Shunxin decoction improves diastolic function in rats with heart failure with preserved ejection fraction induced by abdominal aorta constriction through cyclic guanosine monophosphate-dependent protein kinase Signaling Pathway.

OBJECTIVE: To determine whether Shunxin decoction improves diastolic function in rats with heart failure with preserved ejection fraction (HFpEF) by regulating the cyclic guanosine monophosphate-dependent protein kinase (cGMP-PKG) signaling pathway. METHODS: Except for control group 8 and sham surgery group 8, the remaining 32 male Sprague-Dawlay rats were developed into HFpEF rat models using the abdominal aorta constriction method. These rats in the HFpEF model were randomly divided into the model group, the Shunxin high-dose group, the Shunxin low-dose group, and the Qiliqiangxin capsule group. The three groups received high-dose Shunxin decoction, low-dose Shunxin decoction, and Qiliqiangxin capsule by gavage, respectively, for 14 d. After the intervention, the diastolic function of each rat was evaluated by testing E/A, heart index, hematoxylin-eosin staining, Masson, myocardial ultrastructure, and N-terminal pro-brain natriuretic peptide (NT-proBNP). The Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) software was used to predict targets for which Shunxin decoction acts on the cGMP-PKG pathway. Natriuretic peptide receptor A (NPRA) and guanylate cyclase (GC) were detected by immunohistochemistry, and eNOS, phosphodiesterase 5A (PDE5A), and cGMP-dependent protein kinase 1(PKG I) were determined by Western blotting. RESULTS: Compared to the model group, the thickness of the interventricular septum at the end of diastole (IVSd) and the thickness of the posterior wall at the end of diastole (PWd) of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group were all significantly reduced ( < 0.01). Furthermore, Shunxin decoction high-dose group E/A value was decreased ( < 0.01). Compared to the model group, the expression of NPRA and GC increased in the Shunxin decoction low-dose group and the Qiliqiangxin capsule group ( < 0.01). Compared to the model group, the expressions of eNOS and PKG I increased ( < 0.05) in the Shunxin decoction high-dose group. The expression of PDE5A expression decreased in the myocardium of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group compared to the model group ( < 0.01). CONCLUSIONS: Shunxin decoction can improve diastolic function in rats with HFpEF. It increases the expression of NPRA, GC, and eNOS in the myocardial cell cGMP-PKG signaling pathway, upregulates cGMP expression, decreases PDE5A expression to reduce the cGMP degradation. Thus, the cGMP continually stimulates PKG I, reversing myocardial hypertrophy and improving myocardial compliance in HFpEF rats.

Fetal echocardiographic evaluation before and after nifedipine treatment in preterm labor.

OBJECTIVE: To assess the effect of nifedipine used for tocolysis on cardiac morphology and functions. METHODS: The study included 47 pregnant women diagnosed with preterm labor at 32-33 weeks. Fetal echocardiographic evaluation was performed with two-dimensional (2D) imaging, M-mode, pulsed wave (PW) Doppler, and tissue Doppler imaging (TDI) before and after the 48th hour of nifedipine treatment. RESULTS: No significant change was observed in Doppler parameters (pulsatility indices of the umbilical artery, middle cerebral artery, ductus venosus) and cardiac morphology (cardiothoracic ratio, end-diastolic longitudinal diameters, sphericity indices, wall thickness) after nifedipine treatment. The parameters obtained with TDI (e', a', s', e'/a', E/e' of mitral and tricuspid valves), M- mode (TAPSE, MAPSE), pulsed Doppler (myocardial performance index, left cardiac output, right cardiac output, tricuspid E, A waves, tricuspid E/A ratio, mitral E, A waves, mitral E/A ratio) did not change after nifedipine treatment. CONCLUSION: To date, this is the first study to examine the effects of nifedipine on the fetal heart using the TDI. Since nifedipine is a drug that is frequently used and well-tolerated in the prevention of preterm labor, it is crucial that it does not cause changes in fetal cardiac parameters during tocolysis. Therefore, we used TDI in addition to conventional methods to evaluate the effect of nifedipine, which is frequently used in obstetrics, on cardiac functions in the early period. Nifedipine treatment seems not to affect systolic or diastolic functions. This indicates that nifedipine is reliable on cardiac functions and morphology in pregnancies treated for preterm labor.

Management of central hemodynamic and endothelial function disturbances in patients with myocardial infarction combined with metabolic syndrome.

