Changes in cardiac structure and function with aging

Aging is associated with progressive changes in cardiac structure and function. The prevalence of cardiovascular risk factors and disease also increases profoundly with advancing age. Therefore, understanding the spectrum of physiological changes in the aging heart is crucial for the identification and risk stratification of cardiovascular disease. In this review, we discuss echocardiographic features of age-related cardiac remodeling.

Cardioprotective potential of lithium and role of fractalkine in euthymic patients with bipolar disorder

Objective: Over a half century, lithium has been used as the first-line medication to treat bipolar disorder. Emerging clinical and laboratory studies suggest that lithium may exhibit cardioprotective effects in addition to neuroprotective actions. Fractalkine (CX3CL1) is a unique chemokine associated with the pathogenesis of mood disorders and cardiovascular diseases. Herein we aimed to ascertain whether lithium treatment is associated with favorable cardiac structure and function in relation to the reduced CX3CL1 among patients with bipolar disorder. Methods: We recruited 100 euthymic patients with bipolar I disorder aged over 20 years to undergo echocardiographic study and measurement of plasma CX3CL1. Associations between lithium treatment, cardiac structure and function and peripheral CX3CL1 were analyzed according to the cardiovascular risk. The high cardiovascular risk was defined as (1) age ⩾ 45 years in men or ⩾ 55 years in women or (2) presence of concurrent cardiometabolic diseases. Results: In the high cardiovascular risk group ( n = 61), patients who received lithium as the maintenance treatment had significantly lower mean values of left ventricular internal diameters at end-diastole (Cohen’s d = 0.65, p = 0.001) and end-systole (Cohen’s d = 0.60, p = 0.004), higher mean values of mitral valve E/A ratio (Cohen’s d = 0.51, p = 0.019) and superior performance of global longitudinal strain (Cohen’s d = 0.51, p = 0.037) than those without lithium treatment. In addition, mean plasma levels of CX3CL1 in the high cardiovascular risk group were significantly lower among patients with lithium therapy compared with those without lithium treatment ( p = 0.029). Multiple regression models showed that the association between lithium treatment and mitral value E/A ratio was contributed by CX3CL1. Conclusion: Data from this largest sample size study of the association between lithium treatment and echocardiographic measures suggest that lithium may protect cardiac structure and function in patients with bipolar disorder. Reduction of CX3CL1 may mediate the cardioprotective effects of lithium.

CinE caRdiac magneTic resonAnce to predIct veNTricular arrhYthmia (CERTAINTY)

Better models to identify individuals at low risk of ventricular arrhythmia (VA) are needed for implantable cardioverter-defibrillator (ICD) candidates to mitigate the risk of ICD-related complications. We designed the CERTAINTY study (CinE caRdiac magneTic resonAnce to predIct veNTricular arrhYthmia) with deep learning for VA risk prediction from cine cardiac magnetic resonance (CMR). Using a training cohort of primary prevention ICD recipients (n = 350, 97 women, median age 59 years, 178 ischemic cardiomyopathy) who underwent CMR immediately prior to ICD implantation, we developed two neural networks: Cine Fingerprint Extractor and Risk Predictor. The former extracts cardiac structure and function features from cine CMR in a form of cine fingerprint in a fully unsupervised fashion, and the latter takes in the cine fingerprint and outputs disease outcomes as a cine risk score. Patients with VA (n = 96) had a significantly higher cine risk score than those without VA. Multivariate analysis showed that the cine risk score was significantly associated with VA after adjusting for clinical characteristics, cardiac structure and function including CMR-derived scar extent. These findings indicate that non-contrast, cine CMR inherently contains features to improve VA risk prediction in primary prevention ICD candidates. We solicit participation from multiple centers for external validation.

