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A randomized controlled trial of enhancing hypoxia-mediated right cardiac mechanics and reducing afterload after high intensity interval training in sedentary men.
Huang, YC, Hsu, CC, Fu, TC, Wang, JS
Scientific reports. 2021;(1):12564
Abstract
Hypoxic exposure increases right ventricular (RV) afterload by triggering pulmonary hypertension, with consequent effects on the structure and function of the RV. Improved myocardial contractility is a critical circulatory adaptation to exercise training. However, the types of exercise that enhance right cardiac mechanics during hypoxic stress have not yet been identified. This study investigated how high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) influence right cardiac mechanics during hypoxic exercise A total of 54 young and healthy sedentary males were randomly selected to engage in either HIIT (3-min intervals at 40% and 80% of oxygen uptake reserve, n = 18) or MICT (sustained 60% of oxygen uptake reserve, n = 18) for 30 min/day and 5 days/week for 6 weeks or were included in a control group (CTL, n = 18) that did not engage in any exercise. The primary outcome was the change in right cardiac mechanics during semiupright bicycle exercise under hypoxic conditions (i.e., 50 watts under 12% FiO2 for 3 min) as measured by two-dimensional speckle tracking echocardiography.: After 6 weeks of training, HIIT was superior to MICT in improving maximal oxygen consumption (VO2max). Furthermore, the HIIT group showed reduced pulmonary vascular resistance (PVR, pre-HIIT:1.16 ± 0.05 WU; post-HIIT:1.05 ± 0.05 WU, p < 0.05) as well as an elevated right ventricular ejection fraction (RVEF, pre-HIIT: 59.5 ± 6.0%; post-HIIT: 69.1 ± 2.8%, p < 0.05) during hypoxic exercise, coupled with a significant enhancement of the right atrial (RA) reservoir and conduit functions. HIIT is superior to MICT in dilating RV chamber and reducing radial strain but ameliorating radial strain rate in either systole (post-HIIT: 2.78 ± 0.14 s-1; post-MICT: 2.27 ± 0.12 s-1, p < 0.05) or diastole (post-HIIT: - 2.63 ± 0.12 s-1; post-MICT: - 2.36 ± 0.18 s-1, p < 0.05). In the correlation analysis, the changes in RVEF were directly associated with improved RA reservoir (r = 0.60, p < 0.05) and conduit functions (r = 0.64, p < 0.01) but inversely associated with the change in RV radial strain (r = - 0.70, p < 0.01) and PVR (r = - 0.70, p < 0.01) caused by HIIT. HIIT is superior to MICT in improving right cardiac mechanics by simultaneously increasing RA reservoir and conduit functions and decreasing PVR during hypoxic exercise.
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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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Evaluation and Management of Right-Sided Heart Failure: A Scientific Statement From the American Heart Association.
Konstam, MA, Kiernan, MS, Bernstein, D, Bozkurt, B, Jacob, M, Kapur, NK, Kociol, RD, Lewis, EF, Mehra, MR, Pagani, FD, et al
Circulation. 2018;(20):e578-e622
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Abstract
BACKGROUND AND PURPOSE The diverse causes of right-sided heart failure (RHF) include, among others, primary cardiomyopathies with right ventricular (RV) involvement, RV ischemia and infarction, volume loading caused by cardiac lesions associated with congenital heart disease and valvular pathologies, and pressure loading resulting from pulmonic stenosis or pulmonary hypertension from a variety of causes, including left-sided heart disease. Progressive RV dysfunction in these disease states is associated with increased morbidity and mortality. The purpose of this scientific statement is to provide guidance on the assessment and management of RHF. METHODS The writing group used systematic literature reviews, published translational and clinical studies, clinical practice guidelines, and expert opinion/statements to summarize existing evidence and to identify areas of inadequacy requiring future research. The panel reviewed the most relevant adult medical literature excluding routine laboratory tests using MEDLINE, EMBASE, and Web of Science through September 2017. The document is organized and classified according to the American Heart Association to provide specific suggestions, considerations, or reference to contemporary clinical practice recommendations. RESULTS Chronic RHF is associated with decreased exercise tolerance, poor functional capacity, decreased cardiac output and progressive end-organ damage (caused by a combination of end-organ venous congestion and underperfusion), and cachexia resulting from poor absorption of nutrients, as well as a systemic proinflammatory state. It is the principal cause of death in patients with pulmonary arterial hypertension. Similarly, acute RHF is associated with hemodynamic instability and is the primary cause of death in patients presenting with massive pulmonary embolism, RV myocardial infarction, and postcardiotomy shock associated with cardiac surgery. Functional assessment of the right side of the heart can be hindered by its complex geometry. Multiple hemodynamic and biochemical markers are associated with worsening RHF and can serve to guide clinical assessment and therapeutic decision making. Pharmacological and mechanical interventions targeting isolated acute and chronic RHF have not been well investigated. Specific therapies promoting stabilization and recovery of RV function are lacking. CONCLUSIONS RHF is a complex syndrome including diverse causes, pathways, and pathological processes. In this scientific statement, we review the causes and epidemiology of RV dysfunction and the pathophysiology of acute and chronic RHF and provide guidance for the management of the associated conditions leading to and caused by RHF.
