Single dose of synthetic microRNA-199a or microRNA-149 mimic does not improve cardiac function in a murine model of myocardial infarction.

Intramyocardial injection of synthetic microRNAs (miRs) has recently been reported to be beneficial after myocardial infarction (MI). We conducted a randomized blinded study to evaluate the efficacy and reproducibility of this strategy in a mouse model of reperfused MI using rigorous methodology. Mice undergoing a 60-min coronary occlusion followed by reperfusion were randomly assigned to control miR, hsa-miR-199a-3p, hsa-miR-149-3p, or hsa-miR-149-5p mimic treatment. Intramyocardial injections of miRs were performed in the border zone right after reperfusion. At 8 weeks after MI, there were no significant differences in ejection fraction (EF) among groups (EF = 27.1 ± 0.4% in control group [n = 6] and 25.9 ± 0.5%, 26.0 ± 0.8%, and 26.6 ± 0.6% in hsa-miR-199a-3p, hsa-miR-149-3p, or hsa-miR-149-5p groups, respectively [n = 9 each]). Net change (delta) in EF at 8 weeks compared with day 3 after MI was - 4.1% in control and - 3.2%, - 2.4%, and - 0.4% in the miR-treated groups (P = NS). Assessment of cardiac function by hemodynamic studies (a method independent of echocardiography) confirmed that there was no difference in left ventricular systolic or diastolic function among groups. Consistent with the functional data, histological analysis showed no difference in scar size, cardiomyocyte area, capillary density, collagen content, or apoptosis among groups. In conclusion, this randomized, blinded study demonstrates that intramyocardial injection of a single dose of synthetic hsa-miR-199a-3p, hsa-miR-149-3p, or hsa-miR-149-5p mimic does not improve cardiac function or remodeling in a murine model of reperfused MI. The strategy of using synthetic miR mimics for cardiac repair after MI needs to be evaluated with rigorous preclinical studies before its potential clinical translation.

El efecto de los antihiperglicemiantes en los parámetros ecocardiográficos diastólicos y sistólicos / The effect of antihyperglycemic agents on diastolic and systolic echocardiographic parameters

Resumen La enfermedad metabólica diabetes mellitus tipo 2 ocasiona alteraciones en la estructura y en la funcionalidad miocárdica por diferentes mecanismos bioquímicos los cuales pueden ocasionar disfunción diastólica y sistólica, por lo cual el uso de los antihiperglicemiantes aparte de su efecto en la reducción de la hiperglicemia y la hemoglobina glicosilada, algunos han demostrado reducción en la mortalidad cardiovascular y de las hospitalizaciones por insuficiencia cardiaca, basado en estudios clínicos sobre este impacto en el miocardio. También se ha evaluado el efecto de estos fármacos por medio del ecocardiograma transtorácico. El objetivo de este articulo es analizar los valores de los parámetros ecocardiográficos sistólicos y diastólicos en pacientes diabéticos tipo 2 o alguna cardiopatía de base como antecedente de infarto al miocardio e insuficiencia cardiaca con el uso de metformina, sulfonilureas, los inhibidores de la dipeptidilpeptidasa 4 (sitagliptina, alogliptina y linagliptina, vildagliptina), los análogos de GLP1 (liraglutide, albiglutide y exenatide).

Abstract Metabolic disease type 2 diabetes mellitus causes alterations in both structure and myocardial functionality by different biochemical mechanisms which can cause diastolic and systolic dysfunction, which is why the use of antihyperglycemic agents apart from its effect in the reduction of hyperglycemia and glycosylated hemoglobin, some groups have shown reduction in cardiovascular mortality and hospitalizations for heart failure this based on clinical studies, by hypothesis, theories and pleiotropic mechanisms on this impact on the myocardium. On the other hand, the effect of these drugs on the myocardium has also been evaluated by transthoracic echocardiography. Therefore, the aim of this article is to analyze the values of systolic and diastolic echocardiographic parameters in type 2 diabetic patients or some underlying heart disease as a history of myocardial infarction and heart failure with the use of metformin, sulfonylureas, inhibitors of the dipeptidylpeptidase 4 (sitagliptin, alogliptin and linagliptin, vildagliptin), GLP1 analogues (liraglutide, albiglutide and exenatide).

