Decrease In Left Ventricular Mass Research Articles

Cardiac magnetic resonance findings in patients with type 1 myotonic dystrophy

Abstract Funding Acknowledgements Type of funding sources: None. Background 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 We identified all patients with DM1 evaluated from 2009 to 2020 in a CMR laboratory with an established collaboration with a Neuromuscular Disorder Unit. Results Thirty-four patients were retrieved (21 males, aged 45 ± 12). At the time of CMR examination, 97% had neuromuscular symptoms (mean duration 16 ± 13 years), 12 (35%) presented with atrioventricular block (n = 11 1st degree, n = 1 2nd degree type 1), 15 (44%) with intraventricular conduction disturbances (n = 5 left bundle branch block, n = 5 right bundle branch block, n = 3 left anterior fascicular block, n = 2 other non-specific intraventricular conduction delay), 4 (12%) with atrial fibrillation or flutter. No patient had a device. At CMR, 5 (15%) patients had left ventricular (LV) systolic dysfunction (LV ejection fraction [LVEF] <50%) and 5 (15%) a depressed right ventricular (RV) function (RVEF <50%). Compared to age- and sex-specific reference values for our laboratory, 12 (35%) patients showed a decreased LV end-diastolic volume index (LVEDVi), 7 (21%) a decreased LV mass index (LVMi), and 29 (83%) 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), and 14 (40%) 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 (1,089 ms), and the extracellular volume was slightly increased (33 ± 2%, reference values <30%). Over a median follow-up of 3.3 years (interquartile interval 1.6-4.7), 2 (6%) patients died, one for infectious and respiratory complications and the other for unknown causes, 5 (15%) patients underwent pacemaker implantation for conduction disturbances, 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 pacemaker implantation (p = 0.028), while LGE mass was associated with high-risk VEBs (p = 0.026). 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 pacemaker implantation, ventricular arrhythmias and all-cause or cardiovascular mortality should be verified in larger cohorts.

Long-Term Impact of Arteriovenous Fistula Ligation on Cardiac Structure and Function in Kidney Transplant Recipients: A 5-Year Follow-Up Observational Cohort Study.

The long-term effects of arteriovenous fistula (AVF) ligation on cardiovascular structure following kidney transplantation remain uncertain. A prospective randomized, controlled trial (RCT) examined the effect of AVF ligation at 6 months on cardiovascular magnetic resonance imaging (CMR)-derived parameters in 27 kidney transplant recipients compared with 27 controls. A mean decrease in left ventricular mass (LVM) of 22.1 g (95% CI, 15.0 to 29.1) was observed compared with an increase of 1.2 g (95% CI, -4.8 to 7.2) in the control group (P<0.001). We conducted a long-term follow-up observational cohort study in the treated cohort to determine the evolution of CMR-derived parameters compared with those documented at 6 months post-AVF ligation. We performed CMR at long-term follow-up in the AVF ligation observational cohort from our original RCT published in 2019. Results were compared with CMR at 6 months postintervention. The coprimary end point was the change in CMR-derived LVM and LVM index at long-term follow-up from imaging at 6 months postindex procedure. At a median of 5.1 years (interquartile range, 4.7-5.5 years), 17 patients in the AVF ligation group were studied with repeat CMR with a median duration to follow-up imaging of 5.1 years (IQR, 4.7-5.5 years). Statistically significant further reductions in LVM (-17.6±23.0 g, P=0.006) and LVM index (-10.0±13.0 g/m2, P=0.006) were documented. The benefit of AVF ligation on LVM and LVM index regression appears to persist long term. This has the potential to lead to a significant reduction in cardiovascular mortality.

Long-term outcomes of renal denervation and related sex characteristics: data from a three-year follow-up

Aim. To study the long-term outcomes of renal denervation (RDN) within 3-year follow-up with an assessment of blood pressure (BP) changes, the severity of target organ damage and the levels of pro- and anti-inflammatory cytokines in patients with resistant hypertension (RH), taking into account sex characteristics.Material and methods. A total of 42 patients with RH were examined at baseline, 1, 2, and 3 years after RDN on the background of antihypertensive therapy. Twenty-four-hour BP monitoring, echocardiography, assessment of creatinine level and estimated glomerular filtration rate (eGFR), as well as determination of some cytokines (interleukin (IL)-1β, 6, 10, tumor necrosis factor-α) were performed.Results. There was a persistent BP decrease in men and women for three years compared with the initial level by an average of 17 [4; 31]/10 [0; 18] mm Hg (p&lt;0,05). Decrease in BP variability from 17,9±5,1 to 15,2±3,6 mm Hg was observed mainly by means of women, while the decrease in left ventricular mass from 250,4±64,0 to 229,3±61,9 g was mainly by means of men. Creatinine level was unchanged, while eGFR decreased from 78,8±16,1 to 74,5±20,3 ml/ min/1,73 m2 over 3 years; the mean eGFR decline was 1,4 ml/min/1,73 m2 in year. All studied cytokines tended to decrease regardless of sex: tumor necrosis factor-α — from 2,1 [1,2; 77] to 2,1 [1,7; 2,6] pg/ml (p=0,022); IL-1β — from 2,2 [1,5; 2,4] to 1,6 [1,1; 1,5] pg/ml (p=0,034); IL-6 — from 3,8 [1,6; 4,9] to 2,8 [1,8; 3,0] pg/ml (p&gt;0,05), IL-10 — from 5,8 [3,2; 8,2] to 2,8 [2,6; 2,9] pg/ml (p=0,000), correlating with IL-6 dynamics.Conclusion. Three years after RDN, there is a persistent decrease in mean 24-hour BP, regardless of sex. In women, a more pronounced BP variability decrease is observed, while in men — regression of left ventricular mass. There is no significant decrease in eGFR in the long-term period. The decrease in proinflammatory cytokines maintains, and in some cases becomes more pronounced within three years after RDN.

