Prognostic Relevance of Left Ventricular Global Longitudinal Strain in Patients With Heart Failure and Reduced Ejection Fraction.

Patients with heart failure (HF) and reduced ejection fraction (HFrEF) are complex patients who often have a high prevalence of co-morbidities and risk factors. In the present study, we investigated the prognostic significance of left ventricular (LV) global longitudinal strain (GLS) along with important clinical and echocardiographic variables in patients with HFrEF. Patients who had a first echocardiographic diagnosis of LV systolic dysfunction, defined as LV ejection fraction ≤45%, were selected. The study population was subdivided into 2 groups based on a spline curve analysis derived optimal threshold value of LV GLS (≤10%). The primary end point was occurrence of worsening HF, whereas the composite of worsening HF and all-cause death was chosen for the secondary end point. A total of 1,873 patients (mean age 63 ± 12 years, 75% men) were analyzed. During a median follow-up of 60 months (interquartile range 27 to 60 months), 256 patients (14%) experienced worsening HF and the composite end point of worsening HF and all-cause mortality occurred in 573 patients (31%). The 5-year event-free survival rates for the primary and secondary end point were significantly lower in the LV GLS ≤10% group compared with the LV GLS >10% group. After adjustment for important clinical and echocardiographic variables, baseline LV GLS remained independently associated with a higher risk of worsening HF (hazard ratio 0.95, 95% confidence interval 0.90 to 0.99, p = 0.032) and the composite of worsening HF and all-cause mortality (hazard ratio 0.94, 95% confidence interval 0.90 to 0.97, p = 0.001). In conclusion, baseline LV GLS is associated with long-term prognosis in patients with HFrEF, independent of various clinical and echocardiographic predictors.

Effects of Atrial Ischemia on Left Atrial Remodeling in Patients with ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Adverse left atrial (LA) remodeling after ST-segment elevation myocardial infarction (STEMI) has been associated with poor prognosis. Flow impairment in the dominant coronary atrial branch (CAB) may affect large areas of LA myocardium, potentially leading to adverse LA remodeling during follow-up. The aim of this study was to assess echocardiographic LA remodeling in patients with STEMI with impaired coronary flow in the dominant CAB. METHODS: Of 897 patients with STEMI, 69 patients (mean age, 62 ± 11 years; 83% men) with impaired coronary flow in the dominant CAB (defined as Thrombolysis In Myocardial Infarction flow grade < 3) were retrospectively compared with an age- and sex-matched control group of 138 patients with normal dominant CAB coronary flow. RESULTS: Patients with dominant CAB-impaired flow had higher peak troponin T (3.9 µg/L [interquartile range, 2.2-8.2 µg/L] vs 3.2 µg/L [interquartile range, 1.5-5.6 µg/L], P = .009). No differences in left ventricular ejection fraction or mitral regurgitation were observed between groups at baseline or at follow-up. LA remodeling assessment included maximum LA volume, speckle-tracking echocardiography-derived LA strain, and total atrial conduction time assessed on Doppler tissue imaging at baseline, 6 months, and 12 months. Patients with dominant CAB-impaired flow presented larger LA maximal volumes (26.9 ± 10.9 vs 18.1 ± 7.1 mL/m2, P < .001) and longer total atrial conduction time (150 ± 23 vs 124 ± 22 msec, P < .001) at 6 months, remaining unchanged at 12 months. However, all LA strain parameters were significantly lower from baseline (reservoir, 20.3 ± 10.1% vs 27.1 ± 14.5% [P < .001]; conduit, 9.1 ± 5.6% vs 12.8 ± 8% [P < .001]; booster, 9.1 ± 5.6% vs 12.8 ± 8% [P < .001]), these differences being sustained at 6- and 12-month follow-up. CONCLUSIONS: Atrial ischemia resulting from impaired coronary flow in the dominant CAB in patients with STEMI is associated with LA adverse anatomic and functional remodeling. Reduced LA strain preceded LA anatomic remodeling in early phases after STEMI.

Impact of Worsening Heart Failure on Long-Term Prognosis in Patients With Heart Failure With Reduced Ejection Fraction.

