Decrease In Left Ventricular Mass Research Articles

Coronary Physiological Indexes to Evaluate Myocardial Ischemia in Patients With Aortic Stenosis Undergoing Valve Replacement

BackgroundThe evaluation of myocardial ischemia in patients with aortic valve stenosis (AS) with concomitant coronary artery disease (CAD) and possible microvascular dysfunction (MVD) is challenging because fractional flow reserve (FFR) and the resting full-cycle ratio (RFR) have not been validated in this clinical setting. ObjectivesThe objectives of this study in patients with AS and CAD were 1) to describe the relationship between hyperemic and resting indexes, 2) to investigate the acute and long-term effects of aortic valve replacement (AVR) on epicardial indexes and microvascular function, 3) to assess the impact of these changes on clinical decision making, and 4) to determine FFR/RFR ischemia cutoff points in AS. MethodsIn this prospective multicentric study, we performed serial measurements of FFR and RFR and evaluated MVD by means of coronary flow reserve, the index of microvascular resistance, and microvascular resistance reserve in patients with severe AS and intermediate to severe CAD before and 6 months after AVR. Patients underwent myocardial perfusion single-photon emission computed tomography before AVR. ResultsIn total, 146 coronary lesions in 116 patients were included. Before AVR, we observed high FFR/RFR discordance according to standard cutoff values (FFR negative [>0.80]/RFR positive [≤0.89] in 42.3% [68/137] of these lesions). Acutely after AVR, FFR decreased significantly (−0.0120 ± 0.0192; P = 0.0045), whereas RFR remained stable (0.0140 ± 0.0673; P = 0.3089). Six months after AVR, FFR decreased (−0.0279 ± 0.0368), whereas RFR increased significantly (+0.0410 ± 0.0487) (P < 0.0001 for both), resulting in 21.5% (21/98) and 39.8% (39/98) of lesions crossing traditional FFR and RFR cutoff lines, respectively. Left ventricular mass decreased significantly (153.68 ± 44.22 g before vs 134.66 ± 37.26 g after; P < 0.0001). MVD was frequently observed at baseline (32.1% abnormal index of microvascular resistance and 68.6% abnormal microvascular resistance reserve) with all microvascular parameters improving after AVR. The most accurate cutoffs to predict ischemia were FFR ≤0.83 and RFR ≤0.85 with comparable accuracy (75%-80%). ConclusionsIn patients with severe AS and CAD, FFR ≤0.83 and RFR ≤0.85 appear to predict myocardial ischemia more accurately. Six months after AVR, FFR decreases, whereas RFR increases significantly with a simultaneous decrease of left ventricular mass and an improvement of microvascular function.

Causal relationship between inflammatory markers and left ventricle geometry and function: A 2-sample Mendelian randomization study.

Studies have shown that some inflammatory markers can predict the risk of cardiovascular disease (CVD) and affect the structure and function of the heart. However, a causal relationship between inflammatory markers and the cardiac structure and function has not yet been established. Thus, we conducted a 2-sample Mendelian randomization (MR) study to explore the potential causal relationship between inflammatory markers and prognostically-related left ventricular (LV) parameters. Instrumental variables (IVs) for C-reactive protein (CRP), interleukin-6 (IL-6), and myeloperoxidase (MPO) levels were selected from the databases of large genome-wide association studies (GWAS). Summary statistics for LV parameters, including LV mass, ejection fraction, end-diastolic and systolic volumes, and the ratio of LV mass to end-diastolic volume, were obtained from cardiovascular magnetic resonance studies of the UK Biobank (n = 16923). The inverse-variance weighted (IVW) method was the primary analytical method used, and was complemented with the MR-Egger, weighted median, simple mode, weighted mode, and MR pleiotropy residual sum and outlier (MR-PRESSO) methods. Sensitivity analysis was performed to evaluate the robustness of the results. CRP was significantly associated with the LV mass in the IVW method (β = -0.13 g [95% confidence interval [CI], 0.78 g-1.00 g], P = .046). A higher standard deviation of genetically-predicted CRP levels was associated with a 0.13 ± 0.06 g lower LV mass. No causal relationships of IL-6 and MPO with LV parameters were found. No evidence of heterogeneity and pleiotropy was detected. Sensitivity analyses confirmed the robustness of the results. Two-sample MR analysis revealed a causal association between increased CRP level and decreased LV mass, whereas IL-6 and MPO levels did not influence the LV parameters. However, further research is required to validate our findings.

