Changes In Left Ventricular Mass Research Articles

Association of Changes in Vector Length with Changes in Left Ventricular Mass Among Patients on Maintenance Hemodialysis: A Secondary Analysis of the Frequent Hemodialysis Network Daily Trial.

Hypervolemia is thought to be a major contributor to higher left ventricular mass (LVM), a potent predictor for cardiovascular mortality among patients on maintenance hemodialysis. We hypothesized that a decrease in vector length (a bioimpedance proxy of hypervolemia) would be associated with an increase in LVM. Using data from the Frequent Hemodialysis Network Daily Trial (n=160) we used linear regression to assess the association of changes in vector length from baseline to month 12 with changes in magnetic resonance imaging (MRI) measures of LVM and other cardiac parameters. We adjusted models for the randomized group, baseline vector length, age, sex, race, body mass index, vascular access, dialysis vintage, history of hypertension, heart failure, and diabetes, residual kidney function, pre-dialysis systolic blood pressure (BP), ultrafiltration rate, serum-dialysate sodium gradient, hemoglobin, phosphate, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, erythropoietin dose, and equilibrated Kt/V. The mean age was 50 ±13 years; 35% were female. In the fully adjusted models, a decline in vector length (per 50 Ω/m; i.e., increase in volume) was associated with a 6.8 g (95%CI -0.1, 13.7) and 2.6 g/m2 (95%CI -1.2, 6.3) increase in LVM and LVM index, respectively; and an increase of 15.0 mL (95%CI 7.5, 22.4), 7.3 mL (95%CI 3.0, 12.7), 7.8 mL (95%CI 3.0, 12.7), and -0.9 % (95%CI -3.1, 1.3) in left ventricular (LV) end-diastolic volume (LVEDV), end-systolic volume (LVESV), stroke volume (LVSV), and ejection fraction (LVEF), respectively. The lowest tertile of change in vector length (i.e., greater increase in volume) was associated with greater increases in LVEDV and LVSV, versus the highest tertile. There was no evidence of heterogeneity by randomized group. Change in vector length, a bioimpedance-derived proxy of volume status, was inversely associated with indices of left ventricular mass and volume measured by cardiac MRI in patients randomized to conventional or frequent hemodialysis over 12 months.

Association of an impaired GH-IGF-I axis with cardiac wasting in patients with advanced cancer.

Growth hormone (GH) resistance is characterized by high GH levels but low levels of insulin-like growth factor-I (IGF-I) and growth hormone binding protein (GHBP) and, for patients with chronic disease, is associated with the development of cachexia. We investigated whether GH resistance is associated with changes in left ventricular (LV) mass (cardiac wasting) in patients with cancer. We measured plasma IGF-I, GH, and GHBP in 159 women and 148 men with cancer (83% stage III/IV). Patients were grouped by tertile of echocardiographic LVmass/height2 (women, < 50, 50-61, > 61g/m2; men, < 60, 60-74, > 74g/m2) and by presence of wasting syndrome with unintentional weight loss (BMI < 24kg/m2 and weight loss ≥ 5% in the prior 12months). Repeat echocardiograms were obtained usually within 3-6months for 85 patients. Patients in the lowest LVmass/height2 tertile had higher plasma GH (median (IQR) for 1st, 2nd, and 3rd tertile women, 1.8 (0.9-4.2), 0.8 (0.2-2.2), 0.5 (0.3-1.6) ng/mL, p = 0.029; men, 2.1 (0.8-3.2), 0.6 (0.1-1.7), 0.7 (0.2-1.9) ng/mL, p = 0.003). Among women, lower LVmass was associated with higher plasma IGF-I (68 (48-116), 72 (48-95), 49 (35-76) ng/mL, p = 0.007), whereas such association did not exist for men. Patients with lower LVmass had lower log IGF-I/GH ratio (women, 1.60 ± 0.09, 2.02 ± 0.09, 1.88 ± 0.09, p = 0.004; men, 1.64 ± 0.09, 2.14 ± 0.11, 2.04 ± 0.11, p = 0.002). GHBP was not associated with LVmass. Patients with wasting syndrome with unintentional weight loss had higher plasma GH and GHBP, lower log IGF-I/GH ratio, and similar IGF-I. Overall, GHBP correlated inversely with log IGF-I/GH ratio (women, r = - 0.591, p < 0.001; men, r = - 0.575, p < 0.001). Additionally, higher baseline IGF-I was associated with a decline in LVmass during follow-up (r = - 0.318, p = 0.003). In advanced cancer, reduced LVmass is associated with increased plasma GH and reduced IGF-I/GH ratio, suggesting increasing GH resistance, especially for patients with wasting syndrome with unintentional weight loss. Higher baseline IGF-I was associatedwith a decrease in relative LVmass during follow-up.

