Intensive antihypertensive treatment does not lower cerebral blood flow or cause orthostatic hypotension in frail older adults.

This study aimed to examine the effects of intensive antihypertensive treatment (AHT), i.e., systolic blood pressure target ≤ 140 mmHg, on cerebral blood flow, cerebral autoregulation, and orthostatic hypotension, in a representative population of frail older adults. Fourteen frail hypertensive patients (six females; age 80.3 ± 5.2 years; Clinical Frailty Scale 4-7; unattended SBP ≥ 150 mmHg) underwent measurements before and after a median 7-week AHT targeting SBP ≤ 140 mmHg. Transcranial Doppler measurements of middle cerebral artery velocity (MCAv), reflecting changes in cerebral blood flow (CBF), were combined with finger plethysmography recordings of continuous BP. Transfer function analysis assessed cerebral autoregulation (CA). ANCOVA analysed AHT-induced changes in CBF and CA and evaluated non-inferiority of the relative change in CBF (margin: -10%; covariates: pre-AHT values and AHT-induced relative mean BP change). McNemar-tests analysed whether the prevalence of OH and initial OH, assessed by sit/supine-to-stand challenges, increased with AHT. Unattended mean arterial pressure decreased by 15 mmHg following AHT. Ten (71%) participants had good quality TCD assessments. Non-inferiority was confirmed for the relative change in MCAv (95%CI: -2.7, 30.4). CA remained normal following AHT (P > 0.05), and the prevalence of OH and initial OH did not increase (P ≥ 0.655). We found that AHT in frail, older patients does not reduce CBF, impair autoregulation, or increase (initial) OH prevalence. These observations may open doors for more intensive AHT targets upon individualized evaluation and monitoring of hypertensive frail patients.Clinical Trial Registration: This study is registered at ClinicalTrials.gov (NCT05529147; September 1, 2022) and EudraCT (2022-001283-10; June 28, 2022).

Left and right ventricular strain-volume/area loops: a narrative review of current physiological understanding and potential clinical value.

Traditionally, echocardiography is used for volumetric measurements to aid in assessment of cardiac function. Multiple echocardiographic-based assessment techniques have been developed, such as Doppler ultrasound and deformation imaging (e.g., peak global longitudinal strain (GLS)), which have shown to be clinically relevant. Volumetric changes across the cardiac cycle can be related to deformation, resulting in the Ventricular Strain-Volume/Area Loop. These Loops allow assessment of the dynamic relationship between longitudinal strain change and volumetric change across both systole and diastole. This integrated approach to both systolic and diastolic function assessment may offer additional information in conjunction with traditional, static, measures of cardiac function or structure. The aim of this review is to summarize our current understanding of the Ventricular Strain-Volume/Area Loop, describe how acute and chronic exposure to hemodynamic stimuli alter Loop characteristics, and, finally, to outline the potential clinical value of these Loops in patients with cardiovascular disease. In summary, several studies observed Loop changes in different hemodynamic loading conditions and various (patho)physiological conditions. The diagnostic and prognostic value, and physiological interpretation remain largely unclear and have been addressed only to a limited extent.

Relationship of device measured physical activity type and posture with cardiometabolic health markers: pooled dose-response associations from the Prospective Physical Activity, Sitting and Sleep Consortium.

