Reduction In Left Ventricular Mass Research Articles

Effect of migalastat on cardiac involvement in Fabry disease: preliminary results from MAIORA study

Abstract Background Fabry Disease (FD) is a rare X-linked lysosomal storage disorder. Since 2016, pharmacological chaperone Migalastat has been approved for treatment of FD patients with amenable mutations to stabilize defective forms of the enzyme α-galactosidase A. A small but significant reduction in left ventricular (LV) mass after 18 months of Migalastat treatment has been previously reported by echocardiography. However, an integrated assessment of the effect of Migalastat on cardiac involvement, combining LV morphology and tissue composition by CMR with exercise capacity by cardiopulmonary test, is lacking. Purpose To determine the effects of 18 month treatment with Migalastat on LV mass, native T1 value and functional capacity in naïve patients with genetically confirmed FD cardiomyopathy. Methods Sixteen treatment naïve FD patients (4 females, mean age 46.4±16.2) with amenable mutations and signs of cardiac involvement underwent CMR with T1 mapping and cardio-pulmonary testing before and after 18 months of migalastat therapy as a part of MAIORA Study. Cardiac involvement was defined as presence of reduced native T1 values at CMR (a surrogate of myocardial glycosphingolipid storage) and/or LV hypertrophy (LVH). Nine patients (56%, 2 females, mean age 56.4±12.7 years) had LVH at baseline. Results Migalastat treatment was well tolerated in all patients, with no serious adverse event. No change in LV mass was detected at 18 months compared to baseline (95.2 (66.0–184.0) vs 103.0 (71.0–182.0) g/m2; p=0.5516). The same result was found after stratifying patients according to presence/absence of Late Gadolinium Enhancement (LGE) (LGE+ n=8, 2 females, mean age 56.2±13.1 years). There was a trend towards an increased native septal T1 value (870.0 (848–882) vs 860.0 (833.0–875.0) ms at baseline; p 0.056) with unchanged extracellular volume (ECV) (0.26 (0.23–0.028) vs 0.26 (0.22–0.29) at baseline; p 0.276) in the overall cohort. An improvement in functional capacity with a trend towards an increase in percent-predicted peak VO2 (72.0 (61.25–80.75) vs 67.0 (45.2–79.2) at baseline; p 0.056) and a significant increase in VO2 at anaerobic threshold (14.8 (12.6–20.0) vs 13.10 (6.8–18.6) ml/kg/min at baseline; p 0.004) was reported in the total population. Conclusion In treatment naïve FD patients with amenable mutations and signs of early or overt cardiac involvement, 18-month treatment with Migalastat stabilized LV mass both in patients with and without LGE and was associated with an improvement in exercise tolerance. The trend towards an increase in T1 value associated with unchanged ECV suggests partial clearance of cardiomyocyte glycoshingolipid storage. These real-world data are consistent with a beneficial impact of migalastat on the progression of cardiac involvement in FD. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Amicus Therapeutics

SGLT2 inhibitors and cardiac remodelling: a systematic review and meta-analysis of randomized cardiac magnetic resonance imaging trials.

AimsRecent large randomized controlled trials (RCTs) have demonstrated efficacy of sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) in both preventing and treating heart failure (HF). SGLT2i‐induced reversal of left ventricular remodelling has been proposed as a mechanism contributing to this effect.Methods and resultsWe performed a systematic review and meta‐analysis of RCTs to compare SGLT2i versus placebo (treatment duration >3 months) on cardiac remodelling parameters as measured by cardiac magnetic resonance imaging (cMRI) in patients with HF and/or diabetes. The PubMed and ClinicalTrials.gov databases were searched until 15 June 2021. Our primary outcome was change in absolute left ventricular mass (LVM) from baseline to study endpoint. Secondary outcomes included changes in LVM indexed to body surface area, left ventricular end‐systolic volume (LVESV), left ventricular end‐diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF) from baseline to study endpoint. The Cochrane Collaboration's tool was used to assess risk of bias. Five studies representing 408 patients were included. SGLT2i was associated with greater LVM regression compared to placebo (MD, −5.76 g; 95% CI, −10.87 g to −0.64 g, I 2 = 73%; overall effect, P < 0.03; four RCTs). Statistical subgroup differences were not observed in our sensitivity analysis focusing on HF with reduced ejection fraction (P = 0.37) and were observed in our sensitivity analysis focusing on diabetes (P < 0.001). SGLT2i was not associated with statistical changes in LV mass indexed to body surface area (I 2 = 75%; P = 0.16; five RCTs), LVESV (I 2 = 87%; P = 0.07; five RCTs), LVEDV (I 2 = 81%; P = 0.20; five RCTs), nor LVEF (I 2 = 85%; P = 0.19; five RCTs) versus placebo. Sixty per cent of RCTs had low risk of bias.ConclusionsSodium‐glucose cotransporter‐2 inhibitors treatment was associated with a reduction in left ventricular mass as assessed by cMRI.

Effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on left ventricular remodelling and longitudinal strain: a prospective observational study

BackgroundSodium-glucose cotransporter 2 inhibitors (SGLT2i) lower cardiovascular events in type 2 diabetes mellitus (T2DM) patients, although the mechanisms underlying these benefits are not clearly understood. Our aim was to study the effects of SGLT2i on left ventricular remodelling and longitudinal strain.MethodsBetween November 2019 and April 2020, we included 52 patients with T2DM ≥ 18 years old, with HbA1c between 6.5 and 10.0%, and estimated glomerular filtration ≥ 45 ml/min/1.73 m2. Patients were classified into SGLT2i group and control group, according to prescribed treatment by their referring physician. Conventional and speckle tracking echocardiography were performed by blinded sonographers, at baseline and after 6 months of treatment.ResultsAmong the 52 included patients (44% females, mean age 66.8 ± 8.6 years, mean HbA1c was 7.40 ± 0.7%), 30 patients were prescribed SGLT2i and 22 patients were classified as control group. Mean change in indexed left ventricular mass (LVM) was − 0.85 ± 3.31 g/m2 (p = 0.003) in the SGLT2i group, and + 2.34 ± 4.13 g/m2 (p = 0.58) in the control group. Absolute value of Global Longitudinal Strain (GLS) increased by a mean of 1.29 ± 0.47 (p = 0.011) in the SGLT2i group, and 0.40 ± 0.62 (p = 0.34) in the control group. We did not find correlations between changes in LVM and GLS, and other variables like change in HbA1c.ConclusionsAmong patients with T2DM, SGLT2i were associated with a significant reduction in indexed LVM and a significant increment in longitudinal strain measured by speckle tracking echocardiography, which may explain in part the clinical benefits found in clinical trials.

The relationship between myocardial fibrosis and left ventricular remodeling following aortic valve replacement

Aim. Aortic valve diseases are associated with myocardial fibrosis. The relationship between severity of myocardial fibrosis and left ventricular mass reduction (LVMR) after aortic valve replacement (AVR) still needs to be elucidated. Methods. In a single-center, retrospective trial, 130 patients underwent AVR with/without concomitant surgery. The study population was divided by etiology into aortic stenosis (AS) and aortic regurgitation (AR) groups. LV end-diastolic diameter, LV septal and posterior thicknesses, LV mass, and aortic annulus were obtained in all study patients. Left ventricular mass regression index (iLVMR) was found by the difference between preoperative iLVM and follow-up iLVM. iLVMR in months was calculated by divided iLVMR on the number of months before follow-up visit. Myocardial tissue was embedded in paraffin, and sectioned into 4 µm slices for histological staining (picrosirius red) and scanning. The fraction of myocardial volume occupied by collagen tissue was determined. Results. The left ventricular remodeling of AS and AR patients is presented in Table 3. There was significant LV mass reduction in both aortic valve disease groups in the follow-up period (AS group, p < 0.001; AR group, p < 0.05). The number of LVH cases decreased in both groups in the follow-up period (AS group, p < 0.001; AR group, p < 0.05). In Post-AVR period the ejection fraction of LV did not improve in the AS group, compare to AR group (p<0.05). In both groups number of patients with impaired LV EF was increased in Post-AVR period, but not significantly. Moreover, the LV septal thickness, and iLVEDD significantly decreased in the AS group (p<0.001 and p<0.001), compared to the AR group (p=NS, p<0.05). We did not found correlations between MF and LVM in preoperative, and follow-up periods for AS and AR groups. Moreover, MF did not correlate significantly to iLVMR and iLVMR in months. A significant correlation exists in AS patients between MF and preoperative iLVEDD (r = 0.21, p = 0.04). Conclusion. The LVM reduction was observed in both AS and AR groups. LVM of AS group recovered more quickly than that of AR group. In our study MF does not affect LVM regression. Large cohort of patients with myocardial biopsies and long-term follow-up are needed to access the impact of the MF on the LVMR.

Correlation of Coronary Artery Disease and Left Ventricular Hypertrophy.

