Stages of Valvular Heart Disease Among Older Adults in the Community: The Atherosclerosis Risk in Communities Study.

BACKGROUND: Limited data exist on American College of Cardiology/American Heart Association valvular heart disease (VHD) stage prevalence, progression, and association with incident cardiovascular diseases in late life. METHODS: Participants in the ARIC study (Atherosclerosis Risk in Communities), a prospective community-based cohort study, underwent protocol echocardiography at ARIC visits 5 (2011-2013) and 7 (2018-2019), and their aortic stenosis, aortic regurgitation, mitral stenosis, and mitral regurgitation stage were defined according to American College of Cardiology/American Heart Association guidelines. The overall VHD stage prevalence at visit 5 was measured. The associations between VHD stages and incident adjudicated death, heart failure, coronary heart disease, stroke, and atrial fibrillation were assessed with Cox proportional hazard models adjusted for age, sex, race, hypertension, diabetes, prior myocardial infarction, heart failure, body mass index, study center, systolic blood pressure, estimated glomerular filtration rate, and low-density lipoprotein at visit 5. Longitudinal changes in VHD stage prevalence over ≈6 years were estimated with inverse probability of attrition weights to account for participant attrition. RESULTS: Among 6118 ARIC participants, the mean±SD age was 76±5 years, 42% were male, and 22% reported Black race. Stage A VHD was present in 39%, stage B in 17%, and stage C/D in 1.1%;, 0.7% had previously undergone valve replacement or repair. A graded association was observed between stage A, B, and C/D VHD and risk of all-cause mortality, incident heart failure, incident atrial fibrillation, and incident coronary heart disease, but not incident stroke. Similar findings were observed for stages of each valvular lesion individually. During the 6.6 years (interquartile range, 6.1-7.0 years) between visits 5 and 7 (mean age, 81±4 years), the prevalence of freedom from VHD stage decreased from 43% to 24%, whereas the prevalence of stage C/D VHD increased from 1% to 7%. CONCLUSIONS: Subclinical VHD is common in older adults, with 39% at risk (stage A) and 17% with progressive VHD (stage B), and is independently associated with risk of incident cardiovascular events. VHD stages progress over 6 years in late life, with a several-fold increase in prevalence of severe VHD (stage C/D), highlighting the public health importance of interventions to mitigate VHD progression.

Association of serum calcium and phosphorus with measures of left ventricular structure and function: The ARIC study.

BACKGROUND AND AIMS: Elevated serum calcium and phosphorus have been associated with increased risk of cardiovascular disorders. We evaluated whether abnormal calcium and high serum phosphorus are associated cross-sectionally with echocardiographic measures of left ventricular (LV) structure and function, as doing so may provide insight into the etiology of cardiac disorders. METHODS AND RESULTS: Included in the analysis were 5213 Atherosclerosis Risk in Communities Study (ARIC) participants who in 2011-2013 had echocardiography and serum calcium and phosphorus measurements. We evaluated the association of serum calcium (corrected for albumin) and phosphorus quintiles with measures of LV structure and function, after adjusting for other cardiovascular risk factors. Participants were on average 75.3 years old; 59.1% were female and 19.8% were African American. Mean (±SD) concentrations of calcium and phosphorus were 9.33 ± 0.38 and 3.46 ± 0.45 mg/dL, respectively. Higher calcium was associated with lower LV end-diastolic diameter (LVEDD) but greater prevalence of concentric remodeling (p-trend: 0.005 and 0.004 respectively). We observed association between high phosphorus and high septal E/e' (p-trend: 0.02). Likewise, higher serum phosphorus was associated with higher left atrial volume index (p-trend: 0.001) and LV hypertrophy prevalence (p-trend: 0.04). CONCLUSIONS: In conclusion, higher calcium was associated with more concentric remodeling but lower LVEDD, suggesting complex associations between calcium and cardiac function. Serum phosphorus was related to worse indices of LV diastolic function and LV hypertrophy, but not to LV systolic function. However, the magnitudes of association were modest, so clinical implications of these findings may be limited.