Depressive Symptoms, Cardiac Structure and Function, and Risk of Incident Heart Failure With Preserved Ejection Fraction and Heart Failure With Reduced Ejection Fraction in Late Life

Background Depressive symptoms are associated with heightened risk of heart failure (HF), but their association with cardiac function and with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) in late life is unclear. We aimed to determine the prevalence of depression in HFpEF and in HFrEF in late life, and the association of depressive symptoms with cardiac function and incident HFpEF and HFrEF. Methods and Results We studied 6025 participants (age, 75.3±5.1 years; 59% women; 20% Black race) in the ARIC (Atherosclerosis Risk in Communities) study at visit 5 who underwent echocardiography and completed the Center for Epidemiologic Studies Depression Scale questionnaire. Among HF‐free participants (n=5086), associations of Center for Epidemiologic Studies Depression Scale score with echocardiography and incident adjudicated HFpEF and HFrEF were assessed using multivariable linear and Cox proportional hazards regression. Prevalent HFpEF, but not HFrEF, was associated with a higher prevalence of depression compared with HF‐free participants ( P <0.001 and P =0.59, respectively). Among HF‐free participants, Center for Epidemiologic Studies Depression Scale score was not associated with cardiac structure and function after adjusting for demographics and comorbidities (all P >0.05). Over 5.5‐year follow‐up, higher Center for Epidemiologic Studies Depression Scale score was associated with heightened risk of incident HFpEF (hazard ratio [HR] [95% CI], 1.06 [1.04–1.12]; P =0.02), but not HFrEF (HR [95% CI], 1.02 [0.96–1.08]; P =0.54), independent of echocardiographic measures, NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), troponin, and hs‐CRP (high‐sensitivity C‐reactive protein) (HR [95% CI], 1.06 [1.00–1.12]; P =0.04). Conclusions Worse depressive symptoms predict incident HFpEF in late life, independent of common comorbidities, cardiac structure and function, and prognostic biomarkers. Further studies are necessary to understand the mechanisms linking depression to risk of HFpEF.

Circulating Biomarkers and Cardiac Structure and Function in Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) increases the risk for abnormalities of the cardiac structure and function, which may lead to heart failure (HF). Studying the association between circulating biomarkers and echocardiographic parameters is important to screen patients with RA with a higher risk of cardiac dysfunction.Aim: To study the association between circulating biomarkers and echocardiographic parameters in patients with RA.Methods: Echocardiography was performed in 355 patients with RA from RA Porto cohort and the associations between echocardiographic characteristics and 94 circulating biomarkers were assessed. These associations were also assessed in the Metabolic Road to Diastolic Heart Failure (MEDIA-DHF) [392 patients with HF with preserved ejection fraction (HFpEF)] and the Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux (STANISLAS) (1,672 healthy population) cohorts.Results: In the RA Porto cohort, mean age was 58 ± 13 years, 23% were males and mean RA duration was 12 ± 10 years. After adjustment and multiple testing correction, left ventricular mass index (LVMi), left atrial volume index (LAVi), and E/e′ were independently associated with biomarkers reflecting inflammation [i.e., bone morphogenetic protein 9 (BMP9), pentraxin-related protein 3 (PTX3), tumor necrosis factor receptor superfamily member 11a (TNFRSF11A)], extracellular matrix remodeling [i.e., placental growth factor (PGF)], congestion [i.e., N-terminal pro-brain natriuretic peptide (NT-proBNP), adrenomedullin (ADM)], and myocardial injury (e.g., troponin). Greater LVMi [hazard ratio (HR) (95% CI) per 1 g/m2 = 1.03 (1.02–1.04), p &lt; 0.001], LAVi [HR (95% CI) per 1 ml/m2 = 1.03 (1.01–1.06), p &lt; 0.001], and E/e′ [HR (95% CI) per 1 = 1.08 (1.04–1.13), p &lt; 0.001] were associated with higher rates of cardiovascular events. These associations were externally replicated in patients with HFpEF and asymptomatic individuals.Conclusion: Circulating biomarkers reflecting inflammation, extracellular matrix remodeling, congestion, and myocardial injury were associated with underlying alterations of cardiac structure and function. Biomarkers might be used for the screening of cardiac alterations in patients with RA.