AIMS/HYPOTHESIS: The aim of this study was to examine the dose-response associations of device-measured physical activity types and postures (sitting and standing time) with cardiometabolic health. METHODS: We conducted an individual participant harmonised meta-analysis of 12,095 adults (mean ± SD age 54.5±9.6 years; female participants 54.8%) from six cohorts with thigh-worn accelerometry data from the Prospective Physical Activity, Sitting and Sleep (ProPASS) Consortium. Associations of daily walking, stair climbing, running, standing and sitting time with a composite cardiometabolic health score (based on standardised z scores) and individual cardiometabolic markers (BMI, waist circumference, triglycerides, HDL-cholesterol, HbA1c and total cholesterol) were examined cross-sectionally using generalised linear modelling and cubic splines. RESULTS: We observed more favourable composite cardiometabolic health (i.e. z score <0) with approximately 64 min/day walking (z score [95% CI] -0.14 [-0.25, -0.02]) and 5 min/day stair climbing (-0.14 [-0.24, -0.03]). We observed an equivalent magnitude of association at 2.6 h/day standing. Any amount of running was associated with better composite cardiometabolic health. We did not observe an upper limit to the magnitude of the dose-response associations for any activity type or standing. There was an inverse dose-response association between sitting time and composite cardiometabolic health that became markedly less favourable when daily durations exceeded 12.1 h/day. Associations for sitting time were no longer significant after excluding participants with prevalent CVD or medication use. The dose-response pattern was generally consistent between activity and posture types and individual cardiometabolic health markers. CONCLUSIONS/INTERPRETATION: In this first activity type-specific analysis of device-based physical activity, ~64 min/day of walking and ~5.0 min/day of stair climbing were associated with a favourable cardiometabolic risk profile. The deleterious associations of sitting time were fully attenuated after exclusion of participants with prevalent CVD and medication use. Our findings on cardiometabolic health and durations of different activities of daily living and posture may guide future interventions involving lifestyle modification.

Single and 7-day handgrip and squat exercise prevents endothelial ischemia-reperfusion injury in individuals with cardiovascular disease risk factors.

Whole body exercise provides protection against endothelial ischemia-reperfusion (IR) injury. In this crossover study, we examined the effects of 1) single bout of local exercise (handgrip, squats) on endothelial responses to IR, and 2) if 7 days of daily local exercise bolsters these effects in individuals with cardiovascular disease (CVD) risk factors. Fifteen participants (9 women, 58 ± 5 yr, ≥2 CVD risk factors) attended the laboratory for six visits. Subsequent to familiarization (visit 1), during visit 2 (control) brachial artery flow-mediated dilation (FMD) was measured before and after IR (15-min upper-arm ischemia, 15-min reperfusion). One week later, participants were randomized to 4 × 5-min unilateral handgrip (50% maximal voluntary contraction, 25 rpm) or squat exercises (15 rpm), followed by IR plus FMD measurements. Subsequently, home-based exercise was performed (6 days), followed by another visit to the laboratory for the IR protocol plus FMD measurements (18-24 h after the last exercise bout). After a 2-wk washout period, procedures were repeated with the alternative exercise mode. For a single exercise bout, we found a significant IR injury × exercise mode interaction (P < 0.01) but no main effect of injury (P = 0.08) or condition (P = 0.61). A lower post-IR FMD was evident after control (pre-IR: 4.3 ± 2.1% to post-IR: 2.9 ± 1.9%, P < 0.01) but not after handgrip (pre-IR: 3.8 ± 1.6% to post-IR: 3.4 ± 1.5%, P = 0.31) or squats (pre-IR: 3.9 ± 1.8% to post-IR: 4.0 ± 1.9%, P = 0.74). After 7 days of daily exercise, we found no change in FMD post-IR following handgrip (pre-IR: 4.3 ± 1.9% to post-IR: 4.7 ± 3.2%) or squats (pre-IR: 3.7 ± 2.1% to post-IR: 4.7 ± 3.0%, P > 0.05). Single bouts of dynamic, local exercise (handgrip, squats) provide remote protection against endothelial IR-induced injury in individuals with CVD risk factors, with 1-wk daily, home-based exercise preserving these effects for up to 24 h following the last exercise bout.NEW & NOTEWORTHY We show that single bouts of dynamic handgrip and squat exercise provide remote protection against endothelial ischemia-reperfusion (IR)-induced injury in individuals with cardiovascular disease (CVD) risk factors, with 1-wk daily, home-based exercise preserving these effects for up to 24 h following the last exercise bout.

Exercise-based cardiac rehabilitation in stable angina pectoris: a narrative review on current evidence and underlying physiological mechanisms.

