Contribution of reduced skeletal muscle perfusion reserve to exercise intolerance in heart failure with preserved ejection fraction.

BACKGROUND: Skeletal muscle (SM)-associated mechanisms of exercise intolerance in HFpEF are insufficiently defined, and inadequate augmentation of SM blood flow during physical effort may be one of the contributors. Therefore, we sought to investigate the association of SM perfusion response to exertion with exercise capacity in this clinical condition. METHODS: Echocardiography and SM microvascular perfusion by contrast-enhanced ultrasound were performed at rest and immediately post-exercise test in 77 HFpEF patients in NYHA class II and III, and in 25 subjects with normal exercise tolerance (stage B). Exercise reserve of cardiac function and SM perfusion was calculated by subtracting resting value from exercise value. RESULTS: In addition to decreased cardiac functional reserve, HFpEF patients demonstrated significantly reduced SM perfusion reserve as compared to HF stage B, with the degree of impairment being greater in the subgroup with more profound left ventricular (LV) diastolic abnormalities (E/e' > 15 and TRV > 2.8 m/s). SM perfusion reserve was significantly associated with exercise capacity (beta = 0.33; SE 0.11; p = 0.003), cardiac output reserve (beta = 0.24; SE 0.12; p = 0.039), resting E/e' (beta = -0.33; SE 0.11; p = 0.006), and patient frailty expressed by the PRISMA 7 score (beta = -0.30; SE 0.11; p = 0.008). In multivariable analysis including clinical, demographic and cardiac functional variables, SM perfusion reserve was in addition to patient frailty, sex and LV longitudinal strain reserve among the independent correlates of exercise capacity. CONCLUSIONS: SM perfusion reserve is impaired in HFpEF, and is associated with reduced exercise capacity independent of clinical, demographic and "central" cardiac factors. This supports the need to consider the SM domain in patient management strategies in HFpEF.

Association of Reduced Left Atrial Reserve With Exercise Intolerance and Outcome in Hypertension.

BACKGROUND: Hypertensive heart disease (HHD) is a leading contributor to heart failure with preserved ejection fraction (HFpEF). However, the mechanisms behind the transition to the symptomatic phase remain unclear. OBJECTIVES: We sought to find the association of the exercise response of left atrial (LA) mechanical function with functional capacity, symptoms, and outcome across the heart failure (HF) spectrum in hypertension. METHODS: Echocardiography (including LA reservoir peak atrial longitudinal strain [PALS] and peak atrial contractile strain [PACS] and LA stiffness index) was performed at rest and immediately postexercise in 139 patients with HHD-35 with stage A, 48 with stage B, and 56 with stage C HFpEF. Patients were followed for HF and atrial fibrillation. RESULTS: Exercise capacity was progressively worse from stage A through stage B to stage C and was accompanied by a gradual impairment of changes in PALS and PACS from rest to exercise, whereas LA stiffness reserve remained unchanged until stage C. Peak atrial longitudinal strain and PACS reserves were independently associated with exercise capacity (P = .017 and .008, respectively). Left atrial stiffness reserve and E/e' were the strongest associations of symptomatic HF. Over a median of 25 months, 35 patients developed HF and/or atrial fibrillation. Peak atrial longitudinal strain and PACS reserves were associated with the study end points after adjusting for age, diabetes, N-terminal pro-B type natriuretic peptide, LA volume index, resting E/e', and resting PALS/PACS. CONCLUSIONS: Impaired exercise reserve of LA strain and stiffness are associated with reduced functional capacity in hypertension, and LA strain reserve is independently associated with outcome. These parameters appear to be determinants of progression to overt HF in HHD; however, their contribution may differ depending on HF stage.

Association of arterial hemodynamics with left ventricular systolic function in hypertensive patients: A longitudinal study.

BACKGROUND: Left ventricular (LV) systolic impairment, particularly in the longitudinal direction, is considered an early and sensitive marker of hypertensive heart disease and increased cardiovascular risk. The evidence indicates that aortic stiffness and central hemodynamic factors are important determinants of LV performance, mediating the interaction between the heart and vascular load. Despite the existence of cross-sectional analyses linking central blood pressure (BP) parameters with LV mechanics, no longitudinal data are available which include serial measurements in the course of antihypertensive treatment. OBJECTIVES: To investigate the associations between changes in LV longitudinal and circumferential function with alterations in arterial hemodynamics and ventricular-arterial coupling (VAC) in patients with uncomplicated hypertension during a 12-month follow-up. MATERIAL AND METHODS: In this retrospective study, 216 patients (age 64.3 ±7.6 years) underwent echocardiography including left ventricular longitudinal (GLS) and circumferential strain (GCS) analysis, brachial BP measurements, VAC (combining echocardiography and brachial BP), and arterial hemodynamics using radial tonometry at baseline and after 12 months of antihypertensive therapy. Patients were grouped into 2 subsets: with improvement in GLS (n = 103) and with deterioration in GLS (n = 113). RESULTS: No significant differences were observed in the majority of cardiovascular, demographic or clinical characteristics between the groups. The subset with improvement in GLS demonstrated more favorable changes over follow-up in pulse wave velocity (p = 0.03), central augmentation pressure (p = 0.01) and ventricular-arterial coupling (p = 0.04) compared to patients showing deterioration in GLS. In the multivariable analysis, independent determinants of changes in GLS were: GLS at baseline (-0.48; p < 0.001), changes from baseline to follow-up in central augmentation pressure (-0.29; p = 0.002) and ventricular-arterial coupling (-0.25; p = 0.004). Independent determinants of analogous changes in GCS were: GCS at baseline (-0.46; p < 0.001) and changes in central augmentation pressure (-0.22; p = 0.02). CONCLUSIONS: Left ventricular longitudinal and circumferential functional remodeling over time in hypertensive patients is associated with arterial hemodynamics and ventricular-arterial coupling.