Ischemic heart disease (IHD) is the leading cause of death worldwide, and it is defined as an imbalance between myocardial oxygen supply and demand. Coronary artery disease (CAD) and left ventricular hypertrophy (LVH) are two common causes of IHD that independently result in myocardial ischemia. CAD decreases myocardial blood and oxygen supply whereas LVH increases myocardial oxygen demand. The coexistence of both CAD and LVH results in a significant increase in oxygen demand while simultaneously lowering oxygen supply.Since hypertension is a shared predisposing condition for both CAD and LVH, the left ventricular (LV) mass on noninvasive echocardiography can reflect on the severity of coronary artery stenosis. In clinical practice, it can help physicians decide whether to perform invasive cardiac catheterization to visualize the extent of the coronary block. Although, both CAD and LVH are directly proportional to mortality risk, the addition of eccentric LVH can further increase morbidity and mortality due to myocardial infarction. Therefore, the latest management of both the acute and chronic phases of CAD places an increased emphasis on controlling the predisposing factors to prevent or reverse LVH. For example, angiotensin-converting enzyme inhibitors and diuretics reduce LV mass by lowering the cardiac preload and afterload. This article aims to investigate the deleterious effects of the collaboration between CAD and LVH, establish a causal relationship, and explore the new prevention and management strategies.

Effect of weight loss on early left atrial myopathy in obese patients without known cardiovascular disease

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): BHF &amp; NIHR BRC Introduction Obesity is strongly associated with increased risk of heart failure and ischaemic stroke independently of associated co-morbidities. Left atrial (LA) reservoir dysfunction, a marker of atrial distensibility and compliance, is an early pathophysiological change which precedes the onset of cardiovascular disease in patients with obesity. It is unclear whether a weight loss intervention may be sufficient to reverse LA reservoir dysfunction. Purpose To longitudinally assess whether a weight loss intervention normalizes LA reservoir function by cardiac magnetic resonance (CMR) feature-tracking in patients with obesity and only subclinical cardiovascular disease and compared this age and sex matched non-obese normal weight controls. Methods A total of 45 patients with severe obese (age = 45 ± 11 years, body mass index = 39.1 ± 6.7 kg/m2, 51 ± 18 kg of excess body weight [EBW], 67% female) underwent CMR for quantification of LA and left ventricular (LV) size and function before and a median of 373 days following weight loss intervention. Weight loss was achieved by means of a very-low calorie diet (N = 28; 800 kcal/day) or by bariatric surgery (N = 17). A total of N = 27 non-obese healthy controls (age = 41 ± 12 years, body mass index = 22.3 ± 2.4 kg/m2, 75% female) underwent the same CMR protocol once. Results At baseline, patients with obesity displayed signs of atrial myopathy with increased LA volume and reduced LA reservoir function as compared to normal-weight controls (both P &amp;lt; 0.05, Figure 1) alongside increased LV mass and hyper-normal LV ejection fraction [LVEF] (both p &amp;lt; 0.01). As expected, weight loss led to a significant reduction of LA volume and LV mass with normalization of LVEF regardless of the degree of weight loss achieved (all P &amp;lt; 0.05, Figure 2). By contrast, only a large weight loss (&amp;gt;46.6% EBW, in red in Figure 2) was sufficient to improve and normalize the LA reservoir function (P &amp;lt; 0.05, Figure 2). On the other hand, moderate or milder weight loss (in orange and red) had no significant effect on LA reservoir function (both P &amp;gt; 0.05). Conclusion Successful weight loss can completely revert early LA myopathic phenotype in obese patients without known cardiovascular disease although this can be achieved only with larger weight loss targets.

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.

Low body mass is associated with reduced left ventricular mass in Chinese elderly with severe COPD

There is limited information on the association of body mass index (BMI) with left ventricular (LV) remodeling corresponding to severity of reduced lung function in patients with chronic obstructive pulmonary disease (COPD). Therefore, we investigated whether BMI is associated with cardiac atrial and ventricular dimensions according to severity of lung functional impairment in Chinese COPD elderly. A total of 563 hospitalized COPD patients with lung function impairment and 184 patients with non-COPD (aged 65–92 years) were collected retrospectively in a cross-sectional study in a university affiliated tertiary hospital in China. BMI and cardiac echocardiographic parameters were compared according to severity of lung functional impairment in COPD patients. BMI was 22.9 ± 3.9 kg/m2 in COPD patients, 24.0 ± 4.1 kg/m2 in non-COPD patients respectively. Reduced BMI, LV mass index, LV wall thickness and left atrial diameter, and dilated right ventricle (RV) existed in COPD patients with severe lung dysfunction as compared the COPD patients with mild to moderate lung functional reduction and non-COPD patients (P < 0.05), while there were no differences in BMI and echocardiographic parameters between the COPD patients with mild to moderate lung functional decline and non-COPD patients (P > 0.05). Logistic regression analysis showed that low BMI (BMI < 18.5 kg/m2) was correlated with reduced LV mass and wall thickness, dilated RV and reduced lung function in the COPD patients with severe lung dysfunction. In conclusion, this study demonstrates that lower BMI is associated not only with dilated RV and impaired pulmonary function, but also it is related to reduced LV mass in Asian COPD elderly with severe lung dysfunction.

