5-Year prognostic value of the right ventricular strain-area loop in patients with pulmonary hypertension.

AIMS: Patients with pre-capillary pulmonary hypertension (PH) show poor survival, often related to right ventricular (RV) dysfunction. In this study, we assessed the 5-year prognostic value of a novel echocardiographic measure that examines RV function through the temporal relation between RV strain (ϵ) and area (i.e. RV ϵ-area loop) for all-cause mortality in PH patients. METHODS AND RESULTS: Echocardiographic assessments were performed in 143 PH patients (confirmed by right heart catheterization). Transthoracic echocardiography was utilized to assess RV ϵ-area loop. Using receiver operating characteristic curve-derived cut-off values, we stratified patients in low- vs. high-risk groups for all-cause mortality. Kaplan-Meier survival curves and uni-/multivariable cox-regression models were used to assess RV ϵ-area loop's prognostic value (independent of established predictors: age, sex, N-terminal pro B-type natriuretic peptide, 6-min walking distance). During follow-up 45 (31%) patients died, who demonstrated lower systolic slope, peak ϵ, and late diastolic slope (all P < 0.05) at baseline. Univariate cox-regression analyses identified early systolic slope, systolic slope, peak ϵ, early diastolic uncoupling, and early/late diastolic slope to predict all-cause mortality (all P < 0.05), whilst peak ϵ possessed independent prognostic value (P < 0.05). High RV loop-score (i.e. based on number of abnormal characteristics) showed poorer survival compared to low RV loop-score (Kaplan-Meier: P < 0.01). RV loop-score improved risk stratification in high-risk patients when added to established predictors. CONCLUSION: Our data demonstrate the potential for RV ϵ-area loops to independently predict all-cause mortality in patients with pre-capillary PH. The non-invasive nature and simplicity of measuring the RV ϵ-area loop, support the potential clinical relevance of (repeated) echocardiography assessment of PH patients.

The Impact of Protein Supplementation on Exercise-Induced Muscle Damage, Soreness and Fatigue Following Prolonged Walking Exercise in Vital Older Adults: A Randomized Double-Blind Placebo-Controlled Trial.

BACKGROUND: It is unknown whether protein supplementation can enhance recovery of exercise-induced muscle damage in older adults who have a disturbed muscle protein synthetic response. We assessed whether protein supplementation could attenuate exercise-induced muscle damage and soreness after prolonged moderate-intensity walking exercise in older adults. METHODS: In a double-blind, placebo-controlled intervention study, 104 subjects (81% male, ≥65 years) used either a protein (n = 50) or placebo supplement (n = 54) during breakfast and directly after exercise. Within a walking event, study subjects walked 30/40/50 km per day on three consecutive days. Muscle soreness and fatigue were determined with a numeric rating scale, and creatine kinase (CK) concentrations and serum inflammation markers were obtained. RESULTS: Habitual protein intake was comparable between the protein (0.92 ± 0.27 g/kg/d) and placebo group (0.97 ± 0.23 g/kg/d, p = 0.31). At baseline, comparable CK concentrations were found between the protein and the placebo group (110 (IQR: 84-160 U/L) and 115 (IQR: 91-186 U/L), respectively, p = 0.84). Prolonged walking (protein: 32 ± 9 km/d, placebo: 33 ± 6 km/d) resulted in a cumulative increase of CK in both the protein (∆283 (IQR: 182-662 U/L)) and placebo group (∆456 (IQR: 209-885 U/L)) after three days. CK elevations were not significantly different between groups (p = 0.43). Similarly, no differences in inflammation markers, muscle soreness and fatigue were found between groups. CONCLUSIONS: Protein supplementation does not attenuate exercise-induced muscle damage, muscle soreness or fatigue in older adults performing prolonged moderate-intensity walking exercise.

Acute impact of changes to hemodynamic load on the left ventricular strain-volume relationship in young and older men.