Stable angina pectoris (SAP) is a prevalent condition characterised by a high disease burden. Based on recent evidence, the need for revascularisation in addition to optimal medical treatment to reduce mortality and re-events is heavily debated. These observations may be explained by the fact that revascularisation is targeted at the local flow-limiting coronary artery lesion, while the aetiology of SAP relates to the systemic, inflammatory process of atherosclerosis, causing generalised vascular dysfunction throughout the entire vascular system. Moreover, cardiovascular events are not solely caused by obstructive plaques but are also associated with plaque burden and high-risk plaque features. Therefore, to reduce the risk of cardiovascular events and angina, and thereby improve quality of life, alternative therapeutic approaches to revascularisation should be considered, preferably targeting the cardiovascular system as a whole with a physiological approach. Exercise-based cardiac rehabilitation fits this description and is a promising strategy as a first-line treatment in addition to optimal medical treatment. In this review, we discuss the role of exercise-based cardiac rehabilitation in SAP in relation to the underlying physiological mechanisms, we summarise the existing evidence and highlight future directions.

The Hypoxia Response Pathway: A Potential Intervention Target in Parkinson's Disease?

Parkinson's disease (PD) is a progressive neurodegenerative disorder for which only symptomatic treatments are available. Both preclinical and clinical studies suggest that moderate hypoxia induces evolutionarily conserved adaptive mechanisms that enhance neuronal viability and survival. Therefore, targeting the hypoxia response pathway might provide neuroprotection by ameliorating the deleterious effects of mitochondrial dysfunction and oxidative stress, which underlie neurodegeneration in PD. Here, we review experimental studies regarding the link between PD pathophysiology and neurophysiological adaptations to hypoxia. We highlight the mechanistic differences between the rescuing effects of chronic hypoxia in neurodegeneration and short-term moderate hypoxia to improve neuronal resilience, termed "hypoxic conditioning". Moreover, we interpret these preclinical observations regarding the pharmacological targeting of the hypoxia response pathway. Finally, we discuss controversies with respect to the differential effects of hypoxia response pathway activation across the PD spectrum, as well as intervention dosing in hypoxic conditioning and potential harmful effects of such interventions. We recommend that initial clinical studies in PD should focus on the safety, physiological responses, and mechanisms of hypoxic conditioning, as well as on repurposing of existing pharmacological compounds. © 2023 International Parkinson and Movement Disorder Society.

Left ventricular strain-volume loops and myocardial fibrosis in pediatric patients with Duchenne muscular dystrophy.

BACKGROUND: The left ventricular strain-volume loop (SVL) combines changes in global longitudinal strain (GLS) and LV volume across a cardiac cycle, providing insight into cardiac dynamics. This study explored the association between left ventricular SVL and presence of fibrosis, assessed with late gadolinium enhancement, in patients with Duchenne muscular dystrophy (DMD). METHODS AND RESULTS: 34 pediatric patients with DMD were included. Feature tracking analysis was used to assess endocardial GLS and volumetric measurements to construct the SVL. Mean age at the time of assessment was 14 ± 3 and 11 ± 2 years old (p < 0.01) in the group with (n = 18) versus without fibrosis (n = 16), respectively. Left ventricular ejection fraction was not significantly different between groups (fibrosis: 56.4 ± 3.8% versus without fibrosis: 54.0 ± 6.3%, p = 0.18). After adjusting for age, the late diastolic slope of the SVL was significantly associated with presence of fibrosis (OR 0.39 [95% CI 0.18-0.85]; area under the receiver operating characteristic curve: 0.83 [95% CI 0.70-0.97]) No significant association was observed for peak strain and fibrosis (OR 1.15 [95% CI 0.86-1.546]). CONCLUSION: A lower late diastolic slope of the left ventricular SVL, related to the interplay between longitudinal deformation and volume changes late in diastole, is associated with presence of myocardial fibrosis in pediatric patients with DMD.

The Effect of Remote Ischemic Postconditioning on Quality of Life and Clinical Events after an Ischemic Stroke.