Blood Pressure Lowering in Patients With Central Hypertension: A Randomized Clinical Trial.

Cuff blood pressure (BP) is recommended for guiding hypertension management. However, central BP has been proposed as a superior clinical measurement. This study aimed to determine whether controlling hypertension as measured by central BP was beneficial in reducing left ventricular mass index beyond control of standard cuff hypertension. This multicenter, open-label, blinded-end point trial was conducted in individuals treated for uncomplicated hypertension with controlled cuff BP (<140/90 mm Hg) but elevated central BP (≥0.5 SD above age- and sex-specific normal values). Participants were randomized to 24-months intervention with spironolactone 25 mg/day (n=148) or usual care control (n=153). The primary outcome was change in left ventricular mass index measured by cardiac MRI. Cuff and central BPs were measured by clinic, 7-day home and 24-hour ambulatory BPs. At 24-months, there was a greater reduction in left ventricular mass index (-3.2 [95% CI, -5.0 to -1.3] g/m2; P=0.001) with intervention compared with control. Cuff and central BPs were lowered by a similar magnitude across all BP measurement modes (eg, clinic cuff systolic BP, -6.16 [-9.60 to -2.72] mm Hg and clinic central systolic BP, -4.96 [-8.06 to -1.86] mm Hg; P≥0.48 all). Secondary analyses found that changes in left ventricular mass index correlated to changes in BP, with the magnitude of effect nearly identical for BP measured by cuff (eg, 24-hour systolic BP, β, 0.17 [0.02-0.31] g/m2) or centrally (24-hour systolic BP, β, 0.16 [0.01-0.32] g/m2). Among individuals with central hypertension, spironolactone had beneficial effects in reducing LV mass. Secondary analyses showed that changes in LV mass were equally well associated with lower measured standard cuff BP and central BP. URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12613000053729.

The effect of glucagon-like peptide-1 receptor agonists on cardiac function and structure in patients with or without type 2 diabetes mellitus: An updated systematic review and meta-analysis.

To conduct an updated systematic review and meta-analysis to evaluate the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) with regard to cardiac function and structure in people with or without type 2 diabetes mellitus (T2DM). We conducted a systematic search using the PubMed, Embase and ClinicalTrials.gov online databases. The primary outcome of interest was changes in mitral inflow E-velocity to tissue Doppler e' velocity (E/e') ratio. Secondary outcomes included other indicators of cardiac reverse remodelling and functional capacity comprising changes in left ventricular mass (LVM), left ventricular global longitudinal strain, left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction (LVEF), early to atrial mitral inflow velocity ratio, left atrial volume (LAV), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and 6-min walk test (6MWT) results. A total of 15 trials involving 898 patients were included in this analysis. GLP-1RAs significantly improved E/e' ratio (mean difference [MD] = -0.73; 95% confidence interval [CI] -1.34, -0.13), LVM (MD = -3.86 g; 95% CI -7.60, -0.12), LAV (MD = -8.20 mL; 95% CI -12.37, -4.04), NT-proBNP level (standardized MD = -0.27; 95% CI -0.47, -0.06), and 6MWT result (MD = +22.31 m; 95% CI 1.64, 42.99). However, GLP-1RAs had no effect on LVEF (MD = +0.31%; 95% CI -1.02, 1.64). In this systematic review and meta-analysis, GLP-1RAs were found to have a positive impact on left ventricle diastolic function, hypertrophy, and exercise capacity, but had no effect on systolic function.

The effect of bariatric surgery type on cardiac reverse remodelling.