On a global scale, myocardial infarction (MI) remains one of the most important cardiological challenges of today due to persistent incidence of morbidity, disability and mortality. AIM: The aim of study was to improve the treatment of MI combined with MS by adding a carnitine-arginine combination to the treatment protocol used in these patients. MATERIALS AND METHODS: The study included assessments of 56 patients who had acute coronary syndrome (ACS) with ST segment elevation and concomitant MS. The examined group included 38 patients, in whom a standard per-protocol treatment for ACS/MI was supplemented by a combination of L-arginine (4.2 g)/L-carnitine (2.0 g) supplied as solution for infusions. The combination was administered intravenously, 100 mL once a day for 5 days. The control group enrolled 18 patients who received standard per protocol treatment only. In addition to routine clinical tests and investigations, the patients had echocardiographic assessment for indices of cardiac remodeling and systolic-diastolic function of the left ventricle. The functional status of vascular endothelium was assessed based on plasma concentrations of endothelin-1 (ET-1) and concentrations of stable NO metabolites. RESULTS: In patients with ACS/MI combined with MS, baseline findings included pronounced disturbances of cardiac morpho-functional parameters, development of post-infarction ventricular remodeling with impaired systolic and diastolic heart function and developing clinical signs of cardiac insufficiency in the setting of endothelial vascular dysfunction. Already in 10 days of treatment, patients in the test group (who had additional treatment with L-arginine/L-carnitine) were noted to have increases in DT and EF and reductions in LVEDV and E/A ratio. On day 28 of treatment, there were significant increases in E and EF (by 13%) and reductions in IVRT, A and E/A, which suggested a gradual recovery of myocardial contractility and a reduction in diastolic dysfunction. CONCLUSIONS: The pharmacotherapeutic combination with inclusion of Larginine and L-carnitine produced a significant improvement in parameters of central cardiac hemodynamics and restored endothelial vascular function. This was accompanied by a significant reduction in the incidence and severity of such complications as reperfusion arrhythmias and acute left ventricular failure.

Lactobacillus plantarum probiotic induces Nrf2-mediated antioxidant signaling and eNOS expression resulting in improvement of myocardial diastolic function.

Yorkshire swine were fed standard diet (n = 7) or standard diet containing applesauce rich in caffeic acid with Lactobacillus plantarum (n = 7) for 3 wk. An ameroid constrictor was next placed around the left coronary circumflex artery, and the dietary regimens were continued. At 14 wk, cardiac function, myocardial perfusion, vascular density, and molecular signaling in ischemic myocardium were evaluated. The L. plantarum-applesauce augmented NF-E2-related factor 2 (Nrf2) in the ischemic myocardium and induced Nrf2-regulated antioxidant enzymes heme oxygenase-1 (HO-1), NADPH dehydrogenase quinone 1 (NQO-1), and thioredoxin reductase (TRXR-1). Improved left ventricular diastolic function and decreased myocardial collagen expression were seen in animals receiving the L. plantarum-applesauce supplements. The expression of endothelial nitric oxide synthase (eNOS) was increased in ischemic myocardial tissue of the treatment group, whereas levels of asymmetric dimethyl arginine (ADMA), hypoxia inducible factor 1α (HIF-1α), and phosphorylated MAPK (pMAPK) were decreased. Collateral-dependent myocardial perfusion was unaffected, whereas arteriolar and capillary densities were reduced as determined by α-smooth muscle cell actin and CD31 immunofluorescence in ischemic myocardial tissue. Dietary supplementation with L. plantarum-applesauce is a safe and effective method of enhancing Nrf2-mediated antioxidant signaling cascade in ischemic myocardium. Although this experimental diet was associated with a reduction in hypoxic stimuli, decreased vascular density, and without any change in collateral-dependent perfusion, the net effect of an increase in antioxidant activity and eNOS expression resulted in improvement in diastolic function.NEW & NOTEWORTHY Colonization of the gut microbiome with certain strains of L. Plantarum has been shown to convert caffeic acid readily available in applesauce to 4-vinyl-catechol, a potent activator of the Nrf2 antioxidant defense pathway. In this exciting study, we show that simple dietary supplementation with L. Plantarum-applesauce-mediated Nrf2 activation supports vascular function, ameliorates myocardial ischemic diastolic dysfunction, and upregulates expression of eNOS.