Worsening heart failure (HF), defined as hospitalization for worsening signs and symptoms of HF or the need for urgent intravenous diuretics, is often considered a surrogate of poor prognosis in clinical trials. However, data on the prognostic implications of worsening HF in patients with HF and reduced ejection fraction is limited. Patients who had a first echocardiographic diagnosis of left ventricular systolic dysfunction, defined as left ventricular ejection fraction (LVEF) ≤45%, were identified. Worsening HF was defined as hospitalization for HF or urgent need for intravenous diuretics. All-cause mortality was chosen as the study end point. A total of 1,801 patients (mean age 64 ± 12 years, 74% men) were analyzed. Worsening HF was observed in 275 patients (15%) during a median follow-up of 20 months, while, 435 patients (24%) died during a median follow-up of 60 months (Interquartile range 28 to 60 months). The 5-year survival rate was significantly lower in the worsening HF cohort compared with the non-worsening HF cohort (Log-rank p <0.0001), and it was significantly different between the worsening HF cohort and the nonworsening HF cohort for LVEF ≤25% (log-rank p <0.0001) and LVEF 26% to 34% (log-rank p = 0.038) but not for LVEF 35% to 45% (log-rank p = 0.14). After adjustment for important clinical and echocardiographic predictors, worsening HF was independently associated with a higher risk of all-cause mortality (hazard ratio 1.46, 95% confidence interval 1.09 to 1.96, p = 0.011). In conclusion, worsening HF, defined by HF hospitalization or the urgent need for intravenous diuretics, is independently associated with poor long-term prognosis in patients with HF and reduced ejection fraction.

Right ventricular-pulmonary artery coupling in cardiac resynchronization therapy: evolution and prognosis.

AIMS: Chronic pressure overload and right ventricular (RV) dysfunction can lead to RV-pulmonary artery (PA) uncoupling in patients with heart failure. The evolution and prognostic values of RV-PA coupling assessed by echocardiography in patients undergoing cardiac resynchronization therapy (CRT) have not been thoroughly investigated. The aim of this study was to evaluate the evolution and prognostic value of tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) ratio in CRT recipients. METHODS AND RESULTS: The RV-PA coupling was measured non-invasively with echocardiography using the TAPSE/PASP ratio at baseline and 6 month follow-up in CRT recipients. The cut-off value for TAPSE/PASP uncoupling was derived from spline curve analysis (i.e. <0.45 mm/mmHg). The primary endpoint was all-cause mortality. A total of 807 patients (age 66 ± 11 years, 76% men) were analysed. During a median follow-up of 97 (54-143) months, 483 (60%) patients died. Survival rates at 3 and 5 year follow-up were significantly lower for patients with a TAPSE/PASP ratio <0.45 mm/mmHg (76% and 58%, respectively), compared with those with a TAPSE/PASP ratio ≥0.45 mm/mmHg (91% and 82%, respectively) (P < 0.001). On multivariable analysis, TAPSE/PASP ratio <0.45 mm/mmHg (hazard ratio 1.437; 95% confidence interval: 1.145-1.805; P = 0.002) was independently associated with all-cause mortality, whereas TAPSE <17 mm (hazard ratio 1.237; 95% confidence interval: 0.990-1.546; P = 0.061) was not. In addition, no improvement of the TAPSE/PASP ratio after CRT implantation was independently associated with worse survival. CONCLUSIONS: The TAPSE/PASP ratio at baseline is independently associated with long-term outcomes in CRT recipients. The baseline TAPSE/PASP ratio has incremental value over TAPSE, which does not take account of RV afterload. A lack of improvement in the TAPSE/PASP ratio after CRT implantation is associated with worse survival.

Prognostic Relevance of Right Ventricular Remodeling after ST-Segment Elevation Myocardial Infarction in Patients Treated With Primary Percutaneous Coronary Intervention.

ST-segment elevation myocardial infarction (STEMI) often leads to changes in right ventricular (RV) function and size over time. The prognostic implications of RV remodeling after STEMI, however, are unknown. RV remodeling in patients who underwent STEMI with primary percutaneous coronary intervention (PCI) was defined by RV end-systolic area (RV ESA) change at 6 months after STEMI compared with baseline. The optimal threshold of RV ESA change (≥40%) to define RV remodeling was derived from spline curve analysis. Long-term outcomes were compared between patients with and without RV remodeling. A total of 2,280 patients were analyzed (mean age 60 ± 11 years, 76% were men). RV remodeling was present in 315 patients (14%). After a median follow-up of 76 months (interquartile range 51 to 106 months), 271 patients (12%) died (primary end point) and the composite end point of all-cause mortality and HF hospitalization (secondary end point) was observed in 292 patients (13%). After adjustment for various risk factors, including tricuspid annular plane systolic excursion (TAPSE), post-STEMI RV remodeling was independently associated with a higher risk of all-cause mortality (hazard ratio [HR] = 1.44, 95% confidence interval [CI] 1.02 to 2.02, p = 0.038) and the composite of all-cause mortality and HF hospitalization (HR = 1.41, 95% CI 1.02 to 1.96, p = 0.040). Finally, patients with RV remodeling had a significantly lower survival rate (Log-rank, p = 0.006) and event-free survival rate than those without RV remodeling during follow-up (log-rank, p = 0.006). RV post-infarct remodeling is associated with mortality and HF hospitalization, independent of RV systolic function.

Clinical implications of left atrial reverse remodelling after cardiac resynchronization therapy.

