Greater Left Ventricular Mass Index Research Articles

Association of inflammation with left ventricular mass index in patients with rheumatoid arthritis

Abstract Background Rheumatoid arthritis (RA) is an inflammatory autoimmune disease associated with cardiovascular organ damage. Purpose We explored the association of inflammatory markers with left ventricular (LV) mass index during 22 months of follow-up in patients with RA. Methods Eighty-three outpatients with RA (age 55±12 years, 71 % women) with indication for biological (b) or targeted synthetic (ts) disease modifying antirheumatic drug (DMARD) therapy were examined with echocardiography at baseline and after 22 months. LV mass was indexed for height in the allometric power of 2.7. Serum concentrations of the inflammatory markers, C-reactive protein (CRP), serum amyloid A (SAA) and calprotectin were measured by MALDI-TOF mass spectrometry. Results At baseline, 37% had hypertension, 6% diabetes, 21% obesity and 100% were using b/ts DMARDs. The inflammatory markers decreased during follow-up (all p<0.001), while the LV mass index did not change (33.1±8.1 g/m^2.7 vs. 33.5±7.3 g/m^2.7, p=0.57). The prevalence of hypertension, diabetes and obesity were unchanged at follow-up (p>0.05), but the percentage of patients using b/ts DMARDs had decreased to 83% (p<0.001). In multivariable analyses, higher CRP and SAA at baseline were associated with higher LV mass index at both baseline and follow-up independent of presence of obesity, hypertension, age, sex or treatment with b/ts DMARDs at follow-up (Table 1). Inflammatory markers at follow-up were not associated with LV mass index (Table 1), but use of b/ts DMARDs at follow-up were associated with lower LV mass index after adjusting for inflammatory markers, age, sex, presence of obesity and hypertension (Table 1). Conclusion Higher levels of inflammatory markers at baseline were associated with greater LV mass index in RA patients. The use of immunosuppressive treatment throughout the study period was associated with lower LV mass index at follow-up, pointing to a role of chronic inflammation in LV hypertrophy.

Prediction of the Individual Aortic Stenosis Progression Rate and its Association With Clinical Outcomes

BackgroundThe progression rate of aortic stenosis differs between patients, complicating clinical follow-up and management. ObjectivesThis study aimed to identify predictors associated with the progression rate of aortic stenosis. MethodsIn this retrospective longitudinal single-center cohort study, all patients with moderate aortic stenosis who presented between December 2011 and December 2022 and had echocardiograms available were included. The individual aortic stenosis progression rate was calculated based on aortic valve area (AVA) from at least 2 echocardiograms performed at least 6 months apart. Baseline factors associated with the progression rate of AVA were determined using linear mixed-effects models, and the association of progression rate with clinical outcomes was evaluated using Cox regression. ResultsThe study included 540 patients (median age 69 years and 38% female) with 2,937 echocardiograms (median 5 per patient). Patients had a linear progression with a median AVA decrease of 0.09 cm2/y and a median peak jet velocity increase of 0.17 m/s/y. Rapid progression was independently associated with all-cause mortality (HR: 1.77, 95% CI: 1.26-2.48) and aortic valve replacement (HR: 3.44, 95% CI: 2.55-4.64). Older age, greater left ventricular mass index, atrial fibrillation, and chronic kidney disease were associated with a faster decline of AVA. ConclusionsAVA decreases linearly in individual patients, and faster progression is independently associated with higher mortality. Routine clinical and echocardiographic variables accurately predict the individual progression rate and may aid clinicians in determining the optimal follow-up interval for patients with aortic stenosis.

Abstract 14700: Associations of Left Ventricular Structure With Cumulative Systolic Blood Pressure Load: A Report From Women’s Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction Study

