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1.
Impact of empagliflozin on right ventricular parameters and function among patients with type 2 diabetes.
Sarak, B, Verma, S, David Mazer, C, Teoh, H, Quan, A, Gilbert, RE, Goodman, SG, Bami, K, Coelho-Filho, OR, Ahooja, V, et al
Cardiovascular diabetology. 2021;(1):200
Abstract
BACKGROUND Sodium-glucose cotransporter 2 (SGLT2) inhibition reduces cardiovascular events in type 2 diabetes (T2DM) and is associated with a reduction in left ventricular (LV) mass index. However, the impact on right ventricular (RV) remodeling is unknown. Accordingly, the objective of this study was to assess the impact of SGLT2 inhibition on RV parameters and function in T2DM and coronary artery disease (CAD). METHODS In EMPA-HEART CardioLink-6, 97 patients with T2DM and CAD were randomly assigned to empagliflozin 10 mg (n = 49) once daily or placebo (n = 48). Cardiac magnetic resonance imaging was performed at baseline and after 6 months. RV mass index (RVMi), RV end-diastolic and end-systolic volume index (RVEDVi, RVESVi) and RV ejection fraction (RVEF) were assessed in blinded fashion. RESULTS At baseline, mean RVMi (± SD) (11.8 ± 2.4 g/m2), RVEF (53.5 ± 4.8%), RVEDVi (64.3 ± 13.2 mL/m2) and RVESVi (29.9 ± 6.9 mL/m2) were within normal limits and were similar between the empagliflozin and placebo groups. Over 6 months, there were no significant differences in RVMi (- 0.11 g/m2, [95% CI - 0.81 to 0.60], p = 0.76), RVEF (0.54%, [95% CI - 1.4 to 2.4], p = 0.58), RVEDVi (- 1.2 mL/m2, [95% CI - 4.1 to 1.7], p = 0.41) and RVESVi (- 0.81 mL/m2, [95% CI - 2.5 to 0.90], p = 0.35) in the empaglifozin group as compared with the placebo group. In both groups, there was no significant correlation between RVMi and LVMi changes from baseline to 6 months. CONCLUSIONS In this post-hoc analysis, SGLT2 inhibition with empagliflozin had no impact on RVMi and RV volumes in patients with T2DM and CAD. The potentially differential effect of empagliflozin on the LV and RV warrants further investigation. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov/ct2/show/NCT02998970?cond=NCT02998970&draw=2&rank=1 . Unique identifier: NCT02998970.
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2.
A randomized controlled trial of the effect of spironolactone on left ventricular mass in hemodialysis patients.
Hammer, F, Malzahn, U, Donhauser, J, Betz, C, Schneider, MP, Grupp, C, Pollak, N, Störk, S, Wanner, C, Krane, V, et al
Kidney international. 2019;(4):983-991
Abstract
Mineralocorticoid receptor antagonists have beneficial effects on left ventricular remodeling, cardiac fibrosis, and arrhythmia in heart failure, but efficacy and safety in dialysis patients is less clear. We evaluated the effect of spironolactone on left ventricular mass (LVM), an independent predictor of all-cause and cardiovascular mortality, in hemodialysis patients. In this placebo-controlled, parallel-group trial, 97 hemodialysis patients (23% female; mean age 60.3 years) were randomized to spironolactone 50 mg once daily (n=50) or placebo (n=47). The primary efficacy endpoint was change in LVM index (LVMi) from baseline to 40 weeks as determined by cardiac magnetic resonance imaging. Safety endpoints were development of hyperkalemia and change in residual renal function. There was no significant change in LVMi in participants randomized to spironolactone compared to placebo (-2.86±11.87 vs. 0.41±10.84 g/m2). There was also no difference in the secondary outcomes of mean 24-hour systolic or diastolic ambulatory blood pressure, left ventricular ejection fraction, 6-minute walk test distance, or New York Heart Association functional class. Moderate hyperkalemia (pre-dialysis potassium levels of 6.0-6.5 mmol/L) was more frequent with spironolactone treatment (155 vs. 80 events), but severe hyperkalemia (≥6.5 mmol/L) was not (14 vs. 24 events). Changes in residual urine volume and measured glomerular filtration rate did not differ between groups. There were no deaths in the spironolactone group and 4 deaths in the placebo group. Thus, treatment with 50 mg spironolactone did not change left ventricular mass index, cardiac function, or blood pressure in hemodialysis patients. Spironolactone increased the frequency of moderate hyperkalemia, but did not increase severe hyperkalemia.