Bariatric surgery is effective in reversing adverse cardiac remodelling in obesity. However, it is unclear whether the three commonly performed operations; Roux-en-Y Gastric Bypass (RYGB), Laparoscopic Sleeve Gastrectomy (LSG) and Laparoscopic Adjustable Gastric Band (LAGB) are equal in their ability to reverse remodelling. Fifty-eight patients underwent CMR to assess left ventricular mass (LVM), LV mass:volume ratio (LVMVR) and LV eccentricity index (LVei) before and after bariatric surgery (26 RYGB, 22 LSG and 10 LAGB), including 46 with short-term (median 251-273 days) and 43 with longer-term (median 983-1027 days) follow-up. Abdominal visceral adipose tissue (VAT) and epicardial adipose tissue (EAT) were also assessed. All three procedures resulted in significant decreases in excess body weight (48-70%). Percentage change in VAT and EAT was significantly greater following RYGB and LSG compared to LAGB at both timepoints (VAT:RYGB -47% and -57%, LSG -47% and -54%, LAGB -31% and -25%; EAT:RYGB -13% and -14%, LSG -16% and -19%, LAGB -5% and -5%). Patients undergoing LAGB, whilst having reduced LVM (-1% and -4%), had a smaller decrease at both short (RYGB: -8%, p < 0.005; LSG: -11%, p < 0.0001) and long (RYGB: -12%, p = 0.009; LSG: -13%, p < 0.0001) term timepoints. There was a significant decrease in LVMVR at the long-term timepoint following both RYGB (-7%, p = 0.006) and LSG (-7%, p = 0.021), but not LAGB (-2%, p = 0.912). LVei appeared to decrease at the long-term timepoint in those undergoing RYGB (-3%, p = 0.063) and LSG (-4%, p = 0.015), but not in those undergoing LAGB (1%, p = 0.857). In all patients, the change in LVM correlated with change in VAT (r = 0.338, p = 0.0134), while the change in LVei correlated with change in EAT (r = 0.437, p = 0.001). RYGB and LSG appear to result in greater decreases in visceral adiposity, and greater reverse LV remodelling with larger reductions in LVM, concentric remodelling and pericardial restraint than LAGB.

Porcine Model of Hypertrophy-Independent Left Ventricular Stiffening via Repetitive Pressure Overload.

Diastolic dysfunction arising from alterations in myocardial structure and/or function is a central component of several cardiovascular disorders, including heart failure with preserved ejection fraction (HFpEF). Basic research aimed at understanding underlying mechanisms contributing to the development of diastolic dysfunction has generally centered upon models of left ventricular (LV) hypertrophy arising from persistent and severe elevations in myocardial afterload (e.g., aortic banding). Mechanisms of hypertrophy-independent diastolic dysfunction, on the other hand, have received less attention, even though overt anatomic LV hypertrophy is absent in many HFpEF patients. Here, we describe the development of a novel porcine model of repetitive pressure overload (RPO) in which chronic, intermittent exposure to transient episodes of hypertension produces an increase in LV stiffness, interstitial fibrosis, cardiomyocyte hypertrophy, and capillary rarefaction without significant changes in LV mass. This model offers important insight into how diastolic dysfunction and HFpEF may develop in the absence of comorbidities, sustained hypertension, or LV hypertrophy, while also providing a useful translational research tool for investigation of novel therapeutic approaches to restore myocardial compliance and improve diastolic function.

Effect of empagliflozin on cardiac remodelling in South Asian and non-South Asian individuals: insights from the EMPA-HEART CardioLink-6 randomised clinical trial

BackgroundThis exploratory sub-analysis of the EMPA-HEART CardioLink-6 trial examined whether the previously reported benefit of the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin on left ventricular (LV) mass (LVM) regression differs between individuals of South Asian and non-South Asian ethnicity.MethodsEMPA-HEART CardioLink-6 was a double-blind, placebo-controlled clinical trial that randomised 97 individuals with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) to either empagliflozin 10 mg daily or placebo for 6 months. LV parameters and function were assessed using cardiac magnetic resonance imaging. The 6-month changes in LVM and LV volumes, all indexed to baseline body surface area, for South Asian participants were compared to those for non-South Asian individuals.ResultsCompared to the non-South Asian group, the South Asian sub-cohort comprised more males, was younger and had a lower median body mass index. The adjusted difference for LVMi change over 6 months was -4.3 g/m2 (95% confidence interval [CI], -7.5, -1.0; P = 0.042) for the South Asian group and -2.3 g/m2 (95% CI, -6.4, 1.9; P = 0.28) for the non-South Asian group (Pinteraction = 0.45). There was no between-group difference for the adjusted differences in baseline body surface area-indexed LV volumes and LV ejection fraction.ConclusionsThere was no meaningful difference in empagliflozin-associated LVM regression between South Asian and non-South Asian individuals living with T2DM and CAD in the EMPA-HEART CardioLink-6 trial.Trial registrationClinicalTrials.gov Identifier: NCT02998970 (First posted on 21/12/ 2016).