Background: Recent studies have identified cumulative systolic blood pressure load to be associated with increased risk of adverse cardiovascular disease (CVD) outcomes. Similarly, associations between left ventricular (LV) structure and CVD events have long been recognized. Purpose: The purpose of this study was to assess the association between cumulative systolic blood pressure (CuSBP) load and LV structure in women with suspected ischemia with no obstructive coronary arteries (INOCA). Methods: Women enrolled in the Women’s Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction (WISE-CVD) study (NCT00832702) underwent cardiac magnetic resonance imaging (CMRI) for LV structure and those (n= 225) who had at least 2 blood pressure (BP) measures recorded at a single site before their baseline CMRI were included in this analysis. Cumulative systolic BP (CuSBP) was defined as systolic BP (SBP) ≥ 130 divided by all SBP readings and each mean value multiplied by the years. LV remodeling index was defined as the ratio between LV mass and LV end diastolic volume (LVEDV). Results: The mean age was 55±10 years, body mass index (BMI) 26.3 ± 5.5 kg/m 2 , 36% had a history of hypertension, number of BP medications was mean 2.7 ± 1.6 [median 2 (range 0, 8)], and SBP and DBP were 126 ± 15 and 66 ± 10 mmHg respectively. Age, BMI and history of hypertension were significantly associated with higher CuSBP load. In univariate analyses, LV end diastolic volume and LV end systolic volume decreased, and LV remodeling index increased across CuSBP quartiles while LV mass index did not significantly differ among the quartiles (Figure 1) . In multivariable regression analysis, the association between CuSBP and LV mass index and LV remodeling index remained significant. Conclusions: Among women with suspected INOCA, higher CuSBP load was associated with greater LV mass index and concentric LV remodeling independent of age. Changes in LV volumes may represent age-related changes in LV structure.

Abstract 16730: Neighborhood Deprivation and Left Ventricular Mass in Women, NGHS Longitudinal Cohort Analysis

Left ventricular hypertrophy is an independent predictor of cardiovascular disease. Neighborhood level deprivation is a risk factor for increased morbidity and mortality for a variety of diseases and conditions. However, to date, no study has assessed the relationship between neighborhood level deprivation and left ventricular hypertrophy. Methods: The NHLBI National Growth and Health Study (NGHS) is a 36-year longitudinal study of 871 women (50% white/50% Black). All participants were enrolled between 9-10 years of age in 1987. Annual assessments of anthropometric, echocardiographic and neighborhood level deprivation data, between the ages of 20-28 years (visits 11-17), were analyzed. We assessed the relationship between quartiles of deprivation index (DI) (high/worst, moderately high, moderately low, low/best) at ~age 20 years with levels of systolic blood pressure (SBP), body mass index (BMI) and indexed left ventricular mass (LVMI, g/m 2.7 ), between ages 20-28, adjusting for race. Results: Data from 531 (55% Black) women were examined. Compared to the lowest DI quartile, the highest DI quartile exposure at ~20 years was associated with a 3.37 [1.34, 8.44] greater odds of BMI > 30 (obesity) at age 28, p=0.01 . An interaction between visit and DI quartile was significant, such that women in the highest DI quartile at age 20 had greater increases in BMI by age 28 than those in lower DI quartiles ( p=0.001 , Figure 1). There was no significant relationship between SBP and DI quartile in this cohort (data not shown). Compared with women who resided in the lower 2 DI quartiles at age 20, the LVMI of women exposed to higher (worse) DI was significantly greater after age 23 (visit 14 , p<0.05 , Figure 2). Conclusion(s): In summary, increased deprivation is associated with increased BMI in young adult women, adjusting for race. In addition, increased deprivation is also associated with greater indexed left ventricular mass, an independent predictor of cardiovascular disease.

MMP-2 Associates With Incident Heart Failure and Atrial Fibrillation: The ARIC Study.

MMP (matrix metalloproteinase)-2 participates in extracellular matrix regulation and may be involved in heart failure (HF), atrial fibrillation (AF), and coronary heart disease. Among the 4693 ARIC study (Atherosclerosis Risk in Communities) participants (mean age, 75±5 years; 42% women) without prevalent HF, multivariable Cox proportional hazard models were used to estimate associations of plasma MMP-2 levels with incident HF, HF with preserved ejection fraction (≥50%), HF with reduced ejection fraction (<50%), AF, and coronary heart disease. Mediation of the association between MMP-2 and HF was assessed by censoring participants who developed AF or coronary heart disease before HF. Multivariable linear regression models were used to assess associations of MMP-2 with measures of left ventricular and left atrial structure and function. Compared with the 3 lower quartiles, the highest MMP-2 quartile associated with greater risk of incident HF overall (adjusted hazard ratio, 1.48 [95% CI, 1.21-1.81]), incident HF with preserved ejection fraction (1.44 [95% CI, 1.07-1.94]), incident heart failure with reduced ejection fraction (1.48 [95% CI, 1.08-2.02]), and incident AF (1.44 [95% CI, 1.18-1.77]) but not incident coronary heart disease (0.97 [95% CI, 0.71-1.34]). Censoring AF attenuated the MMP-2 association with HF with preserved ejection fraction. Higher plasma MMP-2 levels were associated with larger left ventricular end-diastolic volume index, greater left ventricular mass index, higher E/e' ratio, larger left atrial volume index, and worse left atrial reservoir and contractile strains (all P<0.001). Higher plasma MMP-2 levels associate with diastolic dysfunction, left atrial dysfunction, and a higher risk of incident HF and AF. AF is a mediator of MMP-2-associated HF with preserved ejection fraction risk.