OBJECTIVES: Repeated remote ischemic postconditioning (rIPostC) may be an easily applicable treatment following ischemic stroke to improve quality of life (QoL) and clinical outcomes. rIPostC consists of repeated, brief periods of limb ischemia (through inflation of a blood pressure cuff), followed by reperfusion. This study investigated the 1-year follow-up of rIPostC on QoL and clinical events. METHODS: As part of a randomized controlled trial, adult patients with an ischemic stroke within 24 hours after onset of symptoms were randomized to repeated rIPostC or sham-conditioning. rIPostC was applied twice daily during hospitalization (maximum of 4 days). QoL and patientreported outcome measures (PROMs) were assessed at 12-week and 1-year follow-ups. Additionally, we explored the effect of repeated rIPostC on clinical events (recurrent cerebrovascular events, hospitalization, and mortality). RESULTS: The trial was preliminarily stopped due to limitations in recruitment after the inclusion of 88 patients (rIPostC: 40; sham-conditioning: 48) (70 years, 68% male). Questionnaires were returned by 69 (78%) and 63 (72%) participants after 12 weeks and 1 year, respectively. The median difference of the stroke-specific QoL between rIPostC and sham-conditioning was 0.05 (p =0.986) and -0.16 (p =0.654) after 12 weeks and 1-year, respectively. No significant effect of rIPostC on the different domains of PROMs was detected. We observed no between-group differences in recurrent cerebrovascular events, hospitalization, or all-cause mortality (Hazard Ratios p >0.05). CONCLUSION: In this exploratory analysis, we observed no significant difference between repeated rIPostC and usual care on QoL and clinical outcomes at 12 weeks and 1 year in patients with an ischemic stroke. CLINICAL TRIAL REGISTRATION NUMBER: NTR6880.

Exercised-based cardiac rehabilitation associates with lower all-cause mortality in patients with primary pulmonary hypertension.

Background: Despite pharmacological therapies to improve outcomes of pulmonary hypertension (PH), poor long-term survival remains. Exercised-based cardiac rehabilitation (ExCR) may be an alternative strategy to improve prognosis. Therefore, using an electronic medical record (EMR) database, the objective of this study was to compare mortality between patients with primary PH with ExCR vs. propensity-matched PH patients without ExCR. Methods: The retrospective analysis was conducted on February 15, 2023 using anonymized data within TriNetX, a global federated health research network. All patients were aged ≥18 years with primary PH recorded in EMRs with at least 1-year follow-up from ExCR. Using logistic regression models, patients with PH with an EMR of ExCR were 1:1 propensity score-matched with PH patients without ExCR for age, sex, race, and comorbidities, and cardiovascular care. Results: In total, 109,736 patients with primary PH met the inclusion criteria for the control group and 784 patients with primary PH met the inclusion criteria for the ExCR cohort. Using the propensity score-matched cohorts, 1-year mortality from ExCR was proportionally lower with 13.6% (n = 101 of 744 patients) in the ExCR cohort compared to 23.3% (n = 174 of 747 patients) in the controls (OR 0.52, 95% CI 0.40-0.68). Conclusion: The present study of 1,514 patients with primary PH suggests that ExCR is associated with 48% lower odds of 1-year mortality, when compared to propensity score-matched patients without ExCR.

A positive neighborhood walkability is associated with a higher magnitude of leisure walking in adults upon COVID-19 restrictions: a longitudinal cohort study.