Effect of atorvastatin on systolic and diastolic function in patients with heart failure with reduced ejection fraction (HFrEF).

Aim To investigate the benefit of high-dose lipophilic statin therapy on cardiac remodelling, function and progression of heart failure (HF) in patients with ischemic heart disease. Methods A total of 80 patients with ischemic HF diagnosis were followed during 6 months, and they were divided in two groups. First group (n=40) was treated by high-dose lipophilic statin therapy (atorvastatin 40 mg) and conventional therapy for HF, while the second group (n=40) had no atorvastatin in the therapy. Results In the beginning of study, from all of the observed parameters, only the ratio of flow rates in early and late diastole (E/A ratio) differed between the test groups (p=0.007). After six months, a statistically significant increase in left ventricular end-diastolic diameter (LVIDD) in patients who had not been treated with atorvastatin was found. In the patients treated with atorvastatin, there was a significant reduction in basal right ventricle diameter in diastole and systole (p<0.001 and p<0.001, respectively), and in tricuspid annular plane systolic excursion (TAPSE) (p<0.001); there was a reduction in LVIDD (p<0.001), and an increase of ejection fraction of the left ventricle according to Teicholtz and Simpson (p<0.001 and p<0.001, respectively). Also, there was an increase of deceleration time of early diastolic velocity (DTE) (p<0.05) and a decrease of isovolumic relaxation time (IVRT) (p<0.001). Conclusion The reduction in the right and left ventricle diameters was noted after the six-month atorvastatin therapy. Atorvastatin in the therapy resulted in increased EFLV and better systolic function and should be a part of a therapeutic modality of HF.

Association between Reduced Serum Zinc and Diastolic Dysfunction in Maintenance Hemodialysis Patients.

Diastolic dysfunction is an emerging challenge among hemodialysis (HD) patients, and the associations between serum zinc with echocardiographic parameters and diastolic function remain uncertain. A total of 185 maintenance HD patients were stratified by the tertiles of serum zinc level to compare their clinical characteristics and echocardiography. Correlations of serum zinc levels with echocardiographic parameters were examined using Pearson's analysis. Univariate and multivariate logistic regression analyses were performed to investigate the determinants of E/e' ratio >15 and left atrial volume index (LAVI) > 34 mL/m2, both indicators of diastolic dysfunction. Patients belonging to the first tertile of serum zinc level had a significantly higher E/e' ratio and LAVI. Serum zinc levels were negatively correlated with E (r = -0.204, p = 0.005), E/e' ratio (r = -0.217, p = 0.003), and LAVI (r = -0.197, p = 0.007). In a multivariate analysis, older age, diabetes, coronary artery disease, and lower serum zinc levels (OR = 0.974, 95% CI = 0.950-0.999, p = 0.039) were significantly associated with E/e' ratio >15. Furthermore, diabetes and lower serum zinc levels (OR = 0.978, 95% CI = 0.958-0.999, p = 0.041) were significantly associated with LAVI >34 mL/m2. Reduced serum zinc level was significantly associated with diastolic dysfunction among HD patients. Further prospective studies are warranted to investigate whether zinc supplementation can attenuate cardiac dysfunction in maintenance HD patients.

Magnesium Deficiency Causes a Reversible, Metabolic, Diastolic Cardiomyopathy.

Background Dietary Mg intake is associated with a decreased risk of developing heart failure, whereas low circulating Mg level is associated with increased cardiovascular mortality. We investigated whether Mg deficiency alone could cause cardiomyopathy. Methods and Results C57BL/6J mice were fed with a low Mg (low-Mg, 15-30 mg/kg Mg) or a normal Mg (nl-Mg, 600 mg/kg Mg) diet for 6 weeks. To test reversibility, half of the low-Mg mice were fed then with nl-Mg diet for another 6 weeks. Low-Mg diet significantly decreased mouse serum Mg (0.38±0.03 versus 1.14±0.03 mmol/L for nl-Mg; P<0.0001) with a reciprocal increase in serum Ca, K, and Na. Low-Mg mice exhibited impaired cardiac relaxation (ratio between mitral peak early filling velocity E and longitudinal tissue velocity of the mitral anterior annulus e, 21.1±1.1 versus 15.4±0.4 for nl-Mg; P=0.011). Cellular ATP was decreased significantly in low-Mg hearts. The changes were accompanied by mitochondrial dysfunction with mitochondrial reactive oxygen species overproduction and membrane depolarization. cMyBPC (cardiac myosin-binding protein C) was S-glutathionylated in low-Mg mouse hearts. All these changes were normalized with Mg repletion. In vivo (2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride treatment during low-Mg diet improved cardiac relaxation, increased ATP levels, and reduced S-glutathionylated cMyBPC. Conclusions Mg deficiency caused a reversible diastolic cardiomyopathy associated with mitochondrial dysfunction and oxidative modification of cMyBPC. In deficiency states, Mg supplementation may represent a novel treatment for diastolic heart failure.