Echocardiographic long-term follow-up of adult survivors of pediatric cancer treated with Dexrazoxane-Anthracyclines association.

AIMS: Cardiovascular disease is a well-recognized cause of increased late morbidity and mortality among survivors of childhood cancer treated with anthracyclines. Co-administration of Dexrazoxane has been shown to significantly reduce short-term and mid-term cardiotoxicity. Aim of this study was to assess cardiac function in long-term (>10 years) survivors of childhood tumors treated with dexrazoxane/anthracycline association. METHODS AND RESULTS: Twenty cancer survivors previously treated with co-administration of anthracyclines-dexrazoxane for childhood renal tumors or sarcoma and a control group of 20 healthy subjects were enrolled in the study. Echocardiographic measurements included 3D left ventricular (LV) ejection fraction (LVEF) and LV and right ventricular (RV) global longitudinal strain (GLS). Among cancer survivors group the median age at diagnosis was 5 years (1-17) and they were evaluated at median follow-up time of 21.5 years (10-26). No evidence of cardiac toxicity, as defined by current guidelines, was reported in all survivors. No significant differences in standard and deformation imaging parameters were observed between survivors and controls (3D LVEF 58 ±â€¯3% vs 60 ±â€¯5% p = NS; LV GLS -21 ±â€¯1% vs -21 ±â€¯2% p = NS; RV GLS -23 ±â€¯2% vs -23 ±â€¯5% p = NS). No second tumor was registered in dexrazoxane-treated survivors. CONCLUSIONS: Our findings may support the role of dexrazoxane as a useful strategy for cardio-protection in children undergoing anthracycline based treatment. However, large randomized trials are needed to confirm the cardio-protective role of dexrazoxane in pediatric setting at long-term follow-up.

Further verification of some postulates of the combined toxicity theory: New animal experimental data on separate and joint adverse effects of lead and cadmium.

Outbred male rats were repeatedly injected intraperitoneally two-level sub-lethal doses of lead acetate and/or cadmium chloride solutions 3 times a week during 6 weeks. The animals developed explicit, even if moderate, subchronic intoxication characterized by a large number of indices, both common to both metals (including increased DNA fragmentation coefficient) and lead-specific. Special attention was paid to hemodynamic and electrocardiographic effects. The combined action of lead and cadmium was modeled with the help of the Response Surface Methodology to obtain additional support for the previously substantiated postulates of combined toxicity's typological ambiguity. This is dependent on which particular effect comes under consideration, on its level, and on the acting dose ratio. For one and the same toxic combination, the type of combined toxic action can vary from synergistic to contra-directional. In particular, the actions of lead and cadmium on blood pressure were found to be opposite in direction. Furthermore, it is shown once again that the systemic toxic effects of a metal combination, its in vivo genotoxicity included, can be more or less attenuated by background administration of a theoretically justified composition of biologically active agents.

Clinicopathologic, hemodynamic, and echocardiographic effects of short-term oral administration of anti-inflammatory doses of prednisolone to systemically normal cats.

OBJECTIVE: To evaluate the clinicopathologic, hemodynamic, and echocardiographic effects of short-term administration of anti-inflammatory dosages of prednisolone to systemically normal cats. ANIMALS: 10 cats with allergic dermatitis and 10 healthy control cats. PROCEDURES: Cats with allergic dermatitis were randomly allocated to 2 groups and received 2 dosages of prednisolone (1 and 2 mg/kg/d, PO, for 7 days) in a crossover design followed by 9-day tapering and 14-day washout periods. Each prednisolone-treated cat was matched to a healthy control cat on the basis of sex, neuter status, age (± 1 year), and body weight (± 10%). Control cats received no treatment during the 35-day observation period. Clinicopathologic, echocardiographic, and hemodynamic variables were measured at baseline (day 0) and predetermined times during and after prednisolone administration and compared within and between the 2 treatment groups. RESULTS: Prednisolone-treated cats had expected clinicopathologic alterations (mild increases in neutrophil and monocyte counts and serum concentrations of albumin, cholesterol, and triglycerides) but systolic arterial blood pressure; blood glucose, serum potassium, and cardiac biomarker concentrations; urinary sodium excretion; and echocardiographic variables did not differ significantly from baseline at any time. Statistically significant, albeit clinically irrelevant, increases in blood glucose and N-terminal pro-B-type natriuretic peptide concentrations were observed between baseline and the prednisolone pharmacokinetic steady state (7 days after initiation) only when the 2-mg/kg dosage was administered. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated short-term oral administration of anti-inflammatory dosages of prednisolone did not cause relevant hemodynamic, echocardiographic, or diabetogenic effects in systemically normal cats with allergic dermatitis.