Reduction of arteriovenous access blood flow leads to biventricular unloading in haemodialysis patients

AimsPatients on chronic haemodialysis have a wide range of changes in cardiac function and structure, including left ventricular hypertrophy, dilation and diastolic dysfunction or pulmonary hypertension. All these changes were linked to increased mortality in previous studies. High-flow arteriovenous fistulas (AVF) are supposed to be a factor contributing to their development. This study investigated the early effect of surgical AVF blood flow (Qa) reduction on these changes in patients with or without heart failure changes. Methods and resultsForty-two patients in chronic haemodialysis programme with high-flow AVF (Qa over 1500 mL/min), indicated for surgery for ≥1 of the following indications: 1.manifest heart failure; 2.hand ischemia; 3.advanced structural heart changes detected by echocardiography. The patients underwent echocardiography on selection visit, before blood flow reducing surgery and six weeks thereafter. The Qa reduction led to decrease of left ventricular mass (p = 0.02), end-diastolic volume (p = 0.008), end-diastolic diameter (p = 0.003) and left atrial volume (p = 0.0006). Diastolic function improved. Similarly, right ventricular diameter and right atrial volume decreased (p = 0.000001 and 0.00009, respectively) together with the decrease of estimated pulmonary artery systolic pressure. 81% of patients suffered from pulmonary hypertension prior to surgery, only 36% thereafter. ConclusionThe surgical restriction of the hyperkinetic circulation leads to several improvements of heart structure and function, which was linked to higher mortality in other studies. The beneficial effect of Qa reduction is present even in patients without symptoms of heart failure. The contribution of AVF must be considered with structural or functional heart changes.

Damage to cardiac vasculature may be associated with breast cancer treatment-induced cardiotoxicity

BackgroundBreast cancer is the most common female cancer worldwide. Effective therapies including doxorubicin and trastuzumab have improved survival, but are associated with a substantial risk of cardiovascular disease. Mechanisms underlying cancer treatment-induced cardiotoxicity (CTC) are poorly understood and have largely focused on cardiomyocyte damage, although other cellular populations in the heart such as the cardiac endothelium, may play an important role in cardiac damage. We treated a breast tumor-bearing mouse model with doxorubicin and trastuzumab to investigate the role of the cardiac endothelium in the development of CTC.MethodsImmune compromised mice were inoculated in the 4th mammary fat pad with human breast cancer cells overexpressing HER2 (BT474). When tumors were palpable, mice were treated weekly with doxorubicin (5 mg/kg) and trastuzumab (4 mg/kg). The cardiac phenotype of mice was assessed by echocardiography and histological evaluation of the heart. Cardiac vascular damage was assayed by in vivo permeability assays and primary cultures of murine cardiac endothelial cells were used to assay doxorubicin toxicity in vitro.ResultsThe growth of BT474 breast tumors in Balb/c Nude mice was suppressed upon treatment with doxorubicin and trastuzumab. Mice treated for 4 months with doxorubicin and trastuzumab maintained body weights, but demonstrated an echocardiographic phenotype consistent with preserved left ventricular (LV) ejection fraction, decreased LV mass and increased filling pressures (E/e’). Histological staining with Masson’s trichrome and Picrosirius red showed extensive fibrosis and increased collagen deposition in the ventricular myocardium surrounding blood vessels of treated mice compared to untreated mice. Evans blue permeability assays demonstrated increased cardiac vasculature permeability while primary cardiac endothelial cells exposed to doxorubicin in vitro showed increased cell death as compared to lung or liver endothelial cells.ConclusionsAn orthotopic mouse model of human breast cancer in Nude mice treated with doxorubicin and trastuzumab resulted in a cardiac vascular defect accompanied by preserved LV ejection fraction, decreased LV mass, suggesting mild diastolic dysfunction and cardiac remodeling consistent with subclinical cardiotoxicity. Our data suggest that cardiac endothelium is more sensitive to doxorubicin therapy as compared to other organ endothelium and cardiac endothelial damage may correlate with breast cancer treatment-induced cardiotoxicity.