Trends in Hospitalizations and Survival of Acute Decompensated Heart Failure in Four US Communities (2005-2014): ARIC Study Community Surveillance.

BACKGROUND: Community trends of acute decompensated heart failure (ADHF) in diverse populations may differ by race and sex. METHODS: The ARIC study (Atherosclerosis Risk in Communities) sampled heart failure-related hospitalizations (≥55 years of age) in 4 US communities from 2005 to 2014 using International Classification of Diseases, Ninth Revision, Clinical Modification codes. ADHF hospitalizations were validated by standardized physician review and computer algorithm, yielding 40 173 events after accounting for sampling design (unweighted n=8746). RESULTS: Of the ADHF hospitalizations, 50% had reduced ejection fraction, and 39% had preserved EF (HFpEF). HF with reduced ejection fraction was more common in black men and white men, whereas HFpEF was most common in white women. Average age-adjusted rates of ADHF were highest in blacks (38.1 per 1000 black men, 30.5 per 1000 black women), with rates differing by HF type and sex. ADHF rates increased over the 10 years (average annual percentage change: black women +4.3%, black men +3.7%, white women +1.9%, white men +2.6%), mostly reflecting more acute HFpEF. Age-adjusted 28-day and 1-year case fatality proportions were ≈10% and 30%, respectively, similar across race-sex groups and HF types. Only blacks showed decreased 1-year mortality over time (average annual percentage change: black women -5.4%, black men -4.6%), with rates differing by HF type (average annual percentage change: black women HFpEF -7.1%, black men HF with reduced ejection fraction -4.7%). CONCLUSIONS: Between 2005 and 2014, trends in ADHF hospitalizations increased in 4 US communities, primarily driven by acute HFpEF. Survival at 1 year was poor regardless of EF but improved over time for black women and black men.

Contemporary Assessment of Left Ventricular Diastolic Function in Older Adults: The Atherosclerosis Risk in Communities Study.

BACKGROUND: Although age-associated changes in left ventricular diastolic function are well recognized, limited data exist characterizing measures of diastolic function in older adults, including both reference ranges reflecting the older adult population and prognostically relevant values for incident heart failure (HF), as well as their associations with circulating biomarkers of HF risk. METHODS: Among 5801 elderly participants in the ARIC study (Atherosclerosis Risk in Communities; age range, 67-90 years; mean age, 76±5 years; 42% male; 21% black), we determined the continuous association of diastolic measures (tissue Doppler imaging [TDI] e', E/e', and left atrial size) with concomitant N-terminal pro-brain natriuretic peptide and subsequent HF hospitalization or death. We also determined sex-specific 10th and 90th percentile limits for these measures using quantile regression in 401 participants free of prevalent cardiovascular disease and risk factors. RESULTS: Each measure of diastolic function was robustly associated with N-terminal pro-brain natriuretic peptide and incident HF or death. ARIC-based reference limits for TDI e' (4.6 and 5.2 cm/s for septal and lateral TDI e', respectively) were substantially lower than guideline cut points (7 and 10 cm/s, respectively), whereas E/e' and left atrial size demonstrated good agreement with guideline cut points. TDI e' was nonlinearly associated with incident HF or death, with inflection points for risk supportive of ARIC-based limits. ARIC-based limits for diastolic function improved risk discrimination over guideline-based cut points based on the integrated discrimination improvement (P<0.001) and continuous net reclassification improvement (P<0.001), reclassifying 42% of the study population as having normal diastolic function. We replicate these findings in the Copenhagen City Heart Study. With these limits, 46% had normal diastolic function and were at low risk of HF hospitalization or death (1%/y over a mean 1.7-year follow-up), 49% had 1 or 2 abnormal measures and were at intermediate risk (2.4%/y), and all 3 diastolic measures were abnormal in 5% who were at high risk (7.5%/y). CONCLUSIONS: Our findings suggest that left ventricular longitudinal relaxation velocity declines as a part of healthy aging and is largely prognostically benign. The use of age-based normative values when considering an elderly population improves the risk discrimination of diastolic measures for incident HF or death.

