Targeting the latest site of left ventricular mechanical activation is associated with improved long-term outcomes for recipients of cardiac resynchronization therapy.

Background: Previous studies have suggested that targeting the site of latest mechanical activation of the left ventricle (LV) results in improved cardiac resynchronization therapy (CRT) outcomes. It is not known whether these benefits are sustained over medium-term follow-up. Objective: To assess the clinical outcome of imaging-guided LV lead position. Methods: We sought to assess the medium-term clinical outcome by performing a patient-level meta-analysis of 2 previously published randomized controlled trials (the "STARTER" trial and the "CRT Clinic" trial). These 2 trials compared imaging-guided LV lead placement in the latest activated scar-free segment (intervention group) to standard of care (control). Mortality and heart failure hospitalization outcomes over extended follow-up were gathered from the medical records and merged. Results were stratified for native electrocardiogram (ECG) morphology. Results: A total of 289 patients were followed for a median of 6.3 years. Seven years post implant, 47 (28%) in the intervention group had died, vs 47 (38%) in the control group (P = .13); 49 (30%) vs 53 (42%) had been hospitalized for heart failure (P = .035); and 47% vs 59% (P = .057) had reached the combined endpoint. In Kaplan-Meier analysis, patients in the intervention group had better survival free of heart failure hospitalization (P = .045) and lower risk of heart failure hospitalization (P = .019). Conclusion: Targeting the latest mechanically activated segment in CRT results in better medium-term clinical outcome, mainly driven by a reduced risk of hospitalization for heart failure. The effect was seen regardless of native ECG morphology.

Impact of bridging with left ventricular assist device on right ventricular function following heart transplantation.

AIMS: Patients awaiting orthotopic heart transplantation (OHT) can be bridged utilizing a left ventricular assist device (LVAD) that reduces left ventricular filling pressures, decreases pulmonary artery wedge pressure, and maintains adequate cardiac output. This study set out to examine the poorly investigated area of if and how pre-treatment with LVAD impacts right ventricular (RV) function following OHT. METHODS AND RESULTS: We prospectively evaluated 59 (LVAD n = 20) consecutive OHT patients. Transthoracic echocardiography (TTE) was performed in conjunction with right heart catheterization (RHC) at 1, 6, and 12 months after OHT. RV function TTE-parameters included tricuspid annular plane systolic excursion (TAPSE), systolic tissue velocity (S'), fractional area change, two-dimensional RV global longitudinal strain and longitudinal strain from the RV lateral wall (RVfree). At 1 month after OHT, the LVAD group had significantly better longitudinal RV function than the non-LVAD group: TAPSE (15 ± 3 mm vs. 12 ± 2 mm, P < 0.001), RV global longitudinal strain (-19.8 ± 2.1% vs. -14.3 ± 2.8%, P < 0.001), and RVfree (-19.8 ± 2.3% vs. -14.1 ± 2.9%, P < 0.001). At this time point, pulmonary vascular resistance (PVR) was also lower [1.2 ± 0.4 Wood Units (WU) vs. 1.6 ± 0.6 WU, P < 0.05] in the LVAD group compared with the non-LVAD group. At 6 and 12 months, no difference was detected in any of the TTE and RHC measured parameters between the two groups. Between 1 and 12 months, all parameters of RV function improved significantly in the non-LVAD group but remained unaltered in the LVAD group. CONCLUSIONS: Our results indicate that pre-treatment with LVAD decreases PVR and is associated with significantly better RV function early following OHT. During the first year following transplantation, RV function progressively improved in the non-LVAD group such that at 6 and 12 months, no difference in RV function was detected between the groups.