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.

Exploring the prognostic value of myocardial inflammation in Fabry cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac involvement in Fabry Disease (FD) manifests as left ventricular hypertrophy (LVH) often complicated by myocardial fibrosis and/or inflammation. Indeed, glycosphingolipid storage does not explain the whole spectrum of FD pathophysiology. Lysosomal deposits of unmetabolized glycolipid substrates stimulate the activation of immunological pathways, taking to a chronic inflammatory process.1 In a subgroup of FD patients with late gadolinium enhancement (LGE), signs of myocardial inflammation can be detected by cardiac magnetic resonance (CMR) using T2-weighted (T2w) sequences and T2 mapping. T2 value in inferolateral wall (IL) has been described as the strongest predictor of increase in troponin level. 2 Aim The aims of the study were: 1) to compare CMR parameters in LVH and LGE positive FD patients with and without myocardial inflammation; 2) to verify if myocardial inflammation plays an incremental prognostic role in FD compared to LVH and LGE. Methods Among 190 consecutive FD patients referred for CMR, 47 patients with LVH and LGE were selected for this study. All patients underwent an extensive CMR protocol to provide a detailed evaluation of cardiac morphology and function, with multiparametric tissue characterization. Myocardial inflammation was detected by T2w and T2 mapping sequences. A comparison of CMR parameters between patients with and without inflammation was performed. A composite endpoint of cardiovascular (CV) events was used for survival analysis. Results No differences in age and Mainz Severity Score Index were found between LVH+/LGE+ FD patients with and without myocardial inflammation. Patients with inflammation showed significantly greater left ventricular mass index (LVMI) compared to patients without inflammation. Regarding tissue characterization, patients with myocardial inflammation had more extensive LGE and significantly higher ECV in IL wall. Native myocardial T1 was reduced in both groups without statistically significant difference. (Table 1) Myocardial inflammation always involved IL wall. During a median follow-up of 30 months, Kaplan-Meier curves showed similar event-free survival probability in patients with and without myocardial inflammation (Log-Rank p = 0,215, Figure 1). Conclusion In a population of LVH+/LGE+ FD patients, the presence of CMR signs of myocardial inflammation was associated with more severe LVH and more extensive LGE. However, the presence of myocardial inflammation did not showed an incremental prognostic value on CV outcomes on top of LVH and LGE. Larger studies are needed to verify this findings.

Interaction between uric acid and obesity with myocardial dysfunction in diabetes

Abstract Funding Acknowledgements Type of funding sources: None. Background Both obesity and hyperuricemia are major risk factors for cardiovascular diseases. Few studies have investigated their impact on cardiac structural and functional changes in patients with diabetes. Purpose This study aims to evaluate the impact of obesity, hyperuricemia and their interaction on myocardial dysfunction in patients with diabetes. Methods A total of 1567 patients with diabetes were recruited from two Hospitals. Uric acid (UA), body mass index (BMI) and myocardial structure and function indicators, including left ventricular hypertrophy (LVH), left ventricular ejection function (LVEF), left ventricular global longitudinal strain (GLS), circumferential strain (CS) and radial strain (RS). Multivariate linear regression was conducted to evaluate the association between myocardial structure and function with UA in obesity and non-obesity. The generalised linear models were used to test for the interaction effects of obesity on the associations between UA level and myocardial structure and function. Results Compared to non-hyperuricemia patients, those who were hyperuricemia had a greater left ventricular mass index (LVMi), a higher proportion of LVH and worse GLS and CS (all P &amp;lt;0.05). Similar patterns were found for those with obesity compared to non-obesity (all P&amp;lt;0.05). In patients with obesity and non-obesity, increasing UA was independently related with decreased GLS and CS. There is a significant interaction between hyperuricemia and obesity on LVMi and GLS in patients with diabetes (P for interaction &amp;lt;0.05) but not on LVEF, CS and RS. Conclusions Obesity and hyperuricemia were associated with worse left ventricular remodeling and left ventricular myocardial function. Those who were obesity and with hyperuricemia had more pronounced LVMi and GLS. Our finding emphasizes lowering UA and BMI in patients with diabetes may effectively prevent myocardial remodeling and dysfunction.