META-ANALYSIS ASSESSING THE EFFECTS OF ALLOPURINOL ON LEFT VENTRICULAR MASS AND OTHER INDICES OF LEFT VENTRICULAR REMODELING AS EVALUATED BY CARDIAC MAGNETIC RESONANCE IMAGING

Objective: Hyperuricemia is a relatively common morbidity, featuring a close relationship with cardiovascular disease, hypertension, heart failure and chronic kidney disease, while it is also related to the development of type 2 diabetes mellitus. Allopurinol remains the mainstay of treatment. We sought to determine whether allopurinol affects left ventricular (LV) mass and other measures of LV remodeling, as assessed by cardiac magnetic resonance imaging (cMRI). Design and method: We performed a systematic search in two major electronic databases, PubMed and Cochrane Central Register of Controlled Trials (CENTRAL), for eligible randomized controlled trials (RCTs), from their inception to September 2020, along with grey literature sources. Results: Our search yielded 84 results in total. Finally, 4 records were included in our quantitative synthesis. Our analysis in a total of 225 patients showed that allopurinol treatment produced a non-significant decrease in LV mass by 1.42 g (MD = -1.42, 95% CI -6.34 to 3.50, I2 = 90%), and a non-significant decrease in LV mass index by 1.47 g/m2 (MD = -1.47, 95% CI -3.91 to 0.96, I2 = 91%). In addition, allopurinol did not decrease significantly neither LV end systolic volume (MD = -0.45 mL, 95% CI -5.53 to 4.64, I2 = 56%) nor LV end diastolic volume (MD = -2.98 mL, 95% CI –9.39 to 3.43, I2 = 35%). Finally, allopurinol did not affect significantly LV stroke volume (MD = 2.06 mL, 95% CI –2.02 to 6.14, I2 = 0%). We consider as major limitations of the present meta-analysis the small number of included RCTs and enrolled participants, which did not permit us to perform subgroup analyses in order to investigate the sources of heterogeneity. Conclusions: Conclusion: Allopurinol does not exert a significant effect on LV mass and other indices of LV remodeling, as quantified by cMRI, in a broad population with significant cardiovascular co-morbidities.

MTOR inhibition improves mitochondria function/biogenesis and delays cardiovascular aging in kidney transplant recipients with chronic graft dysfunction.

CVD remains the major cause of mortality with graft functioning in Kidney transplant recipients (KTRs), with an estimated risk of CV events about 50-fold higher than in the general population. Many strategies have been considered to reduce the CV risk such as the use of mTOR inhibitors. We evaluate whether chronic mTOR inhibition might influence CV aging in KTRs studying the molecular mechanisms involved in this effect. We retrospectively analyzed 210 KTRs with stable graft function on therapy with CNI and mycophenolic acid (Group A, 105 pts.), or with CNI and mTORi (Everolimus, Group B, 105 pts.). The presence of mTOR inhibitor in immunosuppressive therapy was associated to increase serum levels of Klotho with concomitant reduction in FGF-23, with a significant decrease in left ventricular mass. In addition, KTRs with mTORi improved mitochondrial function/biogenesis in PBMC with more efficient oxidative phosphorylation, antioxidant capacity and glutathione peroxidase activity. Finally, group B KTRs presented reduced levels of inflammaging markers such as reduced serum pentraxin-3 and p21ink expression in PBMC. In conclusion, we demonstrated that mTOR inhibition in immunosuppressive protocols prevents the occurrence and signs of CV aging in KTRs.

Abstract P758: Ischemic Stroke Induced Cardiac Dysfunction in Aged Mice

Introduction: Acute ischemic stroke patients with cardiac complications have increased in-hospital mortality. Most of these cardiac complications have been attributed to pre-existing cardiac comorbidities. Aging is a known risk factor for both stroke and myocardial injury. It is being increasingly recognized that ischemic injury to the brain in itself may lead to cardiac injury. However, the post stroke brain- heart interaction is not well defined in the aged. This study was designed to fill this gap in our knowledge. Methods: C57BL6/J young (3 months) and aged (18 months) male mice were subjected to 60 minutes of middle cerebral artery occlusion (MCAO). Mice had electrocardiogram (EKG, using rodent surgical monitor) and Echocardiogram (using vevo 3100 imaging system) pre-stroke, post stroke day 3, 7, and 14. All mice were sacrificed at day 14. EKG and ECHO results were analyzed using generalized estimated equation method with post hoc group comparison test at each time point, Bonferroni correction. Results: There was a significant decrease in cardiac output after stroke in aged but not young mice at three days post stroke, as compared to baseline (young, baseline:18.5±1.6ml/min vs day 3:16.6±5.16 ml/min, n=8; aged, baseline 25.4±6.8 6 ml/min vs. day 3, 16.8±6.8 n=6, p=0.0038). The cardiac output normalized to baseline in young but remained significantly low in aged mice even at day 14. Interestingly, the Left ventricular (LV) mass decreased significantly after stroke in aged mice at day 3, 118.4±23.2 mg as compared to baseline, 160.7±22.9 mg. This remained significantly lower than baseline at post stroke day seven, 124.6±32.9 mg and fourteen, 129.5±37.2 mg, p&lt;0.05. A similar trend was seen in left ventricular anterior and posterior wall thickness. There was no significant change in LV mass in young mice, p&gt;0.05. Conclusion: Our data indicates that cardiac output decreases after stroke in aged mice. Interestingly, there is a significant decrease in left ventricular mass and ventricular wall thickness in aged mice after MCAO, indicating cardiac atrophy. We speculate this may be secondary to cardiac ischemia caused by stroke. Ongoing work in our laboratory is aimed at examining the histological changes in cardiomyocytes after MCAO.