Low Dose of Folic Acid Can Ameliorate Hyperhomocysteinemia-Induced Cardiac Fibrosis and Diastolic Dysfunction in Spontaneously Hypertensive Rats.

To evaluate whether lowering plasma homocysteine (Hcy) levels at different doses of folic acid (FA) could reduce cardiac fibrosis and diastolic dysfunction in spontaneously hypertensive rats (SHRs) with hyperhomocysteinemia (Hhcy) and investigate the possible mechanism of action.We randomly divided 32 male SHRs into control, Hhcy, Hhcy + low-dose FA (LFA), and Hhcy + high-dose FA (HFA) groups. Echocardiography and Masson staining of cardiac tissue were used to assess diastolic function and cardiac fibrosis. Blood pressure (BP) and Hcy levels were measured during the experiment. We also measured the indicators of oxidative stress (OS) and examined the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) genes and proteins using real-time polymerase chain reaction (PCR), immunohistochemistry, and western blotting to explore the possible mechanism of action.FA treatment reversed SHR cardiomyocyte interstitial and perivascular collagen deposition and diastolic dysfunction exacerbated by Hhcy. These effects were associated with promoting the translocation of Nrf2 from the cytoplasm to the nucleus, activating HO-1 expression and inhibiting OS. However, HFA did not show any additional benefit from LFA in reducing cardiac injury.Even at a low dose, FA can ameliorate Hhcy-induced cardiac fibrosis and diastolic dysfunction in SHRs by activating Nrf2/HO-1 pathway and inhibiting OS, independent of BP, providing evidence for the efficacy of LFA in the treatment of hypertension associated with Hhcy.

Low Dose Curcumin Administered in Hyaluronic Acid-Based Nanocapsules Induces Hypotensive Effect in Hypertensive Rats.

BACKGROUND: Vascular drug delivery becomes a promising direction in the development of novel therapeutic strategies in the treatment of cardiovascular pathologies, such as hypertension. However, targeted delivery of hydrophobic substances, with poor bioavailability, remains a challenge. Here, we described the hypotensive effects of a low dose of curcumin delivered to the vascular wall using hyaluronic acid-based nanocapsules. METHODS: The group of hypertensive TGR(m-Ren2)27 rats, was administrated respectively with the vehicle, curcumin solution or curcumin delivered using hyaluronic acid-based nanocapsules (HyC12-Cur), for 7 days each, maintaining the wash-out period between treatments. Arterial blood pressure (systolic - SBP, diastolic - DBP) and heart rate (HR) were monitored continuously using a telemetry system (Data Science International), and Mean Arterial Pressure (MAP) was calculated from SBP and DBP. RESULTS: In hypertensive rats, a low dose of curcumin (4.5 mg/kg) administrated in HyC12-Cur for 7 days resulted in a gradual inhibition of SBP, DBP and MAP increase without an effect on HR. At the end of HyC12-Cur - based treatment changes in SBP, DBP and MAP amounted to -2.0±0.8 mmHg, -3.9±0.7 mmHg and -3.3±0.7 mmHg, respectively. In contrast, the administration of a curcumin solution (4.5 mg/kg) did not result in a significant hypotensive effect and the animals constantly developed hypertension. Vascular delivery of capsules with curcumin was confirmed using newly developed fluorine-rich nanocapsules (HyFC10-PFOB) with a shell based on a HA derivative and similar size as HyC12-Cur. HyFC10-PFOB gave fluorine signals in rat aortas analyzed ex vivo with a 19F NMR technique after a single intragastric administration. CONCLUSION: These results suggest that nanocapsules based on hyaluronic acid, the ubiquitous glycosaminoglycan of the extracellular matrix and an integral part of endothelial glycocalyx, may represent a suitable approach to deliver hydrophobic, poorly bioavailable compounds, to the vascular wall.