Left ventricular mass as a modulator of ventricular arrhythmia risk and sex differences after CRT for nonischemic cardiomyopathy and LBBB

BackgroundThe risk of ventricular arrhythmias (VAs) after cardiac resynchronization therapy (CRT) has been associated with ischemic disease/scar, sex, and possibly left ventricular mass (LVM). ObjectiveThe purpose of this study was to evaluate sex differences and baseline/postimplant change in LVM on VA risk after CRT implantation in patients with nonischemic cardiomyopathy and left bundle branch block. MethodsIn patients meeting the criteria, baseline and follow-up echocardiographic images were obtained for LVM assessment. VA events were reported from device diagnostics and therapies. VA risk was stratified by receiver operating characteristic (Youden index cutoff point) for baseline LVM and baseline/postimplant change in LVM. Multivariate Cox regression model was also used for VA risk stratification. ResultsOne hundred eighteen patients (71 female patients [60.2%]; mean age 60.5 ± 11.3 years; left ventricular ejection fraction 19.2% ± 7.0%; QRS duration 165.6 ± 20 ms; LVM 313.9 ± 108.8 g) were enrolled and followed up for a median of 90 months (interquartile range 44–158 months). Thirty-five patients (29.6%) received appropriate shocks or antitachycardia pacing at a median of 73.5 months (interquartile range 25–130 months) postimplantation. Males had a higher VA incidence (male patients 18 of 47 [38.3%] vs female patients 17 of 71 [23.9%]; P = .02). Baseline LVM > 308.9 g separated patients with higher VA risk (P = .001). Less than a 20% decrease in LVM increased VA risk (P < .001). Baseline LVM was the only baseline characteristic predicting VA events in the Cox regression model (hazard ratio 1.01; 95% confidence interval 1.001–1.009; log-rank, P = .003). Sex differences in VA risk were eliminated by the baseline LVM parameters. ConclusionVA risk after CRT implantation in nonischemic cardiomyopathy was associated with baseline LV > 308.9 g and a decrease in LVM ≤ 20%, without sex differences.

Dietary effects on blood pressure control in primary aldosteronism using a cardiorenal model

Primary aldosteronism (PA) is associated with hypertension (HTN), and these patients have significant lowering of blood pressure (BP) and improved hypokalemia when moving to a DASH dietary intervention (≤65 mEq/day Na+ and ≥120 mEq/day K+). However, current guidelines for PA treatment briefly recommend lowering Na+ intake and make no specific mention of supplementing K+ intake or using DASH in PA. Additionally, high levels of aldosterone increase the risk of developing cardiovascular and chronic kidney disease. However, the impact of DASH diet on hyperkalemia risk and the extent of BP reduction in PA patients with renal dysfunction are unknown. Because continuous monitoring of cardiovascular, neural, and hormonal changes during PA and its treatment cannot be achieved experimentally, we used the mathematical model of human physiology, HumMod, to test the responses to a DASH diet during PA. We hypothesized that both low Na+ and high K+ (DASH) have additive benefits on natriuresis and BP control during PA. We added known renal physiological effects of K+ in HumMod using data from David Young’s work in dogs and further validated the model’s response to changes in Na+ intake based off of chronic salt sensitivity experiments in PA patients. Starting from baseline conditions with normal Na+/K+ intake (150 and 40 mmol/day, respectively), we simulated an aldosterone secreting tumor to gradually increase plasma aldosterone to 20 ng/dL over 3 years. Baseline PA was associated with hypertension (149/85 mmHg), very low endogenous renin and aldosterone secretion, hypokalemia (2.6 mmol/L K+), and tumor aldosterone secretion of 360 μg/day. We simulated a chronic change in dietary intake: 1) Low Na+ diet- Na+ intake fixed at 65 mmol/day with normal K+ intake, 2) High K+ diet - 120 mmol/day K+ intake with normal Na+ intake, or 3) DASH diet- Low Na+ intake and high K+ intake. Lowering Na+ intake without or with high K+ intake (DASH) were associated with lower systolic BP over the first 4 weeks and persisted for 2 years despite continued activation of the renin-angiotensin system and increasing tumor aldosterone secretion. Simulating mineralocorticoid blockade (MCB) was associated with reductions in systolic BP (-17 mmHg), decrease in left ventricular mass, and correction of hypokalemia (~4.0 mmol/L), but BP still remained uncontrolled (134/81 mmHg), partly due to the compensatory increase in renin secretion. Adding DASH to MCB therapy completely normalized BP without inducing hyperkalemia (4.8 mmol/L). Simulating chronic kidney disease by reducing nephron number in the model amplified BP sensitivity to changes in both Na+ and K+ but increased plasma K+ near the hyperkalemic range. These current simulations may help better understand the sequence of physiological events in PA and yield new insights into its diagnosis and management in patients with different baseline renal function. The physiological effects of the DASH diet desperately need to be tested in patients with PA with various baseline renal function as our simulations suggest beneficial effects beyond current treatment guidelines. Supported by the National Institute on Minority Health and Health Disparities (R00 MD014738). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Association between skeletal muscle and left ventricular mass in patients with hyperthyroidism.