Cardiorenal Systems Modeling: Left Ventricular Hypertrophy and Differential Effects of Antihypertensive Therapies on Hypertrophy Regression.

Cardiac and renal function are inextricably connected through both hemodynamic and neurohormonal mechanisms, and the interaction between these organ systems plays an important role in adaptive and pathophysiologic remodeling of the heart, as well as in the response to renally acting therapies. Insufficient understanding of the integrative function or dysfunction of these physiological systems has led to many examples of unexpected or incompletely understood clinical trial results. Mathematical models of heart and kidney physiology have long been used to better understand the function of these organs, but an integrated model of renal function and cardiac function and cardiac remodeling has not yet been published. Here we describe an integrated cardiorenal model that couples existing cardiac and renal models, and expands them to simulate cardiac remodeling in response to pressure and volume overload, as well as hypertrophy regression in response to angiotensin receptor blockers and beta-blockers. The model is able to reproduce different patterns of hypertrophy in response to pressure and volume overload. We show that increases in myocyte diameter are adaptive in pressure overload not only because it normalizes wall shear stress, as others have shown before, but also because it limits excess volume accumulation and further elevation of cardiac stresses by maintaining cardiac output and renal sodium and water balance. The model also reproduces the clinically observed larger LV mass reduction with angiotensin receptor blockers than with beta blockers. We further provide a mechanistic explanation for this difference by showing that heart rate lowering with beta blockers limits the reduction in peak systolic wall stress (a key signal for myocyte hypertrophy) relative to ARBs.

Cardiac abnormalities determined by tissue Doppler imaging and arrhythmias in adolescents with anorexia nervosa.

Anorexia nervosa has a prevalence of 0.5-3% in adolescents, placing this population at increased risk of cardiac anomalies including arrhythmias, pericardial effusion, and myocardial dysfunction. Our objective is to describe cardiovascular anomalies observed by tissue Doppler imaging in patients with anorexia nervosa. We retrospectively reviewed electrocardiogram, Holter, and echocardiography findings in 28 patients diagnosed with anorexia nervosa. Electrocardiogram was abnormal in 71% of patients with sinus bradycardia observed in 57%. Holter confirmed sinus bradycardia without significant pauses. Prolonged QTc, low voltage, and ectopic beats were each seen in 14% of patients. Wenckebach atrioventricular block was observed in one patient. Supraventricular or ventricular tachycardia was not observed. Echocardiography showed structurally normal heart in all patients. Pericardial effusion was seen in 7.1% of patients and left ventricular mass was decreased in 10.7%. Mean ejection fraction was 0.73 and mean fractional shortening was 38.4%. Tissue Doppler imaging revealed systolic or diastolic dysfunction in four patients with e', a', and s' velocities in the lateral and septal basal segments more than two standard deviations below the mean. Two patients had decreased left ventricular mass but no significant difference in disease duration from the group. Basal segment velocities below one standard deviation were also observed in an additional seven patients. A trend for decreased tissue Doppler imaging velocities was seen in 25.0% of patients, while significant systolic and diastolic dysfunction was seen in 14.3% of patients, associated with a significant reduction in left ventricular mass and independent of disease duration.