Abstract 16721: Concentrations of Troponin I but Not Cardiac Troponin T Are Associated With 7-year Changes in Left Ventricular Structure and Function in Older Adults: The Atherosclerosis Risk in Community (ARIC) Study

Introduction: High-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) are strongly associated with incident heart failure (HF) and left ventricular (LV) remodeling. Their associations with longitudinal changes in cardiac structure and function are less clear. Methods: Among 1,908 participants in the Atherosclerosis Risk in Communities (ARIC) study who were free of coronary disease, HF, or atrial fibrillation and had echocardiography at study Visits 5 (2011-2013) and 7 (2017-2019), we assessed the associations of log-transformed hs-cTnT and hs-cTnI at Visit 5 with absolute changes in LV structure and function between Visit 5 and 7 (median of 6.6 [IQR 6.1-7.0] years) using multivariable linear regression with the exposures modeled as restricted cubic spline models. Models were adjusted for age, sex, race, BMI, diabetes, hypertension and eGFR at Visit 5, blood pressure and heart rate at both visits. Results: At Visit 5, the mean age (years) was 74 (SD 4), 60% were female, 24% reported Black race and the median (p25-p75) concentrations of hs-cTnT and hs-cTnI were 9 (6-13) ng/L and 2.7 (1.9-4.0) ng/L respectively. In adjusted models, higher hs-cTnI concentration was associated with 7-year decline in LV systolic function (ejection fraction, global longitudinal and circumferential strain; Figure ). In contrast, hs-cTnT was not consistently associated with changes in cardiac function. Changes in hs-cTnI, but not hs-cTnT, were also associated with greater increases in left atrial volume. Neither were associated with changes in LV mass or volume. Conclusions: Higher hs-cTnI, but not hs-cTnT, concentrations are associated with greater declines in LV function over ~7 years in late life independent of traditional cardiovascular risk factors. These findings support previous findings of cTnI to be more cardiac specific than cTnT.

Abstract 16842: Progression of Myocardial Fibrosis in Hypertrophic Cardiomyopathy

Background: There is limited data on the progression of the scar on LGE in patients with hypertrophic cardiomyopathy (HCM) stratified by age and its relationship with sudden cardiac death (SCD). Objectives: We compared LGE progression as stratified by age and examined the relationship of this risk to SCD. Methods: A total of 102 HCM patients (age &lt;60 years; n=75, age ≥60 years; n=27) undergoing two consecutive cardiovascular magnetic resonance (CMR) at an interval of 4.3 ± 3.3 years from two medical centers were evaluated. LGE was quantified semi-automatically using a 6-SD threshold followed by manual adjustment. Median follow-up from study entry to the most recent evaluation was 7.3 years. The primary endpoint was the composite of resuscitated cardiac arrest and SCD. Results: At the first CMR, LGE was detected in 61 (60%) patients. At the follow-up, 25 patients developed a new LGE; thus, 86 (84%) patients had LGE by the follow-up CMR. Overall, the progression rate was 0.7 ± 1.0%/year, including 21 patients (21%) with LGE progression ≥1% /year and 5 (5%) with LGE &gt;15% at follow-up. The risk of LGE progression ≥1%/year was significantly higher in patients &lt;60 years (25% vs. 7%, p=0.02). There was a trend for the highest risk of LGE progression ≥1%/year in patients &lt;60 years with LGE &gt;10% at baseline scan. LGE progression ≥1%/year was a strong predictor of the primary outcomes (HR 1.88 [95% CI; 1.08-3.26], p=0.03). LGE progression moderately correlated with changes in LV mass, indexed LV mass index, and maximal LV end-diastolic wall thickness (p&lt;0.001 for all). Conclusions: Progressive fibrosis occurs more frequently in young to middle-aged HCM patients and identifies a cohort at high risk of SCD. One-quarter of young to middle-aged patients exhibit LGE progression ≥1%/year, underscoring the importance of repeating CMR to re-evaluate for potential LGE progression in this age group.