Abstract 14042: Weight Loss Favorably Impacts Left Ventricular Mass and Wall Thickness by CMR and CT in Patients With Hypertrophic Cardiomyopathy: A Retrospective Case Series

Introduction: Hypertrophic Cardiomyopathy (HCM) is a relatively common inherited heart disease with variable phenotypic expression. While pathogenic variants in sarcomeric genes are considered responsible for the development of left ventricular (LV) hypertrophy, environmental modulation of phenotype may explain the known heterogeneity. Obesity is common in HCM patients and is associated with increased LV mass in the general population. Hypothesis: We hypothesized that weight loss in obese patients with HCM would be associated with a decrease in LV mass and maximal wall thickness. Methods: Patients with HCM who achieved therapeutic weight loss and underwent cardiac MRI (CMR) or computed tomography (CT) before and afterwards were included. Standard LV measurements including wall thickness in an 18-segment model were performed blindly with respect to name, time and BMI for un-biased comparison. Results: We included 6 patients (2 female, age 55 ± 6.5 years, baseline BMI = 36.7 ± 5.2 kg/m 2 ) who achieved 16.3 ± 10.8 kg weight loss after 35 ± 12 months with diet and exercise (n=4) or bariatric surgery (n=2). After weight loss, we observed a mean proportional decrease in total LV mass of 25 ± 16% (p=0.004), and a 19 ± 7% decrease in indexed LV mass (p=0.007). Furthermore, there was a numerical decrease in mean wall thickness in 14 out of 18 LV segments measured; 9 segments had more than a 10% decrease. The most noticeable changes were at the basal inferolateral wall (25 ± 13% decrease) and basal inferoseptum (19 ± 18%) decrease (Table). Conclusions: In this series of patients with HCM, weight loss favorably affected LV mass and wall thickness. Further research is needed to explore the impact of weight loss on HCM phenotypic expression and symptoms.

Distal renal denervation: cardioprotection in patients with resistant hypertension

Aim. To study the effectiveness of using the anatomically optimized distal renal denervation (RDN) in comparison with the standard approach for reducing myocardial damage and left ventricular (LV) hypertrophy in patients with resistant hypertension (HTN).Material and methods. The randomized double-blind study of the efficacy and safety of distal RDN compared to conventional main renal artery intervention (ClinicalTrials.gov NCT02667912) for the treatment of resistant HTN included 26 patients. All patients were divided into two groups: group 1 (n=16) — distal RDN, group 2 (n=10) — conventional RDN. In addition to 24-hour blood pressure (BP) monitoring, initially and 12 months after the intervention, contrast- enhanced cardiac magnetic resonance imaging was performed to determine the left ventricular mass and non-coronary myocardial damage area. All patients signed informed consent. Twenty-four patients completed the present study.Results. After 12 months, the mean 24-hour BP significantly decreased after both distal RDN (from 167,2±28,5/93,2±19,3 to 147,0±13,7/81,5±9,3 mm Hg (p&lt;0,05)) and conventional RDN (from 157,5±22,5/90,6±23,9 to 139,9±17,7/80,0±16,7 (p&lt;0,05)). Also in both cases, a trend to LV mass decrease was revealed: from 252,6±85,2 to 221,0±60,3 gm (p=0,096) after the distal RDN; from 214,3±54,1 to 186,4±48,1 gm (p=0,071) after the conventional RDN. In contrast, the myocardial damage area decreased only after distal RDN (from 2,33±1,33 to 1,35±0,67 cm3 (p=0,02)) and did not change after conventional RDN.Conclusion. In comparison with the conventional main renal artery intervention, distal RDN in patients with resistant HTN has an additional cardioprotective effect — a decrease in LV myocardial damage area.

Physical Exercise Combined with Antihypertensive Drug Therapy on Left Ventricular Hypertrophy: Systematic Review and Meta-Analysis.

Physical exercise and antihypertensive drugs contribute to reduce or prevent hypertensive heart disease (HHD). The effect on blood pressure (BP) of both combined therapy is well documented, but not for the left ventricular (LV) function. A systematic review and meta-analysis was conducted for LV biomarkers analysis regarding to HHD on subjects treated with antihypertensive drugs combined with physical exercise practice. The search was conducted on the Pubmed, Bireme, Lilacs, Central (Cochrane) and Science direct databases, comprising undetermined period of time, including randomized studies comparing trained and sedentary subjects, both treated with antihypertensive drugs. We analyzed the influence of combined therapy on echocardiogram parameters and BP. A significance level of 5% and 95% CI was considered for all outcomes. Five studies (N=1738) were included in meta-analysis. Combined therapy decreased significantly LV mass (CI -21.63 to -1.81, N=783) and heart rate (HR; CI -4.23 to -1.59, N=1738), compared to antihypertensive drugs alone. There was a trend to decrease LV mass index (LVMI; CI -5.57 to 0.71, N=1674), systolic BP (CI -2.47 to 1.23, N=1674) and diastolic BP (CI -2.16 to 0.28, N=1674), a trend to increase of ejection fraction (EF; 95% CI -0.50 to 2.12, N=783) and LV end-diastolic diameter (CI -0.85 to 0.92, N=847) was similar. The antihypertensive therapy combined with physical exercise practice can reduce LV mass and HR. Therefore, combined therapy prescription should be considered for prevention and treatment of LV hypertrophy of hypertensive subjects.