Impacts of different anesthetic agents on left ventricular systolic function in mice assessed by echocardiography.

The present experiments were performed to study the effects and time trends of different anesthetic agents on the left ventricular (LV) systolic function and heart rate by high-resolution echocardiography in mice. Ten male C57BL/6J mice were submitted to echocardiography imaging separated by 72-hour intervals under the following conditions: 1) conscious mice, 2) mice anesthetized with isoflurane (ISO, inhaled), 3) mice anesthetized with tribromoethanol (TBE, intraperitoneal), 4) mice anesthetized with chloral hydrate (CH, intraperitoneal), and 5) mice anesthetized with pentobarbital sodium (PS, intraperitoneal). The effect of ISO, TBE, CH, and PS on LV systolic function was measured at 0, 1, 2, 3, 4, 6, 8, and 10 min after anesthesia. The results showed that LV systolic function and heart rate (HR) of anesthetized mice were reduced significantly (P<0.05), compared with results in the same mice studied in the conscious state. In addition, the results indicated that the anesthetic with the least effect on LV function was CH, and followed by TBE, PS, ISO. We conclude that different anesthetic agents always depressed the HR and LV systolic function of mice, and, furthermore, the effects and time trends of different anesthetics on LV function are different. In echocardiographic experiments, we should choose proper anesthetic agents according to the experimental requirements.

Acute cardiac effects of high dose steroid treatment: A speckle tracking echocardiography study.

PURPOSE: High-dose steroid therapy (HDST) has frequent side-effects that appear at its cessation and depend on its dose. However, there is a lack of studies about the acute effects of HDST on cardiac function in adult patients. METHODS: We included in this study 30 patients who underwent HDST (intravenously at doses ranging from 250 to 1000 mg) and 30 healthy control subjects with similar demographic and clinical characteristics, between September and December 2016. Echocardiographic measurements were made before and during the first 3 hours after the end of treatment, and results were compared between patients and controls. RESULTS: There was no difference in baseline biochemical and echocardiographic characteristics between the patient and control groups. While left ventricular global longitudinal strain (LVGLS) and strain rate E were higher after treatment, no significant change was observed in conventional echocardiographic variables. CONCLUSIONS: LVGLS, but not conventional echocardiographic variables, showed an increase in cardiac systolic function at the acute phase of HDST.

Effects of short-term anti-inflammatory glucocorticoid treatment on clinicopathologic, echocardiographic, and hemodynamic variables in systemically healthy dogs.

OBJECTIVE To investigate mechanisms by which anti-inflammatory doses of orally administered intermediate-acting glucocorticoids (prednisone) could predispose dogs to progression of heart disease or congestive heart failure. ANIMALS 11 client-owned dogs with allergic dermatitis and 11 matched healthy control dogs. PROCEDURES Clinicopathologic, echocardiographic, and hemodynamic variables were measured. Dogs with allergic dermatitis then received prednisone (1 mg/kg, PO) once daily for 14 consecutive days beginning on day 0 (baseline), followed by a tapering and washout period; control dogs received no treatment. Measurements were repeated on days 7, 14, and 35. Linear mixed modeling was used to compare changes in variables across measurement points and between dog groups. RESULTS Prednisone administration caused no significant changes in serum sodium or potassium concentration, blood glucose concentration, or target echocardiographic variables. The change from baseline in systolic arterial blood pressure at day 7 was significantly greater in prednisone-treated dogs than in control dogs. Expected changes in hematologic and serum biochemical values with prednisone administration (neutrophilia, eosinopenia, isosthenuria, and high serum alkaline phosphatase and alanine aminotransferase activities) also occurred in the prednisone-treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that anti-inflammatory doses of orally administered glucocorticoids have the potential to adversely impact cardiac function in dogs by causing an increase in blood pressure and thus increased cardiac afterload.