This study aims to investigate the relationship between skeletal muscle and left ventricular mass (LVM) in patients with hyperthyroidism, providing theoretical and data-based foundations for further research on the interaction between secondary muscle atrophy and cardiac remodeling. A retrospective data collection was conducted, including 136 patients with hyperthyroidism (Study group) and 50 healthy participants (control group). The Study group was further divided into Group A (high LVM) and Group B (low LVM) based on LVM size. Multiple linear regression analysis was performed to examine the correlation between skeletal muscle and LVM, with model evaluation. Based on the results, further nonlinear regression analysis was conducted to explore the detailed relationship between skeletal muscle and LVM. Compared to the control group, the Study group exhibited significantly lower LVM, skeletal muscle mass index (SMI), and skeletal muscle mass (SMM) (P<0.05). Within the subgroups, Group A had significantly higher SMI, SMM, and hand grip strength compared to Group B (P<0.05). The results of the multiple linear regression showed a certain correlation between SMI (β=0.60, P=0.042, 95% CI=0.02~1.17) and hand grip strength (β=0.34, P=0.045, 95% CI=0.01~0.67) with LVM. However, the residuals of the multiple regression did not follow a normal distribution (K-S=2.50, P<0.01). Further results from a generalized linear model and structural equation modeling regression also demonstrated a correlation between SMI (β=0.60, P=0.040, 95% CI=0.03~1.17) (β=0.60, P=0.042, 95% CI=0.02~1.17) and hand grip strength (β=0.34, P=0.043, 95% CI=0.01~0.67) (β=0.34, P=0.045, 95% CI=0.01~0.67) with LVM. Patients with hyperthyroidism may exhibit simultaneous decreases in LVM, SMM, and SMI. The LVM in patients is correlated with SMM and hand grip strength, highlighting the need for further exploration of the causal relationship and underlying mechanisms. These findings provide a basis for the prevention and treatment of secondary sarcopenia and cardiac pathology in patients with hyperthyroidism.

Abstract 15096: miR-132 Inhibition Shows Anti-Hypertrophic Effects in Preclinical Heart Failure Models and in Exploratory Pharmacodynamic Parameters of a First-in-Human Phase 1b Clinical Trial

Introduction: Cardiac expression levels of miR-132 are elevated in patients with heart failure (HF) and have been associated and provoke pathological cardiac hypertrophy. To inhibit these cardiac remodeling processes and restore normal cardiac function, we developed the synthetic antisense oligonucleotide inhibitor CDR132L targeting miR-132. Anti-hypertrophic effects of miR-132 inhibition have been shown previously in cell culture models and a mouse model of pressure overload-induced HF. Methods and Results: MiR-132 inhibition with CDR132L was now tested in a mouse model of pressure overload induced HF induced by transverse aortic constriction (TAC) and in three different porcine HF models to further confirm the translatability of therapeutic effects. The first pig model was an early post-myocardial infarction (MI). Pigs were treated with CDR132L by intravenous (IV) or intracoronary (IC) infusion on day 3 and day 28 and analyzed on day 56 post-MI. As a second model, chronic post-MI HF pigs received monthly IV treatments over 3 or 5 months starting from month 1 post-MI. Third, percutaneous aortic constriction was induced in pigs by reduction stent implantation and CDR132L was administered IC on day 0 and day 28 followed by analysis on day 56. Hypertrophy was determined by cell size measurements in wheat germ agglutinin (WGA) stained cardiac sections and was significantly decreased between 15% and 29% in CDR132L-treated groups with sufficient dose levels compared to placebo-treatment independent from the large animal model and dosing regimen. Furthermore, TAC mice treated with CDR132L showed a significant decrease in left ventricular mass by 14 % compared to placebo. In line with these data, the cardiac remodeling marker lipocalin-2 (NGAL) was reduced in plasma of chronic HF patients assessed in a first-in-human phase 1b clinical to test safety, efficacy, and also exploratory pharmacodynamics of CDR132L (NCT04045405). Conclusions: Our results confirm beneficial effects of CDR132L treatment on pathological cardiac remodeling in HF.

Abstract 15581: Increasing Myocardial Carnosine Levels Reduces Adverse Remodeling During Heart Failure