Sacubitril/Valsartan Inhibits Cardiomyocyte Hypertrophy in Angiotensin II-Induced Hypertensive Mice Independent of a Blood Pressure-Lowering Effect.

BackgroundHypertensive left ventricular hypertrophy is associated with the risk of heart failure, coronary heart disease and cerebrovascular disease. Although sacubitril/valsartan (SAC/VAL), a first-in-class angiotensin receptor neprilysin inhibitor, reduces the risks of death and hospitalization for patients with heart failure, its mechanism of action is not fully understood. We hypothesized that SAC/VAL is superior to other conventional drugs in reducing cardiac hypertrophy.MethodsMale C57BL/6J mice were implanted with an osmotic pump containing angiotensin II (Ang II). After 7 days of Ang II infusion, mice were also treated with either SAC/VAL, valsartan, enalapril or vehicle alone each day for 2 weeks. Blood pressure measurement was done weekly, and echocardiography was performed before and 3 weeks after infusion of Ang II. Histological analyses were done using extracted heart to investigate cardiac hypertrophy and fibrosis.ResultsAng II markedly elevated blood pressures in all of the treatment groups, and there were no differences in the degree of blood pressure reduction among the SAC/VAL-, valsartan- and enalapril-treated groups. Echocardiography showed that SAC/VAL significantly suppressed the increase in left ventricular (LV) wall thickness and tended to decrease LV mass. In a histological analysis, SAC/VAL inhibited Ang II-induced cardiomyocyte hypertrophy, and individual cardiomyocytes in the SAC/VAL group were smaller than those in the valsartan and enalapril groups. Although previous studies using animal models of heart failure have indicated that SAC/VAL attenuates cardiac fibrosis, we found no supporting evidence in this setting.ConclusionsSAC/VAL, valsartan and enalapril all attenuated cardiomyocyte hypertrophy in a mouse model of Ang II-induced cardiac hypertrophy. Of note, SAC/VAL most strongly suppressed hypertrophy in spite of similar blood pressure-lowering effects as valsartan and enalapril. The present study suggests that SAC/VAL may have a beneficial effect on the early stage of hypertensive heart disease.

P586Left ventricular volume and mass adaptation after 58-days head-down bed-rest assessed by cine-MRI, and effectiveness of high-intensity jump training countermeasure

Abstract Aims Prolonged immobilization generates cardiac deconditioning, a risk factor for cardiovascular disease, and efficient countermeasures (CM) are needed to prevent it. Our aim was to assess by Cine-MRI the effects of long-term strict head-down (−6 degrees) bed-rest (BR) deconditioning, and the effectiveness of high-intensity jump training CM, on left ventricular (LV) function and mass. Methods 23 male participants (29±6 years, 181±6 cm, 77±7 kg) were enrolled. The experiment was conducted at: envihab (Koln, DLR, Germany) as part of the European Space Agency BR studies. Volunteers were randomly allocated to the jump training group (JUMP, n=12) or the control group (CTRL, n=11). A typical training session consisted of 4x10 countermovement jumps and 2x10 hops in a sledge jump system, with 5–6 sessions per week. Steady-state free precession cine-MRI images were obtained (25 frames/cardiac cycle, 8mm thickness, no gap, no overlap) as stack of short-axis images covering the whole LV from base to apex, before (PRE) and after 58-days (HDT58) of BR. Endocardial and epicardial semi-automated contouring was performed using custom software. Results In CTRL group, at HDT58 a reduction in LV mass (9%), end-diastolic (21%), end-systolic (8%) and stroke volume (23%) were observed, while ejection fraction did not change. In JUMP group, the reduction in LV end-diastolic volume was only by 9%, followed by a decrease in end-systolic (10%) and stroke volume (10%), with a preservation of LV mass. In both groups, ejection fraction did not change. Left ventricular changes after 58d BR EDV (ml) ESV (ml) SV (ml) EF (%) Mass (g) CTRL PRE 171 (163; 191) 60 (58; 65) 113 (102; 124) 64 (63; 67) 133 (121; 160) HDT58 143 (131; 149)* 56 (50; 58)* 86 (83; 92)* 62 (60; 63)* 127 (106; 138)* JUMP PRE 156 (140; 204) 70 (61; 84) 91 (78; 117) 58 (56; 60) 118 (104; 134) HDT58 141 (135; 175)* 63 (54; 69)* 90 (78; 92)* 58 (55; 60) 113 (105; 128) Results expressed as median (25th; 75th percentiles). *p&lt;0.05 Wilcoxon non parametric paired test (PRE vs HDT58). CTRL: control group; JUMP: countermeasure group. Conclusions Cardiac adaptation to deconditioning due to immobilization induced by BR resulted in a reduction of cardiac volumes and function, together with a decrease in LV mass. Interestingly, the applied JUMP countermeasure appeared able to partially reverse these effects, in particular by reducing the decrease in end-diastolic volume and preserving LV mass. This information could be useful for better understanding physiologic changes in patients undergoing long periods of immobilization, as well as to apply the studied countermeasure during space flight to reduce cardiac deconditioning. Acknowledgement/Funding Italian Space Agency (contract 2018-7-U.0),CNES/DAR 48ehz747.01950965,BELSPO, via the European Space Agency PRODEX program (PEA 4000110826)