Comparison of Intranasal Dexmedetomidine and Oral Pentobarbital Sedation for Transthoracic Echocardiography in Infants and Toddlers: A Prospective, Randomized, Double-Blind Trial.

BACKGROUND: Acquisition of transthoracic echocardiographic (TTEcho) images in children often requires sedation. The optimal sedative for TTEcho has not been determined. Children with congenital heart disease are repeatedly exposed to sedatives and anesthetics that may affect brain development. Dexmedetomidine, which in animals alters brain structure to a lesser degree, may offer advantages in this vulnerable population. METHODS: A prospective, randomized, double-blind trial enrolled 280 children 3-24 months of age undergoing outpatient TTEcho, comparing 2.5 µg·kg intranasal dexmedetomidine to 5 mg·kg oral pentobarbital. Rescue sedation, for both groups, was intranasal dexmedetomidine 1 µg·kg. The primary outcome was adequate sedation within 30 minutes without rescue sedation, assessed by blinded personnel. Secondary outcomes included number of sonographer pauses, image quality in relation to motion artifacts, and parental satisfaction. RESULTS: Success rates with a single dose were not different between sedation techniques; 85% in the pentobarbital group and 84% in the dexmedetomidine group (P = .8697). Median onset of adequate sedation was marginally faster with pentobarbital (16.5 [interquartile range, 13-21] vs 18 [16-23] minutes for dexmedetomidine [P = .0095]). Time from drug administration to discharge was not different (P = .8238) at 70.5 (64-83) minutes with pentobarbital and 70 (63-82) minutes with dexmedetomidine. Ninety-five percent of sedation failures with pentobarbital and 100% of dexmedetomidine failures had successful rescue sedation with intranasal dexmedetomidine. CONCLUSIONS: Intranasal dexmedetomidine was comparable to oral pentobarbital sedation for TTEcho sedation in infants and did not increase the risk of clinically important adverse events. Intranasal dexmedetomidine appears to be an effective "rescue" sedative for both failed pentobarbital and dexmedetomidine sedation. Dexmedetomidine could be a safer option for repeated sedation in children, but further studies are needed to assess long-term consequence of repeated sedation in this high-risk population.

A dose-escalation study of combretastatin A4-phosphate in healthy dogs.

Combretastatin A4-Phosphate (CA4P) is a vascular disrupting agent revealing promising results in cancer treatments for humans. The aim of this study was to investigate the safety and adverse events of CA4P in healthy dogs as a prerequisite to application of CA4P in dogs with cancer. Ten healthy dogs were included. The effects of escalating doses of CA4P on physical, haematological and biochemical parameters, systolic arterial blood pressure, electrocardiogram, echocardiographic variables and general wellbeing were characterised. Three different doses were tested: 50, 75 and 100 mg m-2 . At all 3 CA4P doses, nausea, abdominal discomfort as well as diarrhoea were observed for several hours following administration. Likewise, a low-grade neutropenia was observed in all dogs. Doses of 75 and 100 mg m-2 additionally induced vomiting and elevation of serum cardiac troponine I levels. At 100 mg m-2 , low-grade hypertension and high-grade neurotoxicity were also observed. In healthy dogs, doses up to 75 mg m-2 seem to be well tolerated. The severity of the neurotoxicity observed at 100 mg m-2 , although transient, does not invite to use this dose in canine oncology patients.

Early assessment of the left ventricular function by epirubicin-induced cardiotoxicity in postoperative breast cancer patients.