Heart Failure Stages Among Older Adults in the Community: The Atherosclerosis Risk in Communities Study.

BACKGROUND: Although heart failure (HF) disproportionately affects older adults, little data exist regarding the prevalence of American College of Cardiology/American Heart Association HF stages among older individuals in the community. Additionally, the role of contemporary measures of longitudinal strain and diastolic dysfunction in defining HF stages is unclear. METHODS: HF stages were classified in 6118 participants in the Atherosclerosis Risk in Communities study (67-91 years of age) at the fifth study visit as follows: A (asymptomatic with HF risk factors but no cardiac structural or functional abnormalities), B (asymptomatic with structural abnormalities, defined as left ventricular hypertrophy, dilation or dysfunction, or significant valvular disease), C1 (clinical HF without prior hospitalization), and C2 (clinical HF with earlier hospitalization). RESULTS: Using the traditional definitions of HF stages, only 5% of examined participants were free of HF risk factors or structural heart disease (Stage 0), 52% were categorized as Stage A, 30% Stage B, 7% Stage C1, and 6% Stage C2. Worse HF stage was associated with a greater risk of incident HF hospitalization or death at a median follow-up of 608 days. Left ventricular (LV) ejection fraction was preserved in 77% and 65% in Stages C1 and C2, respectively. Incorporation of longitudinal strain and diastolic dysfunction into the Stage B definition reclassified 14% of the sample from Stage A to B and improved the net reclassification index (P=0.028) and integrated discrimination index (P=0.016). Abnormal LV structure, systolic function (based on LV ejection fraction and longitudinal strain), and diastolic function (based on e', E/e', and left atrial volume index) were each independently and additively associated with risk of incident HF hospitalization or death in Stage A and B participants. CONCLUSIONS: The majority of older adults in the community are at risk for HF (Stages A or B), appreciably more compared with previous reports in younger community-based samples. LV ejection fraction is robustly preserved in at least two-thirds of older adults with prevalent HF (Stage C), highlighting the burden of HF with preserved LV ejection fraction in the elderly. LV diastolic function and longitudinal strain provide incremental prognostic value beyond conventional measures of LV structure and LV ejection fraction in identifying persons at risk for HF hospitalization or death.

Shared Risk Factors in Cardiovascular Disease and Cancer.

Cardiovascular disease (CVD) and cancer are the 2 leading causes of death worldwide. Although commonly thought of as 2 separate disease entities, CVD and cancer possess various similarities and possible interactions, including a number of similar risk factors (eg, obesity, diabetes mellitus), suggesting a shared biology for which there is emerging evidence. Although chronic inflammation is an indispensable feature of the pathogenesis and progression of both CVD and cancer, additional mechanisms can be found at their intersection. Therapeutic advances, despite improving longevity, have increased the overlap between these diseases, with millions of cancer survivors now at risk of developing CVD. Cardiac risk factors have a major impact on subsequent treatment-related cardiotoxicity. In this review, we explore the risk factors common to both CVD and cancer, highlighting the major epidemiological studies and potential biological mechanisms that account for them.

Development and Validation of a Sudden Cardiac Death Prediction Model for the General Population.