DIABETES MELLITUS AND ASSOCIATED HYPERTENSION, A TOXIC COMBINATION FOR CARDIOVASCULAR RISK

Objective: The coexistence of hypertension in diabetic patients greatly enhances their likelihood of developing CVD. Other important risk factors for CVD in these patients include the following: obesity, atherosclerosis, dyslipidemia, microalbuminuria, inflammation, retinopathy, and “diabetic cardiomyopathy”. We aimed to assess the impact of type 2 diabetes mellitus associated with high blood pressure over these cardiovascular risk factors. Design and method: We performed a transversal study, lasting 12 months, in which 100 patients with essential hypertension, and type 2 diabetes, with medium age 60.7 ± 9.3 years were evaluated in comparison with 100 patients with only hypertension. We evaluate these patients for: BMI; waist circumference; IMT by carotid ultrasonography; microalbuminuria in a spot morning urine; fundus oculi, LVMI for left ventricular hypertrophy by echocardiography. Serum PCR and lipid concentrations were measured. Results: The diabetic hypertensive subjects significantly had higher BMI (p = 0.01) and waist circumference statistically significant (p = 0.005). Patients with hypertension and diabetes had a greater left ventricular mass index (66% vs 51%, P = 0.04). Mean value for IMT was 1.1 ± 0,3 mm for diabetic patients and 0.93 ± 0,2 mm for the other group (P &lt; 0.001) and its prevalence was high in diabetics (75% vs 64%, P = 0.1). Prevalence of microalbuminuria was significantly high in diabetics (44% vs 14%, P &lt; 0.001). PCR as marker of inflammation was prevalently high in people with diabetes and hypertension (32% vs 16%, P = 0.013) Also, prevalence of retinopathy was significantly high in people with diabetes and hypertension compare to other group (27% vs 12%, P = 0.012). There was strong relation between LVMI, microalbuminuria, IMT and PCR. Waist circumference had correlation with IMT and microalbuminuria. Conclusions: DM is an independent risk factor for the increased LV mass and impaired diastolic function regardless of association with hypertension or not. Central obesity is associated with an increased risk for cardio metabolic diseases such as atherosclerosis and diabetic nephropathy. Atherosclerosis is characterized by chronic inflammation affecting the arterial intimae. Thus, individuals with type 2 diabetes and hypertension had increased risk for CVD.

Is non-alcoholic fatty liver disease a sign of left ventricular diastolic dysfunction in patients with type 2 diabetes mellitus? A systematic review and meta-analysis

Recent studies have associated non-alcoholic fatty liver disease (NAFLD) with impaired cardiac function. However, patients with type 2 diabetes mellitus (T2DM), a high-risk group for left ventricular diastolic dysfunction (LVDD),...

Abstract 12085: Cardiac Structural and Functional Differences Between the Types of Sleep Apnea in Patients With Heart Failure With Reduced Ejection Fraction

Introduction: In patients with heart failure with reduced ejection fraction (HFrEF), sleep-disordered breathing (SDB) may affect, or be affected by cardiac structure and function. We hypothesized that patients with OSA would demonstrate left ventricular (LV) remodeling and impaired LV function intermediate between that of patients with CSA and patients with no SDB. Methods: ADVENT-HF is a multinational randomized trial investigating the effect of adaptive servo ventilation in patients with HFrEF and SDB. Inclusion required LV ejection fraction (LVEF) ≤45%, and a polysomnographic (PSG) apnea-hypopnea index (AHI) ≥15. Subjects with an AHI &lt;15 were excluded from randomization but comprised a no-SDB (NSDB) group. All transthoracic echocardiograms (TTE) and PSGs were analyzed in core laboratories at University Health Network in Toronto. Patients with SDB were subdivided into those with OSA and those with CSA. We then compared baseline demographic and TTE characteristics of the NSDB, OSA and CSA cohorts. Results: Among them, 665 with acceptable TTE were analyzed. As shown in the table, the CSA group was older, more predominantly male, and had a higher AHI than the other groups, and a higher prevalence of atrial fibrillation and a lower minimum arterial oxyhemoglobin saturation level than the NSDB group. The CSA group also had greater LV mass index than the other groups, greater LV volume indices and lower LVEF than the OSA group, and lower cardiac index than the NSDB group. Although the OSA group had no significant differences in TTE findings compared to the NSDB group, the OSA group was older, more predominantly male, and had a greater AHI than the NSDB group and a higher BMI than the CSA group and lower minSaO 2 than the other groups. Conclusion: In patients with HFrEF, the degree of LV remodeling and dysfunction did not differ between the OSA and NSDB groups, but those with CSA had more advanced LV remodeling and dysfunction than the other groups signaling more advanced HF.