OBJECTIVE: Epirubicin (Epi) is a potent and effective drug for many malignant cancers with serious cardiotoxicity. Therefore, layer-specific two-dimensional speckle tracking echocardiography (2D-STE) was used to evaluate the longitudinal and circumferential systolic function of the left ventricular for the early detection of cardiotoxicity in this retrospective work. METHODS: Overall, 130 female patients with postoperative breast cancer who did not receive radiotherapy were classified into three groups: Group A (control group, n = 40) without any chemotherapy; Group B (n = 44) administered Epi at 180 ~ 240 mg/m2 ; and Group C (n = 46) administered Epi at ≥360 mg/m2 . Peak and global systolic longitudinal strains (GLS) in the total and endocardium, mid-myocardium, and epicardium were measured and calculated from apical four-chamber, apical two-chamber, and left ventricular long-axis views, respectively. Peak and global circumferential strains (GCS) in the total and endocardium, mid-myocardium, and epicardium were measured and calculated from mitral annulus, papillary muscle, and apical levels of the short-axis view, respectively. RESULTS: The total GLS and GLS of the endocardium in every view were significantly reduced in group C compared with both groups A and B (P < .05), but there was no significant difference between groups A and B (P > .05). The GLS of the epicardium and mid-myocardium in groups B and C were not significantly reduced (P > .05). There were no significant differences in the total GCS and layer-specific GCS of endocardium, mid-myocardium, and epicardium among the three groups (P > .05). CONCLUSIONS: Left ventricular longitudinal systolic dysfunction was detected. Moreover, an impaired endocardium was also detected in an early assessment by layer-specific 2DSTE.

Intravenous nicorandil for treatment of the urgent phase acute heart failure syndromes: A randomized, controlled trial.

BACKGROUND: Vasodilators, such as nitroglycerin, have long been first-line treatments for acute heart failure syndromes (AHFS). Nicorandil is a vasodilator with dual potassium channel opening and nitrate properties. However, there are no randomized controlled studies of intravenous nicorandil safety and efficacy in the urgent phase AHFS. We examined the symptomatic, hemodynamic, and echocardiographic effects and safety, and 60-day clinical outcomes of intravenous nicorandil, in addition to standard therapy, in patients with AHFS in the urgent phase. METHODS: In this prospective, randomized controlled trial, 106 AHFS patients were randomized within one hour of arrival to receive either standard therapy (control group, n=56) or standard therapy plus simultaneous intravenous nicorandil (0.2 mg/kg bolus followed by 0.2 mg/kg/h for 24 h; nicorandil group, n=50). Outcomes were assessed at 60 days. RESULTS: Patients in the nicorandil group exhibited greater improvement of dyspnea as measured by change in a five-point Likert scale compared to those in the control group (after 1 h infusion: p=0.006, 6 h; p<0.001). The nicorandil group also showed significantly improved E/e', an estimate of left ventricular filling pressure, at 1 and 24 h ( p=0.001 and p=0.004, respectively). In addition, intravenous nicorandil therapy was safe and did not cause side effects such as excessive hypotension or reflex tachycardia. However, it did not reduce all-cause mortality and readmission rates at 60 days. CONCLUSIONS: Addition of intravenous nicorandil to standard therapy for urgent phase AHFS improved dyspnea and left ventricular diastolic function but not 60-day outcome.

Effects of Acute Carbon Monoxide Poisoning on ECG and Echocardiographic Parameters in Children.

The aim of the current study is to investigate the effects of CO (carbon monoxide) on the cardiovascular system via electrocardiographic, echocardiographic and biochemical findings in children. This prospective study included 22 children with CO poisoning and 24 healthy children as a control group. The CO-intoxicated children were evaluated via electrocardiography and echocardiography 1 h after admission to the emergency department and daily until their discharge from the hospital. Blood gasses, complete blood account, troponin I and creatinine kinase-MB(CK-MB) were assessed daily. Tpeak-end (p:0.001), QTc durations (p:0.02), Tpeak-end dispersion (p:0.001) and Tpeak-end/QT ratio (p:0.001) of CO-intoxicated patients were significantly higher than those in the control group. Mitral E duration (p:0.001), mitral E/A ratio (p:0.001) and left ventricle contractile fraction (p:0.023) at admission were significantly lower, and left ventricle myocardial performance index was higher (p:0.001) in the CO poisoning group. Troponin I and CK-MB levels were higher at admission in 6 (27 %) and 4 (18 %) patients, respectively. The heart is the most critical organ in pediatric CO poisoning. These children present subclinical systolic and diastolic left ventricle dysfunction even in mild cases. Although, in children with acute CO-intoxication ventricular repolarization is impaired, it seems to be reversible like other findings.