Abstract 15044: The Relationship of Pericardial Fat With Metabolic Change and Myocardial Remodelling Following Bariatric Surgery

Introduction: Pericardial fat is a cardiometabolic risk factor that can be quantified from routine cardiovascular magnetic resonance (CMR) studies. However the extent to which this is modifiable, and its relationship with cardiometabolic markers remains unclear. Aims: Determine the effect of bariatric surgery on pericardial fat and associate with cardiometabolic improvements post-surgery. Methods: Thirty-eight people referred for bariatric surgery were assessed pre-operatively using CMR, blood biomarkers and anthropometry. Six months post-operatively, twenty-seven participants underwent paired follow-up assessments. Pericardial fat was quantified manually from routine short axis cine stacks by a single blinded clinical observer. Linear regression was used to assess the association of pericardial fat volume and cardiometabolic parameters, at baseline and changes pre- vs post-surgery. Results: At baseline, pericardial fat volume was associated with multiple cardiometabolic parameters including weight (r=0.46 p=0.004), fasting insulin (r=-0.46, p=0.007) hepatic fat concentration (Hepafat) (r=0.37 p=0.029) and LV mass (r=0.38, p=0.019). Pericardial fat remained independently associated with waist circumference after adjusting for the above (β=0.68, 95% CI: 1.24,9.23, p=0.012). At 6 months post-bariatric surgery pericardial adipose tissue reduced by an average of 29% (95% CI: -21-36%, p&lt;0.001). This change was associated with improvements in fasting insulin levels even after adjusting for changes in weight, Hepafat and LV mass (β=0.72, 95% CI: 0.15, 0.70, p=0.005). Conclusion: Pericardial fat in obesity associates with multiple adverse cardiometabolic parameters, including waist circumference. Bariatric surgery causes a significant reduction in pericardial fat which associates with reduced insulin resistance, providing a potential modifiable mechanism to reduce cardiovascular risk in patients living with obesity.

Abstract 16990: Empagliflozin Therapy is Associated With Improved Left Ventricular Diastolic Function in Patients With Transthyretin Amyloid Cardiomyopathy

Introduction: Although SGLT-2 inhibitors demonstrated beneficial clinical effects in patients with heart failure with preserved ejection fraction, their role in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) remains undefined. Hypothesis: We investigated the effects of empagliflozin on myocardial function in patients with ATTR-CM. Methods: In a prospective single-center non-randomized cohort study we enrolled 15 consecutive patients with ATT-CM receiving tafamidis 61 mg qd and standard heart failure therapy for at least six months prior to enrolment. At the time of inclusion, all patients started receiving empagliflozin 10 mg qd. Biochemical and echocardiographic parameters were evaluated at baseline and again at 6-months. Results: At the time of inclusion, the average age of patients was 74.8±5.7 years, 14 (93%) were male, and 14 (93%) had NYHA class II symptoms; 10 (67%) patients were receiving ARNI/ACEI/ARB, 5 (33%) were treated with beta blockers, and 3 (20%) were receiving mineralocorticoid receptor antagonists. At 6-months follow-up we found no change in NT-proBNP levels (1694±1237 ng/L at baseline vs. 1549±1203 ng/L at follow up; P=0.78), hs-Troponin I levels (33±19 ng/L vs. 39±26 ng/L; P=0.50), or eGFR (65.9±14.4 mL/min vs. 64.9±14.8 mL/min; P=0.87). Furthermore, we observed no changes in LVEDV (84±19 mL vs. 88±17 mL; P=0.61), LVEF (57±8% vs. 57±7%; P=0.94), LV mass (265±74 g vs. 279±88 g; P=0.67), or RVIDd (39±8 mm vs. 36±7 mm; P=0.39). However, at 6 months we found a significant decrease in E/e’ (19.2±5.1 vs. 14.9±5.4; P=0.05). When stratifying patients according to the baseline E/e’ value we found a significant improvement of right ventricular FAC (44.1±6.2% vs. 31.9±8.9%; P=0.04) and TR pressure gradient (26.0±5.7 mmHg vs. 39.7±5.2 mmHg; P=0.04) in patients with E/e’ below median compared to patients with E/e’ above median value. Conclusion: In patients with ATTR-CM, empagliflozin therapy appears to reduce left ventricular filling pressures and may be associated with improved right ventricular systolic function in a subset of this patient population.