Abstract 12501: Stronger Positive Correlation Between Left Ventricular Mass Index and E/e' in Patients With Diabetes Compared to Non-Diabetic Subjects

Introduction: Diabetes mellitus (DM) has been considered as a background of cardiomyopathy. The aim is to characterize the structural and functional features of the heart in diabetic patients by cardiac magnetic resonance imaging (CMR). Methods: This was a multicenter, retrospective, observational study: patients aged 45 years or older who underwent contrast-enhanced CMR were included. Patients with low left ventricular ejection fraction (LVEF) (LVEF&lt;40%), known cardiomyopathy, history of myocardial infarction, or type 1 DM were excluded. Left ventricular mass index (LVMi), LVEF, and extracellular volume (ECV), which may represent myocardial fibrosis, were evaluated by CMR. Left atrial pressure was estimated by echocardiographic indices such as E/e’. Results: We analyzed 322 patients (age (median [interquartile range]) = 64 [53 - 73], DM (n) = 53). After multivariable adjustment, DM was independently associated with greater LVMi (standard regression coefficient (β) = 0.11, p = 0.037) and lower LVEF (β = -0.12, p = 0.036). In DM patients, LVMi and E/e' were positively correlated (correlation coefficient (R) = 0.46, p = 0.001), with a higher correlation coefficient than those in non-DM patients (R = 0.15, p = 0.022). There was a significant interaction between LVMi and DM for increased E/e' (p = 0.020) (Figure A). ECV also correlated with E/e' only in DM patients (DM, R = 0.55, p = 0.011; non-DM, R = 0.14, p = 0.14), with a significant interaction between ECV and DM for increased E/e' (p = 0.037) (Figure B). Conclusions: CMR revealed that diabetic patients without myocardial infarction had increased LVMi with declined LVEF. Both increased LVMi and ECV were also revealed to be associated with higher E/e' especially in diabetic patients.

FGF23 and Cardiovascular Structure and Function in Advanced Chronic Kidney Disease.

Fibroblast growth factor 23 (FGF23) is a bone-derived phosphatonin that is elevated in chronic kidney disease (CKD) and has been implicated in the development of cardiovascular disease. It is unknown whether elevated FGF23 in CKD is associated with impaired cardiovascular functional capacity, as assessed by maximum exercise oxygen consumption (VO2Max). We sought to determine whether FGF23 is associated with cardiovascular functional capacity in patients with advanced CKD and after improvement of VO2Max by kidney transplantation. We performed secondary analysis of 235 patients from the Cardiopulmonary Exercise Testing in Renal Failure and After Kidney Transplantation (CAPER) cohort, which recruited patients with stage 5 CKD who underwent kidney transplantation or were waitlisted and hypertensive controls. All patients underwent cardiopulmonary exercise testing (CPET) and echocardiography and were followed longitudinally for 1 year after study enrollment. Patients across FGF23 quartiles differed in BMI (P=0.004) and mean arterial pressure (P<0.001) but did not significantly differ in sex (P=0.5) or age (P=0.08) compared with patients with lower levels of FGF23. Patients with higher FGF23 levels had impaired VO2Max (Q1: 24.2±4.8 ml/min per kilogram; Q4: 18.6±5.2 ml/min per kilogram; P<0.001), greater left ventricular mass index (LVMI; P<0.001), reduced HR at peak exercise (P<0.001), and maximal workload (P<0.001). Kidney transplantation conferred a significant decline in FGF23 at 2 months (P<0.001) before improvement in VO2Max at 1 year (P=0.008). Multivariable regression modeling revealed that changes in FGF23 was significantly associated with VO2Max in advanced CKD (P<0.001) and after improvement after kidney transplantation (P=0.006). FGF23 was associated with LVMI before kidney transplantation (P=0.003), however this association was lost after adjustment for dialysis status (P=0.4). FGF23 was not associated with LVMI after kidney transplantation in all models. FGF23 levels are associated with alterations in cardiovascular functional capacity in advanced CKD and after kidney transplantation. FGF23 is only associated with structural cardiac adaptations in advanced CKD but this was modified by dialysis status, and was not associated after kidney transplantation.