SERCA2a stimulation by istaroxime improves intracellular Ca2+ handling and diastolic dysfunction in a model of diabetic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by CVie Therapeutics Limited (Taipei, Taiwan) and Windtree Therapeutics (Warrington, USA) Diabetic cardiomyopathy is a multifactorial disease characterized by an early onset of diastolic dysfunction (DD) that precedes the development of systolic impairment. Mechanisms that can restore cardiac relaxation improving intracellular Ca2+ dynamics represent a promising therapeutic approach for cardiovascular diseases associated to DD. Istaroxime has the double property to accelerate Ca2+ uptake into sarcoplasmic reticulum (SR) through the SR Ca2+ pump (SERCA2a) stimulation and to inhibit Na+/K+ ATPase (NKA). The project aims to characterize istaroxime effects at a concentration (100 nM) marginally affecting NKA, in order to highlight its effects dependent on the stimulation of SERCA2a in a model of mild diabetes. Streptozotocin (STZ) treated diabetic rats were studied at 9 weeks after STZ injection in comparison to controls (CTR). Istaroxime effects were evaluated in vivo and in left ventricular (LV) preparations. STZ animals showed 1) marked DD not associated to cardiac fibrosis, 2) LV mass reduction associated to reduced LV cell dimension and T-tubules loss, 3) reduced LV SERCA2 protein level and activity and 4) slower SR Ca2+ uptake rate, 5) LV action potential (AP) prolongation and increased short-term variability (STV) of AP duration, 6) increased diastolic Ca2+, 7) unaltered SR Ca2+ content and stability in intact cells. Acute istaroxime infusion (0.11 mg/kg/min for 15 min) reduced DD in STZ rats. Accordingly, in STZ myocytes istaroxime (100 nM) stimulated SERCA2a activity and blunted STZ-induced abnormalities in LV Ca2+ dynamics. In CTR myocytes, istaroxime increased diastolic Ca2+ level due to NKA blockade albeit minimal, while its effects on SERCA2a were almost absent. SERCA2a stimulation by istaroxime improved STZ-induced DD and intracellular Ca2+ handling anomalies. Thus, SERCA2a stimulation can be considered a promising therapeutic approach for DD treatment. Abstract Figure.

Intradialytic exercise improves left ventricular mass in hemodialysis patients

Graham-Brown etal. report the results of a randomized controlled trial in patients on hemodialysis in which a 6-month intradialytic cycling program led to significant reduction in left ventricular mass as compared to the control group. However, there was no significant effect on physical function, physical activity or health-related quality of life.

Cardiac reverse remodelling and health status in patients with chronic heart failure.

AimsThis study aims to assess long‐term changes in left ventricular ejection fraction (LVEF) together with echocardiographic markers of cardiac remodelling and their association with prognosis and patient‐reported quality of life (QoL).Methods and resultsWe conducted a retrospective analysis of serial echocardiograms performed between January 2009 and December 2019 in 1089 patients (median age 63 years, 71.0% men) enrolled in the Mazankowski Heart Function Clinic Registry who had at least two echocardiograms separated by ≥12 months. We classified the patients into four subgroups by their baseline and LVEF trajectories: persistent heart failure with reduced ejection fraction (persistent HFrEF, n = 364), recovered ejection fraction (HFrecEF, n = 325), transient recovery in ejection fraction (HFtrecEF, n = 117), and preserved ejection fraction (HFpEF, n = 283); 4490 echocardiograms were included in the present analysis, with 4.1 ± 1.8 echocardiograms available per patient during follow‐up. Reductions in echocardiographic markers of cardiac remodelling, including LVIDd [adjusted odds ratio (aOR): 2.22, 95% confidence interval (CI) 1.75–2.86], LVIDs (aOR: 2.44, 95% CI 2.00–2.94), left ventricular mass index (aOR: 1.15, 95% CI 1.09–1.22), E/e′ ratio (aOR: 1.15, 95% CI 1.02–1.30), left atrial volume index (aOR: 1.10, 95% CI 1.03–1.16), along with an increase in the maximum recommended daily dose of renin‐angiotensin system inhibitors (aOR: 1.04, 95% CI 1.01–1.07) and mineralocorticoid‐receptor antagonists (aOR: 1.06, 95% CI 1.01–1.11) at 2 years, strongly predicted the HFrecEF classification, which was further sustained at 5 years of follow‐up. However, changes in these parameters were mostly absent in patients experiencing only a transient recovery in LVEF (HFtrecEF), closely resembling patients with persistent HFrEF. In the multivariable analysis, HFrecEF patients had lower risk of all‐cause mortality alone [adjusted hazard ratio (aHR): 0.46, 95% CI 0.23–0.93], and composite all‐cause (aHR: 0.59, 95% CI 0.49–0.73), cardiovascular (aHR: 0.47, 95% CI 0.36–0.61), and heart failure (aHR: 0.50, 95% CI 0.35–0.70) related hospitalizations with mortality than patients with persistent HFrEF. QoL assessed through the shortened Kansas City Cardiomyopathy Questionnaire‐12 at the end of follow‐up was greater in patients with HFrecEF by 5.2, 12.4, and 9.4 points than persistent HFrEF, HFtrecEF, and HFpEF, respectively.ConclusionsPatients with HFrecEF experienced progressive normalization in echocardiographic markers of cardiac remodelling characterized by reductions in left ventricular dimensions and mass in tandem with reductions in left atrial volume and E/e′ ratio, which is associated with better prognosis and QoL.