A prospective, randomized study: Evaluation of the effect of rosuvastatin in patients with chronic obstructive pulmonary disease and pulmonary hypertension.

OBJECTIVES: Statins by their anti-inflammatory and endothelial stabilizing effect can be beneficial in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH). The present study was done to evaluate the effect of rosuvastatin on pulmonary functions and quality of life (QOL) in patients with concomitant COPD and PH. MATERIALS AND METHODS: It was a prospective, randomized, double-blind, placebo-controlled, study conducted in patients with COPD and PH. A total of sixty patients were assigned to receive either rosuvastatin 10 mg or placebo once a day in addition to their conventional treatment for 12 weeks. Routine blood investigations, pulmonary functions, echocardiogram, exercise capacity, and QOL using a questionnaire were assessed at the baseline and after 12 weeks. RESULTS: In patients of rosuvastatin group, there was a statistically significant increase in peak expiratory flow rate (PEFR) (P = 0.04) but no significant change in other pulmonary functions: Forced vital capacity (FVC), forced expiratory volume at 1 s (FVC, FEV1, FEV1/FVC), and echocardiogram parameters. There was a significant increase in 6-min walk test (6-min walk distance) (P = 0.03) at the end of 12 weeks. On comparing with placebo, rosuvastatin showed a significant reduction (P = 0.045) in COPD exacerbations while adverse effects did not differ. CONCLUSION: Statins have a favorable effect on patients with COPD and PH regarding the improvement in PEFR, COPD exacerbations, and exercise capacity. Such effects can be beneficial in these patients and more so in patients with concomitant coronary artery disease or hyperlipidemia where long-term benefits of statins have been established.

Biventricular takotsubo cardiomyopathy in an elderly woman with uncontrolled type 2 diabetes: the biphasic echocardiographic and clinical pattern.

We describe a case of an elderly woman who was diagnosed with a biventricular takotsubo cardiomyopathy (TTC) with combination of emotional stress and poorly controlled type 2 diabetes. We observed significant correlation between biphasic improvement of right (after 4 days) and left ventricle function (after 4 weeks) with normalization glycemic status. To our knowledge, this is the first reported case in the literature of biventricular TTC with such metabolic disturbances.

Epinephrine and left atrial and left ventricular diastolic function decrease in normal subjects.

BACKGROUND: We assessed the effect of epinephrine over left atrial and left ventricular diastolic function in subjects without structural heart disease. METHODS: Twenty-seven, 34.6±17.2year-old patients without structural heart disease were included. Intravenous epinephrine (50 to 100ng/kg/min) was infused. Left atrial and ventricular functions were evaluated by means of echocardiography before and during the epinephrine infusion. RESULTS: No complications were observed. Significant increases in heart rate and systolic blood pressure were recorded. Both left atrial (minimal and maximal) volumes increased but increase in the minimal volume was more pronounced, and the ejection fraction diminished. Left atrial expansion index decreased and the fraction of left ventricular inflow volume resulting from atrial contraction increased. Two patients displayed abnormal left ventricular diastolic function. During epinephrine infusion, E/A and e' decreased, and isovolumetric relaxation time increased. CONCLUSIONS: In this group of young adults without structural heart disease, epinephrine infusion was safe, did not produce any complications, and induced a small but significant decrease in left atrial function and left ventricular diastolic function.

Nitroglycerin mediated dilation evaluated by ultrasound is associated with sTWEAK in hemodialysis patients.