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Perioperative Management of the Right and Left Ventricles.
Lampert, BC
Cardiology clinics. 2018;(4):495-506
Abstract
Left ventricular assist devices (LVADs) improve survival in select advanced heart failure patients and rates of LVAD implantation are growing. LVAD support carries significant morbidity and mortality with the greatest risk in the perioperative period. Strategies have evolved to minimize this risk. Medical and mechanical support is used for right and left ventricular optimization. Other strategies emphasize improving nutrition, hematologic abnormalities, infection risk, and renal function. Intraoperative approaches highlight anesthesia-related issues, management of concomitant valve disease, right ventricular failure, and weaning from cardiopulmonary bypass. Postoperative efforts concentrate on augmenting right ventricular function, supporting end-organ recovery, and quickly identifying complications.
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Diuretics versus volume expansion in acute submassive pulmonary embolism.
Schouver, ED, Chiche, O, Bouvier, P, Doyen, D, Cerboni, P, Moceri, P, Ferrari, E
Archives of cardiovascular diseases. 2017;(11):616-625
Abstract
BACKGROUND The benefit of volume expansion (VE) in submassive pulmonary embolism (PE) with right ventricular (RV) dysfunction is unclear. AIM: To compare the effects of diuretic treatment versus VE in patients hospitalized for PE with RV dysfunction. METHODS We prospectively included 46 consecutive patients with submassive PE treated on admission with a 40mg bolus of furosemide (D group, n=24) or 500mL of saline infusion (VE group, n=22). The primary endpoint was the timing of normalization of B-type natriuretic peptide and troponin Ic concentrations. The secondary endpoints were variations in RV function variables, recorded at baseline, at the 4th hour after treatment initiation (H4) and every day until discharge, and a clinical composite endpoint of thrombolysis or death at 7 and 30 days. RESULTS No differences were observed between patients at baseline. The primary endpoint occurred earlier in the D group than in the VE group (67.5±34.8 vs 111.6±63.3hours; P=0.006). Furosemide treatment on admission was well tolerated, and was not associated with serious adverse events. At H4, substantial improvements were observed in the D group versus the VE group in terms of heart rate reduction (-8.15±21.0 vs -0.71±6.30 beats/min; P<0.01) and peak tricuspid annular systolic velocity (Doppler tissue imaging) (11.4±2.10 vs 9.90±2.80cm/s; P=0.02). There was no significant difference between groups in terms of severe outcomes at 7 and 30 days. CONCLUSIONS In the acute management of submassive PE patients, a single furosemide bolus on admission seems to produce significant and earlier improvements in RV function markers compared with VE, without adverse events.
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Effects of combined deferiprone with deferoxamine on right ventricular function in thalassaemia major.
Alpendurada, F, Smith, GC, Carpenter, JP, Nair, SV, Tanner, MA, Banya, W, Dessi, C, Galanello, R, Walker, JM, Pennell, DJ
Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance. 2012;(1):8
Abstract
BACKGROUND Combination therapy with deferoxamine and oral deferiprone is superior to deferoxamine alone in removing cardiac iron and improving left ventricular ejection fraction (LVEF). The right ventricle (RV) is also affected by the toxic effects of iron and may cause additional cardiovascular perturbation. We assessed the effects of combination therapy on the RV in thalassaemia major (TM) using cardiovascular magnetic resonance (CMR). METHODS We retrieved imaging data from 2 treatment trials and re-analyzed the data for the RV responses: Trial 1 was a randomized controlled trial (RCT) of 65 TM patients with mild-moderate cardiac siderosis receiving combination therapy or deferoxamine with placebo; Trial 2 was an open label longitudinal trial assessing combination therapy in 15 TM patients with severe iron loading. RESULTS In the RCT, combination therapy with deferoxamine and deferiprone was superior to deferoxamine alone for improving RVEF (3.6 vs 0.7%, p = 0.02). The increase in RVEF was greater with lower baseline T2* 8-12 ms (4.7 vs 0.5%, p = 0.01) than with T2* 12-20 ms (2.2 vs 0.8%, p = 0.47). In patients with severe cardiac siderosis, substantial improvement in RVEF was seen with open-label combination therapy (10.5% ± 5.6%, p < 0.01). CONCLUSIONS In the RCT of mild to moderate cardiac iron loading, combination treatment improved RV function significantly more than deferoxamine alone. Combination treatment also improved RV function in severe cardiac siderosis. Therefore adding deferiprone to deferoxamine has beneficial effects on both RV and LV function in TM patients with cardiac siderosis.
