Inciardi, Riccardo M.

Background This study aims to characterize right ventricular dysfunction (RVD) in heart failure (HF) with preserved ejection fraction and understand the cumulative prognostic value of abnormal RV echocardiographic parameters in HF with preserved ejection fraction. Methods and Results Data from 809 patients in the PARAGON‐HF (Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor With Angiotensin‐Receptor Blocker Global Outcomes in HF With Preserved Ejection Fraction) echocardiographic substudy (55% women, mean age 74±8 years) were analyzed. Correlates of RVD (defined as tricuspid annular plane systolic excursion <1.7 cm, fractional area change <35% or absolute RV free wall longitudinal strain <20%) were identified using multivariable logistic regression models. We further assessed the prognostic value of the number of abnormal RV parameters (0, 1, ≥2) on total HF hospitalizations (HFH) and cardiovascular death, total HFH, first HFH or cardiovascular death, all‐cause death, and cardiovascular death. RVD was identified in 461 (57%) patients. Correlates of RVD included older age, higher heart rate, atrial fibrillation/flutter, greater left ventricle wall thickness, higher N‐terminal pro‐B‐type natriuretic peptide levels, lower systolic blood pressure, and lower left ventricle absolute global longitudinal strain. These results were consistent across sexes, except atrial fibrillation/flutter and LV wall thickness, which were associated with a higher risk of RVD in men but not in women. Participants with ≥2 abnormal RV parameters had a significantly higher adjusted risk of total HFH and cardiovascular death (rate ratio, 2.13 [95% CI, 1.13–4.01]), first HFH or cardiovascular death, all‐cause death, and cardiovascular death. Conversely, an isolated abnormal RV parameter was not associated with a worse outcome. Conclusions RV measures may underestimate the burden of RVD in HF with preserved ejection fraction when considered in isolation. Clinicians should consider multiple dimensions to comprehensively assess RV function in patients with HF with preserved ejection fraction.

AbstractBackground and purposeLower left atrial (LA) function is associated with higher dementia risk and may be mechanistically linked through vascular brain injury, an established correlate for higher dementia risk. Using data from the Atherosclerosis Risk in Communities study, we assessed the cross‐sectional association between LA function and brain magnetic resonance imaging (MRI) markers of vascular brain injury.MethodsWe included 1488 participants who were free of prevalent dementia, stroke, or atrial fibrillation and who underwent a two‐dimensional echocardiogram and brain MRI in 2011–2013 (mean [± standard deviation] age 76 [± 5] years, 60% female, 27% Black). LA function measures (reservoir, conduit, contractile strain) were assessed in quartiles. Brain MRI measures included cerebral microbleeds, brain infarcts, and white matter hyperintensity (WMH) volume. Logistic regression was used for dichotomous outcomes. Linear regression was used for WMH volume.ResultsOverall, 343 (23%) and 344 participants (23%) had ≥1 cerebral microbleed or brain infarct. After multivariable adjustments, the lowest LA reservoir and conduit strain quartiles (vs. highest quartile) were associated with higher odds of the presence of ≥1 cerebral microbleed (odds ratios [95% confidence intervals] 1.78 [1.42–2.22] and 1.52 [1.22–1.90]). Compared to the highest quartile, participants in the lowest LA conduit strain quartile had 1.51 (95% confidence interval 1.22–1.88) times higher odds of having ≥1 brain infarct. Lower LA contractile strain was associated with lower odds of brain infarcts. No association with WMH volume was noted.ConclusionsWe found that LA reservoir and conduit strain were associated with cerebral microbleeds and brain infarcts. Lower LA function may be linked to dementia risk via vascular brain injury. Prospective studies are needed to confirm these findings.

Abstract Aims Left ventricular (LV) subclinical impairment has been described in heart failure with preserved ejection fraction (HFpEF). We assessed the relationship between LV myocardial deformation by strain imaging and recurrent hospitalization for heart failure (HF) or cardiovascular death in a large international HFpEF population. Methods and results We assessed two-dimensional speckle-tracking based global longitudinal strain (GLS) in 790 patients (mean age 74 ± 8 years, 54% female) with adequate image quality enrolled in the PARAGON-HF echocardiography study. We examined the relationship of GLS with total HF hospitalizations and cardiovascular death (the primary composite outcome) after accounting for clinical confounders. Approximately 47% of the population had evidence of LV subclinical dysfunction, defined as absolute GLS &lt;16%. Impaired GLS was significantly associated with higher values of circulating baseline N-terminal pro-B-type-natriuretic peptide. After a median follow-up of 3.0 years, there were 407 total HF hospitalizations and cardiovascular deaths. After multivariable adjustment, worse GLS was associated with a greater risk for the primary composite outcome (adjusted hazard ratio per 1% decrease: 1.06; 95% confidence interval 1.02–1.11; p = 0.008). GLS did not modify the treatment effect of sacubitril/valsartan compared with valsartan for the composite outcome (p for interaction &gt;0.1). Conclusions In a large HFpEF population, impaired LV function was observed even among patients with preserved ejection fraction, and was associated with an increased risk of total HF hospitalizations or cardiovascular death, accounting for clinical confounders. These findings highlight the key role of subtle LV systolic impairment in the pathophysiology of HFpEF.