A randomized controlled trial to investigate the effects of intra-dialytic cycling on left ventricular mass

Cardiovascular disease is the leading cause of death for patients receiving hemodialysis. Since exercise mitigates many risk factors which drive cardiovascular disease for these patients, we assessed effects of a program of intra-dialytic cycling on left ventricular mass and other prognostically relevant measures of cardiovascular disease as evaluated by cardiac MRI (the CYCLE-HD trial). This was a prospective, open-label, single-blinded cluster-randomized controlled trial powered to detect a 15g difference in left ventricular mass measured between patients undergoing a six-month program of intra-dialytic cycling (exercise group) and patients continuing usual care (control group). Pre-specified secondary outcomes included measures of myocardial fibrosis, aortic stiffness, physical functioning, quality of life and ventricular arrhythmias. Outcomes were analyzed as intention-to-treat according to a pre-specified statistical analysis plan. Initially, 130 individuals were recruited and completed baseline assessments (65 each group). Ultimately, 101 patients completed the trial protocol (50 control group and 51 exercise group). The six-month program of intra-dialytic cycling resulted in a significant reduction in left ventricular mass between groups (-11.1g; 95% confidence interval -15.79, -6.43), which remained significant on sensitivity analysis (missing data imputed) (-9.92g; 14.68, -5.16). There were significant reductions in both native T1 mapping and aortic pulse wave velocity between groups favoring the intervention. There was no increase in either ventricular ectopic beats or complex ventricular arrhythmias as a result of exercise with no significant effect on physical function or quality of life. Thus, a six-month program of intradialytic cycling reduces left ventricular mass and is safe, deliverable and well tolerated.

IMPACT OF PERCUTANEOUS TRANSLUMINAL RENAL ANGIOPLASTY ON LEFT VENTRICULAR MASS AND ITS RELATIONSHIP TO CARDIOVASCULAR OUTCOME IN HYPERTENSIVE PATIENTS WITH RENAL ARTERY STENOSIS

Objective: Renal artery stenosis (RAS) is associated with secondary hypertension, which is often resistant to antihypertensive medication.The aim of the present study was to evaluate the impact of renal angioplastry on left ventricular (LV) mass, as measured by echocardiography, and further to determine whether LV mass reduction is associated with reduced rates of cardiovascular events in hypertensive patients with RAS. Design and method: A total of 144 hypertensive patients with RAS (mean age 69 years; 22.2% fibromuscular dysplasia [FMD]) who underwent angioplasty were included. Echocardiography was performed at baseline and after one year, and were thereafter followed up for a median of 5.6 years for the primary composite outcomes. The primary endpoint of this study was first occurrence of the composite of cardiovascular events including all-cause death, myocardial infarction, stroke, or adverse aortic event. Results: In both the FMD and atherosclerotic stenosis (ARAS) groups, LV mass decreased after angioplasty, but the decrease in LV mass index (-15.4 ± 18.3% versus -0.8 ± 27.8%, p &lt; 0.01) as well as the regression rate of LV hypertrophy was greater in FMD. Multiple logistic regression analysis indicated that FMD (odds ratio [OR] 2.94, p &lt; 0.01), severe RAS (greater than or equal to 90%) (OR 2.94, p &lt; 0.05), and higher LV mass index at baseline (OR 2.94 for 1 standard deviation increase, p &lt; 0.001) were independent predictors of LV mass index decrease of at least 20%. The primary composite outcomes occurred in 45 patients (31.3%). In FMD, lower LV mass index after one year (hazard ratio 2.81 for 1 standard deviation increase, p &lt; 0.05) or regression of LV mass (hazard ratio 0.75 for 5% decrease, p = 0.054) showed a tendency to be associated with better outcomes; however, these associations were not found in ARAS. Conclusions: Hypertensive patients with ARAS have less regression of LV mass in response to angioplasty than those with FMD, and LV mass regression is less useful as a surrogate marker of outcomes especially in ARAS.