Regional contributions to left ventricular stroke volume determined by cardiac magnetic resonance imaging in cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) restores ventricular synchrony and induces left ventricular (LV) reverse remodeling in patients with heart failure (HF) and dyssynchrony. However, 30% of treated patients are non-responders despite all efforts. Cardiac magnetic resonance imaging (CMR) can be used to quantify regional contributions to stroke volume (SV) as potential CRT predictors. The aim of this study was to determine if LV longitudinal (SVlong%), lateral (SVlat%), and septal (SVsept%) contributions to SV differ from healthy controls and investigate if these parameters can predict CRT response. METHODS: Sixty-five patients (19 women, 67 ± 9 years) with symptomatic HF (LVEF ≤ 35%) and broadened QRS (≥ 120 ms) underwent CMR. SVlong% was calculated as the volume encompassed by the atrioventricular plane displacement (AVPD) from end diastole (ED) to end systole (ES) divided by total SV. SVlat%, and SVsept% were calculated as the volume encompassed by radial contraction from ED to ES. Twenty age- and sex-matched healthy volunteers were used as controls. The regional measures were compared to outcome response defined as ≥ 15% decrease in echocardiographic LV end-systolic volume (LVESV) from pre- to 6-months post CRT (delta, Δ). RESULTS: AVPD and SVlong% were lower in patients compared to controls (8.3 ± 3.2 mm vs 15.3 ± 1.6 mm, P < 0.001; and 53 ± 18% vs 64 ± 8%, P < 0.01). SVsept% was lower (0 ± 15% vs 10 ± 4%, P < 0.01) with a higher SVlat% in the patient group (42 ± 16% vs 29 ± 7%, P < 0.01). There were no differences between responders and non-responders in neither SVlong% (P = 0.87), SVlat% (P = 0.09), nor SVsept% (P = 0.65). In patients with septal net motion towards the right ventricle (n = 28) ΔLVESV was - 18 ± 22% and with septal net motion towards the LV (n = 37) ΔLVESV was - 19 ± 23% (P = 0.96). CONCLUSIONS: Longitudinal function, expressed as AVPD and longitudinal contribution to SV, is decreased in patients with HF scheduled for CRT. A larger lateral contribution to SV compensates for the abnormal septal systolic net movement. However, LV reverse remodeling could not be predicted by these regional contributors to SV.

Right ventricular stroke work index by echocardiography in adult patients with pulmonary arterial hypertension.

BACKGROUND: In adult patients with pulmonary arterial hypertension (PAH), right ventricular (RV) failure may worsen rapidly, resulting in a poor prognosis. In this population, non-invasive assessment of RV function is challenging. RV stroke work index (RVSWI) measured by right heart catheterization (RHC) represents a promising index for RV function. The aim of the present study was to comprehensively evaluate non-invasive measures to calculate RVSWI derived by echocardiography (RVSWIECHO) using RHC (RVSWIRHC) as a reference in adult PAH patients. METHODS: Retrospectively, 54 consecutive treatment naïve patients with PAH (65 ± 13 years, 36 women) were analyzed. Echocardiography and RHC were performed within a median of 1 day [IQR 0-1 days]. RVSWIRHC was calculated as: (mean pulmonary arterial pressure (mPAP)-mean right atrial pressure (mRAP)) x stroke volume index (SVI)RHC. Four methods for RVSWIECHO were evaluated: RVSWIECHO-1 = Tricuspid regurgitant maximum pressure gradient (TRmaxPG) x SVIECHO, RVSWIECHO-2 = (TRmaxPG-mRAPECHO) x SVIECHO, RVSWIECHO-3 = TR mean gradient (TRmeanPG) x SVIECHO and RVSWIECHO-4 = (TRmeanPG-mRAPECHO) x SVIECHO. Estimation of mRAPECHO was derived from inferior vena cava diameter. RESULTS: RVSWIRHC was 1132 ± 352 mmHg*mL*m-2. In comparison with RVSWIRHC in absolute values, RVSWIECHO-1 and RVSWIECHO-2 was significantly higher (p < 0.001), whereas RVSWIECHO-4 was lower (p < 0.001). No difference was shown for RVSWIECHO-3 (p = 0.304). The strongest correlation, with RVSWIRHC, was demonstrated for RVSWIECHO-2 (r = 0.78, p < 0.001) and RVSWIECHO-1 ( r = 0.75, p < 0.001). RVSWIECHO-3 and RVSWIECHO-4 had moderate correlation (r = 0.66 and r = 0.69, p < 0.001 for all). A good agreement (ICC) was demonstrated for RVSWIECHO-3 (ICC = 0.80, 95% CI 0.64-0.88, p < 0.001), a moderate for RVSWIECHO-4 (ICC = 0.73, 95% CI 0.27-0.87, p < 0.001) and RVSWIECHO-2 (ICC = 0.55, 95% CI - 0.21-0.83, p < 0.001). A poor ICC was demonstrated for RVSWIECHO-1 (ICC = 0.45, 95% CI - 0.18-0.77, p < 0.001). Agreement of absolute values for RVSWIECHO-1 was - 772 ± 385 (- 50 ± 20%) mmHg*mL*m-2, RVSWIECHO-2 - 600 ± 339 (-41 ± 20%) mmHg*mL*m-2, RVSWIECHO-3 42 ± 286 (5 ± 25%) mmHg*mL*m-2 and for RVSWIECHO-4 214 ± 273 (23 ± 27%) mmHg*mL*m-2. CONCLUSION: The correlation with RVSWIRHC was moderate to strong for all echocardiographic measures, whereas only RVSWIECHO-3 displayed high concordance of absolute values. The results, however, suggest that RVSWIECHO-1 or RVSWIECHO-3 could be the preferable echocardiographic methods. Prospective studies are warranted to evaluate the clinical utility of such measures in relation to treatment response, risk stratification and prognosis in patients with PAH.