Abstract 13469: A Comprehensive Echocardiographic Assessment of Patients With Chronic Myeloid Leukemia on Dasatinib

Background: Dasatinib, a tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia (CML), is known to cause cardiotoxicities; however, little is known about the echocardiographic changes associated with this drug. Here we present a comprehensive echocardiographic assessment of patients with CML on dasatinib receiving care at a quaternary facility. Methods: We performed a retrospective cohort analysis on consecutive adult patients with CML receiving dasatinib between 2017-2022 who had a baseline and follow-up echocardiogram. Comprehensive clinical, laboratory and advanced echocardiographic data with speckle-tracking analyses (Tomtec Arena, Germany) were included. Results: Among 41 adult patients with CML (average age 64±16 years old, 39% female) who were prescribed with dasatinib (initial dose 100mg once daily), at baseline, 7 (17%) patients had heart failure with preserved ejection fraction (HFpEF), 11 (27%) coronary artery disease, and 3 (7%) pulmonary hypertension. There was a statistically significant increase in the indexed LV end-diastolic diameter and LV mass in pre- vs post-dasatinib echocardiograms; however, there was no significant change in ejection fraction or global longitudinal strain. There was no significant change in RV structure or function measures. There was a significant increase in LA volume index and decrease in lateral e’ velocity in pre- vs post-dasatinib echocardiograms. A trend towards declining LA reservoir strain post-dasatinib was noted. Ten (24%) patients had a progression in diastology grading after the initiation of dasatinib. Five out of 7 patients with HFpEF at baseline had progression in diastolic function post-dasatinib. Conclusions: Dasatinib was associated with significant changes in LV end-diastolic diameter, LV mass, LA volume, and diastolic parameters in patients with CML. These findings require further corroboration with a larger patient cohort and correlation with clinical outcomes.

Empagliflozin effects on iron metabolism as a possible mechanism for improved clinical outcomes in non-diabetic patients with systolic heart failure

Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve clinical outcomes in patients with heart failure (HF), but mechanisms of action are incompletely understood. In the EMPA-TROPISM trial, empagliflozin reversed cardiac remodeling and increased physical capacity in stable non-diabetic patients with systolic HF. Here we explore, post hoc, whether treatment effects in this cohort, comprising patients who had a high prevalence of iron deficiency, were related to iron metabolism. Myocardial iron content estimated by cardiac magnetic resonance T2* quantification increased after initiation of empagliflozin but not placebo (treatment effect: P = 0.01). T2* changes significantly correlated with changes in left ventricular volumes, mass and ejection fraction, peak oxygen consumption and 6-minute walking distance; concomitant changes in red blood cell indices were consistent with augmented hematopoiesis. Exploratory causal mediation analysis findings indicated that changes in myocardial iron content after treatment with empagliflozin may be an important mechanism to explain its beneficial clinical effects in patients with HF.ClinicalTrials.gov: NCT03485222.

Effects of detraining on left ventricular mass in endurance-trained individuals: a systematic review and meta-analysis.

Detraining refers to a loss of training adaptations resulting from reductions in training stimulus due to illness, injury, or active recovery breaks in a training cycle and is associated with a reduction in left ventricular mass (LVM). The purpose of this study was to conduct a systematic review and meta-analysis to determine the influence of detraining on LVM in endurance-trained, healthy individuals. Using electronic databases (e.g. EMBASE and MEDLINE), a literature search was performed looking for prospective detraining studies in humans. Inclusion criteria were adults, endurance-trained individuals with no known chronic disease, detraining intervention >1 week, and pre- and post-detraining LVM reported. A pooled statistic for random effects was used to assess changes in LVM with detraining. Fifteen investigations (19 analyses) with a total of 196 participants (ages 18-55 years, 15% female) met inclusion criteria, with detraining ranging between 1.4 and 15 weeks. The meta-analysis revealed a significant reduction in LVM with detraining (standardized mean difference = -0.586; 95% confidence interval = -0.817, -0.355; P < 0.001). Independently, length of detraining was not correlated with the change in LVM. However, a meta-regression model revealed length of the detraining, when training status was accounted for, was associated with the reduction of LVM (Q = 15.20, df = 3, P = 0.0017). Highly trained/elite athletes had greater reductions in LVM compared with recreational and newly trained individuals (P < 0.01). Limitations included relatively few female participants and inconsistent reporting of intervention details. In summary, LVM is reduced following detraining of one week or more. Further research may provide a greater understanding of the effects of sex, age, and type of detraining on changes in LVM in endurance-trained individuals.

Colchicine added to standard therapy further reduces fibrosis in pigs with myocardial infarction.