P3454Myocardial reverse remodeling occurs to a comparable extent in male and female aortic-banded rats following pressure unloading

Abstract Background Sex differences have been intensely investigated during the development of pressure overload (PO; e.g. aortic stenosis, arterial hypertension)-induced left ventricular (LV) myocardial hypertrophy (LVH). However, it is less clear whether sex-related differences also affect the regression of pathological LVH after pressure unloading. Purpose Therefore, we investigated the potential influential effect of sex on myocardial reverse remodeling in a relevant rat model of banding and debanding of the abdominal aorta. Methods PO of the left ventricle was induced in male (M) and female (F) rats by abdominal aortic banding (AB) for 6 or 12 weeks. Sham operated animals served as controls. Pressure unloading was evoked by removing the aortic constriction at week 6 (debanded). Serial echocardiography was performed to detect temporal alterations in LV morphology and geometry. Furthermore, distinct aspects of LV systolic and diastolic function were assessed by pressure-volume analysis. Structural changes, such as cardiomyocyte hypertrophy and interstitial fibrosis were measured on histological sections. Fetal gene expression (a molecular marker of pathological LVH) was analyzed by quantitative real-time PCR. Results In both male and female AB rats, PO induced the development of marked LVH as confirmed by increased LV mass, heart weight-to-tibial length ratio (HW/TL [g/cm]: 0.47±0.01 AB-M vs. 0.36±0.01 Sham-M, p&lt;0.05; 0.36±0.02 AB-F vs. 0.26±0.01 Sham-F, p&lt;0.05) and cardiomyocyte diameter. Similarly, reactivation of fetal gene expression (indicated by increased atrial natriuretic peptide [ANP]) and enhanced interstitial collagen accumulation was also observed in male and female AB groups as well. The extent of myocardial hypertrophy was greater among female AB animals, while fibrosis was more severe in male AB rats. In both genders, LVH was associated with prolonged ventricular relaxation (active relaxation time constant, Tau [ms]: 19.6±0.8 AB-M vs. 13.1±0.4 Sham-M, p&lt;0.05; 15.2±1.3 AB-F vs. 12.2±0.3 Sham-F, p&lt;0.05). However, systolic function was impaired only in males (ejection fraction, [%]: 44.4±2.3 AB-M vs. 57.5±2.1 Sham-M, p&lt;0.05; 49.7±2.2 AB-F vs. 53.4±1.7 Sham-F, n.s.). Contrary to the sex-dependent differences during the development of LVH, removing the aortic constriction resulted in a comparable degree of reverse remodeling on the morphological (decreased LV mass, HW/TL), histological (decreased CD and interstitial fibrosis), molecular (reduced ANP expression) and functional (recovered ejection fraction and Tau) levels in both male and female rats. Conclusion Pressure unloading at a relatively early time point leads to myocardial reverse remodeling to a comparable degree in male and female rats. Acknowledgement/Funding NVKP-16-1-2016-0017; ÚNKP-18-3-I-SE-9

Short-term exercise training improves cardiac function associated to a better antioxidant response and lower type 3 iodothyronine deiodinase activity after myocardial infarction.

AimsWe assessed the effects of a short-term exercise training on cardiac function, oxidative stress markers, and type 3 iodothyronine deiodinase (D3) activity in cardiac tissue of spontaneously hypertensive rats (SHR) following experimental myocardial infarction (MI).MethodsTwenty-four SHR (aged 3 months) were allocated to 4 groups: sham+sedentary, sham+trained, MI+sedentary and MI+trained. MI was performed by permanent ligation of the coronary artery. Exercise training (treadmill) started 96 hours after MI and lasted for 4 weeks (~60% maximum effort, 4x/week and 40 min/day). Cardiac function (echocardiography), thioredoxin reductase (TRx), total carbonyl levels, among other oxidative stress markers and D3 activity were measured. A Generalized Estimating Equation was used, followed by Bonferroni’s test (p<0.05).ResultsMI resulted in an increase in left ventricular mass (p = 0.002) with decreased cardiac output (~22.0%, p = 0.047) and decreased ejection fraction (~41%, p = 0.008) as well as an increase in the carbonyl levels (p = 0.001) and D3 activity (~33%, p<0.001). Exercise training resulted in a decrease in left ventricular mass, restored cardiac output (~34%, p = 0.048) and ejection fraction (~20%, p = 0.040), increased TRx (~85%, p = 0.007) and reduced carbonyl levels (p<0.001) and D3 activity (p<0.001).ConclusionsOur short-term exercise training helped reverse the effects of MI on cardiac function. These benefits seem to derive from a more efficient antioxidant response and lower D3 activity in cardiac tissue.