Echocardiographic assessment of chamber size and ventricular function during the first year after heart transplantation.

AIMS: Detecting changes in ventricular function after orthotopic heart transplantation (OHT) using transthoracic echocardiography (TTE) is important but interpretation of findings is complicated by lack of data on early graft adaptation. We sought to evaluate echocardiographic measures of ventricular size and function the first year following OHT including speckle tracking derived strain. We also aimed to compare echocardiographic findings to haemodynamic parameters obtained by right heart catheterization (RHC). METHODS AND RESULTS: Fifty OHT patients were examined prospectively with TTE and RHC at 1, 6, and 12 months after OHT. Left ventricle (LV) was assessed with fractional shortening, ejection fraction and systolic tissue velocities. Right ventricular (RV) evaluation included tricuspid annular plane systolic excursion (TAPSE), systolic tissue velocity (S´) and fractional area change (FAC). LV global longitudinal and circumferential strain and RV global longitudinal strain (GLS) and RV lateral wall strain (RVfree) were analysed. No relevant changes occurred in LV echocardiographic parameters, whereas all measures of RV function improved significantly during follow-up. There was an increase in TAPSE (12.4 ± 3.3 mm to 14.4 ± 4.3 mm, p < .01), FAC (36% ± 8% to 41% ± 8%, p < .01), RV GLS (-15.8% ± 4% to -17.8% ± 3.6%, p < .01), and RVfree (-15.5% ± 3.7% to -18.6% ± 3.6%, p < .001). Between 1 and 12 months, pulmonary pressures decreased, whereas pulmonary vascular resistance did not. CONCLUSION: Stable OHT recipients reached steady state regarding LV function 1 month after transplantation. In contrast, RV function displayed gradual improvement the first year following OHT, indicating delayed RV adaptation as compared to the LV. Improved RV function parameters were independent of invasively measured pulmonary pressures.

Cardiac Resynchronization Therapy Guided by Echocardiography, MRI, and CT Imaging: A Randomized Controlled Study.