The anti-inflammatory drug colchicine improves the outcome of patients with myocardial infarction (MI). As an intense inflammatory and fibrotic response after MI may lead to scar expansion and left ventricular (LV) remodeling, the clinical benefit of colchicine could be related to a positive effect on the infarct scar and LV remodeling. Pigs underwent left anterior descending artery occlusion through an angioplasty balloon for 90 min and were then randomized into two groups: standard therapy [ACE inhibitor, beta blocker, mineralocorticoid receptor antagonist (MRA), aspirin] plus colchicine (n = 14) or standard therapy alone (n = 13). The pigs were treated for 30 days and underwent two cardiac magnetic resonance (CMR) scans at 72 h and 30 days. The pigs were then sacrificed the day after the second CMR. The primary efficacy end point was the extent of fibrosis in the infarct zone (calculated on eight samples from this zone and averaged). In the hearts explanted after 31 days, pigs in the colchicine group had less fibrosis in the infarct zone than the other animals [41.6% (20.4-51.0) vs. 57.4% (42.9-66.5); P = 0.022]. There was a trend toward a higher myocardial salvage index (MSI; an index of the efficacy of revascularization) in pigs on colchicine (P = 0.054). Conversely, changes in LV volumes, ejection fraction and mass did not differ between groups. Colchicine therapy for 1 month after reperfused MI further reduces myocardial fibrosis when added to standard therapy, while it does not have additional effects on LV remodeling.

Tafamidis decreased cardiac amyloidosis deposition in patients with Ala97Ser hereditary transthyretin cardiomyopathy: a 12-month follow-up cohort study

BackgroundTransthyretin cardiac cardiomyopathy (ATTR-CM) is a rare but life-threatening disease. Tafamidis is an effective treatment for patients with ATTR-CM, however its long-term effects on cardiac remodeling and cardiac amyloid deposition are unknown. This study aimed to used cardiac magnetic resonance (CMR) to investigate the effects of tafamidis on patients with hereditary A97S ATTR-CM.MethodsWe retrospectively analyzed a prospective cohort of ATTR-CM patients, including 14 with hereditary A97S ATTR-CM and 17 healthy controls with baseline CMR data. All ATTR-CM patients received tafamidis treatment and received CMR with extracellular volume (ECV) at baseline and after 1 year of follow-up.ResultsBaseline N-terminal pro-B-type natriuretic peptide, left ventricular (LV) mass, LV ejection fraction, global radial, circumferential and longitudinal strain, T1 mapping and ECV were significantly worse in the patients with ATTR-CM compared with the healthy controls. After 1 year of tafamidis treatment, ECV decreased from 51.5 ± 8.9% to 49.0 ± 9.4% (P = 0.041), however there were no significant changes in LV mass, LV ejection fraction, global radial strain, global circumferential strain, global longitudinal strain and T1 mapping.ConclusionsAfter a one-year treatment period, tafamidis exhibited subtle but statistically significant reductions in ECV, potentially indicating a decrease in amyloid deposition among patients diagnosed with hereditary A97S ATTR-CM.

Sacubitril/valsartan versus valsartan in regressing myocardial fibrosis in hypertension: a prospective, randomized, open-label, blinded endpoint clinical trial protocol.

Diffuse interstitial myocardial fibrosis is a key common pathological manifestation in hypertensive heart disease (HHD) progressing to heart failure (HF). Angiotensin receptor-neprilysin inhibitors (ARNi), now a front-line treatment for HF, confer benefits independent of blood pressure, signifying a multifactorial mode of action beyond hemodynamic regulation. We aim to test the hypothesis that compared with angiotensin II receptor blockade (ARB) alone, ARNi is more effective in regressing diffuse interstitial myocardial fibrosis in HHD. Role of ARNi in Ventricular Remodeling in Hypertensive LVH (REVERSE-LVH) is a prospective, randomized, open-label, blinded endpoint (PROBE) clinical trial. Adults with hypertension and left ventricular hypertrophy (LVH) according to Asian sex- and age-specific thresholds on cardiovascular magnetic resonance (CMR) imaging are randomized to treatment with either sacubitril/valsartan (an ARNi) or valsartan (an ARB) in 1:1 ratio for a duration of 52 weeks, at the end of which a repeat CMR is performed to assess differential changes from baseline between the two groups. The primary endpoint is the change in CMR-derived diffuse interstitial fibrosis volume. Secondary endpoints include changes in CMR-derived left ventricular mass, volumes, and functional parameters. Serum samples are collected and stored to assess the effects of ARNi, compared with ARB, on circulating biomarkers of cardiac remodeling. The endpoints will be analyzed with reference to the corresponding baseline parameters to evaluate the therapeutic effect of sacubitril/valsartan vs. valsartan. REVERSE-LVH will examine the anti-fibrotic potential of sacubitril/valsartan and will offer mechanistic insights into the clinical benefits of sacubitril/valsartan in hypertension in relation to cardiac remodeling. Advancing the knowledge of the pathophysiology of HHD will consolidate effective risk stratification and personalized treatment through a multimodal manner integrating complementary CMR and biomarkers into the conventional care approach.Clinical Trial Registration: ClinicalTrials.gov, identifier, NCT03553810.