Background : Lipid peroxidation products, such as acrolein, are highly toxic aldehydes generated during pathological remodeling and associated with heart failure. Until now, no translatable therapy has been tested to remove these toxic products from heart and examine the subsequent effects on failing hearts. The heart contains small histidyl dipeptides, such as carnosine (β-alanine-histidine), which bind lipid peroxidation products. Carnosine is decreased in failing hearts and its levels can be increased by supplementing the precursor, β-alanine. This study investigates the cardioprotective and translational potential of β-alanine supplementation in a transaortic constriction (TAC) model of heart failure. Hypothesis : Increasing myocardial carnosine via β-alanine supplementation will improve cardiac function during heart failure. Approach : Male wild-type C57BL/6J mice were treated either (a) water alone, (b) β-alanine 1 week prior to TAC, or (c) β-alanine (20g/L) in water 4 weeks post TAC. Supplementation of β-alanine was continued for 8 weeks, followed by serial echocardiography, biochemical, and mass spectrometry analysis. Results : Myocardial carnosine increased ~3-4-fold after 1 week of β-alanine feeding compared with water alone (p &lt; 0.05). β-alanine pre-feeding compared with water alone, after 8 weeks of TAC, decreased left ventricular (LV) mass (β-alanine: 174 ± 29 vs water: 241 ± 17 mg, p &lt; 0.05) and LV inner diameter at systole (β-alanine: 2.2 ± 0.6 vs water: 3.5 ± 0.4 mm, p &lt; 0.05) and diastole (β-alanine: 3.5 ± 0.4 vs water: 4.4 ± 0.3 mm, p &lt; 0.05), and increased ejection fraction (β-alanine: 67 ± 14% vs water: 42 ± 9%, p &lt; 0.05) and cardiac output (β-alanine:13.6 ± 2.6 vs water: 10.7 ± 1.0 mL/min, p &lt; 0.05). Post-TAC β-alanine intervention decreased LV mass (β-alanine :177 ± 8 vs water: 214 ± 11 mg, p &lt; 0.05), hypertrophic markers Nppa and Myh7 , and increasingly removed acrolein from heart by conjugation (β-alanine: carnosine-propanal: 12.2 ± 0.4 vs water: 0.7 ± 0.4 pmoles/mg protein, p &lt; 0.0001). Conclusion : Increasing myocardial carnosine via oral supplementation alleviates pathological remodeling, possibly through quenching reactive aldehydes. These findings lay foundation to test the feasibility of β-alanine in heart failure patients.

Abstract 15376: Nrf2 Agonist Omaveloxolone Improves Cardiac Function in Mice With Friedreich's Ataxia

Introduction: Friedreich’s ataxia (FA) is an inherited, life-shortening, degenerative neuromuscular disorder affecting ~1 in every 50,000 people in the USA and Europe. Initial symptoms, typically seen in children and teenagers, include loss of balance and coordination, muscle weakness placing these patients in wheelchairs. Early death is common and most of FA patients die in their 30s or earlier from cardiac failure, caused by deficient frataxin (FXN) expression in the heart. Omaveloxolone (OMAV), a known Nrf-2 activator, has been recently proposed as the first treatment of the neurological symptoms of FA; however less is known about OMAV effects on cardiac function in FA. Aim: To test the hypothesis that OMAV improves cardiac function in a mouse model of FA via Nfr2 signaling pathway activation. Methods and Results: Cardiospecific FXN knockout (FXN Mck-Cre KO) mice were used as a model of severe cardiomyopathy which is characteristic for the late stage of FA. Animals of either sex were randomly split in vehicle and OMAV-treated groups. Treatment with 24 mg/kg OMAV started at 3 weeks of age and continued for 5 weeks. Cardiac function was examined in-vivo by echocardiography. We found that FXN cKO mice developed severe heart failure with 45% reduction in ejection fraction, increased left ventricular (LV) mass (+80%) and diameter (+308%), decreased stroke volume (-26%) and cardiac output (-38%, n=10) as compared to WT mice (n=12). Cardiac deficits were more pronounced in FA males compared to females. OMAV (n=14) significantly decreased LV mass (-24%), LV diameter (-28%), and partially recovered a decrease in ejection fraction (+40%), stroke volume (+22%) and cardiac output (+35%). Gene expression of NADP(H) quinoline oxidoreductase-1 (NQO1), superoxide dismutase 2 (SOD2), and glutathione S-transferase were decreased by 60-90% in FA and recovered by 60-90% by OMAV. Aconitase activity, used as a surrogate measure of frataxin's iron-sulfur biogenesis function, was decreased in FA by 49% and recovered 33% by OMAV. Conclusions: This is the first study to demonstrate sexual dimorphism in FA hearts and show that OMAV can improve cardiac function in FA mice with severe cardiomyopathy.

Echocardiographic changes after arteriovenous fistula creation in hemodialysis patients.

Pulmonary hypertension (PH) is common in end-stage renal disease (ESRD) patients and is associated with increased all-cause and cardiovascular mortality in this group. There is scarce data on the long-term effect of arteriovenous fistula (AVF) creation on pulmonary hypertension (PH) and the reflected changes in echocardiographic measurements. This is a retrospective study of 54 patients who underwent AVF creation between 2009 and 2014 and with echocardiographic evaluations before and after surgery. We analyzed pairwise changes in right ventricular systolic pressure (RVSP), right atrial pressure (RAP) during systole, left ventricular mass (LVM), tricuspid regurgitation (TR), mitral E/E' ratio, and ejection fraction (EF), as well as the factors that predicted change in RVSP after surgery. The median time for the preoperative echocardiogram was 0.3 years (interquartile range (IQR) 0.2-0.7 years) prior to AVF creation, while the follow-up echo was done 1.3 (0.6-2.1) years after surgery. 67% of the patients had RVSP&gt;37 mmHg at baseline. There was a significant reduction in RVSP after AVF creation compared to baseline (median 33 (IQR 26-43) vs. 46mmHg, p=0.0015), with 59% of the patients experiencing a decrease and 19% remaining stable. There were also significant decreases in LVM (201 (143-256) vs. 215 (163-276), p=0.045) and RAP systole (10 (10-15) vs. 3 (3-8); p&lt;0.001) after surgery. Higher preoperative weight (p=0.038) and RVSP (p=0.006), and use of loop diuretics (p=0.015) were significantly associated with improvement in RVSP after AVF creation. Our results suggest that AVF creation is associated with a significant reduction or stable measurements of RVSP in the ESRD population, likely due to an improvement in volume status.