AIMS: The main cause of death in hemodialysis (HD) patients is cardiovascular disease. Ultrasound assessment of the brachial artery dysfunction is easily achievable and can non-invasively detect atherosclerosis in various stages. In HD patients the cardiovascular risk profile is different and the determinants of brachial arterial function can be distinct comparing with general population. The aim of the study is to assess the determinants of arterial brachial function (flow-mediated and nitroglycerin-mediated dilation) evaluated by ultrasound in HD patients and their relation with tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) described as atherosclerotic marker in chronic kidney disease patients. MATERIAL AND METHODS: We conducted a cross-sectional observational study on 54 hemodialysis patients. We recorded clinical and biological data and we measured sTWEAK serum levels by ELISA. We evaluated the arterial brachial function by measurement of flow-mediated and nitroglycerin-mediated dilation, using B mode ultrasound. RESULTS: The determinants of flow-mediated dilation were: Kt/V (r=0.47, p<0.001), LDL-cholesterol (r=0.29, p=0.04), and total cholesterol (r=0.31, p=0.02). Flow-mediated dilation correlated with nitroglycerin-mediated dilation (r=0.70, p<0.001). In multivariate analysis kt/V was the only significant predictor for flow-mediated dilation (p=0.04). Nitroglycerin-mediated dilation correlates with sTWEAK (r=-0.30, p=0.03), systolic blood pressure (r=-0.28, p=0.04) and pulse pressure (r=-0.31, p=0.02). In multivariate analysis sTWEAK was the only significant predictor for nitroglycerin-mediated dilation (p=0.04). CONCLUSIONS: The main determinant of nitroglycerin-mediated dilation was sTWEAK. In addition, decreased nitroglycerin-mediated dilation was associated with higher systolic blood pressure and pulse pressure. The main determinant of FMD was Kt/V. Increased flow-mediated dilation was associated with better dialysis efficiency and high total cholesterol and LDL-cholesterol.

Evaluation of Trastuzumab-induced early cardiac dysfunction using two-dimensional Strain Echocardiography.

AIM: Trastuzumab, a chemotherapeutic agent used in the treatment of breast cancer. has been shown to induce subclinical left ventricular (LV) dysfunction during a three to six month period as evidenced by strain echocardiographic examination without any change occurring in the ejection fraction of LV. The present study evaluated the presence of subclinical LV dysfunction using strain echocardiography 1 day and 7 days after the initiation of trastuzumab therapy. MATERIAL AND METHODS: The patients with breast cancer receiving adjuvant trastuzumab therapy underwent 2-dimensional, tissue Doppler, and strain echocardiographic examination at baseline and 1 day and 7 days after therapy. LV global longitudinal strain (GLS), global circumferential strain (GCS) values, and other echocardiographic parameters were calculated. RESULTS: A total of 40 females, mean age 50+/-10 years, were evaluated. Of these patients, 97% received anthracycline and 73% received radiotherapy before the initiation of trastuzumab therapy. No change was observed in any of the echocardiographic parameters 1 day after the initiation of trastuzumab therapy (p>0.05). The LV ejection fraction, tissue Doppler parameters, and GCS values did not show any changes 7 days after the initiation of therapy, whereas significant decreases were observed in GLS value (19.2+/-4.0% vs. 17.2+/-3.4, p=0.001) and systolic annular velocity of the lateral LV wall (S' velocity) (10.5+/-3.2 vs. 8.6+/-2.2, p=0.002). CONCLUSION: Trastuzumab therapy is associated with subclinical LV dysfunction as early as 7 days after initiation of the therapy as evidenced by the decreases in GLS value of LV and systolic annular velocity of the lateral LV wall.

The Medical Treatment of New-Onset Peripartum Cardiomyopathy: A Systematic Review of Prospective Studies.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare disorder with potentially fatal consequences, which occurs mainly in previously healthy women. The aetiology of PPCM remains unknown and various pathologic mechanisms have been proposed, including immune-mediated injuries and impaired response to oxidative stress and inflammatory cytokines. Several therapies have been studied, but few have been validated in a well-designed randomized controlled trial. METHODS: In the present study we sought to review the medical treatment intended for acute PPCM. To this end, we performed a systematic review of the literature of randomized and nonrandomized prospective clinical studies. RESULTS: We identified 2 randomized controlled trials that evaluated the dopamine agonist bromocriptine and the inotrope levosimendan, respectively, and 1 nonrandomized study that evaluated the nonselective phosphodiesterase inhibitor pentoxifylline. We reviewed the pathophysiological, pharmacological, and clinical properties for each treatment option identified. Bromocriptine and pentoxifylline both improved left ventricular systolic function and patient-oriented clinical end points and levosimendan did not improve mortality or echocardiographic findings of PPCM. CONCLUSIONS: In this review we identified bromocriptine and pentoxifylline, but not levosimendan, as potentially useful agents to improve left ventricle function and outcomes in PPCM.