BACKGROUND: Most sudden cardiac death (SCD) events occur in the general population among persons who do not have any prior history of clinical heart disease. We sought to develop a predictive model of SCD among US adults. METHODS: We evaluated a series of demographic, clinical, laboratory, electrocardiographic, and echocardiographic measures in participants in the ARIC study (Atherosclerosis Risk in Communities) (n=13 677) and the CHS (Cardiovascular Health Study) (n=4207) who were free of baseline cardiovascular disease. Our initial objective was to derive a SCD prediction model using the ARIC cohort and validate it in CHS. Independent risk factors for SCD were first identified in the ARIC cohort to derive a 10-year risk model of SCD. We compared the prediction of SCD with non-SCD and all-cause mortality in both the derivation and validation cohorts. Furthermore, we evaluated whether the SCD prediction equation was better at predicting SCD than the 2013 American College of Cardiology/American Heart Association Cardiovascular Disease Pooled Cohort risk equation. RESULTS: There were a total of 345 adjudicated SCD events in our analyses, and the 12 independent risk factors in the ARIC study included age, male sex, black race, current smoking, systolic blood pressure, use of antihypertensive medication, diabetes mellitus, serum potassium, serum albumin, high-density lipoprotein, estimated glomerular filtration rate, and QTc interval. During a 10-year follow-up period, a model combining these risk factors showed good to excellent discrimination for SCD risk (c-statistic 0.820 in ARIC and 0.745 in CHS). The SCD prediction model was slightly better in predicting SCD than the 2013 American College of Cardiology/American Heart Association Pooled Cohort risk equations (c-statistic 0.808 in ARIC and 0.743 in CHS). Only the SCD prediction model, however, demonstrated similar and accurate prediction for SCD using both the original, uncalibrated score and the recalibrated equation. Finally, in the echocardiographic subcohort, a left ventricular ejection fraction <50% was present in only 1.1% of participants and did not enhance SCD prediction. CONCLUSIONS: Our study is the first to derive and validate a generalizable risk score that provides well-calibrated, absolute risk estimates across different risk strata in an adult population of white and black participants without a clinical diagnosis of cardiovascular disease.

Cardio-oncology Related to Heart Failure: Common Risk Factors Between Cancer and Cardiovascular Disease.

There is a growing body of evidence that suggests cancer and cardiovascular disease have a shared biological mechanism. Although there are several shared risk factors for both diseases, including advancing age, gender, obesity, diabetes, physical activity, tobacco use, and diet, inflammation and biomarkers, such as insulinlike growth factor 1, leptin, estrogen, and adiponectin, may also play a role in the biology of these diseases. This article provides an overview of the shared biological mechanism between cancer and cardiovascular disease.

Alcohol Consumption and Cardiac Biomarkers: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: The role of alcohol in the development of subclinical cardiovascular disease is unclear. We examined the association between alcohol consumption and markers of subclinical cardiac damage and wall stress. METHODS: We studied the cross-sectional and prospective associations of alcohol consumption with high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) measured at 2 time points, 6 years apart (baseline, 1990-1992; follow-up, 1996-1998), in over 11000 participants of the Atherosclerosis Risk in Communities (ARIC) Study with no history of cardiovascular disease. Alcohol consumption was categorized as follows: never, former, current: ≤1, 2-7, 8-14, and ≥15 drinks/week. RESULTS: Compared to never drinkers, persons who consumed 2-7 drinks per week were less likely to have increased hs-cTnT (≥14 ng/L) at baseline (odds ratio = 0.67, 95% CI, 0.46-0.96), and had a lower risk of incident increases in hs-cTnT at follow-up (relative risk = 0.70, 95% CI, 0.49-1.00). Conversely, there was a positive association between alcohol intake and NT-proBNP concentrations at baseline. Consumption of ≥15 drinks/week was positively associated with incident increases in NT-proBNP (≥300 pg/mL) at the 6-year follow-up visit (relative risk = 2.38, 95% CI, 1.43-3.96). CONCLUSIONS: In this community-based study of middle-aged adults without a history of cardiovascular disease, moderate drinking was associated with lower concentrations of hs-cTnT, a marker of chronic subclinical myocardial damage, and positively associated with NT-proBNP, a biomarker of cardiac wall stress. Our results suggest that the cardiac effects of alcohol are complex. Cardiac biomarkers may help improve our understanding of the full cardiovascular effects of alcohol consumption.

Hematopoietic stem cell transplantation in patients with systolic dysfunction: can it be done?