Implications of a Soy-Based Diet for Animal Models.

The use of animal models in fundamental or pre-clinical research remains an absolute requirement for understanding human pathologies and developing new drugs. In order to transpose these results into clinical practice, many parameters must be taken into account to limit bias. Attention has recently been focused on the sex, age or even strain of each animal, but the impact of diet has been largely neglected. Soy, which is commonly used in the diet in varying quantities can affect their physiology. In order to assess whether the presence of soy can impact the obtained results, we studied the impact of a soy-based diet versus a soy-free diet, on diastolic function in a rat model based on transgenic overexpression of the ß3-adrenergic receptors in the endothelium and characterized by the appearance of diastolic dysfunction with age. Our results show that the onset of diastolic dysfunction is only observed in transgenic male rats fed with a soy-free diet in the long term. Our study highlights the importance of the diet's choice in the study design process, especially regarding the proportion of soy, to correctly interpret the outcome as low-cost diets are more likely to be highly concentrated in soy.

Tai Ji Quan as antihypertensive lifestyle therapy: A systematic review and meta-analysis.

BACKGROUND: Professional health organizations are not currently recommending Tai Ji Quan alongside aerobic exercise to treat hypertension. We aimed to examine the efficacy of Tai Ji Quan as antihypertensive lifestyle therapy. METHODS: Tai Ji Quan interventions published in English and Chinese were included when they involved healthy adults, reported pre- and post-intervention blood pressure (BP), and had a non-exercise/non-diet control group. We systematically searched 11 electronic databases for studies published through July 31, 2018, yielding 31 qualifying controlled trials. We (1) evaluated the risk of bias and methodological study quality, (2) performed meta-regression analyses following random-effects assumptions, and (3) generated additive models representing the largest possible clinically relevant BP reductions. RESULTS: Participants (n = 3223) were middle-aged (56.6 ± 15.1 years of age, mean ± SD) adults with prehypertension (systolic BP (SBP) = 136.9 ± 15.2 mmHg, diastolic BP (DBP) = 83.4 ± 8.7 mmHg). Tai Ji Quan was practiced 4.0 ± 1.4 sessions/week for 54.0 ± 10.6 min/session for 22.3 ± 20.2 weeks. Overall, Tai Ji Quan elicited significant reductions in SBP (-11.3 mmHg, 95%CI: -14.6 to -8.0; d+ = -0.75) and DBP (-4.8 mmHg, 95%CI: -6.4 to -3.1; d+ = -0.53) vs. control (p < 0.001). Controlling for publication bias among samples with hypertension, Tai Ji Quan trials published in English elicited SBP reductions of 10.4 mmHg and DBP reductions of 4.0 mmHg, which was half the magnitude of trials published in Chinese (SBP reductions of 18.6 mmHg and DBP reductions of 8.8 mmHg). CONCLUSION: Our results indicate that Tai Ji Quan is a viable antihypertensive lifestyle therapy that produces clinically meaningful BP reductions (i.e., 10.4 mmHg and 4.0 mmHg of SBP and DBP reductions, respectively) among individuals with hypertension. Such magnitude of BP reductions can lower the incidence of cardiovascular disease by up to 40%.

Effects of regular dance therapy intervention on blood pressure in hypertension individuals: a systematic review and meta-analysis.

INTRODUCTION: Dance therapy is a non-conventional aerobic exercise in cardiovascular rehabilitation. This meta-analysis aimed to update and assess evidence from randomized controlled trials of dance therapy on patients with hypertension. EVIDENCE ACQUISITION: PubMed, web of science, EBSCO, EMBESE, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure databases in English or Chinese were searched and randomized controlled trials were conducted for this meta-analysis to investigate the effects of dance therapy on blood pressure in hypertension patients. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed by I2 test. EVIDENCE SYNTHESIS: Five studies were included according to the eligibility criteria. Dance therapy could significantly reduce the systolic/diastolic pressure of hypertension individuals (SBP:WMD -11.07mmHg; 95%CI, -14.3 to -8.12mmHg, P<0.00001;DBP:WMD-4.16mmHg;95% CI, -6.44to-1.88mmHg, P=0.0004) when compared with the control group. low heterogeneity was observed in this research (P=0.65; I2=0% to SBP; P=0.57; I2 =0% to DBP). Subgroup analysis results showed that the subgroup of less than 12 weeks intervention group reduce the blood pressure more than those of 12 weeks intervention. Dance therapies reduce the SPB of hypertension individuals in African region better than Europe and America hypertension population. CONCLUSIONS: Despite the limited number of studies and people involved, the meta-analysis further demonstrated that dance therapy could reduce SBP and DBP in patients with hypertension. The effect of dance therapy intervention on hypertension might be related to duration of intervention and population gene.