Abnormalities in Cardiac Structure and Function among Individuals with CKD: The COMBINE Trial

Background: Individuals with chronic kidney disease (CKD) have a high burden of cardiovascular disease (CVD). Abnormalities in cardiac structure and function represent subclinical CVD and can be assessed by cardiac magnetic resonance imaging (cMRI). Methods: We investigated differences in cMRI parameters in 140 individuals with CKD stages 3b-4 who participated in the CKD Optimal Management with BInders and NicotinamidE (COMBINE) trial and in 24 age-and sex matched healthy volunteers. Among COMBINE participants, we examined the associations of estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), phosphate, fibroblast growth factor 23 (FGF23), and parathyroid hormone (PTH) with baseline (N=140) and 12-month change (N=112) in cMRI parameters. Results: Mean (standard deviation [SD]) age of the COMBINE participants and healthy volunteers were 64.9 (11.9) and 60.4 (7.3) years. The mean (SD) baseline eGFR in COMBINE participants was 32.1 (8.0) and 85.9 (16.0) ml/ min/1.73m2 in healthy volunteers. The median (interquartile range [IQR]) UACR in COMBINE participants was 154 (20.3 - 540.0) mg/g. Individuals with CKD had lower mitral valve E/A ratio compared to healthy volunteers (β estimate -0.13 CKD vs. non-CKD, 95% confidence interval [CI] -0.24, -0.012). Among COMBINE participants, multivariable linear regression analyses showed that higher UACR was significantly associated with lower mitral valve E/A ratio (β-estimate per 1 unit increase in natural log UACR -0.06, 95% CI -0.09, -0.03). This finding was preserved among individuals without baseline CVD. UACR was not associated with 12-month change in any cMRI parameter. eGFR, phosphate, FGF23, and PTH were not associated with any cMRI parameter in cross-sectional or change analyses. Conclusions: Individuals with CKD stages 3b-4 have evidence of cMRI abnormalities. Albuminuria was independently associated with diastolic dysfunction assessed by mitral valve E/A ratio in individuals with CKD with and without clinical CVD, but was not associated with change in any cMRI parameter.

A Prospective Comparative Study on Cardiac Alterations After Surgery and Drug Treatment of Primary Aldosteronism

BackgroundCurrent guideline recommends both surgery and drug treatment for primary aldosteronism. Treatment effects on the cardiac structure and function remain under investigation.ObjectiveWe performed a prospective study in patients with primary aldosteronism to compare effects of surgery and drug treatment on the cardiac structure and function as assessed by the left ventricular (LV) pressure-strain loop, a novel echocardiographic technique that incorporates myocardial deformation and LV pressure.MethodsOur study included 39 and 28 patients treated with surgery and a mineralocorticoid antagonist, respectively. We performed conventional and speckle tracking echocardiography at baseline and 3 and 6 months of follow-up.ResultsDuring follow-up, both surgery and drug treatment normalized serum potassium concentration and significantly reduced blood pressure. Both treatments significantly and similarly decreased LV mass index and left atrial volume index. However, only in the surgery group did global wasted work significantly decrease (200.8 ± 86.7 at baseline vs. 142.1 ± 58.1 mmHg% at 6 months) and global work efficiency (91.5 ± 3.1 vs. 93.6 ± 2.3%) and global longitudinal strain (−18.3 ± 2.7 vs. −19.2 ± 1.9%) significantly (p &lt; 0.01) increase at 6 months of follow-up. The corresponding differences from the changes in the drug treatment group were 39.5 mmHg% (95% CI, 17.1, 62.0 mmHg%), −1.64% (95% CI, −2.56, −0.71%), and −0.85% (95% CI, −1.51, −0.20%), respectively. In addition, the changes in global wasted work at 6 months of follow-up was significantly correlated with that in 24-h urinary aldosterone excretion in the drug treatment group (r = 0.54) and two groups combined (r = 0.55), but not the surgery group.ConclusionIn spite of similar serum potassium normalization and blood pressure control, surgical removal of an adrenal gland, but not mineralocorticoid receptor antagonism, showed early improvement in cardiac function.