Hematopoietic cell transplantation (HCT) is a potential cure for certain hematologic malignancies. However, because of risks of complications and mortality, this treatment option is limited to patients with minimal comorbidities. We performed a retrospective cohort study evaluating the impact of pre-HCT systolic dysfunction on outcomes. We identified 49 subjects with systolic dysfunction, defined as left ventricular ejection fraction (LVEF) < 50% and 49 controls (matched by age, gender, conditioning regimen, and HCT donor number; all with LVEF ≥ 50%) undergoing HCT at the University of Minnesota between 2002 and 2012. Treatment complications, use of beta-blockers and angiotensin-converting enzyme inhibitors, and overall survival (OS) after HCT out to 24 months were analyzed. The median LVEF was 45% (range, 27.5% to 49%) for the study group and 60% (range, 50% to 69%) for controls. The majority of patients in both groups (81.6%) received reduced-intensity conditioning (RIC). Treatment-related mortality (TRM) at day 100 was identical, with a cumulative incidence of 14% in the study (95% confidence interval [CI], 5% to 24%) versus 14% in controls (95% CI, 5% to 24%) (P = .89). Two-year OS was similar in the study group (53%; 95% CI, 38% to 66%) versus controls (61%; 95% CI, 46% to 73%) (P = .34). LVEF ≥ 43% was associated with improved OS at 1 year (hazard ratio [HR], .36; 95% CI, .15 to .87; P = .02). There was no significant difference in the incidence of non-life-threatening cardiac complications (12.2% in cases versus 8.2% in controls, P = .50) or serious (life-threatening or fatal) cardiac complications (4.1% in cases versus 2.0% in controls, P = .56). Pre-existing coronary artery disease was associated with increased TRM at 100 days (HR, 4.35; 95% CI, 1.24 to 15.32; P = .02). Cardiac medication use had no effect on TRM. Our study demonstrates that patients with asymptomatic borderline systolic dysfunction can safely undergo HCT with RIC. Coronary artery disease remains a risk factor for increased TRM. Patients with borderline systolic dysfunction can safely undergo HCT, but may need particular vigilance for potential hemodynamic or ischemic cardiac complications.

Radiation recall reaction causing cardiotoxicity.

Radiation recall phenomenon is a tissue reaction that develops within a previously irradiated area, precipitated by the subsequent administration of certain chemotherapeutic agents. It commonly affects the skin, but can also involve internal organs with functional consequences. To our best knowledge, this phenomenon has never been reported as a complication on the heart and should be consider as a potential cause of cardiotoxicity.

A comparison of risk factors for mortality from heart failure in Asian and non-Asian populations: an overview of individual participant data from 32 prospective cohorts from the Asia-Pacific Region.

BACKGROUND: Most of what is known regarding the epidemiology of mortality from heart failure (HF) comes from studies within Western populations with few data available from the Asia-Pacific region where the burden of heart failure is increasing. METHODS: Individual level data from 543694 (85% Asian; 36% female) participants from 32 cohorts in the Asia Pacific Cohort Studies Collaboration were included in the analysis. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) for mortality from HF were estimated separately for Asians and non-Asians for a quintet of cardiovascular risk factors: systolic blood pressure, diabetes, body mass index, cigarette smoking and total cholesterol. All analyses were stratified by sex and study. RESULTS: During 3,793,229 person years of follow-up there were 614 HF deaths (80% Asian). The positive associations between elevated blood pressure, obesity, and cigarette smoking were consistent for Asians and non-Asians. There was evidence to indicate that diabetes was a weaker risk factor for death from HF for Asians compared with non-Asians: HR 1.26 (95% CI: 0.74-2.13) versus 3.04 (95% CI 1.76-5.25) respectively; p for interaction = 0.022. Additional adjustment for covariates did not materially change the overall associations. There was no good evidence to indicate that total cholesterol was a risk factor for HF mortality in either population. CONCLUSIONS: Most traditional cardiovascular risk factors including elevated blood pressure, obesity and cigarette smoking appear to operate similarly to increase the risk of death from HF in Asians and non-Asians populations alike.

High Throughput Plasma Proteomics and Risk of Heart Failure and Frailty in Late Life.