Abnormal diastolic function and Global longitudinal strain in patients with Thalassemia Major on long term chelation therapy.

Cardiac complications are the major cause of mortality in patients with Thalassemia major (TM). Cardiac T2* MRI is currently the gold standard for assessing myocardial iron concentration. The aim of our study was to assess whether any echocardiographic parameter would correlate with these findings in patients well established on chelation therapy. This was a prospective study on patients with TM who are regularly followed in our clinic. Patients had a cardiac MRI and echocardiogram within 2 months of each other. Echo parameters included global longitudinal strain and diastolic function. We also compared these findings with those from a cohort of thalassemia intermedia (TI) and normal controls. A total of 84 patients (mean age 26.3 ± 6.1 years, 42.8% male) with TM were enrolled. All had normal left ventricular ejection fraction and only 8 patients had MRI T2* < 10. As compared to 17 patients with TI and 53 controls, these patients had significantly higher E/E' and lower pulmonary vein s/dd ratio suggesting early diastolic dysfunction. 28 patients fulfilled criteria for diastolic dysfunction even in the presence of normal MRI T2*. Global longitudinal strain (GLS) was significantly lower in the TM group as compared to the TI and controls. We found no correlation between any of the echo findings and the MRI T2*in TM patients. In patients with thalassemia and MRI T2* > 20 ms features of diastolic dysfunction persist even in the presence of normal LV function and normal GLS. This suggests that diastolic function remains abnormal even when myocardial iron concentrations are normal and follow up therefore is essential.

[ALTERATIONS IN SENSITIVE MEASURES OF CARDIAC FUNCTION IN HEALTHY NEONATES DURING PHOTOTHERAPY].

OBJECTIVES: Phototherapy has been reported to reduce coronary blood flow in neonates but without affecting gross measures of cardiac function. The aim of our current study was to evaluate earlier, more sensitive changes in cardiac function during phototherapy. METHODS: Nineteen neonates with jaundice treated with phototherapy had Doppler echocardiographic evaluation, before, during and after phototherapy and were compared to 25 matched controls. Sensitive measures for cardiac performance in this study included left ventricular dimension, ventricular Doppler parameters and regional function assessment. RESULTS: Phototherapy was associated with a significant increase in heart rate. In addition, atrioventricular valve closure to opening interval decreased significantly during phototherapy while ventricular ejection times tended to decrease. However, left and right ventricular filling parameters and outflow velocity parameters, longitudinal tissue-Doppler annular velocities and myocardial performance indices were not affected by phototherapy and were similar to those in controls. Coronary blood velocities and integrals decreased significantly during phototherapy. CONCLUSIONS: Our study found no differences in early and sensitive measures of cardiac performance including the diastolic and systolic function, despite modestly lower flow in coronary arteries among healthy neonates during phototherapy.

Complete Electroanatomic Imaging of the Diastolic Pathway Is Associated With Improved Freedom From Ventricular Tachycardia Recurrence.

BACKGROUND: The development of multielectrode mapping catheters has expanded the spectrum of mappable ventricular tachycardias (VTs). Full diastolic pathway recording has been associated with a high rate of VT termination during radiofrequency ablation as well as noninducibility at study end. However, the role of diastolic pathway mapping on VT recurrence has yet to be clearly elucidated. We aimed to explore the role of complete diastolic pathway activation mapping on VT recurrence. METHODS: Eighty-five consecutive patients who underwent VT ablation guided by high-density mapping were enrolled. During activation mapping, the presence of electrical activity in all segments of diastole defined the evidence of having had recorded the whole diastolic interval. Patients were categorized as having recorded the full diastolic pathway, partial diastolic pathway, or no diastolic pathway map performed. Recurrences of VT were defined as appropriate implantable cardioverter defibrillator therapies or on the basis of ECG-documented arrhythmia. RESULTS: Eighty-five patients were included. Complete recording of the diastolic pathway was achieved in 36/85 (42.4%) patients. Partial recording of the diastolic pathway of the clinical VT was achieved in 24/85 (28.2%) patients. No recording of the diastolic pathway of the clinical VT was feasible in 25/85 patients (29.4%). At a mean of 12.8 months, freedom from VT recurrence was 67% in the overall cohort. At a mean of 12.8 months, freedom from VT recurrence was 88%, 50%, and 55% in patients who had full diastolic activity recorded, partial diastolic activity recorded, or underwent substrate modification, respectively; the observed differences were statistically significant (P=0.02). CONCLUSIONS: Mapping of the entire diastolic pathway was associated with a higher freedom from VT recurrence as compared with partial diastolic pathway recording and substrate modification. The use of multielectrode mapping catheters in recording diastolic activity may help predict those VTs employing intramural circuits and further optimize ablation strategies.