Prediction of AF in Heart Failure With Preserved Ejection Fraction: Incremental Value of Left Atrial Strain.

OBJECTIVES: This study sought to identify the factors associated with incident atrial fibrillation (AF) in a well-characterized heart failure with preserved ejection fraction (HFpEF) population, with special focus on left atrial (LA) strain. BACKGROUND: AF is associated with HFpEF, with adverse consequences. Effective risk evaluation might allow the initiation of protective strategies. METHODS: Clinical evaluation and echocardiography, including measurements of peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS), and LA volume index (LAVI), were obtained in 170 patients with symptomatic HFpEF (mean age, 65 ± 8 years), free of baseline AF. AF was identified by standard 12-lead electrocardiogram, review of relevant medical records (including Holter documentation), and surveillance with a portable single-lead electrocardiogram device over 2 weeks. Results were validated in the 103 patients with HFpEF from the Karolinska-Rennes (KaRen) study. RESULTS: Over a median follow-up of 49 months, incident AF was identified in 39 patients (23%). Patients who developed AF were older; had higher clinical risk scores, brain natriuretic peptide, creatinine, LAVI, and LV mass; lower LA strain and exercise capacity; and more impaired LV diastolic function. PACS, PALS, and LAVI were the most predictive parameters for AF (area under receiver-operating characteristic curve: 0.76 for PACS, 0.71 for PALS, and 0.72 for LAVI). Nested Cox regression models showed that the predictive value of PACS and PALS was independent from and incremental to clinical data, LAVI, and E/e' ratio. Classification and regression trees analysis identified PACS ≤12.7%, PALS ≤29.4%, and LAVI >34.3 ml/m2 as discriminatory nodes for AF, with a 33-fold greater hazard of AF (p < 0.001) in patients categorized as high risk. The classification and regression trees algorithm discriminated high and low AF risk in the validation cohort. CONCLUSIONS: PACS and PALS provide incremental predictive information about incident AF in HFpEF. The inclusion of these LA strain components to the diagnostic algorithm may help guide screening and further monitoring for AF risk in this population.

Association of central blood pressure with left atrial structural and functional abnormalities in hypertensive patients: Implications for atrial fibrillation prevention.

AIMS: Functional and structural abnormalities of the left atrium have been demonstrated to be clinically and prognostically significant in a range of cardiovascular disorders, increasing the risk of atrial fibrillation. Among the potential contributors to these aberrations, central arterial factors remain insufficiently defined. Accordingly, we sought to investigate the determinants of left atrium abnormalities in hypertension, with special focus on central haemodynamics. METHODS: In this retrospective, cross-sectional study, 263 patients (age 63.8 ± 8.0 years) with uncomplicated hypertension underwent echocardiography including left atrium strain (LAS) and volume analysis, and central haemodynamics assessment using radial tonometry. RESULTS: Patients were grouped depending on LAS and left atrium volume index (LAVI), using externally validated cutpoints (34.1% for LAS and 34 ml/m2 for LAVI). The subset with lower LAS (n = 124) demonstrated higher central (cPP) and brachial pulse pressure (bPP), ventricular- arterial coupling, left ventricular mass index (LVMI) and LAVI, and lower global left ventricular longitudinal strain and early diastolic tissue velocity (e'). Patients with higher LAVI (n = 119) presented higher systolic blood pressure, cPP, bPP, central augmentation pressure, LVMI and E/e' ratio and lower LAS. In multivariable analysis, cPP was independently associated with both LAS (ß = -0.22; p = 0.002) and LAVI (ß = 0.21; p = 0.003). No independent associations with left atrium parameters were shown for bPP. CONCLUSION: Higher cPP is detrimentally associated with left atrium structural and functional characteristics, thus providing a possible pathophysiological link with the development of substrate for atrial fibrillation. Prophylaxis of atrial fibrillation might be another argument for consideration in the treatment strategy in hypertension targeted measures addressing central blood pressure.