Cardiomyopathy correlates to nerve damage in p.A117Slate‐onset transthyretin amyloid polyneuropathy

ObjectiveLate‐onset hereditary transthyretin amyloidosis with polyneuropathy (ATTRv‐PN) is often associated with heart involvement. Recent advances in cardiac imaging allow the detection of cardiac amyloidosis. This study aimed to explore cardiomyopathy by cardiac imaging and its clinical correlates with polyneuropathy in late‐onset ATTRv‐PN.MethodsPolyneuropathy was assessed by intraepidermal nerve fiber (IENF) density, nerve conduction study (NCS), autonomic function tests, quantitative sensory testing, and clinical questionnaires. Cardiomyopathy was evaluated by echocardiography, 99mTc‐pyrophosphate (PYP) single‐photon emission computed tomography (SPECT) imaging, cardiac magnetic resonance imaging (CMR), and serum Pro‐B‐type natriuretic peptide. Healthy controls and patients with Brugada syndrome were enrolled for comparison of CMR.ResultsFifty late‐onset ATTRv‐PN patients (38 men, 46 with p. A117S mutation), aged 63.7 ± 5.5 years, of polyneuropathy disability stage 1–4 were enrolled. All patients presented polyneuropathy in NCS, and 74.5% of patients had reduced IENF density in distal legs. All patients showed significant radiotracer uptake in the heart on 99mTc‐PYP SPECT imaging, and 87.8% of patients had abnormally increased left ventricular (LV) septum thickness on echocardiography. CMR showed longer myocardial native T1, larger extracellular volume, greater LV mass index, and higher LV mass to end‐diastolic volume ratio in ATTRv‐PN patients than healthy controls and patients with Brugada syndrome. These CMR parameters were associated with skin denervation, absent sympathetic skin responses, elevated thermal thresholds, worsened NCS profiles, and functional deficits of polyneuropathy.InterpretationLate‐onset ATTRv‐PN coexisted with cardiomyopathy regardless of the clinical severity of polyneuropathy. The cardiac amyloid burden revealed by CMR was correlated with pathophysiology and clinical disability of nerve degeneration.

Structural Cardiac Abnormalities in Patients with Atrial Fibrillation/Flutter and Myocardial Injury

BackgroundHigh-sensitivity cardiac troponin (hs-cTnT) is often increased in patients with atrial fibrillation/flutter, portending a poor prognosis. The etiologies for these increases have not been systematically investigated. Our aim was to define prevalence/significance of structural cardiac abnormalities in patients with atrial fibrillation/flutter and high-sensitivity cardiac troponin T (hs-cTnT) increases. MethodsThis is a retrospective observational cohort study of patients with atrial fibrillation/flutter diagnosis with hs-cTnT measurements, echocardiograms, and coronary angiograms. Myocardial injury was defined as hs-cTnT >10 ng/L for women and >15 ng/L for men. Cases with myocardial injury were adjudicated according to the Fourth Universal Definition of Myocardial Infarction. ResultsPatients with definite causes for increased hs-cTnT (n = 875) were tabulated but not evaluated further; common diagnoses were type 1 myocardial infarction, critical illness, and known heart failure. Of the remaining 401, increased hs-cTnT was present in 336 (84%) patients. Of those, 78% had nonischemic myocardial injury, the remaining (n = 75, 22%) had type 2 myocardial infarction. Patients with elevated hs-cTnT had greater left ventricular mass index, left ventricular filling pressures, and right ventricular systolic pressure. They more frequently had significant coronary artery disease (47% vs 31%, P = .016), especially in type 2 myocardial infarction. With logistic regression, age, sex (F), diabetes, left ventricular mass index, e′ medial velocity, and right ventricular systolic pressure were independent determinants of myocardial injury. One-year mortality was higher in patients with myocardial injury. ConclusionsStructural heart abnormalities are common in patients with atrial fibrillation/flutter and increased hs-cTnT. Causes of myocardial injury should be elucidated in each patient to craft appropriate therapies.