Regression of Left Ventricular Mass in Athletes Undergoing Complete Detraining Is Mediated by Decrease in Intracellular but Not Extracellular Compartments.

Background:Athletic cardiac remodeling can occasionally be difficult to differentiate from pathological hypertrophy. Detraining is a commonly used diagnostic test to identify physiological hypertrophy, which can be diagnosed if hypertrophy regresses. We aimed to establish whether athletic cardiac remodeling assessed by cardiovascular magnetic resonance is mediated by changes in intracellular or extracellular compartments and whether this occurs by 1 or 3 months of detraining.Methods:Twenty-eight athletes about to embark on a period of forced detraining due to incidental limb bone fracture underwent clinical assessment, ECG, and contrast-enhanced cardiovascular magnetic resonance within a week of their injury and then 1 month and 3 months later.Results:After 1 month of detraining, there was reduction in left ventricular (LV) mass (130±28 to 121±25 g; P<0.0001), increase in native T1 (1225±30 to 1239±30 ms; P=0.02), and extracellular volume fraction (24.5±2.3% to 26.0±2.6%; P=0.0007) with no further changes by 3 months. The decrease in LV mass was mediated by a decrease in intracellular compartment volume (94±22 to 85±19 mL; P<0.0001) with no significant change in the extracellular compartment volume. High LV mass index, low native T1, and low extracellular volume fraction at baseline were all predictive of regression in LV mass in the first month.Conclusions:Regression of athletic LV hypertrophy can be detected after just 1 month of complete detraining and is mediated by a decrease in the intracellular myocardial compartment with no change in the extracellular compartment. Further studies are needed in athletes with overt and pathological hypertrophy to establish whether native T1 and extracellular volume fraction may complement electrocardiography, echocardiography, cardiopulmonary exercise testing, and genetic testing in predicting the outcome of detraining.

Guiding Hypertension Management Using Different Blood Pressure Monitoring Strategies (GYMNs study): comparison of three different blood pressure measurement methods: study protocol for a randomized controlled trial

BackgroundHome blood pressure (BP) and unattended automated BP (uAOBP) monitoring have been recommended by guidelines for the care of hypertensive subjects. However, BP measurements in the peripheral arteries cannot serve as direct substitutes for their central counterparts. Moreover, the comparative effectiveness and safety of BP-guided strategies using these BP measuring devices have never been evaluated.Methods/designPatients with uncontrolled or newly diagnosed hypertension aged 20–90 years will be recruited via outpatient clinics and allocated into three arms by stratified randomization (baseline systolic BP 130–155 mmHg and 155–180 mmHg): home BP, uAOBP, and central BP-guided treatment. At each scheduled visit to the clinic, a patient’s BP will be measured by each of the three methods of measuring BP. The blood pressure from three different methods will be confirmed available at each visit. Patients and physicians will be blinded to the allocated interventions because they will use measured BP values in the clinic through a standardized report format. A common BP target for systolic blood pressure (SBP) of 130 mmHg is adopted for these BP-guided strategies. The primary outcome is the change of 24-h mean ambulatory SBP at 3 months. A key secondary outcome is to determine the percentage achieving their target BPs at 3 months and the decrease of left ventricular mass at 12 months.DiscussionTo our knowledge, this is the first prospective double-blind randomized controlled trial to assess the optimal guiding strategy for hypertension. It will help to define which BP monitoring method is the most effective for guiding the clinical management of hypertension. It will provide good evidence to support future guideline recommendations for BP monitoring devices.Trial registrationClinicalTrials.gov, NCT03578848. Registered on 4 June 2018.

Can the echocardiographic LV mass equation reliably demonstrate stable LV mass following acute change in LV load?

Limited data are available on performance of the left ventricular (LV) mass equation when there is a dynamic change to LV load. We aimed to test this equation in the immediate post-operative period following aortic valve replacement (AVR) for aortic regurgitation (AR) to see if it would reliably demonstrate stable LV mass before and after surgery. Since LV mass would be unlikely to change in the immediate postoperative period, we hypothesized that a decrease in LV diameter postoperatively would be accompanied by concomitant increases in LV wall thickness as predicted by the LV mass equation. We reviewed echocardiograms of adult patients with AR who underwent AVR from 2007-2017 at Montefiore Medical Center (n=28). Three independent readers performed septal wall thickness (SWT), posterior wall thickness (PWT) and left ventricular internal diameter (LVID) measurements on pre-operative and post-operative echocardiograms. LV masses were calculated using the American Society of Echocardiography (ASE) equation. Post-operatively, LVID decreased from 5.7±1.2 to 4.9±1.0 cm, P<0.001. SWT was noted to increase from 1.08±0.20 to 1.18±0.27 cm, P=0.03, but PWT was unchanged, 1.11±0.21 to 1.16±0.27 cm, P=0.21. Accordingly, the LV mass equation calculated a decrease in LV mass from 266±126 to 232±99 gm, P=0.01. A control group of coronary artery bypass grafting alone (n=14) did not demonstrate any significant change in SWT, LVID, PWT and LV mass measurements. Similar findings were found for all three readers. Following aortic valve replacement for regurgitation, the LV mass equation calculated a reduction in LV mass in the immediate postoperative period. Since an immediate change in LV mass after AVR is unlikely, we feel that these results highlight an important limitation of the mass equation, when used with acutely changing loading conditions.