CILNIDIPINE DECREASES LEFT ATRIAL VOLUME INDEX SUPERIOR THAN ATENOLOL IN THE PATIENTS WITH HYPERTENSION

Objective: This study was designed as a prospective, randomized, double-blind, parallel-group to test whether cilnidipine achieves greater left ventricular (LV) mass reduction and improves LV diastolic function than does atenolol. Design and method: Seventy-two patients with uncomplicated essential hypertension and increased LV mass index at screening echocardiography were randomly assigned and forced-titrated to 20 mg/d cilnidipine or 100 mg of atenolol for 36 weeks. Echocardiography, ambulatory blood pressure monitoring, biochemical studies including NT pro-BNP and 24-hours urine microalbumin were measured at baseline and after 36-weeks therapy. Results: Clinical examination and blinded echocardiogram in a per-protocol analysis of 28 cilnidipine-treated and 26 atenolol-treated patients revealed similar reductions in systolic/diastolic pressure (-16.5/8.9 mmHg versus -23.9/14.8 mmHg) and LV mass index (-21.4 g/m2 versus -19.5 g/m2). Interestingly, cilnidipine-treated group showed reduction on left atrial (LA) volume index but atenolol-treated group showed more enlarged LA (-5.1 % versus 7.3 %, p = 0.035). Conclusions: Both cilnidipine and atenolol similarly and effectively reduced blood pressure and LV mass index. However, only cilnidipine reduced LA volume index, whereas atenolol increased. Cilnidipine may provide more beneficial effect on the management in essential hypertension with diastolic dysfunction.

SERCA2a stimulation by istaroxime improves intracellular Ca2+ handling and diastolic dysfunction in a model of diabetic cardiomyopathy.

Aims Diabetic cardiomyopathy is a multifactorial disease characterized by an early onset of diastolic dysfunction (DD) that precedes the development of systolic impairment. Mechanisms that can restore cardiac relaxation improving intracellular Ca2+ dynamics represent a promising therapeutic approach for cardiovascular diseases associated to DD. Istaroxime has the dual properties to accelerate Ca2+ uptake into sarcoplasmic reticulum (SR) through the SR Ca2+ pump (SERCA2a) stimulation and to inhibit Na+/K+ ATPase (NKA). This project aims to characterize istaroxime effects at a concentration (100 nmol/L) marginally affecting NKA, in order to highlight its effects dependent on the stimulation of SERCA2a in an animal model of mild diabetes.Methods and results Streptozotocin (STZ) treated diabetic rats were studied at 9 weeks after STZ injection in comparison to controls (CTR). Istaroxime effects were evaluated in vivo and in left ventricular (LV) preparations. STZ animals showed (i) marked DD not associated to cardiac fibrosis, (ii) LV mass reduction associated to reduced LV cell dimension and T-tubules loss, (iii) reduced LV SERCA2 protein level and activity and (iv) slower SR Ca2+ uptake rate, (v) LV action potential (AP) prolongation and increased short-term variability (STV) of AP duration, (vi) increased diastolic Ca2+, and (vii) unaltered SR Ca2+ content and stability in intact cells. Acute istaroxime infusion (0.11 mg/kg/min for 15 min) reduced DD in STZ rats. Accordingly, in STZ myocytes istaroxime (100 nmol/L) stimulated SERCA2a activity and blunted STZ-induced abnormalities in LV Ca2+ dynamics. In CTR myocytes, istaroxime increased diastolic Ca2+ level due to NKA blockade albeit minimal, while its effects on SERCA2a were almost absent.Conclusions SERCA2a stimulation by istaroxime improved STZ-induced DD and intracellular Ca2+ handling anomalies. Thus, SERCA2a stimulation can be considered a promising therapeutic approach for DD treatment.

Impact of surgical aortic valve replacement on global and regional longitudinal strain across four flow gradient patterns of severe aortic stenosis.