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3.
The impact of torasemide on haemodynamic and neurohormonal stress, and cardiac remodelling in heart failure - TORNADO: a study protocol for a randomized controlled trial.
Balsam, P, Ozierański, K, Tymińska, A, Główczyńska, R, Peller, M, Fojt, A, Cacko, A, Sieradzki, B, Bakuła, E, Markulis, M, et al
Trials. 2017;(1):36
Abstract
BACKGROUND Approximately 50% of heart failure patients are readmitted to hospital within 6 months, owing to deterioration of their condition. Thus, symptomatic treatment of heart failure requires significant improvement. The aim of this study is to compare the effects of torasemide and furosemide on biochemical parameters of haemodynamic and neurohormonal compensation, myocardial remodelling, clinical outcomes and quality of life in patients with chronic heart failure. METHODS This is a multicentre, randomized, open, blinded endpoint phase-IV trial. The study includes 120 heart failure patients in NYHA (New York Heart Association) functional class II-IV, treated with optimal heart failure therapy, with indications for use of loop diuretics. At enrolment, patients are stable, with a fixed dose of loop diuretics. Patients are randomized to treatment with furosemide or torasemide (randomization 1:1). After randomization, the current fixed dose of furosemide is continued or is replaced by an equipotential dose of torasemide (4:1). The study consists of two control visits (3 and 6 months after enrolment) with minimal follow-up of 6 months. Assessment involves clinical examination, Quality of Life Questionnaire, laboratory tests, echocardiography, electrocardiography, 24 h Holter-electrocardiography monitoring, 6 -min walk test and assessment of fluid retention. Any need for dose adjustment is assessed during the observation. The primary objective is to compare the effects of torasemide and furosemide on clinical and biochemical parameters of haemodynamic and neurohormonal compensation and myocardial remodelling. Secondary objectives include monitoring of: changes in signs and symptoms of heart failure, NYHA functional class, quality of life, dosage changes, rate of readmissions and mortality. DISCUSSION Despite decades of the diuretic's history, knowledge about diuretic therapy is still unsatisfactory. The most widely used diuretic, furosemide, has a stormy pharmacokinetics and pharmacodynamics, and is associated with a high risk of mortality and hospitalization for worsening heart failure. Reports are very encouraging and suggest beneficial effects of torasemide. Hence, there is a need for further studies of the overall effect of torasemide, compared with furosemide. This can translate into improved quality of life and better prognosis of patients with heart failure. TRIAL REGISTRATION ClinicalTrials.gov, NCT01942109 . Registered on 24 August 2013.
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4.
Research into the effect Of SGLT2 inhibition on left ventricular remodelling in patients with heart failure and diabetes mellitus (REFORM) trial rationale and design.