Cardiac remodeling accompanied by increased arrhythmia susceptibility in a dog model of chronic high-intensity endurance training

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by NKFIH grants (K-19992, K-135464) and GINOP-2.3.2-15-2016-00047. Background Despite the cardiovascular benefits of regular physical exercise, chronic high-level exercise can evoke malignant arrhythmias, including ventricular fibrillation and even sudden cardiac death, especially in young top athletes. In some cases the underlying mechanisms are unclear. Objectives The goal of this study was to assess mechanisms underlying cardiac structural-electrical changes and arrhythmia vulnerability by high-level vigorous exercise training in animal species that are electrophysiologically relevant to the human heart. Methods Beagle dogs were randomly assigned to matched sedentary (Sed) or intensive exercise-training (Ex) groups (n=12-12). Ex dogs underwent a 4-month-long intensive treadmill-running protocol (5 days a week, 6 hours a day at a speed of 14-21 km/h with an inclination from 5% to 12%). In vivo echocardiography and electrophysiological measurements were performed. Proarrhythmic sensitivity was tested and the autonomic alterations were examined. At study end, arrhythmia susceptibility was tested with high-frequency burst stimulation in open-chest anaesthetized dogs. This was followed by cardiac excision and cardiomyocyte isolation, formalin preservation for histology, snap-freezing in liquid nitrogen for molecular biology. Results The vigorous endurance training was resulted in increased left ventricular end-diastolic diameter, increased septal wall thickness and greater left ventricular mass index (Ex vs. Sed: 98±12 vs. 136±7 g/m2, p&amp;lt;0.05). Some degree of enhanced fibrosis was observed. Endurance training decreased heart rate both in whole animal and in vitro dog experiments. ECG recordings presented enhanced heart rate variability parameters, prolonged PQ (Ex vs. Sed: 98.3±2.9 vs. 116.7±3.6 ms, p&amp;lt;0.05), QRS (Ex vs. Sed : 60.5±2.4 vs 70.8±1.6 ms, p&amp;lt;0.05), QTc (Ex vs. Sed: 213.6±2.8 vs. 237.1±3.4 ms, p&amp;lt;0.05), Tp-Te (Ex vs. Sed: 27.9±2.5 vs.36.5±1.7 ms, p&amp;lt;0.05) intervals associated with significantly enhanced QT interval variability (eg. Ex vs. Sed: QT-STV, 2.5±0.2 vs. 3.6±0.4 ms, p&amp;lt;0.05), reflecting elevated level of repolarization dispersion. Ectopic activity was also enhanced in the exercised dog ventricle. Atropine treatment resulted in moderate heart rate increase in the Ex animals. Chronic endurance exercise elevated the proarrhythmic risk and consequent ventricular fibrillation in dogs subjected to burst electrical stimulation. Conclusion We developed a new animal model that shares similarities with the human endurance-trained athlete’s heart. The model represents increased arrhythmia susceptibility, an important clinical paradigm, and explores potential underlying mechanisms, including vagal enhancement, increased repolarization dispersion and enhanced fibrotic changes. Increased arrhythmia susceptibility is supported by the enhanced arrhythmia incidence in the exercised group. Similar changes may be present in young human top athletes, however further investigations are required.

Cystatin C Predicts Adverse Outcomes In Heart Failure With Preserved Ejection Fraction

<h3>Background</h3> Serum creatinine (Cr) is used to estimate glomerular filtration rate (GFR). Cr levels vary with lean muscle mass and diet, confounding measurement of renal function. Cystatin C (CysC) is an alternative marker used to estimate GFR which is not subject to these sources of variability. In conditions where frailty and low muscle mass are common, such as heart failure with preserved ejection fraction (HFpEF), Cr may overestimate GFR, leading to under detection of renal disease. Chronic kidney disease (CKD) is a common co-morbidity in HFpEF and portends worse prognosis; however, there are currently minimal data on CysC in HFpEF. <h3>Methods</h3> Patients enrolled in the Johns Hopkins HFpEF Program from July 2014 to March 2020 were included for study. Patients underwent a comprehensive clinical evaluation and echocardiography. Estimated GFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations for Cr (CKD-EPIcr) and CysC (CKD-EPIcys). Distributions of GFR were compared with a Wilcoxon matched-pairs test. Trends in clinical and echocardiographic variables with CysC were assessed using multivariate linear regression. Cox proportional hazard models examined the association of CysC with the combined outcome of heart failure hospitalization and all-cause mortality. <h3>Results</h3> The study cohort included 190 patients. The average age was 64 years; 65% of patients were female and 59% were black. Median follow-up was 28 months. The median estimated GFR by CKD-EPIcr and CKD-EPIcys were 54.0 mL/min/1.73m² and 46.7 mL/min/1.73m², respectively (<b>Figure A and C;</b> z=3.81, p<0.001). As compared to CKD-EPIcr, CKD-EPIcys reclassified 74 patients (39% of cohort) to a higher stage of CKD (<b>Figure B and D</b>). CysC was significantly associated with greater left ventricular mass index (β =7.16 [0.23-14.01], p=0.043) and E/e' ratio (β=2.28 [0.33-4.22], p=0.022) after adjustment for GFR by CKD-EPIcr. CysC was predictive of the combined outcome in the univariate model and after adjustment for relevant medical comorbidities and estimated GFR by CKD-EPIcr (<b>Figure</b>). <h3>Conclusion</h3> In this prospective study, CysC estimated a lower median GFR in HFpEF patients as compared to Cr. CysC was predictive of worse diastolic function and adverse outcomes, even after accounting for GFR by CKD-EPIcr and relevant comorbidities. These results suggest CysC provides clinical and prognostic information beyond traditional Cr-based assessment of renal function in HFpEF. Further investigation of the use of CysC in clinical practice is warranted.