BACKGROUND: Previous cross-sectional and longitudinal observational studies revealed positive relationships between contextual built environment components and walking behavior. Due to severe restrictions during COVID-19 pandemic lockdowns, physical activity was primarily performed within the immediate living area. Using this unique opportunity, we evaluated whether built environment components were associated with the magnitude of change in walking activity in adults during COVID-19 restrictions. METHODS: Data on self-reported demographic characteristics and walking behaviour were extracted from the prospective longitudinal Lifelines Cohort Study in the Netherlands of participants ≥ 18 years. For our analyses, we made use of the data acquired between 2014-2017 (n = 100,285). A fifth of the participants completed the questionnaires during COVID-19 restrictive policies in July 2021 (n = 20,806). Seven spatial components were calculated for a 500m and 1650m Euclidean buffer per postal code area in GIS: population density, retail and service destination density, land use mix, street connectivity, green space density, sidewalk density, and public transport stops. Additionally, the walkability index (WI) of these seven components was calculated. Using multivariable linear regression analyses, we analyzed the association between the WI (and separate components) and the change in leisure walking minutes/week. Included demographic variables were age, gender, BMI, education, net income, occupation status, household composition and the season in which the questionnaire was filled in. RESULTS: The average leisure walking time strongly increased by 127 min/week upon COVID-19 restrictions. All seven spatial components of the WI were significantly associated with an increase in leisure walking time; a 10% higher score in the individual spatial component was associated with 5 to 8 more minutes of leisure walking/week. Green space density at the 500m Euclidean buffer and side-walk density at the 1650m Euclidean buffer were associated with the highest increase in leisure walking time/week. Subgroup analysis revealed that the built environment showed its strongest impact on leisure walking time in participants not engaging in leisure walking before the COVID-19 pandemic, compared to participants who already engaged in leisure walking before the COVID-19 pandemic. CONCLUSIONS: These results provide strong evidence that the built environment, corrected for individual-level characteristics, directly links to changes observed in leisure walking time during COVID-19 restrictions. Since this relation was strongest in those who did not engage in leisure walking before the COVID-19 pandemic, our results encourage new perspectives in health promotion and urban planning.

Menopausal stage differences in endothelial resistance to ischemia-reperfusion injury.

BACKGROUND: In postmenopausal women, reduced ovarian function precedes endothelial dysfunction and attenuated endothelial resistance to ischemia-reperfusion (IR) injury. We hypothesized that IR injury would lower endothelial function, with premenopausal women demonstrating the greatest protection from injury, followed by early, then late postmenopausal women. METHODS: Flow-mediated dilation (FMD) was assessed at baseline and following IR injury in premenopausal (n = 11), early (n = 11; 4 ± 1.6 years since menopause), and late (n = 11; 15 ± 5.5 years since menopause) postmenopausal women. RESULTS: There were significant group differences in baseline FMD (p = 0.007); post hoc analysis revealed a similar resting FMD between premenopausal (7.8% ± 2.1%) and early postmenopausal (7.1% ± 2.7%), but significantly lower FMD in late postmenopausal women (4.5% ± 2.3%). Results showed an overall decline in FMD after IR injury (p < 0.001), and a significant condition*time interaction (p = 0.048), with early postmenopausal women demonstrating the most significant decline in FMD following IR. CONCLUSION: Our findings indicate that endothelial resistance to IR injury is attenuated in healthy early postmenopausal women.

Relationship of Daily Step Counts to All-Cause Mortality and Cardiovascular Events.

BACKGROUND: The minimal and optimal daily step counts for health improvements remain unclear. OBJECTIVES: A meta-analysis was performed to quantify dose-response associations of objectively measured step count metrics in the general population. METHODS: Electronic databases were searched from inception to October 2022. Primary outcomes included all-cause mortality and incident cardiovascular disease (CVD). Study results were analyzed using generalized least squares and random-effects models. RESULTS: In total, 111,309 individuals from 12 studies were included. Significant risk reductions were observed at 2,517 steps/d for all-cause mortality (adjusted HR [aHR]: 0.92; 95% CI: 0.84-0.999) and 2,735 steps/d for incident CVD (aHR: 0.89; 95% CI: 0.79-0.999) compared with 2,000 steps/d (reference). Additional steps resulted in nonlinear risk reductions of all-cause mortality and incident CVD with an optimal dose at 8,763 (aHR: 0.40; 95% CI: 0.38-0.43) and 7,126 steps/d (aHR: 0.49; 95% CI: 0.45-0.55), respectively. Increments from a low to an intermediate or a high cadence were independently associated with risk reductions of all-cause mortality. Sex did not influence the dose-response associations, but after stratification for assessment device and wear location, pronounced risk reductions were observed for hip-worn accelerometers compared with pedometers and wrist-worn accelerometers. CONCLUSIONS: As few as about 2,600 and about 2,800 steps/d yield significant mortality and CVD benefits, with progressive risk reductions up to about 8,800 and about 7,200 steps/d, respectively. Additional mortality benefits were found at a moderate to high vs a low step cadence. These findings can extend contemporary physical activity prescriptions given the easy-to-understand concept of step count. (Dose-Response Relationship Between Daily Step Count and Health Outcomes: A Systematic Review and Meta-Analyses; CRD42021244747).