OBJECTIVES: This study evaluated if selecting the left ventricular (LV) target segment by echocardiography-derived late mechanical activation, with access to multimodality imaging for scar and venous anatomy, could help to increase responder rates to cardiac resynchronization therapy (CRT). BACKGROUND: LV lead placement is important for clinical outcome, but the optimal strategy for LV lead placement in CRT is still debated. METHODS: This study conducted a prospective, blinded randomized controlled trial on 102 patients with indication for CRT (27% women, 46% with ischemic cardiomyopathy, 63% in New York Heart Association functional class III, 74% with left bundle branch block, and with mean ejection fraction of 23%). Optimal LV lead location was defined as the latest mechanically activated available segment (free of transmural scar), determined by radial strain echocardiography, cardiac computed tomography, and cardiac magnetic resonance (n = 70). The primary endpoint was reduction of LV end-systolic volume by ≥15% at 6 months post-implantation. RESULTS: Patients were followed for 47 ± 21 months. Based on imaging, optimal or adjacent lead placement was feasible in 96% of all cases and was obtained in 83% of the intervention group versus 80% of the control group. Fifty-six percent of the patients were LV end-systolic volume responders compared with the control group (55%) (p = 0.96), and 71% improved ≥1 New York Heart Association functional class (74% vs. 67%; p = 0.43). Death or heart failure hospitalization within 2 years occurred in 6% (2% of the intervention group vs. 10% of the control group; p = 0.07). CONCLUSIONS: Radial strain-guided LV lead placement, in combination with multimodality imaging, did not result in increased clinical or echocardiographic response, nor in a significant reduction of death or heart failure hospitalization. (Combining Myocardial Strain and Cardiac CT to Optimize Left Ventricular Lead Placement in CRT Treatment [CRT Clinic]; NCT01426321).

Impact of gender on echocardiographic characteristics in heart transplant recipients.

AIMS: Assessment following heart transplantation (HTx) is routinely performed using transthoracic echocardiography. Differences in long-term mortality following HTx related to donor-recipient matching have been reported, but effects of gender on cardiac size and function are not well studied. The aims of this study were to evaluate differences in echocardiographic characteristics of HTx recipients defined by gender. METHODS AND RESULTS: The study prospectively enrolled 123 (n = 34 female) HTx recipients of which 23 recipients was donor-recipient gender mismatched. Patients were examined with 2-dimensional echocardiography using Philips iE33 ultrasound system. Data were analysed across strata based on recipient gender and gender mismatch. Male recipients had larger left ventricular (LV) mass, thicker septal wall (P<0·001) and larger absolute LV volumes (P<0·001). Mean LV ejection fraction (EF) was higher in females (P<0·05), but no differences in conventional parameters of right ventricular (RV) function were found. Ventricular strain was higher in females than in males: LV global longitudinal strain (P<0·01), RV global longitudinal strain (P<0·05) and RV lateral free wall (P<0·05). The male group receiving a female donor heart had comparable EF and strain parameters to the female group receiving a gender-matched heart. CONCLUSION: We found that female recipient gender was associated with smaller chamber size, higher LV EF and better LV and RV longitudinal strain. Gender-mismatched male recipients appeared to exhibit function parameters similar to gender-matched female recipients. Our results indicate that the gender aspect, analogous to current reference guidelines in general population, should be taken into consideration when examining patients post-HTx.

Discriminatory ability of right atrial volumes with two- and three-dimensional echocardiography to detect elevated right atrial pressure in pulmonary hypertension.