Biomarkers of inflammation and left ventricular remodelling in psoriasis patients treated with infliximab.

Objective: Psoriasis is an immune mediated disorder associated with T cell activation and cardiovascular disease (CVD). We explored the association of inflammation with left ventricular (LV) remodelling in psoriasis patients receiving treatment with the tumour necrosis factor-α (TNF-α) blocker infliximab. Methods: Psoriasis patients (n = 47, age 47 ± 14 years, 66% men) and 99 control subjects without psoriasis (age 47 ± 11 years, 72% men) were examined by echocardiography in a cross-sectional study. LV remodelling was assessed by LV mass index for height in the allometric power of 2.7. Serum concentrations of C-reactive protein (CRP), serum amyloid A (SAA), neopterin, kynurenine:tryptophan ratio (KTR) and the pyridoxic acid ratio (PAr) index were measured. Results: Serum concentration of neopterin (p = .007) was higher in psoriasis patients, while the other inflammatory biomarkers had similar levels. LV mass index was lower in patients than controls (35.6 ± 9.6 g/m2.7 vs. 40.3 ± 9.8 g/m2.7, p = .008). In the total study population, serum SAA (β = 0.18, p = .02), KTR (β = 0.20, p = .02) and the PAr index (β = 0.26, p = .002) were all associated with higher LV mass index independent of age, sex, body mass index, hypertension, smoking, renal function and psoriasis. Also in psoriasis patients, higher SAA level (β = 0.34, p = .02), KTR (β = 0.32, p = .02) and the PAr index (β = 0.29, p = .05) were associated with higher LV mass index independent of body mass index, hypertension and diabetes. Conclusion: Higher levels of the inflammatory biomarkers SAA, KTR and the PAr index were associated with greater LV mass index in psoriasis patients, indicating a role of chronic inflammation in LV remodelling evident even during treatment with TNF-α blockers.

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 < 0.001], LAVi [HR (95% CI) per 1 ml/m2 = 1.03 (1.01–1.06), p < 0.001], and E/e′ [HR (95% CI) per 1 = 1.08 (1.04–1.13), p < 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.

Impaired Cardiac Sympathetic Innervation Increases the Risk of Cardiac Events in Heart Failure Patients with Left Ventricular Hypertrophy and Mechanical Dyssynchrony.

Background. Left ventricular mechanical dyssynchrony (LVMD), left ventricular hypertrophy, and impaired cardiac sympathetic innervation are closely related to the development of heart failure (HF) and unfavorable outcomes. Methods and Results. A total of 705 consecutive HF patients with reduced left ventricular ejection fraction (EF) < 50% were registered in our hospital HF database. LVMD and left ventricular mass index (LVMI) were evaluated three-dimensionally by gated myocardial perfusion SPECT. LVMD was measured as a heterogeneity index (phase SD) of the regional contraction phase angles calculated by Fourier analysis. Cardiac sympathetic innervation was quantified as a normalized heart-to-mediastinum ratio (HMR) of the 123I-metaiodobenzylguanidine (MIBG) activity. The patients were followed up with a primary end point of lethal cardiac events (CEs) for 42 months. CEs were documented in 246 of the HF patients who had a greater phase SD, greater LVMI, and lower MIBG HMR than those in HF patients without CEs. In the overall multivariate analysis, phase SD, LVMI, and MIBG HMR were identified as significant CE determinants. The three biomarkers were incrementally related to increases in CE risks. Conclusions. Assessment of cardiac sympathetic innervation can further stratify patients with systolic heart failure at increased cardiac risk identified by left ventricular hypertrophy and mechanical dyssynchrony.