Handgrip exercise in patients scheduled for cardiac surgery to attenuate troponin release: a feasibility study.

Cardiac surgery, including surgical aortic valve repair (SAVR) and coronary artery bypass grafting (CABG), are associated with ischemia-reperfusion (I/R) injury. Single bouts of exercise, including handgrip exercise, may protect against I/R injury. This study explored 1) the feasibility of daily handgrip exercise in the week before SAVR and/or CABG and 2) its impact on cardiac I/R injury, measured as postoperative cardiac troponin-T (cTnT) release. Sixty-five patients undergoing elective SAVR and/or CABG were randomized to handgrip exercise + usual care (intervention, n = 33) or usual care alone (control, n = 32). Handgrip exercise consisted of daily 4 × 5-min handgrip exercise (30% maximal voluntary contraction) for 2-7 days before cardiac surgery. Feasibility was assessed using validated questionnaires. Postoperative cTnT release was assessed at 0, 6, 12, 18, and 24 h [primary outcome area under the curve (cTnTAUC)]. Most patients (93%) adhered to handgrip exercise and 77% was satisfied with this intervention. Handgrip exercise was associated with lower cTnTAUC (402,943 ± 225,206 vs. 473,300 ± 232,682 ng · min/L), which is suggestive of a medium effect size (Cohen's d 0.31), and lower cTnTpeak (313 [190-623] vs. 379 [254-699] ng/L) compared with controls. We found that preoperative handgrip exercise is safe and feasible for patients scheduled for SAVR and/or CABG and is associated with a medium effect size to reduce postoperative cardiac I/R injury. This warrants future studies to assess the potential clinical impact of exercise protocols before cardiac surgery.NEW & NOTEWORTHY Daily handgrip exercise in the week before elective cardiac surgery is safe and feasible. Handgrip exercise is associated with a medium effect size for less troponin-T release. Future larger-sized studies are warranted to explore the impact of (handgrip) exercise prior to cardiac surgery on clinical outcomes and direct patient benefits.

Central and local arterial stiffness in White Europeans compared to age-, sex-, and BMI-matched South Asians.

BACKGROUND: Ethnicity impacts cardiovascular disease (CVD) risk, and South Asians demonstrate a higher risk than White Europeans. Arterial stiffness is known to contribute to CVD, and differences in arterial stiffness between ethnicities could explain the disparity in CVD risk. We compared central and local arterial stiffness between White Europeans and South Asians and investigated which factors are associated with arterial stiffness. METHODS: Data were collected from cohorts of White Europeans (the Netherlands) and South Asians (India). We matched cohorts on individual level using age, sex, and body mass index (BMI). Arterial stiffness was measured with ARTSENS® Plus. Central stiffness was expressed as carotid-femoral pulse wave velocity (cf-PWV, m/s), and local carotid stiffness was quantified using the carotid stiffness index (Beta) and pressure-strain elastic modulus (Epsilon, kPa). We compared arterial stiffness between cohorts and used multivariable linear regression to identify factors related to stiffness. RESULTS: We included n = 121 participants per cohort (age 53±10 years, 55% male, BMI 24 kg/m2). Cf-PWV was lower in White Europeans compared to South Asians (6.8±1.9 vs. 8.2±1.8 m/s, p<0.001), but no differences were found for local stiffness parameters Beta (5.4±2.4 vs. 5.8±2.3, p = 0.17) and Epsilon (72±35 vs. 70±31 kPa, p = 0.56). Age (standardized ß, 95% confidence interval: 0.28, 0.17-0.39), systolic blood pressure (0.32, 0.21-0.43), and South Asian ethnicity (0.46, 0.35-0.57) were associated with cf-PWV; associations were similar between cohorts (p>0.05 for interaction). Systolic blood pressure was associated with carotid stiffness in both cohorts, whereas age was associated to carotid stiffness only in South Asians and BMI only in White Europeans. CONCLUSION: Ethnicity is associated with central but not local arterial stiffness. Conversely, ethnicity seems to modify associations between CVD risk factors and local but not central arterial stiffness. This suggests that ethnicity interacts with arterial stiffness measures and the association of these measures with CVD risk factors.