Singh, JS, Fathi, A, Vickneson, K, Mordi, I, Mohan, M, Houston, JG, Pearson, ER, Struthers, AD, Lang, CC
Cardiovascular diabetology. 2016;:97
Abstract
BACKGROUND Heart failure (HF) and diabetes (DM) are a lethal combination. The current armamentarium of anti-diabetic agents has been shown to be less efficacious and sometimes even harmful in diabetic patients with concomitant cardiovascular disease, especially HF. Sodium glucose linked co-transporter type 2 (SGLT2) inhibitors are a new class of anti-diabetic agent that has shown potentially beneficial cardiovascular effects such as pre-load and after load reduction through osmotic diuresis, blood pressure reduction, reduced arterial stiffness and weight loss. This has been supported by the recently published EMPA-REG trial which showed a striking 38 and 35 % reduction in cardiovascular death and HF hospitalisation respectively. METHODS The REFORM trial is a novel, phase IV randomised, double blind, placebo controlled clinical trial that has been ongoing since March 2015. It is designed specifically to test the safety and efficacy of the SLGT2 inhibitor, dapagliflozin, on diabetic patients with known HF. We utilise cardiac-MRI, cardio-pulmonary exercise testing, body composition analysis and other tests to quantify the cardiovascular and systemic effects of dapagliflozin 10 mg once daily against standard of care over a 1 year observation period. The primary outcome is to detect the change in left ventricular (LV) end systolic and LV end diastolic volumes. The secondary outcome measures include LV ejection fraction, LV mass index, exercise tolerance, fluid status, quality of life measures and others. CONCLUSIONS This trial will be able to determine if SGLT2 inhibitor therapy produces potentially beneficial effects in patients with DM and HF, thereby replacing current medications as the drug of choice when treating patients with both DM and HF. Trial registration Clinical Trials.gov: NCT02397421. Registered 12th March 2015.
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Extracellular remodeling in patients with wild-type amyloidosis consuming epigallocatechin-3-gallate: preliminary results of T1 mapping by cardiac magnetic resonance imaging in a small single center study.
aus dem Siepen, F, Buss, SJ, Andre, F, Seitz, S, Giannitsis, E, Steen, H, Katus, HA, Kristen, AV
Clinical research in cardiology : official journal of the German Cardiac Society. 2015;(8):640-7
Abstract
OBJECTIVES T1 mapping by cardiac magnetic resonance imaging (CMR) is able to determine the extracellular volume fraction. Wild-type transthyretin amyloidosis (WT-ATTR) is characterized by extracellular amyloid deposition in the heart. Recent reports indicated a reduction of left ventricular (LV) myocardial mass in WT-ATTR after consumption of epigallocatechin-3-gallate, the main catechin in green tea. It remained unclear, whether reduction of LV myocardial mass reflects decrease of amyloid load or progressive atrophy of cardiomyocytes. METHODS This study included 7 male patients with CMR repetitively performed before and 12 months after daily consumption of green tea extract (600 mg epigallocatechin-3-gallate). Short axis slices as well as 2-, 3-, and 4-chamber views were acquired using SSFP sequences. T1 mapping was created out of 11 mid-ventricular short axis views with increasing inversion times using a single breath-hold modified look-locker inversion recovery sequence before and 15 min after Gadolinium contrast administration. RESULTS After 12 months, a significant decrease of LV myocardial mass [198 (160; 212) vs. 180 (142; 204) g; p < 0.05] was observed. Moreover, a significant decrease of native [T1 1110 (1072; 1150) ms vs. 1080 (970; 1101), p < 0.05 or p = 0.03] was noticed. The calculated extracellular volume decreased in 5 patients (62.5%) by 7% and increased in 2 patients (37.5%) by 9.5%, in trend resulting in a (not significant) decrease of median ECV by 2.4%. Left ventricular ejection fraction (LVEF) [57 (48; 65) vs. 55 (47; 64) %; p = 0.3] remained unchanged. CONCLUSIONS This study provided further evidence of LV myocardial mass reduction in patients with WT-ATTR daily consuming green tea extract. Additionally, this study gave first insights into the histomorphological correlate of LV mass reduction using T1 mapping. LV mass reduction appeared to be rather due to a decrease of amyloid load than atrophy of cardiomyocytes.
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6.
Beneficial effects of statin treatment on coronary microvascular dysfunction and left ventricular remodeling in patients with acute myocardial infarction.