Chronic changes in left ventricular (LV) hemodynamics, such as those induced by increased afterload (i.e., hypertension), mediate changes in LV function. This study examined the proof of concept that 1) the LV longitudinal strain (ε)-volume loop is sensitive to detecting an acute increase in afterload, and 2) these effects differ between healthy young versus older men. Thirty-five healthy male volunteers were recruited, including 19 young (24 ± 2 yr) and 16 older participants (67 ± 5 yr). Tests were performed before, during, and after 10-min recovery from acute manipulation of afterload. Real-time hemodynamic data were obtained and LV longitudinal ε-volume loops were calculated from four-chamber images using two-dimensional echocardiography. Inflation of the anti-gravity (anti-G) suit resulted in an immediate increase in heart rate, blood pressure, and systemic vascular resistance and a decrease in stroke volume (all P < 0.05). This was accompanied by a decrease in LV peak ε, slower slope of the ε-volume relationship during early diastole, and an increase in uncoupling (i.e., compared with systole; little change in ε per volume decline during early diastole and large changes in ε per volume decline during late diastole) (all P < 0.05). All values returned to baseline levels after recovery (all P > 0.05). Manipulation of cardiac hemodynamics caused comparable effects in young versus older men (all P > 0.05). Acute increases in afterload immediately change the diastolic phase of the LV longitudinal ε-volume loop in young and older men. This supports the potency of the LV longitudinal ε-volume loop to provide novel insights into dynamic cardiac function in humans in vivo.

Changes in dynamic left ventricular function, assessed by the strain-volume loop, relate to reverse remodeling after aortic valve replacement.

Aortic valve replacement (AVR) leads to remodeling of the left ventricle (LV). Adopting a novel technique to examine dynamic LV function, our study explored whether post-AVR changes in dynamic LV function and/or changes in aortic valve characteristics are associated with LV mass regression during follow-up. We retrospectively analyzed 30 participants with severe aortic stenosis who underwent standard transthoracic echocardiographic assessment before AVR [88 (IQR or interquartile range: 22-143) days], post-AVR [13 (6-22) days], and during follow-up [455 (226-907) days]. We assessed standard measures of LV structure, function, and aortic valve characteristics. Novel insight into dynamic LV function was provided through a four-chamber image by examination of the temporal relation between LV longitudinal strain (ε) and volume (ε-volume loops), representing the contribution of LV mechanics to volume change. AVR resulted in immediate changes in structural valve characteristics, alongside a reduced LV longitudinal peak ε and improved coherence between the diastolic and systolic part of the ε-volume loop (all P < 0.05). Follow-up revealed a decrease in LV mass (P < 0.05) and improvements in LV ejection fraction and LV longitudinal peak ε (P < 0.05). A significant relationship was present between decline in LV mass during follow-up and post-AVR improvement in coherence of the ε-volume loops (r = 0.439, P = 0.03), but not with post-AVR changes in aortic valve characteristics or LV function (all P > 0.05). We found that post-AVR improvements in dynamic LV function are related to long-term remodeling of the LV. This highlights the potential importance of assessing dynamic LV function for cardiac adaptations in vivo.NEW & NOTEWORTHY Combining temporal measures of left ventricular longitudinal strain and volume (strain-volume loop) provides novel insights in dynamic cardiac function. In patients with aortic stenosis who underwent aortic valve replacement, postsurgical changes in the strain-volume loop are associated with regression of left ventricular mass during follow-up. This provides novel insight into the relation between postsurgery changes in cardiac hemodynamics and long-term structural remodeling, but also supports the potential utility of the assessment of dynamic cardiac function.

Prognostic value of right ventricular longitudinal strain in patients with pulmonary hypertension: a systematic review and meta-analysis.