Understanding of metals dysregulation in patients with systolic and diastolic dysfunction in ischemic heart disease.

Ischemic heart disease (IHD) is the leading cause of death and chronic disability in the world. IHD affects both the systolic and diastolic function of the heart which progressively leads to heart failure; a structural and functional impairment of filling or ejection of blood from the heart. In this study, the progression of systolic and diastolic dysfunction characterized according to their echocardiographic parameters including left ventricular ejection fraction (EF), grades of diastolic dysfunction and ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e'), were correlated with differential regulation of various metals in patients sera samples (n = 62) using inductive coupled plasma-mass spectrometry (ICP-MS). Chromium, nickel and selenium were found significant (p < 0.05) in patients having EF < 45% compared with EF > 45%. In patients with systolic dysfunction (EF < 45%), the level of selenium was decreased while the level of chromium and nickel was increased compared to patients with EF > 45%. Selenium level was also decreased significantly (p < 0.05) in grade 1A and 2 patients that are considered as higher grades of diastole dysfunction in comparison to grade 0-1. Overall, selenium deficiency was identified in both systolic and diastolic dysfunctions of IHD patients corresponding to the progression of disease that could be related to many metabolic and translational pathways specifically which involve selenoproteins.

Occupational Exposures and Cardiac Structure and Function: ECHO-SOL (Echocardiographic Study of Latinos).

Background Our objective was to determine associations of occupational exposures with cardiac structure and function in Hispanic/Latino adults. Methods and Results Employed participants were included (n=782; 52% women, mean age 52.9 years). Occupational exposures to burning wood, vehicle exhaust, solvents, pesticides, and metals at the current and longest-held job were assessed by questionnaire. Survey multivariable linear regression analyses were used to model the relationship of each self-reported exposure with echocardiographic measures of cardiac structure and function. Exposure to burning wood at the current job was associated with decreased left ventricular (LV) ejection fraction (-3.1%; standard error [SE], 1.0 [P=0.002]). When the analysis was restricted to exposure at the longest-held job, occupational exposure to burning wood was associated with increased LV diastolic volume (6.7 mL; SE, 1.6 [P<0.0001]), decreased LV ejection fraction (-2.7%; SE, 0.6 [P<0.0001]), worse LV global longitudinal strain (1.0%; SE, 0.3 [P=0.0009]), and decreased right ventricular fractional area change (-0.02; SE, 0.004 [P<0.001]). Exposure to pesticides was associated with worse average global longitudinal strain (0.8%; SE, 0.2 [P<0.0001]). Exposure to metals was associated with worse global longitudinal strain in the 2-chamber view (1.0%; SE, 0.5 [P=0.04]), increased stroke volume (3.6 mL; SE, 1.6 [P=0.03]), and increased LV mass indexed to BSA (9.2 g/m2; SE, 3.8 [P=0.01]) or height (4.4 g/m2.7; SE, 1.9 [P=0.02]). Conclusions Occupational exposures to burning wood, vehicle exhaust, pesticides, and metals were associated with abnormal parameters of LV and right ventricular systolic function. Reducing exposures to toxic chemicals and particulates in the workplace is a potential opportunity to prevent cardiovascular disease in populations at risk.

Safety of Short-Term Supplementation with Methylliberine (Dynamine®) Alone and in Combination with TeaCrine® in Young Adults.