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Effects of quinidine on the action potential duration restitution property in the right ventricular outflow tract in patients with brugada syndrome.
Ashino, S, Watanabe, I, Kofune, M, Nagashima, K, Ohkubo, K, Okumura, Y, Mano, H, Nakai, T, Kunimoto, S, Kasamaki, Y, et al
Circulation journal : official journal of the Japanese Circulation Society. 2011;(9):2080-6
Abstract
BACKGROUND On a cellular level, Brugada syndrome has been attributed to a deep phase 1 notch and subsequent shallow and prolonged repolarization in the right ventricular outflow tract (RVOT). A sodium channel mutation that leads to early inactivation of the late sodium current has been identified in some patients. Thus, drugs that inhibit the transient outward current (I(to)) responsible for the phase 1 notch and/or enhance the late sodium current might suppress arrhythmic events in patients with Brugada syndrome. The effects of quinidine gluconate, a potent inhibitor of I(to), on RVOT action potential duration (APD) restitution kinetics in patients with Brugada syndrome were evaluated. METHODS AND RESULTS Programmed ventricular stimulation was performed in 9 Brugada syndrome patients by delivering up to 3 extrastimuli from the right ventricular apex and RVOT. RVOT monophasic action potentials (MAPs) were recorded before and after intravenous administration of quinidine (n=6) or ibutilide (n=3). All patients had inducible ventricular fibrillation (VF) before drug administration. Both quinidine and ibutilide increased steady-state and minimum RVOT MAP duration during programmed stimulation. Quinidine decreased the maximum slope of the RVOT APD restitution curve and VF could not be induced after administration of quinidine in 5 of the 6 patients. CONCLUSIONS Quinidine appears to suppress the induction of VF by increasing RVOT MAP duration and decreasing the maximum slope of the restitution curve.
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Effect of deferiprone or deferoxamine on right ventricular function in thalassemia major patients with myocardial iron overload.
Smith, GC, Alpendurada, F, Carpenter, JP, Alam, MH, Berdoukas, V, Karagiorga, M, Ladis, V, Piga, A, Aessopos, A, Gotsis, ED, et al
Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance. 2011;(1):34
Abstract
BACKGROUND Thalassaemia major (TM) patients need regular blood transfusions that lead to accumulation of iron and death from heart failure. Deferiprone has been reported to be superior to deferoxamine for the removal of cardiac iron and improvement in left ventricular (LV) function but little is known of their relative effects on the right ventricle (RV), which is being increasingly recognised as an important prognostic factor in cardiomyopathy. Therefore data from a prospective randomised controlled trial (RCT) comparing these chelators was retrospectively analysed to assess the RV responses to these drugs. METHODS In the RCT, 61 TM patients were randomised to receive either deferiprone or deferoxamine monotherapy, and CMR scans for T2* and cardiac function were obtained. Data were re-analysed for RV volumes and function at baseline, and after 6 and 12 months of treatment. RESULTS From baseline to 12 months, deferiprone reduced RV end systolic volume (ESV) from 37.7 to 34.2 mL (p=0.008), whilst RV ejection fraction (EF) increased from 69.6 to 72.2% (p=0.001). This was associated with a 27% increase in T2* (p<0.001) and 3.1% increase in LVEF (p<0.001). By contrast, deferoxamine showed no change in RVESV (38.1 to 39.1 mL, p=0.38), or RVEF (70.0 to 69.9%, p=0.93) whereas the T2* increased by 13% (p<0.001), but with no change in LVEF (0.32%; p=0.66). Analysis of between drugs treatment effects, showed significant improvements favouring deferiprone with a mean effect on RVESV of -1.82 mL (p=0.014) and 1.16% for RVEF (p=0.009). Using regression analysis the improvement in RVEF at 12 months was shown to be greater in patients with lower baseline EF values (p<0.001), with a significant difference in RVEF of 3.5% favouring deferiprone over deferoxamine (p=0.012). CONCLUSION In this retrospective analysis of a prospective RCT, deferiprone monotherapy was superior to deferoxamine for improvement in RVEF and end-systolic volume. This improvement in the RV volumes and function may contribute to the improved cardiac outcomes seen with deferiprone.