Ishida, K, Geshi, T, Nakano, A, Uzui, H, Mitsuke, Y, Okazawa, H, Ueda, T, Lee, JD
International journal of cardiology. 2012;(3):442-7
Abstract
BACKGROUND Statin treatment has been shown to improve coronary endothelial function, irrespective of lipid-lowering effects. This study's aim was to elucidate the effects of statin treatment on coronary microvascular dysfunction and left ventricular remodeling in acute myocardial infarction (AMI) patients. METHODS Thirty-five patients undergoing successful reperfusion following AMI were assigned to a statin-treated (Group S, 16) or a non-statin-treated (Group NS, 19) group, according to fasting serum low-density lipoprotein-cholesterol. (13)N-ammonia positron emission tomography was performed to assess myocardial flow reserve (MFR) in the infarct area. RESULTS Infarct sizes and lipid profiles during the chronic period were similar between the two groups. At 2 weeks after AMI onset, mean MFR in the infarct area was significantly higher in Group S than in Group NS (2.34 ± 0.63 vs. 1.91 ± 0.43, p=0.0214). At 6 months post-AMI, Group S had a smaller left-ventricular end-diastolic volume index (69.4 ± 11.7 mL/m(2) vs. 88.5 ± 32.5 mL/m(2), p=0.0328) and higher left-ventricular ejection fraction (67.7 ± 9.2% vs. 59.2 ± 13.3%, p=0.0394) than Group NS. Serum asymmetric dimethylarginine was significantly increased in Group NS at 1 month post-AMI (0.43 ± 0.12 μmol/L (baseline) vs. 0.52 ± 0.14 μmol/L, p=0.0186), but unchanged in Group S. CONCLUSIONS Statin treatment appears to beneficially attenuate left ventricular remodeling after AMI, which may be associated with restoring coronary endothelial function via endogenous nitric oxide.
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7.
Aging adversely affects postinfarction inflammatory response and early left ventricular remodeling after reperfused acute anterior myocardial infarction.
Mahara, K, Anzai, T, Yoshikawa, T, Maekawa, Y, Okabe, T, Asakura, Y, Satoh, T, Mitamura, H, Suzuki, M, Murayama, A, et al
Cardiology. 2006;(2):67-74
Abstract
BACKGROUND AND AIMS We have demonstrated that an increased peak serum C-reactive protein (CRP) level after acute myocardial infarction (AMI) was a major predictor of left ventricular (LV) remodeling. We sought to clarify the effect of aging on the postinfarction inflammatory response and LV remodeling. METHODS We studied 102 patients who underwent primary angioplasty for a first anterior Q-wave AMI. Serum CRP levels, plasma neurohormones and interleukin-6 (IL-6) levels, and LV volume by left ventriculography were serially measured. Patients were divided into two groups according to their age (>or=70 years, n=33; <70 years, n=69). RESULTS There was no difference in use of cardiovascular drugs and coronary angiographic findings. Older patients had a greater increase in LV end-diastolic volume during 2 weeks after AMI (p=0.0007) and a higher peak CRP level (12.4+/-7.3 vs. 5.5+/-4.2 mg/dl, p<0.0001), although peak CK level was comparable between the two groups. Plasma atrial natriuretic peptide, brain natriuretic peptide and IL-6 levels were higher in older patients at 2 weeks and 6 months after AMI. CONCLUSIONS Augmented and prolonged activation of the inflammatory system after AMI was observed in older patients, in association with exaggerated LV remodeling. Aging may adversely affect LV remodeling through modification of the inflammatory response after AMI.
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8.
Effects of levosimendan on left ventricular functional remodelling and exercise intolerance: a tissue Doppler study.
Kasikcioglu, HA, Unal, S, Tartan, Z, Uyarel, H, Okmen, E, Kasikcioglu, E, Cam, N
The Journal of international medical research. 2005;(4):397-405
Abstract
Levosimendan is a calcium sensitizer that demonstrates enhanced myocardial contractility. There is little information concerning the effect of levosimendan on left ventricular tissue parameters and exercise capacity. We evaluated the effects of a 24-h course of levosimendan therapy on cardiac tissue parameters in 30 patients, aged 48 - 70 years, admitted to our hospital for the management of decompensated heart failure. All patients underwent echocardiographic examination using tissue Doppler imaging (TDI) and a 6-min walk test. Systolic myocardial velocity of the mitral annulus (Sm) was significantly increased in levosimendan-treated patients compared with placebo-treated patients. There was a positive correlation between Sm and exercise capacity. Levosimendan might be expected to increase cardiac contractile force, especially Sm velocity, in parallel with exercise tolerance. The study has also shown that the progress of ventricular function after levosimendan treatment in patients with exercise intolerance could be monitored effectively by Sm velocity measurements using TDI.