Myocardial edema during chemotherapy for gynecologic malignancies: A cardiac magnetic resonance T2 mapping study.

ObjectiveMyocardial edema is an early manifestation of chemotherapy-related myocardial injury. In this study, we used cardiac magnetic resonance (CMR) T2 mapping to assess myocardial edema and its changes during chemotherapy for gynecologic malignancies.MethodsWe enrolled 73 patients receiving chemotherapy for gynecologic malignancies, whose the latest cycle was within one month before the beginning of this study, and 41 healthy volunteers. All participants underwent CMR imaging. Of the 73 patients, 35 completed CMR follow-up after a median interval of 6 (3.3 to 9.6) months. The CMR sequences included cardiac cine, T2 mapping, and late gadolinium enhancement.ResultsMyocardial T2 was elevated in patients who were treated with chemotherapy compared with healthy volunteers [41ms (40ms to 43ms) vs. 41ms (39ms to 41ms), P = 0.030]. During follow-up, myocardial T2 rose further [40ms (39ms to 42ms) vs. 42.70 ± 2.92ms, P < 0.001]. Multivariate analysis showed that the number of chemotherapy cycles was associated with myocardial T2 elevation (β = 0.204, P = 0.029). After adjustment for other confounders, myocardial T2 elevation was independently associated with a decrease in left ventricular mass (β = −0.186; P = 0.024).ConclusionIn patients with gynecologic malignancies, myocardial edema developed with chemotherapy cycles increase, and was associated with left ventricular mass decrease. T2 mapping allows the assessment of myocardial edema and monitoring of its change during chemotherapy.

Evaluation of left ventricle systolic functions with 2D strain echocardiography after transcatheter aortic valve replacement in patients with severe aortic stenosis

ObjectiveThere is deterioration in global left ventricular (LV) longitudinal function in patients with severe aortic valve stenosis, and the decrease in LV global longitudinal strain (GLS) is associated with worsening prognosis. The aim of the study is to examine LV mechanical changes with LV strain imaging in addition to routine examination in patients who underwent transcatheter aortic valve replacement (TAVR). MethodsFifty patients who had been scheduled for the TAVR procedure between 2016 and 2018 were enrolled. The patients were evaluated before TAVR, 1 and 6 months after the procedure. The patients’ LV ejection fraction (LVEF), LVGLS, LV mass (LVM), LV mass index (LVMI), relative wall thickness (RWT), and left atrial volume index (LAVI) were calculated with transthoracic echocardiography. The patients’ performance scores were evaluated with Kansas City Cardiomyopathy Questionnaire (KCCQ-12). ResultsTwenty-six patients were female (52%), and the mean ages of patients were 75.30 ± 12.26 years. The mean LVEF of the patients was measured at 54.04 ± 13.48%, 58.10 ± 11.49%, and 59.36 ± 11.85 preprocedure and at first and 6 months, respectively. This increase in LVEF was statistically significant (p < 0.001). The mean LVGLS was measured −15.83 ± 2.78 preprocedure. The means of LVGLS were −18.73 ± 3.49 and −19.87 ± 4.05 at first and 6 months, respectively. Performance scores of patients significantly improved after the procedure (p < 0.001). The significant decreases in LVM, LVMI, RWT, and LAVI at 6 months compared to the preprocedural evaluation (p < 0.001). ConclusionIn severe aortic stenosis with deformation of LV myocardial mechanics, including GLS, a successful TAVR procedure provides a significant improvement in myocardial mechanics in early and midterm follow-up with.

Left Ventricular Mass Following Detraining In Endurance Trained Individuals: Systematic Review And Meta-analysis

Exercise training has been shown to cause unique cardiac adaptations, such as increases in left ventricular (LV) mass. Detraining or cessation of training reportedly decreases LV mass, however this has not been systematically evaluated. Furthermore, the dose-response relationship between cardiac dimensions and detraining is unknown. Purpose: This investigation aimed to systematically review the literature and conduct a meta-analysis to assess the impact of detraining on LV mass in endurance trained individuals. Methods: A literature search of prospective detraining studies was conducted using electronic databases (eg. EMBASE & MEDLINE). Inclusion criteria comprised those who were adults, endurance trained, detrained for at least one week, and findings that reported changes in LV mass. In studies that assessed LV mass at multiple time points, we used final time points in the meta-analysis. The association between the changes in LV mass and detraining was calculated using a pooled statistic for random effects; statistical significance was set at p < 0.05. Study quality was assessed by two reviewers using a modified version of the National Institute of Health (NIH) quality assessment tool. Results: Thirteen studies with a total of 189 participants (ages 18-55, 15% female) satisfied the inclusion criteria, each with various detraining programs lasting from 1.42-15 weeks. The meta-analysis revealed a significant decrease in LV mass following detraining (standardized mean difference = -0.710, 95%CI = -.874 - -0.546, p > 0.001). Changes in LV mass were not associated with length of the detraining period which appears to stabilize over detraining blocks longer than 2 weeks. Mean change in LV mass did not differ according to training level. Study quality was rated poor to fair, with inconsistent participant details and varying workloads during detraining (i.e., reduced frequency of training vs. no exercise). Conclusion: LV mass decreases as a result of detraining in healthy, endurance-trained individuals, and appears to be unaffected by length of the detraining period or training history /athlete status. Study findings are limited due to poor to fair study quality and lack of female participants. Further investigations are warranted to understand the impact of detraining on cardiac structure in healthy individuals.