Left ventricular deformation and myocardial fibrosis in pediatric patients with Duchenne muscular dystrophy.

BACKGROUND: Left ventricular (LV) strain and rotation are emerging functional markers for early detection of LV dysfunction and have been associated with the burden of myocardial fibrosis in several disease states. This study examined the association between LV deformation (i.e., LV strain and rotation) and extent and location of LV myocardial fibrosis in pediatric patients with Duchenne muscular dystrophy (DMD). METHODS AND RESULTS: 34 pediatric patients with DMD underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) to assess LV myocardial fibrosis. Offline CMR feature-tracking analysis was used to assess global and segmental longitudinal and circumferential LV strain, and LV rotation. Patients with fibrosis (n = 18, 52.9%) were older than those without fibrosis (14 ± 3 years (yrs) vs 11 ± 2 yrs., p = 0.01). There was no significant difference in LV ejection fraction (LVEF) between subjects with and without fibrosis (54 ± 6% vs 56 ± 4%, p = 0.18). However, lower endocardial global circumferential strain (GCS), but not LV rotation, was associated with presence of fibrosis (adjusted Odds Ratio 1.25 [95% CI 1.01-1.56], p = 0.04). Both GCS and global longitudinal strain correlated with the extent of fibrosis (r = .52, p = 0.03 and r = .75, p < 0.01, respectively). Importantly, segmental strain did not seem to correspond to location of fibrosis. CONCLUSION: A lower global, but not segmental, strain is associated with presence and extent of LV myocardial fibrosis in pediatric DMD patients. Therefore, strain parameters might detect structural myocardial alterations, however currently more research is needed to evaluate its value (e.g., prognostic) in clinical practice.

Association of left ventricular strain-volume loop characteristics with adverse events in patients with heart failure with preserved ejection fraction.

AIMS: Patients with heart failure with preserved ejection fraction (HFpEF) are characterized by impaired diastolic function. Left ventricular (LV) strain-volume loops (SVL) represent the relation between strain and volume during the cardiac cycle and provide insight into systolic and diastolic function characteristics. In this study, we examined the association of SVL parameters and adverse events in HFpEF. METHODS AND RESULTS: In 235 patients diagnosed with HFpEF, LV-SVL were constructed based on echocardiography images. The endpoint was a composite of all-cause mortality and Heart Failure (HF)-related hospitalization, which was extracted from electronic medical records. Cox-regression analysis was used to assess the association of SVL parameters and the composite endpoint, while adjusting for age, sex, and NYHA class. HFpEF patients (72.3% female) were 75.8 ± 6.9 years old, had a BMI of 29.9 ± 5.4 kg/m2, and a left ventricular ejection fraction of 60.3 ± 7.0%. Across 2.9 years (1.8-4.1) of follow-up, 73 Patients (31%) experienced an event. Early diastolic slope was significantly associated with adverse events [second quartile vs. first quartile: adjusted hazards ratio (HR) 0.42 (95%CI 0.20-0.88)] after adjusting for age, sex, and NYHA class. The association between LV peak strain and adverse events disappeared upon correction for potential confounders [adjusted HR 1.02 (95% CI 0.96-1.08)]. CONCLUSION: Early diastolic slope, representing the relationship between changes in LV volume and strain during early diastole, but not other SVL-parameters, was associated with adverse events in patients with HFpEF during 2.9 years of follow-up.