Cardiac Effects of Long-Duration Space Flight

BackgroundVentricular mass responds to changes in physical activity and loading, with cardiac hypertrophy after exercise training, and cardiac atrophy after sustained inactivity. Ventricular wall stress (ie, loading) decreases during microgravity. Cardiac atrophy does not plateau during 12 weeks of simulated microgravity but is mitigated by concurrent exercise training. ObjectivesThe goal of this study was to determine whether the current exercise countermeasures on the International Space Station (ISS) offset cardiac atrophy during prolonged space flight. MethodsWe measured left ventricular (LV) and right ventricular (RV) mass and volumes (via magnetic resonance imaging) in 13 astronauts (4 females; age 49 ± 4 years), between 75 and 60 days before and 3 days after 155 ± 31 days aboard the ISS. Furthermore, we assessed total cardiac work between 21 and 7 days before space flight and 15 days before the end of the mission. Data were compared via paired-samples t-tests. ResultsTotal cardiac work was lower during space flight (P = 0.008); however, we observed no meaningful difference in LV mass postflight (pre: 115 ± 30 g vs post: 118 ± 29 g; P = 0.053), with marginally higher LV stroke volume (P = 0.074) and ejection fraction postflight (P = 0.075). RV mass (P = 0.999), RV ejection fraction (P = 0.147), and ventricular end-diastolic (P = 0.934) and end-systolic volumes (P = 0.145) were not different postflight. There were strong positive correlations between the relative change in LV mass with the relative changes in total cardiac output (r = 0.73; P = 0.015) and total cardiac work (r = 0.53; P = 0.112). ConclusionsThe current exercise countermeasures used on the ISS appear effective in offsetting reductions in cardiac mass and volume, despite overall reductions in total cardiac work, during prolonged space flight.

Effects of empagliflozin on cardiac structure, function and biomarkers in patients with heart failure with preserved ejection fraction: study protocol for a randomised, placebo-controlled prospective trial

IntroductionHeart failure (HF) with preserved ejection fraction (HFpEF) has become the main type of HF worldwide. Although large randomised controlled studies have demonstrated the beneficial effects of sodium–glucose cotransporter 2...

Rationale and Design of the SOTA-P-CARDIA Trial (ATRU-V): Sotagliflozin in HFpEF Patients Without Diabetes.

Heart failure with preserved ejection fraction (HFpEF) is now the most common form of heart failure (HF). This syndrome is associated with an elevated morbi-mortality, and effective therapies are urgently needed. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are the first pharmacological class that has demonstrated to reduce hospitalization and cardiovascular mortality in large clinical trials in HFpEF. Furthermore, the dual SGLT 1/2 inhibitor sotagliflozin has shown a reduction in cardiovascular outcomes in diabetic HF patients, regardless of ejection fraction Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure (SOLOIST-WHF) Trial, and prevents the development of HF in patients with diabetes and chronic kidney diseaseSotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk (SCORED) trial. The major objective of theSotagliflozin in Heart Failure With Preserved Ejection Fraction Patients(SOTA-P-CARDIA) trial (NCT05562063) is to investigate whether the observed cardiorenal benefits of sotagliflozin in HF patients with diabetes can be extended to a non-diabetic population. The SOTA-P-CARDIA is a prospective, randomized, double-blinded, placebo-controlled study that will randomize non-diabetic patients with the universal definition of HFpEF (ejection fraction > 50% assessed the day of randomization). Qualifying patients will be randomized, in blocks of 4, to receive either sotagliflozin or placebo for a period of 6months. The primary outcome is changes in left ventricular mass by cardiac magnetic resonance from randomization to end of the study between the groups. Secondary end points include changes in peak VO2; myocardial mechanics, interstitial myocardial fibrosis, and volume of epicardial adipose tissue; distance in the 6-min walk test; and quality of life. Finally, the authors expect that this trial will help to clarify the potential benefits of the use of sotagliflozin in non-diabetic HFpEF patients.