Modeling the Progression of Hypertensive Kidney Disease in African Americans

Chronic kidney disease (CKD) is associated with the progressive functional loss of nephrons and hypertension (HTN). Several clinical studies demonstrate calcium channel blocker (CCB) therapy mitigates the decline in renal function in humans with essential HTN, but there are few long‐term clinical studies that determine the impact of CCBs in patients with hypertensive CKD. African Americans (AA) have a faster progression to end stage renal disease as compared to the white population which may be partially explained by factors such as salt‐sensitive blood pressure (BP) and greater prevalence of uncontrolled HTN. Observational studies demonstrate BP to be a strong independent risk factor for CKD progression, yet intense BP lowering in AA does not diminish the renal function decline any more than standard therapy. The African American Study of Kidney Disease and Hypertension (AASK) trial suggests AA with proteinuric CKD may have detrimental responses to CCB as compared to an angiotensin converting enzyme (ACE) inhibitor. Therefore, using a large physiological model, we set out to replicate the AASK trial findings and predict the roles of the renin‐angiotensin system, salt intake, and intensive antihypertensive therapy in a virtual population during CCB therapy. Our current mathematical model, HumMod, is a large physiological simulator that is comprised of key systems that play an integral role in BP control such as neural, endocrine, circulatory, and renal systems. All of the parameters (n=335) that control these systems were randomly varied and resulted in over 3,000 unique models that we define as a virtual population. We calibrated this virtual population to patient level data from the AASK trial (BP and glomerular filtration rate [GFR] before and after 3 years of amlodipine). After matching the virtual population to individual level data, the virtual population (n=140) was associated with statistically similar BP and GFR before and after CCB therapy (Figure) as well as similar increases in glomerular damage. Baseline factors such as elevated single nephron GFR and increased tubuloglomerular feedback were correlated with greater declines in renal function and increased glomerulosclerosis after 3 years of CCB. Interestingly, when looking at the models with severe CKD (&lt;35 mL/min), glomerulosclerosis and angiotensin II significantly increased with CCB despite significant falls in mean BP (‐7 ± 7 mmHg). Adding an ACE inhibitor decreased angiotensin II levels and abrogated the increase in glomerulosclerosis while further decreasing BP (‐12 ± 9 mmHg). Decreasing salt intake in addition to the CCB+ACE inhibitor therapy further benefited systemic and glomerular pressures but significantly decreased overall GFR independent of any glomerular damage. Finally, all antihypertensive therapies were associated with significant decreases in left ventricular mass. These data suggest the current clinical markers of renal function such as eGFR may not fully reflect the actual progression of CKD, especially with intensive antihypertensive treatment. Our simulation also supports that angiotensin system inhibitors are renoprotective and cardioprotective when combined with CCB therapy in African American CKD patients.

Echocardiographic assessment of intravenous administration of medetomidine and xylazine hydrochloride at different sedative doses inone-humped camel calves (Camelus dromedarious).

Echocardiography illustrates a convenient and noninvasive tool for measuring cardiac output (CO) changes after administration of sedative drugs, but it is unknown in camelids practice. The aim of present study was to investigate echocardiographic effects of intravenous (IV) injection of medetomidine and xylazine in camel calves. Twenty apparently healthy immature male one-humped camel calves (Camelus dromedarious) were divided into four groups (five animals in each treatment). Medetomidine and xylazine were injected into the left jugular vein at two different doses of 10.00 and 20.00 μg kg-1 and 0.20 and 0.40 mg kg-1, respectively. Effects on some selected echocardiographic parameters were recorded at different intervals, before drug administrations (baseline) and after 3, 60 and 120 min. Data were analyzed by repeated measure, ANOVA test, then relevance and significance were taken as p ≤ 0.05. Significant decrease in fractional shortening percentage (FS%), ejection fraction percentage (EF%), stroke volume (SV), heart rate (HR) and subsequent CO were noticeable 3 min after drug administration in medetomidine high dose (MH), medetomidine low dose (ML) and xylazine high dose (XH) groups (p ≤ 0.05), furthermore at this time significant decrease in left ventricular mass (LVmass) and left ventricular systolic time intervals were seen in these groups, however, in xylazine low dose (XL) group, the lowest level of most echocardiographic parameters were detectable after 60 min. High dose IV injection of medetomidine was associated with significant decrease in most echocardiographic parameters without echocardiographic arrhythmia. Although, ML and XH groups had the same effects on echocardiographic indices but the intensity and duration were less than MH group.