AIMS: Pulmonary hypertension (PH) is associated with high morbidity and mortality and the predictive capacity of traditional functional echocardiographic measures is poor. Recent studies assessed the predictive capacity of right ventricular longitudinal strain (RVLS). Diversity in methods between these studies resulted in conflicting outcomes. The purpose of this systematic review and meta-analysis was to determine the independent prognostic value of RVLS for PH-related events and all-cause mortality. METHODS AND RESULTS: A systematic search in Pubmed (MEDLINE), Embase, the Cochrane Library, and Web of Science was performed to identify studies that examined the prognostic value of RVLS in patients with PH. Studies reporting Cox regression based hazard ratios (HRs) for a combined endpoint of mortality and PH-related events or all-cause mortality for echocardiographic derived RVLS were included. A weighted mean of the multivariate HR was used to determine the independent predictive value of RVLS. Eleven studies met our criteria, including 1169 patients with PH (67% female, 0.6-3.8 years follow-up). PH patients with a relative reduction of RVLS of 19% had a significantly higher risk for the combined endpoint [HR 1.22, 95% confidence interval (CI) 1.07-1.40], while patients with a relative reduction of RVLS of 22% had a significantly higher risk for all-cause mortality (HR 2.96, 95% CI 2.00-4.38). CONCLUSION: This systematic review and meta-analysis showed that RVLS has independent prognostic value for a combined endpoint and all-cause mortality in patients with PH. Collectively, these findings emphasize that RVLS may have value for optimizing current predictive models for clinical events or mortality in patients with PH.

Exploratory assessment of left ventricular strain-volume loops in severe aortic valve diseases.

KEY POINTS: Severe aortic valve diseases are common cardiac abnormalities that are associated with poor long-term survival. Before any reduction in left ventricular (LV) function, the left ventricle undergoes structural remodelling under the influence of changing haemodynamic conditions. In this study, we combined temporal changes in LV structure (volume) with alterations in LV functional characteristics (strain, ԑ) into a ԑ-volume loop, in order to provide novel insight into the haemodynamic cardiac consequences of aortic valve diseases in those with preserved LV ejection fraction. We showed that our novel ԑ-volume loop and the specific loop characteristics provide additional insight into the functional and mechanical haemodynamic consequences of severe aortic valve diseases (with preserved LV ejection fraction). Finally, we showed that the ԑ-volume loop characteristics provide discriminative capacity compared with conventional measures of LV function. ABSTRACT: The purpose of this study was to examine left ventricular (LV) strain (ԑ)-volume loops to provide novel insight into the haemodynamic cardiac consequences of aortic valve stenosis (AS) and aortic valve regurgitation (AR). Twenty-seven participants were retrospectively recruited: AR (n = 7), AS (n = 10) and control subjects (n = 10). Standard transthoracic echocardiography was used to obtain apical four-chamber images to construct ԑ-volume relationships, which were assessed using the following parameters: early systolic ԑ (ԑ_ES); slope of ԑ-volume relationship during systole (Sslope); end-systolic peak ԑ (peak ԑ); and diastolic uncoupling (systolic ԑ-diastolic ԑ at same volume) during early diastole (UNCOUP_ED) and late diastole (UNCOUP_LD). Receiver operating characteristic curves were used to determine the ability to detect impaired LV function. Although LV ejection fraction was comparable between groups, longitudinal peak ԑ was reduced compared with control subjects. In contrast, ԑ_ES and Sslope were lower in both pathologies compared with control subejcts (P < 0.01), but also different between AS and AR (P < 0.05). UNCOUP_ED and UNCOUP_LD were significantly higher in both patient groups compared with control subjects (P < 0.05). Receiver operating characteristic curves revealed that loop characteristics (AUC = 0.99, 1.00 and 1.00; all P < 0.01) were better able then peak ԑ (AUC = 0.75, 0.89 and 0.76; P = 0.06, <0.01 and 0.08, respectively) and LV ejection fraction (AUC = 0.56, 0.69 and 0.69; all P > 0.05) to distinguish AS vs control, AR vs control and AS vs AR groups, respectively. Temporal changes in ԑ-volume characteristics provide novel insight into the haemodynamic cardiac impact of AS and AR. Contrary to traditional measures (i.e. ejection fraction, peak ԑ), these novel measures successfully distinguish between the haemodynamic cardiac impact of AS and AR.