Impact of Metabolic Syndrome and/or Diabetes Mellitus on Left Ventricular Mass and Remodeling in Patients With Aortic Stenosis Before and After Aortic Valve Replacement

In aortic stenosis (AS), metabolic syndrome (MetS), and diabetes mellitus (DM) are associated with more pronounced left ventricular (LV) hypertrophy and more concentric remodeling. We aimed to assess the impact of MetS and DM on LV mass, remodeling, and LV mass regression after aortic valve replacement (AVR) in patients with severe AS. We included 177 patients with severe AS and preserved LV ejection fraction (>50%). All patients underwent a complete echocardiogram before and 1 year after AVR. Forty-seven (27%) patients had MetS, 37 (21%) DM, and 93 (52%) neither MetS nor DM (No MetS-DM). Before AVR, indexed LV mass was higher in MetS and DM groups compared with No MetS-DM group (56.1 ± 14.2, 56.2 ± 18.2 vs 49.2 ± 14.1 g/m2.7, respectively; p <0.01). Prevalence of LV hypertrophy was higher in MetS and DM than in No MetS-DM patients (66%, 65% vs 44%, p <0.01) as well as LV mass to end-diastolic volume ratio (2.10 ± 0.44 and 2.21 ± 0.63 vs 1.96 ± 0.41 g/ml, respectively, p = 0.03). After multivariate analysis, DM and MetS were independently associated with higher baseline LV mass (p <0.05). One year after AVR, decrease in LV mass was significant (p <0.001) in all 3 groups. MetS was independently associated with less LV mass regression and higher LV mass 1 year after AVR. Therefore, MetS and DM patients showed more residual LV hypertrophy than those with No MetS-DM (57%, 38%, and 17%, p <0.01). In conclusion, MetS and DM were associated with higher preoperative LV mass, more LV hypertrophy, and more concentric remodeling. One year after AVR, MetS showed less significant LV mass regression and both DM and MetS persisted with more residual LV hypertrophy.

Anthracycline Therapy Is Associated With Cardiomyocyte Atrophy and Preclinical Manifestations of Heart Disease

ObjectivesThe goal of this study was to demonstrate that cardiac magnetic resonance could reveal anthracycline-induced early tissue remodeling and its relation to cardiac dysfunction and left ventricular (LV) atrophy. BackgroundSerum biomarkers of cardiac dysfunction, although elevated after chemotherapy, lack specificity for the mechanism of myocardial tissue alterations. MethodsA total of 27 women with breast cancer (mean age 51.8 ± 8.9 years, mean body mass index 26.9 ± 3.6 kg/m2), underwent cardiac magnetic resonance before and up to 3 times after anthracycline therapy. Cardiac magnetic resonance variables were LV ejection fraction, normalized T2-weighted signal intensity for myocardial edema, extracellular volume (ECV), LV cardiomyocyte mass, intracellular water lifetime (τic; a marker of cardiomyocyte size), and late gadolinium enhancement. ResultsAt baseline, patients had a relatively low (10-year) Framingham cardiovascular event risk (median 5%), normal LV ejection fractions (mean 69.4 ± 3.6%), and normal LV mass index (51.4 ± 8.0 g/m2), a mean ECV of 0.32 ± 0.038, mean τic of 169 ± 69 ms, and no late gadolinium enhancement. At 351 to 700 days after anthracycline therapy (240 mg/m2), mean LV ejection fraction had declined by 12% to 58 ± 6% (p < 0.001) and mean LV mass index by 19 g/m2 to 36 ± 6 g/m2 (p < 0.001), and mean ECV had increased by 0.037 to 0.36 ± 0.04 (p = 0.004), while mean τic had decreased by 62 ms to 119 ± 54 ms (p = 0.004). Myocardial edema peaked at about 146 to 231 days (p < 0.001). LV mass index was associated with τic (β = 4.1 ± 1.5 g/m2 per 100-ms increase in τic, p = 0.007) but not with ECV. Cardiac troponin T (mean 4.6 ± 1.4 pg/ml at baseline) increased significantly after anthracycline treatment (p < 0.001). Total LV cardiomyocyte mass, estimated as: (1 − ECV) × LV mass, declined more rapidly after anthracycline therapy, with peak cardiac troponin T >10 pg/ml. There was no evidence for any significant interaction between 10-year cardiovascular event risk and the effect of anthracycline therapy. ConclusionsA decrease in LV mass after anthracycline therapy may result from cardiomyocyte atrophy, demonstrating that mechanisms other than interstitial fibrosis and edema can raise ECV. The loss of LV cardiomyocyte mass increased with the degree of cardiomyocyte injury, assessed by peak cardiac troponin T after anthracycline treatment. (Doxorubicin-Associated Cardiac Remodeling Followed by CMR in Breast Cancer Patients; NCT03000036)