AIMS: Pulmonary hypertension (PH) patients have high mortality due to right ventricular failure. Predictors of poor prognostic outcome are increased right atrial volume (RAV) and elevated mean right atrial pressure (mRAP). Our aim was to determine whether RAV measured with 2D echocardiography (2DE) and 3D echocardiography (3DE) can detect elevated mRAP in patients evaluated for PH. METHODS: Of 85 patients prospectively evaluated for PH, 44 patients (63 ± 15 years, 57% female) had 2DE, 3DE and right heart catheterization within 48 h and were in sinus rhythm. Maximum (RAVmax ) and minimum (RAVmin ) volumes were measured with 3DE. 2D maximum RAV and RA area, inferior vena cava diameter and collapsibility were measured. Invasive mRAP > 8 mmHg was predefined as elevated. RESULTS: RAVmax and RAVmin correlated with mRAP (r = 0·40 and r = 0·35, P<0·05, for both), and so did 2DE maximum RAV (r = 0·42, P = 0·005) and RA area (r = 0·40, P = 0·008). Area under the curve (AUC) from receiver-operating characteristics curves was for 3DE 0·77 for RAVmax , 0·74 for RAVmin , from 2DE, 0·76 for maximum RAV and 0·75 for RA area to discriminate elevated mRAP (P<0·01 for all). PH patients had larger 3D RAV compared with controls (P<0·01). IVC diameter correlated with mRAP (r = 0·41, P = 0·007), but collapsibility did not (P = 0·078). AUC was neither significant for IVC diameter nor for collapsibility for predicting mRAP>8 mmHg. The optimal threshold was 57 ml m-2 for RAVmax , 31 ml m-2 for RAVmin and 36 ml m-2 for 2DE RAV. CONCLUSIONS: Enlarged RA measures with 2DE and 3DE have better discriminatory ability compared with IVC measures, to detect elevated mRAP in patients evaluated for PH.

Normal Reference Ranges for Transthoracic Echocardiography Following Heart Transplantation.

BACKGROUND: Heart function following heart transplantation (HTx) is influenced by numerous factors. It is typically evaluated using transthoracic echocardiography, but reference values are currently unavailable for this context. The primary aim of the present study was to derive echocardiographic reference values for chamber size and function, including cardiac mechanics, in clinically stable HTx patients. METHODS: The study enrolled 124 healthy HTx patients examined prospectively. Patients underwent comprehensive two-dimensional echocardiographic examinations according to contemporary guidelines. Results were compared with recognized reference values for healthy subjects. RESULTS: Compared with guidelines, larger atrial dimensions were seen in HTx patients. Left ventricular (LV) diastolic volume was smaller, and LV wall thickness was increased. With respect to LV function, both ejection fraction (62 ± 7%, P < .01) and global longitudinal strain (-16.5 ± 3.3%, P < .0001) were lower. All measures of right ventricular (RV) size were greater than reference values (P < .0001), and all measures of RV function were reduced (tricuspid annular plane systolic excursion 15 ± 4 mm [P < .0001], RV systolic tissue Doppler velocity 10 ± 6 cm/sec [P < .0001], fractional area change 40 ± 8% [P < .0001], and RV free wall strain -16.9 ± 4.2% [P < .0001]). Ejection fraction and LV global longitudinal strain were significantly lower in patients with previous rejection. CONCLUSION: The findings of this study indicate that the distribution of routinely used echocardiographic measures differs between stable HTx patients and healthy subjects. In particular, markedly larger RV and atrial volumes and mild reductions in both LV and RV longitudinal strain were evident. The observed differences could be clinically relevant in the assessment of HTx patients, and specific reference values should be applied in this context.

Right ventricular speckle tracking assessment for differentiation of pressure- versus volume-overloaded right ventricle.

BACKGROUND: Right ventricular (RV) dysfunction may be caused by either pressure or volume overload. RV function is conventionally assessed with echocardiography using tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RVFAC), tricuspid lateral annular systolic velocity (S') and RV index of myocardial performance (RIMP). The purpose of this study was to evaluate whether RV global longitudinal strain (RVGLS) and RV-free wall strain (RV-free) could add additional information to differentiate these two causes of RV overload. METHODS AND RESULTS: The study enrolled 89 patients with an echocardiographic trans-tricuspid gradient >30 mmHg. Forty-five patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension (pressure overload) were compared with 44 patients with an atrial septum defect (volume overload). RV size was larger in the volume group (P<0·05). TAPSE and S' were lower in the pressure group (P<0·05, P<0·01). RVFAC was lower in the pressure group (P<0·001) as well as RVGLS (-12·1 ± 3·3% versus -20·2 ± 3·4%, P<0·001) and RV-free (-12·9 ± 3·3% versus -19·4 ± 3·4%, P<0·001). CONCLUSION: In this study, RVGLS and RV-free could more accurately discriminate RV pressure from volume overload than conventional measures. The reason could be that TAPSE and S' are unable to differentiate active deformation from passive entrainment caused by the left ventricle. The pressure group had evidence of marked RV hypertrophy despite standard functional parameters (TAPSE and S) within normal range. This would enhance the value of strain to more sensitively detect abnormal function. A cut-off value of below -16% for RVGLS and RV-free predicts RV pressure overload with high accuracy.