Importance: Heart failure (HF) and frailty frequently coexist and may share a common pathobiology, although the underlying mechanisms remain unclear. Understanding these mechanisms may provide guidance for preventing and treating both conditions. Objective: To identify shared pathways between incident HF and frailty in late life using large-scale proteomics. Design, Setting, and Participants: In this cohort study, 4877 aptamers (Somascan v4) were measured among participants in the community-based longitudinal Atherosclerosis Risk In Communities (ARIC) cohort study at visit 3 (V3; 1993-1995; n = 10 638) and at visit 5 (V5; 2011-2013; n = 3908). Analyses were externally replicated among 3189 participants in the Cardiovascular Health Study (CHS). Data analysis was conducted from February 2022 to June 2023. Exposures: Protein aptamers, measured at study V3 and V5. Main Outcomes and Measures: Outcomes assessed included incident HF hospitalization after V3 and after V5, prevalent frailty at V5, and incident frailty between V5 and visit 6 (V6; 2016-2017; n = 4131). Frailty was assessed using the Fried criteria. Analyses were adjusted for age, gender, race, field center, hypertension, diabetes, smoking status, body mass index, estimated glomerular filtration rate, prevalent coronary heart disease, prevalent atrial fibrillation, and history of myocardial infarction. Mendelian randomization (MR) analysis was performed to assess potential causal effects of candidate proteins on HF and frailty. Results: A total of 4877 protein aptamers were measured among 10 638 participants at V3 (mean [SD] age, 60 [6] years; 4886 [46%] men). Overall, 286 proteins were associated with incident HF after V3 (822 events; P < 1.0 × 10-5), 83 of which were also associated with incident after V5 (336 events; P < 1.7 × 10-4). Among HF-free participants at V5 (n = 3908; mean [SD] age, 75 [5] years; 1861 [42%] men), 48 of 83 HF-associated proteins were associated with prevalent frailty (223 cases; P < 6.0 × 10-4), 18 of which were also associated with incident frailty at V6 (152 cases; P < 1.0 × 10-3). These proteins enriched fibrosis and inflammation pathways and demonstrated stronger associations with incident HF with preserved ejection fraction (HFpEF) than HF with reduced ejection fraction. All 18 proteins were associated with both prevalent frailty and incident HF in CHS. MR identified potential causal effects of several proteins on frailty and HF. Conclusions and Relevance: In this study, the proteins associated with risk of HF and frailty enrich for pathways related to inflammation and fibrosis as well as risk of HFpEF. Several of these proteins could potentially contribute to the shared pathophysiology of frailty and HF.

Agreement of Proximal Thoracic Aorta Size by Two-Dimensional Transthoracic Echocardiography and Magnetic Resonance Angiography.

There is currently a lack of uniformity in methods of aortic diameter measurements across different imaging modalities. In this study, we sought to evaluate the accuracy of transthoracic echocardiography (TTE) in comparison with magnetic resonance angiography (MRA) for the measurement of proximal thoracic aorta diameters. This is a retrospective analysis of 121 adult patients at our institution who had TTE and electrocardiogram  (ECG)-gated MRA performed within 90 days of each other between 2013 and 2020. Measurements were made at the level of sinuses of Valsalva (SoV), sinotubular junction (STJ), and ascending aorta (AA) using leading edge-to-leading edge (LE) convention for TTE and inner-edge-to-inner-edge (IE) convention for MRA. Agreement was assessed using Bland-Altman methods. Intra- and interobserver variability were assessed by intraclass correlation. The average age of patients in the cohort was 62 years, and 69% of patients were male. The prevalence of hypertension, obstructive coronary artery disease, and diabetes was 66%, 20%, and 11%, respectively. The mean aortic diameter by TTE was SoV 3.8 ± 0.5 cm, STJ 3.5 ± 0.4 cm, and AA 4.1 ± 0.6 cm. The TTE-derived measurements were larger than the MRA ones by 0.2 ± 2 mm, 0.8 ± 2 mm, and 0.4 ± 3 mm at the level of SoV, STJ, and AA, respectively, but the differences were not statistically significant. There were no significant differences in the aorta measurements by TTE compared with MRA, when stratified by gender. In conclusion, transthoracic echocardiogram-derived proximal aorta measurements are comparable to MRA measurements. Our study validates current recommendations that TTE is an acceptable modality for screening and serial imaging of the proximal aorta.