Introduction: Impaired tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC) and right ventricular free wall longitudinal strain (RVFWLS) have been individually associated with a worse prognosis in patients with heart failure with preserved ejection fraction (HFpEF). However, these parameters measure different aspects of RV function and understanding their cumulative effect may provide insights into the overall impact of RV dysfunction (RVD) in HFpEF patients. Goal: Assess the association between the number of echocardiographic RVD parameters and clinical outcomes. Methods: Patients from the echocardiographic sub-study of the PARAGON-HF trial with adequate image quality (N=809, 53% women, mean age 74±8 years) were categorized based on the number of measures of RVD, which included TAPSE <1.7 cm, FAC <35% or RVFWLS <20% (absolute value). Associations with total HF hospitalizations (HFH) and CV death, total HFH alone, first HFH or CV death, all-cause death and CV death were assessed by Groups, after accounting for confounders. Results: A total of 348 patients (43%) in Group 0 (no abnormal parameter), 355 (44%) in Group 1 (one abnormal parameter) and 106 (13%) in Group 2 (two or more abnormal parameters) were identified. After multivariable adjustment ( Table ), Group 2 was significantly associated with an increased risk of total HFH and CV death (RR 2.13, 95%CI 1.13-4.01), first HFH or CV death (RR 2.07, 95%CI 1.15-3.73), all-cause death (RR 2.61, 95%CI 1.19-5.74) and CV death (RR 3.08, 95%CI 1.14-8.31). The treatment effect of sacubitril/valsartan for total HFH and CV death was not modified by RVD Group (p-value for interaction=0.94). Conclusions: The presence of two or more RVD parameters was associated with a significantly worse prognosis, while an isolated RVD measure was not. These findings suggest that a more comprehensive approach to assessment of RV function may have better prognostic value in HFpEF.

Introduction: Right ventricular dysfunction (RVD) is a major prognostic factor in patients with heart failure with preserved ejection fraction (HFpEF), however determinants of RVD in HFpEF are not well described. Although sex-specific mechanisms have been incriminated in the development of HFpEF, it is unclear whether this is also true for RVD. Goals: (1) Assess the prevalence of RVD (defined as a tricuspid annular plane systolic excursion [TAPSE] <1.7 cm, a fractional area change [FAC] <35% or a RV free wall longitudinal strain [RVFWLS] <20%, absolute value) in patients with HFpEF; (2) identify determinants of RVD, overall and according to sex, in patients with HFpEF. Methods: We used data from patients enrolled in the echocardiographic sub-study of the PARAGON-HF trial with adequate image quality (N=809, 53% women, mean age 74±8 years). Determinants of RVD, in the whole study population and according to sex, were identified using a multivariable logistic regression model. Results: There were 461 patients (57%) with RVD. After multivariable adjustment, RVD was cross-sectionally associated with a history of atrial fibrillation of flutter (AFF), older age, higher heart rate, greater LV mean wall thickness and higher NT-proBNP values. Systolic blood pressure and LV global longitudinal strain (absolute value) showed an inverse association ( Figure ). These results were consistent between men and women, except for AFF and LV mean wall thickness, which were associated with a greater likelihood of RVD in men (OR 2.46, 95%CI 1.33-4.56, OR 1.61, 95%CI 1.18-2.21 respectively) but not in women (OR 0.99, 95%CI 0.58-1.68, OR 0.90 95%CI 0.69-1.17 respectively, p-values for interaction=0.028 and 0.006). Conclusions: RVD was highly prevalent in our study population. Determinants of RVD included AFF, LV remodeling and systolic impairment, and increased NT-proBNP levels. Differences between men and women suggest gender-specific mechanisms in the development of RVD in HFpEF.

Background: Lower (worse) left atrial (LA) function is associated with higher dementia risk. It is unclear whether lower LA function is associated with vascular brain injury on brain MRI, an established correlate for higher dementia risk. Using data from the Atherosclerosis Risk in Communities (ARIC) study, we assessed the cross-sectional association between LA function measures and brain MRI markers of vascular brain injury (cerebral microbleeds, brain infarcts). Hypothesis: Participants with lower LA function will be more likely to have presence of > 1 cerebral microbleed or brain infarct. Methods: ARIC participants who had both an echocardiogram and brain MRI at visit 5 (2011-13) were included. We excluded those with prevalent dementia, stroke, or atrial fibrillation. LA function measures were obtained from 2D-echocardiograms and assessed in quartiles (highest quartile was the reference). Brain MRI measures were assessed as the presence or absence of > 1 cerebral microbleed or brain infarct. Logistic regression was used. Results: Of the 1502 participants (mean [SD] age 76 [5], 60% female, 27% Black) in this analysis, 345 (23%) and 351 (23%) had > 1 cerebral microbleed or brain infarct present. Compared to the highest quartile, lower LA reservoir and conduit strain quartiles were associated with higher odds of cerebral microbleeds. LA contractile strain was not associated with cerebral microbleeds. Compared to the highest quartile, the lowest LA conduit strain quartile, but not reservoir strain, was associated with higher odds of brain infarcts. LA contractile strain was inversely associated with brain infarcts. Conclusion: In this community-based cohort, lower LA function was cross-sectionally associated with cerebral microbleeds and brain infarcts. The inverse relationship with LA contractile strain may be due to contractile function compensating for a decrease in early diastolic filling. Prospective studies are needed to confirm these findings.