Cardiac Alterations on 3T MRI in Young Adults With Sedentary Lifestyle-Related Risk Factors.

BackgroundYoung adult populations with the sedentary lifestyle-related risk factors overweight, hypertension, and type 2 diabetes (T2D) are growing, and associated cardiac alterations could overlap early findings in non-ischemic cardiomyopathy on cardiovascular MRI. We aimed to investigate cardiac morphology, function, and tissue characteristics for these cardiovascular risk factors.MethodsNon-athletic non-smoking asymptomatic adults aged 18–45 years were prospectively recruited and underwent 3Tesla cardiac MRI. Multivariate linear regression was performed to investigate independent associations of risk factor-related parameters with cardiac MRI values.ResultsWe included 311 adults (age, 32 ± 7 years; men, 49%). Of them, 220 subjects had one or multiple risk factors, while 91 subjects were free of risk factors. For overweight, increased body mass index (per SD = 5.3 kg/m2) was associated with increased left ventricular (LV) mass (+7.3 g), biventricular higher end-diastolic (LV, +8.6 ml), and stroke volumes (SV; +5.0 ml), higher native T1 (+7.3 ms), and lower extracellular volume (ECV, −0.38%), whereas the higher waist-hip ratio was associated with lower biventricular volumes. Regarding hypertension, increased systolic blood pressure (per SD = 14 mmHg) was associated with increased LV mass (+6.9 g), higher LV ejection fraction (EF; +1.0%), and lower ECV (−0.48%), whereas increased diastolic blood pressure was associated with lower LV EF. In T2D, increased HbA1c (per SD = 9.0 mmol/mol) was associated with increased LV mass (+2.2 g), higher right ventricular end-diastolic volume (+3.2 ml), and higher ECV (+0.27%). Increased heart rate was linked with decreased LV mass, lower biventricular volumes, and lower T2 values.ConclusionsYoung asymptomatic adults with overweight, hypertension, and T2D show subclinical alterations in cardiac morphology, function, and tissue characteristics. These alterations should be considered in cardiac MRI-based clinical decision making.

Copper chelation in patients with hypertrophic cardiomyopathy

BackgroundDisturbances of copper (Cu) homeostasis can lead to hypertrophic cardiac phenotypes (eg, Wilson’s disease). We previously identified abnormal Cu homeostasis in patients with hypertrophic cardiomyopathy (HCM) and, therefore, hypothesised that...

31 Cardiac magnetic resonance findings in patients with Type 1 myotonic dystrophy

Abstract Aims Heart disease is a major determinant of prognosis in type 1 myotonic dystrophy (DM1), second only to respiratory complications. Cardiac imaging, possibly including cardiac magnetic resonance (CMR), is recommended in patients with DM1. However, limited information is available on CMR findings and their prognostic significance in DM1. Methods and results We identified all patients with DM1 evaluated from 2009 to 2020 in a CMR laboratory with an established collaboration with a Neuromuscular Disorder Unit. Thirty-four patients were retrieved (21 males, aged 45 ± 12). By the time of CMR examination, 90% had neuromuscular symptoms (mean duration 17 ± 13 years), 13 (38%) had previous reports of atrioventricular block (n = 12 1st degree, n = 1 2nd degree type 1), 30 (88%) of intraventricular conduction disturbances (n = 5 left bundle branch block, n = 5 right bundle branch block, n = 3 left anterior fascicular block, n = 17 other non-specific or incomplete intraventricular conduction delay), 4 (12%) of atrial fibrillation or flutter. No patient had a device. At CMR, 5 (15%) patients had left ventricular (LV) systolic dysfunction [LV ejection fraction (LVEF) &amp;lt;50%] and 4 (12%) a depressed right ventricular (RV) function (RVEF &amp;lt;50%). Compared to age- and sex-specific reference values for our laboratory (Figure 1 left), 12 (35%) patients showed a decreased LV end-diastolic volume index (LVEDVi), 7 (21%) a decreased LV mass index (LVMi), and 29 (85%) a decreased LVMi/LVEDVi ratio. Nine (26%) patients had mid-wall late gadolinium enhancement (LGE, mean extent 4.5 ± 2.0% of LVM; n = 8 septal, n = 4 inferolateral, n = 2 inferior, n = 1 anterolateral, see Figure 1 middle), and 14 (41%) some areas of fatty infiltration (n = 9 involving the LV, n = 13 the RV). Native T1 in the interventricular septum (1,041 ± 53 ms) approached the upper reference limit (1089 ms), and the extracellular volume was slightly increased (33 ± 2%, reference values &amp;lt;30%). Over a median follow-up of 2.5 years (interquartile interval: 1.5–4.0), 2 (6%) patients died for infectious and respiratory complications, 5 (15%) underwent device implantation (n = 4 PM; n = 1 ICD), and 4 (12%) had a documentation of high-risk (Lown class ≥4) ventricular ectopic beats (VEBs). Among all CMR variables collected, higher values of LVMi/LVEDVi ratio emerged as univariate predictor of all-cause death (P = 0.044). At logistic regression analysis, anteroseptal wall thickness was associated with the need for device implantation (P = 0.028), while LGE mass was associated with high-risk VEBs (P = 0.026) (Figure 1 right). Conclusions Patients with DM1 display several structural and functional cardiac abnormalities, with variable degrees of cardiac muscle hypotrophy, fibrosis, and fatty infiltration. The possibility to predict the need for device implantation, ventricular arrhythmias, and all-cause or cardiovascular mortality should be verified in larger cohorts.