Bidirectional Association Between Frailty and Cardiac Structure and Function: The Atherosclerosis Risk in Communities Study.

Background Frailty and heart failure frequently coexist in late life. Limited data exist regarding the longitudinal associations of frailty and subclinical cardiac dysfunction. We aim to quantify the association of frailty with longitudinal changes in cardiac function and of cardiac function with progression in frailty status in older adults. Methods and Results Participants in the Atherosclerosis Risk in Communities cohort underwent frailty assessments at Visit 5 (V5; 2011-2013), V6 (2016-2017), and V7 (2018-2019), and echocardiographic assessments at V5 and V7. We assessed the association between frailty status at V5 and changes in frailty status from V5 to V7 and changes in cardiac function over 6 years. We then evaluated the association of cardiac function measured at Visit 5 with progression in frailty status over 4 years. Multivariable regression models adjusted for demographics and comorbidities. Among 2574 participants free of heart failure at V5 and V7 (age 74±4 years at V5 and 81±4 years at V7), 3% (n=83) were frail. Frailty at V5 was associated with greater left atrial volume index and E/e' ratio at V5 and 7. Participants who transitioned from robust at V5 to frail at V7 demonstrated greater increases in left ventricular mass index, left atrial volume index, and E/e' over the same period. Among 1648 robust participants at Visit 5, greater left ventricular mass index and mean wall thickness, lower tissue Doppler imaging e', and higher E/e' ratio at Visit 5 were associated with progression in frailty status. Conclusions Among robust, older adults free of heart failure, progression in frailty and subclinical left ventricular remodeling and diastolic dysfunction are interrelated.

Longitudinal Changes in Left Ventricular Diastolic Function in Late Life: The ARIC Study.

BACKGROUND: There is limited data regarding longitudinal changes of diastolic function in the very old, who are at the highest risk for heart failure (HF). OBJECTIVES: This study aims to quantify intraindividual longitudinal changes of diastolic function over 6 years in late life. METHODS: The authors studied 2,524 older adult participants in the prospective community-based ARIC (Atherosclerosis Risk In Communities) study who underwent protocol-based echocardiography at study visits 5 (2011-2013) and 7 (2018-2019). The primary diastolic measures were tissue Doppler e', E/e' ratio, and left atrial volume index (LAVI). RESULTS: Mean age was 74 ± 4 years at visit 5 and 80 ± 4 at visit 7, 59% were women, and 24% were Black. At visit 5, mean e'septal was 5.8 ± 1.4 cm/s, E/e'septal 11.7 ± 3.5, and LAVI 24.3 ± 6.7 mL/m2. Over a mean of 6.6 ± 0.8 years, e'septal decreased by 0.6 ± 1.4 cm/s, E/e'septal increased by 3.1 ± 4.4, and LAVI increased by 2.3 ± 6.4 mL/m2. The proportion with 2 or more abnormal diastolic measures increased from 17% to 42% (P < 0.001). Compared with participants free of cardiovascular (CV) risk factors or diseases at visit 5 (n = 234), those with prevalent CV risk factors or diseases but without prevalent or incident HF (n = 2,150) demonstrated greater increases in E/e'septal and LAVI. Increases of E/e'septal and LAVI were both associated with the development of dyspnea between visits in analyses adjusted for CV risk factors. CONCLUSIONS: Diastolic function generally deteriorates over 6.6 years in late life, particularly among persons with CV risk factors, and is associated with development of dyspnea. Further studies are necessary to determine if risk factor prevention or control will mitigate these changes.