AIMS: Left atrial (LA) function is a marker of prognosis in patients with heart failure. The prognostic implications of an improvement in LA function in addition to an improvement in left ventricular (LV) function after cardiac resynchronization therapy (CRT) implantation are unknown. This study aimed to evaluate the prognostic value of a significant change in LA reservoir strain (RS) and/or LV global longitudinal strain (GLS) after initiation of CRT. METHODS AND RESULTS: LARS and LVGLS were measured with speckle-tracking echocardiography. Significant improvement in LARS and LVGLS was defined as a percentage change of +5% and +20% at 6 months after CRT implantation, respectively. Patients were divided into three groups: no significant reverse remodelling (no improvement in LARS and LVGLS), incomplete reverse remodelling (improvement in LARS or LVGLS), and complete reverse remodelling (improvement in LARS and LVGLS). The primary endpoint was all-cause mortality. A total of 923 patients (mean age 65 ± 10 years, 77% male) were included, of which 221 (24%) had complete reverse remodelling, 414 (45%) incomplete reverse remodelling, and 288 (31%) no significant reverse remodelling. Five-years' mortality was 24%, 29%, and 36% for patients with complete, incomplete, and no significant reverse remodelling, respectively (P < 0.001). On multivariable analysis, complete reverse remodelling (hazard ratio 0.477; 95% confidence interval: 0.362-0.628; P < 0.001) was associated with the lowest risk of mortality. CONCLUSIONS: Patients with complete reverse remodelling have a lower mortality risk than those showing incomplete or no significant reverse remodelling. The use of integrated LA and LV deformation imaging may improve risk-stratification of CRT recipients.

Impact of baseline left ventricular volume on left ventricular reverse remodeling after cardiac resynchronization therapy.

BACKGROUND: Left ventricular (LV) dilatation may limit LV reverse remodeling after cardiac resynchronization therapy (CRT). OBJECTIVE: The purpose of this study was to evaluate the impact of baseline LV volumes on LV reverse remodeling after CRT and whether this is associated with improved survival. METHODS: Patients were stratified into quintiles according to baseline LV end-diastolic volume indexed for body surface area (LVEDVi). LV reverse remodeling was defined as ≥15% reduction in LV end-systolic volume at 6-month follow-up after CRT. Independent associates of LV remodeling were assessed and long-term mortality rates were compared between patients with and without LV reverse remodeling (across LVEDVi quintiles). RESULTS: A total of 864 patients were included (mean age 66 ± 10 years; 657 patients (76%) were male), of whom 101 (12%) were in quintile 1 (<65 mL/m2), 272 (32%) in quintile 2 (65-95 mL/m2), 247 (29%) in quintile 3 (95-125 mL/m2), 151 (18%) in quintile 4 (125-155 mL/m2), and 93 (11%) in quintile 5 (>155 mL/m2). Patients with larger baseline LVEDVi had worse survival after CRT (log-rank, P = .019). The cumulative 10-year survival was significantly better in patients with vs without LV reverse remodeling (48.7% vs 33.9%; P < .001). Significant LV reverse remodeling was observed in all LVEDVi quintiles. In addition, patients with LV reverse remodeling had superior survival than did patients without LV reverse remodeling, regardless of baseline LVEDVi quintile (log-rank, P < .05 for all). CONCLUSION: Many patients with larger baseline LV volumes still show significant LV reverse remodeling after CRT and had superior survival (regardless of baseline LV volumes) than did patients without LV reverse remodeling. Therefore, CRT should not be denied on the basis of severe LV dilatation.

Functional classification of left ventricular remodelling: prognostic relevance in myocardial infarction.

AIMS: The current definition of post ST-segment elevation myocardial infarction (STEMI) left ventricular (LV) remodelling is purely structural (LV dilatation) and does not consider LV function (ejection fraction, EF), even though it is known to be a predictor of long-term post-STEMI outcome. This study aimed to reclassify LV remodelling after STEMI by integrating LV dilatation and function (LVEF) and to investigate the prognostic implications. METHODS AND RESULTS: Data from an ongoing registry of STEMI patients who were treated with primary percutaneous coronary intervention (PCI) were retrospectively evaluated. Four distinct remodelling subgroups were identified: (i) no LV dilatation, no LVEF impairment,(ii) no LV dilatation but LVEF impairment, (iii) LV dilatation but no LVEF impairment, and (iv) LV dilatation and LVEF impairment. The impact of functional LV remodelling on outcomes was analysed. A total of 2346 patients were studied (mean age 60 ± 11 years, 76% men). During a median follow-up of 76 (interquartile range 52 to 107) months, 282 (12%) died, while the composite of death and heart failure hospitalization occurred in 305 (13%) patients. Those with LV remodelling and LVEF impairment had a significantly lower survival rate (P < 0.001) and event-free survival rate (P < 0.001) compared with other functional LV remodelling groups. CONCLUSIONS: Employing a functional LV post-infarct remodelling classification has the potential to improve risk stratification beyond structural LV remodelling alone. Identification of patients with the worst prognosis by using a functional LV remodelling approach may allow institution of early preventative therapies.