To evaluate the impact of surgical aortic valve replacement (SAVR) on global (GLS) and regional longitudinal strain (RLS) across four flow-gradient patterns of severe aortic stenosis (AS) 3 months after surgery.A total of 103 patients with severe AS (aortic valve area < 1.0 cm2) were examined by speckle tracking echocardiography the day before SAVR and at 3-months follow-up. Patients were stratified into four flow-gradient patterns by stroke volume index (>35 mL/m2 vs. ≤35 mL/m2) and mean transaortic gradients (>40 mmhg vs. ≤40 mmhg): normal-flow, high gradient (NF/HG); low-flow, high gradient (LF/HG); normal-flow, low gradient (NF/LG); low-flow, low gradient (LF/LG). Strain analysis comprised GLS and RLS at a basal (BLS), mid-ventricular (MLS) and apical level (ALS).Patients with high gradients improved GLS (NF/HG: 16.1 ± 3.5 % vs. 17.3 ± 3.4 %, p = 0.03 and LF/HG: 15.4 ± 3.6 % vs. 16.9 ± 3.1 %, p = 0.03), BLS (NF/HG: 12.7 ± 3.1 % vs. 14.2 ± 3.1 %, p = 0.003 and LF/HG: 11.4 ± 3.2 % vs. 13.8 ± 2.7 %, p = 0.005) and MLS (NF/HG: 15.4 ± 3.3 % vs. 16.5 ± 3.3 %, p = 0.04 and LF/HG: 14.5 ± 3.1 % vs. 16.2 ± 2.7 %, p = 0.01) whereas patients with low gradients showed no improvements three months after SAVR. ALS did not change significantly in any group. Patients with high gradients demonstrated a reduction in left ventricular (LV) mass index (p < 0.001) and N-terminal pro-Brain Natriuretic Peptide levels (p < 0.001) following SAVR in contrast to patients with low gradients.Patients with high gradient severe AS improve GLS and RLS three months after SAVR with concomitant reduction of LV mass and neurohormonal activation whereas patients with low gradients do not improve longitudinal strain, LV mass or neurohormonal activation.

Effects of Angiotensin II Receptor Blockers on Ventricular Hypertrophy in Hypertrophic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials.

Animal studies have suggested that angiotensin II receptor blockers (ARBs) can attenuate or reverse the progression of hypertrophic cardiomyopathy, while clinical studies yielded conflicting results. We sought to conduct a meta-analysis to investigate the effect of ARBs in patients with hypertrophic cardiomyopathy. PubMed and EMBASE databases were searched through June 2020. Only randomized controlled trials (RCTs) were included, and each study's quality was assessed using the Jadad scale. The primary outcome was left ventricular mass reduction, and the secondary outcome was the change in left ventricular ejection fraction (LVEF). Data were pooled using the random effects model. A total of 1294 articles were screened. Five RCTs were included in the final analysis, enrolling 209 patients with hypertrophic cardiomyopathy (101 patients were in the ARB arm). ARB treatment was not associated with either significant left ventricular mass reduction (standardized mean difference: - 0.25; 95% CI: - 0.73, 0.22; p = 0.29) or change in LVEF (weighted mean difference: 0.73%; 95% CI: - 1.10%, 2.56%; p = 0.43). Subgroup analysis showed that losartan, one of the most investigated and commonly used ARBs, was also not associated with significant decreases of left ventricular mass (standardized mean difference: - 0.13; 95% CI: - 0.61, 0.36; p = 0.61). This meta-analysis showed that ARB treatment is not associated with reduced left ventricular mass nor remarkable LVEF change among patients with hypertrophic cardiomyopathy. Further studies with a larger number of patients will be required to confirm these findings.

Early myocardial remodeling after aortic valve replacement

Background: Aortic valve disease leads to eccentric or concentric left ventricular (LV) hypertrophy and changes in the left ventricle function. The goal of aortic valve replacement (AVR) is to alleviate the pressure and volume overload on the left ventricle, allowing myocardial remodeling and regression of LV mass. Objectives: The objective of this study was to assess early LV remodeling in patients with severe aortic valve stenosis and/or moderate-to-severe aortic regurgitation after AVR. Materials and Methods: This prospective study was conducted in the department of cardiovascular and thoracic surgery between January 2015 and February 2016. All patients undergoing AVR exclusively over 1 year were included in the study. Patients were assessed at 1 week, 6 weeks, 3 months, and 6 months after AVR by transthoracic echocardiography. Peak and mean pressure gradients across aortic valve, LV ejection fraction, fractional shortening, LV dimensions, and LV mass along with other parameters were measured in the pre- and postoperative period. Results: A total of 33 patients with different lesions who underwent AVR were evaluated. All but one child (aged 12 years) were adults with a median age of 52 years ± 14.6 years including 21 males and 12 females. The LV mass index (LVMI) regression occurred over time in all cases. Mean LVMI decreased to 149.20 ± 53.7 g/m2 at 1 week and 120.8 ± 45.49 g/m2 at 6 weeks of AVR from its baseline value of 180.8 ± 58.9 g/m2 (P < 0.001). Six patients who were followed up to 1 year had mean LVMI 122.46 ± 50.0 g/m2. Conclusion: Marked reduction in LV mass was discerned after AVR as early as 1 week and further reduction continued up to 6 weeks; however, regression thereafter was not statistically significant.