Cardiovascular drug utilization post-implant is related to clinical outcome in heart failure patients receiving cardiac resynchronization therapy.

BACKGROUND: In select patients with heart failure, cardiac resynchronization therapy (CRT) is the most common complementary treatment besides medical treatment. We aimed to assess the association between post CRT-implant changes in cardiovascular medication and cardiovascular mortality and heart failure hospitalization. METHODS: 211 patients on optimal medical therapy eligible for CRT were retrospectively included in this study (72 ± 7 years, 80% male, 66% left bundle branch block, 48% dilated cardiomyopathy and investigated at baseline and after 6 months. Follow-up with medication, biochemical markers and echocardiography was performed and 3-year mortality data was collected. RESULTS: At 6 months post-implant the cohort was divided into two groups; 157 patients had low dosage furosemide treatment (up to 40 mg) and 54 patients were treated with high dosage (> 40 mg). A composite endpoint of heart failure hospitalization and all-cause mortality was evaluated at 30 months (881 ± 267 days) after the 6-month visit. In multivariate Cox regression analysis, pa-tients in the high dose diuretics group had a higher risk of the primary endpoint (HR 1.9 [1.1-3.4], p = 0.033), but treatment with high dose diuretics was not associated with improved clinical symptoms (r = 0.031, p = 0.64). CONCLUSIONS: High dosage of loop-diuretics was associated with worse medium-term clinical outcome in CRT treated patients. It is unclear whether there is a direct causality between these associations, or if higher prescribed dosage of loop-diuretics is just a marker of more severe disease. Higher dose loop diuretics do not necessarily improve the symptoms and may be harmful to the patient. Prospective trials are warranted to further elucidate these findings. (Cardiol J 2017; 24, 4: 374-384).

A comparison between radial strain evaluation by speckle-tracking echocardiography and cardiac magnetic resonance imaging, for assessment of suitable segments for left ventricular lead placement in cardiac resynchronization therapy.

AIMS: A cut-off of 9.8% maximum speckle-tracking radial strain in the segment with the latest mechanical delay has been proposed as predictive for selecting the best left ventricular lead placement for positive response on cardiac resynchronization therapy (CRT). However, pacing transmural scar should be avoided, and the purpose of this study was to evaluate the ability of echocardiographic radial strain to predict the presence of scar in the left ventricle segments. METHODS AND RESULTS: A total of 404 left ventricular segments were analysed, from 34 patients eligible for CRT. Pre-operative cardiac magnetic resonance (CMR) and echocardiography were performed, and maximal strain values from echocardiography speckle tracking were compared with CMR data. Hypokinesia and strain values showed a strong correlation (P < 0.001). Even though segments with CMR-verified scar had lower strain values than segments without scar (14.8 ± 7 vs. 16.0 ± 10), the predictive value of the proposed 9.8% cut-off was low (sensitivity 33% and specificity 72%). Scar burden was higher in ischaemic patients (13.5 vs. 5.3% P = 0.0001). Relative difference in strain values (target segment strain compared with the average strain value of the adjacent segments) was higher if there was transmural scar in the target segment as compared with a hypokinetic but viable target segment (87 vs. 38% difference, P = 0.03). CONCLUSION: Speckle tracking radial strain should ideally be complemented by CMR for accurate assessment of viability, especially for patients with ischaemic aetiology of heart failure where transmural scar is more common. Comparison of strain values with the adjacent segments may be helpful for assessing viability.