocity (TMF-E). RV-free ≤19 % and TMF-E <60 cm/s were adopted as pre-defined cut-offs for RV systolic dysfunction and LV under-filling, respectively, associated with worse outcomes. Long-term outcome was tracked over 2.2 years. RV-free correlated significantly with TMF-E (r = 0.57, p < 0.001).TMF-E and RV-free were significantly lower in patients with than in those without cardiac events. RV systolic dysfunction and LV under-filling was observed in 35 patients. These features were associated with worse long-term survival compared to other sub-groups (log-rank p = 0.012). A sequential Cox model based on clinical variables including world health organization functional class IV and brain natriuretic peptide >150 pg/dl (χ(2) = 1.2) was improved by the addition of RV-free (χ(2) = 5.5, p = 0.04) as well as of TMF-E (χ(2) = 11.5, p = 0.01). In conclusions, RV systolic function was shown to correlate significantly with LV filling in PH patients. In addition, not only assessment of RV systolic function, but also of a combined bi-ventricular parameter comprising RV systolic function and LV filling may well have clinical implications for more successful management of PH patients.

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.

Mechanical dyssynchrony after cardiac resynchronization therapy for severely symptomatic heart failure is associated with risk for ventricular arrhythmias.

BACKGROUND: Risk factors for ventricular arrhythmias after cardiac resynchronization defibrillator therapy (CRT-D) for severely symptomatic heart failure are of clinical importance but are not clearly defined. The objective of this study was to test the hypothesis that mechanical dyssynchrony after CRT-D is a risk factor for ventricular arrhythmias. METHODS: A total of 266 consecutive CRT-D patients with class III or IV heart failure, QRS duration ≥120 msec, and ejection fractions ≤ 35% were prospectively studied. Dyssynchrony was assessed before and 6 months after CRT-D using speckle-tracking radial strain anteroseptal-to-posterior wall delay, predefined as ≥130 msec. Ventricular arrhythmias were predefined as appropriate antitachycardia pacing or shock, and the combined end point of ventricular arrhythmias, death, transplantation, or left ventricular assist device implantation was followed over 2 years. RESULTS: Of the initial 266 patients, 11 died, five underwent transplantation, three received left ventricular assist devices before their 6-month echocardiographic examinations, 19 (7%) had inadequate speckle-tracking at 6-month follow-up, and 27 (10%) were lost to follow-up. Accordingly, the study group consisted of 201 patients. Dyssynchrony after CRT-D was observed in 79 (39%) and was associated with a significantly higher ventricular arrhythmic event rate: 21% (P < .001) with persistent dyssynchrony and 35% (P < .001) with new dyssynchrony, compared with 8% with no dyssynchrony after CRT-D. The combined end point of ventricular arrhythmias, death, transplantation, or left ventricular assist device implantation was significantly associated with dyssynchrony after CRT-D (hazard ratio, 2.53; 95% confidence interval, 1.49-4.28; P = .001). Dyssynchrony after CRT-D was associated with ventricular arrhythmias or death in patient subgroups by cardiomyopathy type, QRS width, and morphology (P < .05 for all). CONCLUSIONS: Persistent or new radial dyssynchrony after CRT-D in severely symptomatic patients with heart failure with widened QRS complexes and reduced ejection fractions was associated with an increased rate of ventricular arrhythmias or death and appears to be a marker for a less favorable prognosis.

Usefulness of echocardiographically guided left ventricular lead placement for cardiac resynchronization therapy in patients with intermediate QRS width and non-left bundle branch block morphology.

The current guidelines most strongly support cardiac resynchronization therapy (CRT) for patients with heart failure with a QRS width of ≥150 ms and left bundle branch block (LBBB). Our objective was to assess the potential benefit of echocardiographically guided left ventricular (LV) lead positioning for patients with a QRS width <150 ms or non-LBBB as a substudy of the Speckle Tracking Assisted Resynchronization Therapy for Electrode Region (STARTER) prospective, randomized controlled trial. The STARTER trial randomized 187 patients with heart failure, a QRS of ≥120 ms, and ejection fraction of ≤35% to LV lead guided to the site of latest mechanical activation by speckle tracking radial strain versus routine implantation. The predefined primary end point was heart failure hospitalization or death within 2 years. This substudy included 151 CRT patients with matching echocardiographic and LV lead position data and complete follow-up data. Patients with a QRS width of 120 to 149 ms or non-LBBB and LV lead concordant or adjacent to the site of latest mechanical activation had favorable outcomes after CRT similar to those with LBBB or a QRS width of ≥150 ms. In contrast, patients with a QRS of 120 to 149 ms or non-LBBB and remote LV leads had unfavorable outcomes (hazard ratio 5.45, 95% confidence interval 2.36 to 12.6, p <0.001, and hazard ratio 4.92, 95% confidence interval 2.12 to 11.39, p <0.001, respectively, with significant interaction after adjusting for baseline variables, p = 0.038 and p = 0.008). In conclusion, LV lead positioning with respect to the echocardiographic site of latest activation was significantly associated with more favorable clinical outcomes in patients with a QRS duration <150 ms and/or non-LBBB. Additional prospective study is warranted.

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.

Right ventricular apical pacing-induced left ventricular dyssynchrony is associated with a subsequent decline in ejection fraction.

BACKGROUND: In patients with normal left ventricular (LV) ejection fraction (EF), the interposition of chronic, high-dose right ventricular apical (RVA) pacing may produce late EF decline. OBJECTIVE: To test the hypothesis that LV dyssynchrony, defined echocardiographically and apparent early after interposition of pacing, would be greater in patients who subsequently demonstrated EF decline. METHODS: Ninety-one patients with normal prepacing EF who underwent atrioventricular node ablation and subsequent high-dose RVA pacing were studied. Transthoracic echocardiograms were performed early (median 4 months) and late (median 28 months) after interposition of pacing, with a significant decline in EF between these studies defined as ≥5%. Speckle-tracking longitudinal strain analysis of the early echocardiogram was performed to quantify dyssynchrony. In addition to standard dyssynchrony indices, a novel index of apex-to-base mechanical propagation delay (MPD) was used. RESULTS: Multivariable analysis determined that MPD of the septum correlated with a significant decline in EF, independent of all other dyssynchrony, clinical, or pacing variables. A septal MPD value exceeding 50 ms was associated with EF decline at 81% sensitivity and 88% specificity. CONCLUSIONS: Dyssynchrony, in particular septal MPD, measured early after interposition of high-dose RVA pacing predicted a significant late decline in EF in patients who had normal prepacing EF.