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9.
The effect of combination therapy on regression of left ventricular hypertrophy in cases with hypertension.
Boydak, B, Nalbantgil, S, Yilmaz, H, Zoghi, M, Ozerkan, F, Nalbantgil, I, Onder, R
Saudi medical journal. 2004;(12):1975-8
Abstract
OBJECTIVE Up to this date, it is well shown that several antihypertensive drugs have different regressive effect on left ventricular hypertrophy (LVH). However, there are different studies regarding the effect of antihypertensive combination therapies on regression of LVH. In this study, 2 different combinations ACE-I plus calcium channel blocker and ACE-I plus diuretic were compared in cases with hypertension whose BPs were not controlled by ACE-I alone. METHODS Forty patients with mild to moderate hypertension were included in this study. The treatment was continued for 6 months in the Faculty of Medicine at Ege University, Turkey, between January and December 2003. Adequate response with lisinopril 20 mg/daily failed to be achieved in all patients. Patients divided into 2 groups. There were no differences between the groups in patients' age, blood pressure (BP) and other clinical and laboratory range. First group patients received lisinopril 20 mg + nifedipine GITS 30 mg and second group patients received lisinopril 20 mg + hydrochlorothiazide 25 mg. The treatment was continued for 6 months. Blood pressure were measured every 2 weeks, echocardiographic findings, and blood and urinary analysis were performed before and at the end of treatment. RESULTS Systolic and diastolic BP decreased significantly in both groups and no significant difference regarding BP was found between the 2 groups. Left ventricular mass index also decreased significantly in both groups. However, in the first group left ventricular mass index decreased more compared to the second group. CONCLUSION The effect of combination therapies with angiotensin converting enzyme inhibitor (ACE-I) plus diuretic and ACE-I plus calcium channel blocker on systolic and diastolic BP are similar. However, when LVH is present, regressive effect of the combination of ACE-I plus calcium channel blocker is superior to the combination of ACE-I plus diuretic.
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10.
Angina pectoris prior to myocardial infarction protects against subsequent left ventricular remodeling.
Solomon, SD, Anavekar, NS, Greaves, S, Rouleau, JL, Hennekens, C, Pfeffer, MA, ,
Journal of the American College of Cardiology. 2004;(9):1511-4
Abstract
OBJECTIVES To investigate the hypothesis that prior angina pectoris confers protection from remodeling occurring after myocardial infarction (MI), we analyzed echocardiograms from the Healing and Early Afterload Reducing Therapy (HEART) trial. BACKGROUND Ischemia occurring before MI has been shown to reduce infarct size in experimental models and to improve outcomes in patients. The extent to which ischemia occurring before MI influences subsequent changes in ventricular size and function is unclear. METHODS We studied 283 patients enrolled in the HEART trial who had echocardiograms at days 1 and 90 after MI. Left ventricular (LV) dilation from days 1 to 90 was used as a measure of LV remodeling. We explored the relationship between symptomatic angina occurring before infarction and subsequent LV remodeling. RESULTS In patients who reported angina (n = 111) during the three months preceding MI, LV volume change was -0.73 +/- 2.6 ml over the 90-day post-MI period, compared with 6.8 +/- 2.6 ml for patients (n = 172) without angina (p = 0.017). In contrast, there were no differences in changes in ejection fraction based on prior angina. Maximal creatine kinase was significantly lower in patients with prior angina (2,119 +/- 1,729 vs. 2,701 +/- 2,088, p = 0.016). In a multivariate model, prior angina remained protective for ventricular remodeling after adjusting for age, gender, baseline ejection fraction, Killip class, baseline end-diastolic volume, and drug treatment group (p = 0.042). However, the protective effect of pre-infarction angina appeared to be attenuated in diabetic patients. CONCLUSIONS Ischemic symptoms occurring before MI may protect against LV remodeling. These protective effects may be secondary to recruitment of collaterals or ischemic preconditioning of the myocardium, and they appear to be attenuated in diabetic patients.