Changes in Pulmonary Artery Pressure Late in Life: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Although the prognostic implications of higher pulmonary artery systolic pressure (PASP) are well established, few data exist regarding longitudinal change in pulmonary pressure in late life. OBJECTIVES: The aim of this study was to quantify changes in PASP over 6 years and determine the relative contributions of cardiac and pulmonary dysfunction. METHODS: Among 1,420 participants in the ARIC (Atherosclerosis Risk in Communities) study with echocardiographic measures of PASP at both the fifth (2011-2013) and seventh (2018-2019) visits, longitudinal changes in PASP over about 6.5 years were quantified. Multivariable regression was used to determine the extent to which cardiac and pulmonary dysfunction were associated with changes in PASP and to define the relationship of changes in PASP with dyspnea development. RESULTS: The mean age was 75 ± 5 years at visit 5 and 81 ± 5 years at visit 7, 24% of subjects were Black adults, and 68% were women. Over the 6.5 years, PASP increased by 5 ± 8 mm Hg, from 28 ± 5 to 33 ± 8 mm Hg. PASP increased more in older participants. Predictors of greater increases in PASP included worse left ventricular (LV) systolic and diastolic function, pulmonary function, and renal function. Increases in PASP were associated with concomitant increases in measures of LV filling pressure, including E/e' ratio and left atrial volume index. Each 5 mm Hg increase was associated with 16% higher odds of developing dyspnea (OR: 1.16; 95% CI: 1.07-1.27; P < 0.001). CONCLUSIONS: Pulmonary pressure increased over 6.5 years in late life, was associated with concomitant increases in LV filling pressure, and predicted the development of dyspnea. Interventions targeting LV diastolic function may be effective at mitigating age-related increases in PASP.

Chronic Kidney Disease, Heart Failure, and Adverse Cardiac Remodeling in Older Adults: The ARIC Study.

BACKGROUND: The associations of kidney dysfunction and damage with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), as well as adverse cardiac remodeling, in late-life remain incompletely understood. OBJECTIVES: The authors sought to define the associations between kidney dysfunction and damage and incident HFrEF and HFpEF and cardiac structure and function in late-life. METHODS: This study included 5,170 adults initially free of a heart failure (HF) diagnosis who had estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) measured at visit 5 (2011-2013) of the ARIC (Atherosclerosis Risk In Communities) study. Multivariable Cox proportional hazards models were used to estimate the associations of eGFR and UACR with incident HF, HFrEF, and HFpEF through 2019. Multivariable linear regression models were used to investigate the associations of eGFR and UACR at visit 5 with changes in cardiac structure and function between visits 5 and 7 in 2,313 participants with available echocardiograms. RESULTS: The mean age of participants was 76 ± 5 years, and 2,225 (43%) were men. The mean eGFR and median UACR were 66 ± 18 mL/min/1.73 m2 and 11 mg/g (25th, 75th percentile: 6, 22 mg/g), respectively. In fully adjusted models, both lower eGFR and higher UACR were associated with greater risk of any HF, HFrEF, and HFpEF. Lower eGFR was associated with larger increases in left ventricular end-diastolic volume index and worsening of diastolic measures. UACR did not associate with changes in cardiac structure or function. CONCLUSIONS: Mild to moderate kidney dysfunction and damage associate with incident HF and adverse cardiac remodeling in late-life.

Priorities in Cardio-Oncology Basic and Translational Science: GCOS 2023 Symposium Proceedings: JACC: CardioOncology State-of-the-Art Review.

Despite improvements in cancer survival, cancer therapy-related cardiovascular toxicity has risen to become a prominent clinical challenge. This has led to the growth of the burgeoning field of cardio-oncology, which aims to advance the cardiovascular health of cancer patients and survivors, through actionable and translatable science. In these Global Cardio-Oncology Symposium 2023 scientific symposium proceedings, we present a focused review on the mechanisms that contribute to common cardiovascular toxicities discussed at this meeting, the ongoing international collaborative efforts to improve patient outcomes, and the bidirectional challenges of translating basic research to clinical care. We acknowledge that there are many additional therapies that are of significance but were not topics of discussion at this symposium. We hope that through this symposium-based review we can highlight the knowledge gaps and clinical priorities to inform the design of future studies that aim to prevent and mitigate cardiovascular disease in cancer patients and survivors.