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Effect of L-arginine or L-citrulline oral supplementation on blood pressure and right ventricular function in heart failure patients with preserved ejection fraction.
Orozco-Gutiérrez, JJ, Castillo-Martínez, L, Orea-Tejeda, A, Vázquez-Díaz, O, Valdespino-Trejo, A, Narváez-David, R, Keirns-Davis, C, Carrasco-Ortiz, O, Navarro-Navarro, A, Sánchez-Santillán, R
Cardiology journal. 2010;(6):612-8
Abstract
BACKGROUND The effect of L-arginine and L-citrulline on blood pressure and right ventricular function in heart failure patients with preserved ejection fraction (HFpEF) is unknown. We have therefore evaluated, in a randomized clinical trial, the effect of these aminoacids in chronic outstanding and stable patients with HFpEF. METHODS AND RESULTS All patients underwent an echocardiogram and radioisotopic ventriculography rest/exercise, and were randomized in a consecutive manner to the L-arginine group (n = 15; 8 g/day); and the citrulline malate group (n = 15; 3 g/day). The duration of follow-up was two months. The principal echocardiographic finding was a statistically significant decrease in pulmonary artery pressure in the L-arginine (56.3 ± 10 vs 44 ± 16.5 mm Hg, p < 0.05) and the citrulline (56.67 ± 7.96 vs 47.67 ± 8.59 mm Hg, p < 0.05) groups. Duration on treadmill and right ventricular ejection fraction post exercise increased, while diastolic and systolic artery pressure decreased significantly in both groups. There were no other statistically significant differences between the groups. CONCLUSIONS Administration of L-arginine and citrulline to patients with HFpEF improved right ventricular function by increasing right ventricular ejection fraction, and probably decreasing systolic pulmonary artery pressure.
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Effects of darbepoetin alpha on right and left ventricular systolic and diastolic function in anemic patients with chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.
Parissis, JT, Kourea, K, Panou, F, Farmakis, D, Paraskevaidis, I, Ikonomidis, I, Filippatos, G, Kremastinos, DT
American heart journal. 2008;(4):751.e1-7
Abstract
BACKGROUND Anemia is a frequent condition in chronic heart failure (CHF) that affects adversely long-term cardiac outcomes. We sought to investigate the effects of recombinant human erythropoietin analogue darbepoetin alpha on left (LV) and right ventricular (RV) function and neurohormonal activation in patients with CHF and anemia. METHODS Thirty-two CHF patients (New York Heart Association class II-III, LV ejection fraction [EF] <40%, hemoglobin level <12.5 g/dL, serum creatinine level <2.5 mg/dL) were randomized (2:1) to receive either a 3-month darbepoetin alpha regimen at 1.5 microg/kg every 20 days plus oral iron (n = 21) or placebo plus oral iron (n = 11). Echocardiographic indices of LV systolic and diastolic function and RV function, plasma B-type natriuretic peptide (BNP) and 6-minute walked distance were assessed at baseline and posttreatment. RESULTS Regarding LV function, only treatment with darbepoetin alpha caused a significant improvement in LVEF (F = 22.001, P < .001), end-systolic wall stress (F = 4.934, P = .034), mitral annulus systolic displacement (F = 6.710, P < .015), isovolumic relaxation time (F = 4.909, P = .035), and E/e ratio (F = 7.833, P = .009). The RV systolic pressure (F = 7.715, P = .009) as well as tricuspid annulus systolic displacement and RVEF (F = 9.264, P = .005) were significantly improved only in the darbepoetin alpha group. Darbepoetin alpha had also alpha beneficial effect on New York Heart Association class (F = 14.586, P = .001), plasma BNP (F = 14.781, P = .001), and 6-minute walk test (F = 19.926, P < .001), whereas these parameters did not significantly change in the placebo-treated patients. CONCLUSION Darbepoetin alpha improves both LV and RV performance and exercise capacity and counteracts neurohormonal activation in CHF patients with anemia. The drug effects on LV diastolic function, RV function, and LV end-systolic wall stress, in particular, are novel findings, with a potential important contribution to patients' symptomatic improvement.