Effect of sodium-glucose co-transporter 2 inhibitors on left ventricular mass and left atrial volume indices assessed either by cardiovascular magnetic resonance or transthoracic echocardiography

Abstract Background Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are a novel class of antidiabetic regimens linked with a significant reduction in the risk for surrogate cardiovascular and renal outcomes. Specific patient populations, for example subjects with heart failure with reduced ejection fraction (HFrEF), also benefit from this drug class, regardless the presence of T2DM. Left ventricular (LV) hypertrophy is a strong, independent predictor of cardiovascular morbidity and mortality; left atrial volume index (LAVI), an indicator of severity of LV diastolic dysfunction and filling properties, has been shown to predict “hard” cardiovascular outcomes among patients with T2DM, while it might predict the recovery of left ventricular ejection fraction in patients with HFrEF. Purpose We sought to determine the effect of SGLT-2 inhibitors on the above indices, in order to evaluate additional cardioprotective mechanisms of this drug class. Methods We searched 2 major electronic databases (PubMed and Cochrane/CENTRAL) along with grey literature sources for parallel-group RCTs investigating the effect of SGLT-2 inhibitors compared to placebo or active control on LV mass, LV mass index (LVMI) and LAVI, evaluated either by TTE or CMR, on adult patients regardless the presence of T2DM or HF. Results After screening the potentially eligible records, 9 studies were included in our analysis with a total of 843 patients. Treatment with SGLT-2 inhibitors compared to placebo or active control leads to a statistically significant decrease in LV mass by 6.01 g (95% CI −11.33 to −0.69, I2=76%) (Figure 1a). A significant decrease in LVMI by 2.61 g/m2 was observed (MD=−2.61, 95% CI −4.94 to −0.29, I2=65%) (Figure 1b). Of note, the effect on LAVI was marginally non-significant (MD=−1.51 ml/m2, 95% CI −3.05 to 0.03, I2=0%) (Figure 1c). Subgroup analysis for patients with HFrEF demonstrated a non-significant reduction in LV mass (MD=−11.72 g, 95% CI −30.61 to 7.16, I2=90%) and in LVMI (MD=−6.28 g/m2, 95% CI −30.61 to 0.25, I2=80%) (Figure 2a and 2b). Conclusions SGLT-2 inhibitors demonstrate a clear benefit on LV mass and LVMI, regardless of diabetes status, while a marginally non-significant effect is observed on LAVI. These results provide further insights into the cardioprotective mechanisms mediated by this drug class, besides those already established. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Long term effects of surgical and transcatheter aortic valve replacement on FFRCT in patients with severe aortic valve stenosis.

The long-term variations of fractional flow reserve derived from coronary computed tomography (FFRCT) after surgical (SAVR) or transcatheter (TAVR) aortic valve replacement in patients with severe aortic valve stenosis (AS) have not been investigated. A total of 25 patients with isolated, severe AS underwent coronary computed tomography with 3-vessel FFRCT analysis (Heartflow Inc.-Redwood City, California, USA) and measurement of total coronary volume (V), left ventricular mass (M) and their ratio (V/M) before and 6months after SAVR or TAVR. A significant increase in V/M due to a decrease in left ventricular mass 6months after intervention was observed, whereas total coronary volume did not change (coronary volume pre: 2924.5 ± 867.9mm3, coronary volume post: 2844.2 ± 792.8mm3, P = 0.158; LV mass pre: 151.7 ± 40.7g, LV mass post: 127.3 ± 34.7g, P < 0.001; V/M pre: 19.5 ± 4.1mm3/g, V/M post: 22.7 ± 4.28mm3/g, P = 0.002). FFRCT (expressed as area under the virtual pullback curve) remained constant. This proof-of-concept study showed that FFRCT was not subject to the confounding effect of left ventricular mass regression after SAVR or TAVR. Despite significant left ventricular remodeling at 6months after AS treatment, FFRCT values remained constant. Further studies are needed comparing the performance of the different invasive and non-invasive coronary physiological indices in this patient cohort.

Sodium-glucose co-transporter 2 inhibitors in heart failure with preserved ejection fraction: reasons for optimism.

Sodium-glucose co-transporter 2 inhibitors in heart failure with preserved ejection fraction: reasons for optimism.