Methylliberine (Dynamine®; DYM) and theacrine (Teacrine®; TCR) are purine alkaloids purported to have similar neuro-energetic effects as caffeine. There are no published human safety data on DYM, and research on TCR is limited. The purpose of this study was to examine the effect of four weeks of DYM supplementation with and without TCR on cardiovascular function and blood biomarkers. One-hundred twenty-five men and women (mean age 23.0 yrs, height 169.7 cm, body mass 72.1 kg; n = 25/group) were randomly assigned to one of five groups: low-dose DYM (100 mg), high-dose DYM (150 mg), low-dose DYM with TCR (100 mg + 50 mg), high-dose DYM with TCR (150 mg + 25 mg) , and placebo. Regardless of group and sex, significant main effects for time were noted for heart rate, systolic blood pressure, and QTc (p < 0.001), high-density lipoproteins (p = 0.002), mean corpuscular hemoglobin (p = 0.018), basophils (p = 0.006), absolute eosinophils (p = 0.010), creatinine (p = 0.004), estimated glomerular filtration rate (p = 0.037), chloride (p = 0.030), carbon dioxide (p = 0.023), bilirubin (p = 0.027), and alanine aminotransferase (p = 0.043), among others. While small changes were found in some cardiovascular and blood biomarkers, no clinically significant changes occurred. This suggests that DYM alone or in combination with TCR consumed at the dosages used in this study does not appear to negatively affect markers of health over four weeks of continuous use.

Decreasing Delirium Through Music: A Randomized Pilot Trial.

BACKGROUND: Management of delirium in intensive care units is challenging because effective therapies are lacking. Music is a promising nonpharmacological intervention. OBJECTIVES: To determine the feasibility and acceptability of personalized music (PM), slow-tempo music (STM), and attention control (AC) in patients receiving mechanical ventilation in an intensive care unit, and to estimate the effect of music on delirium. METHODS: A randomized controlled trial was performed in an academic medical-surgical intensive care unit. After particular inclusion and exclusion criteria were applied, patients were randomized to groups listening to PM, relaxing STM, or an audiobook (AC group). Sessions lasted 1 hour and were given twice daily for up to 7 days. Patients wore noise-canceling headphones and used mp3 players to listen to their music/audiobook. Delirium and delirium severity were assessed twice daily by using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the CAM-ICU-7, respectively. RESULTS: Of the 1589 patients screened, 117 (7.4%) were eligible. Of those, 52 (44.4%) were randomized, with a recruitment rate of 5 patients per month. Adherence was higher in the groups listening to music (80% in the PM and STM groups vs 30% in the AC group; P = .01), and 80% of patients surveyed rated the music as enjoyable. The median number (interquartile range) of delirium/coma-free days by day 7 was 2 (1-6) for PM, 3 (1-6) for STM, and 2 (0-3) for AC (P = .32). Median delirium severity was 5.5 (1-7) for PM, 3.5 (0-7) for STM, and 4 (1-6.5) for AC (P = .78). CONCLUSIONS: Music delivery is acceptable to patients and is feasible in intensive care units. Further research testing use of this promising intervention to reduce delirium is warranted.

Increase in diastolic blood pressure induced by fragrance inhalation of grapefruit essential oil is positively correlated with muscle sympathetic nerve activity.

Fragrance inhalation of essential oils is widely used in aromatherapy, and it is known to affect blood pressure (BP) and heart rate (HR) via autonomic control of circulation. In this study, we aimed to test the hypothesis that the changes in hemodynamics with fragrance inhalation were observed along with changes in muscle sympathetic nerve activity (MSNA). In study 1, thirteen healthy men were exposed to fragrance stimulation of grapefruit essential oil for 10 min, and BP, HR, and MSNA were continuously measured. In study 2, another nine healthy men were exposed to the same fragrance stimulation; responses in BP and HR were continuously measured, and plasma noradrenaline and cortisol concentrations were determined. We found that diastolic BP increased significantly during fragrance inhalation, while the other variables remained unchanged in both studies. Although MSNA burst frequency, burst incidence, and total activity remained unchanged during fragrance inhalation, we found a significant linear correlation between changes in diastolic BP in the last 5 min of fragrance inhalation and changes in MSNA burst frequency. The plasma cortisol concentration decreased significantly at 10 min of fragrance inhalation, though the noradrenaline concentration remained unchanged. These results suggest, for the first time, that changes in BP with fragrance inhalation of essential oil are associated with changes in MSNA even with decreased stress hormone.